Quantitative assessment of ecological risk from pollution source based on geostatistical analysis and APCS-MLR model.

The safety of human health and agricultural production depends on the quality of farmland soil. Risk assessment of heavy metal pollution sources could effectively reduce the hazard of soil pollution from various sources. This study has identified and quantitatively analyzed pollution sources with geostatistical analysis and the APCS-MLR model. The potential ecological risk index was combined with the APCS-MLR model which has quantitatively calculated the source contribution. The results revealed that As, Cr, Cd, Pb, Zn, and Cu were enriched in soil. Geostatistical analysis and the APCS-MLR model have apportioned four pollution sources. The Mn and Ni were attributed to natural sources; As and Cr were from agricultural activities; Cu and Zn were originated from natural sources; Cd and Pb were derived from atmospheric deposition. Atmospheric deposition and agricultural activities were the largest contributors to ecological risk of heavy metals in soil, which accounted for 56.21% and 36.01% respectively. Atmospheric deposition and agricultural activities are classified as priority sources of pollution. The combination of source analysis receptor model and risk assessment is an effective method to quantify source contribution. This study has quantified the ecological risks of soil heavy metals from different sources, which will provide a reliable method for the identification of primary harmfulness sources of pollution for future studies.

Changes in physicochemical properties and formation process of colloidal nanoparticles (CNPs) during the lamb soup stewing.

Colloidal nanoparticles (CNPs), as carriers of nutrients, naturally exist in food or form during cooking. In this study, the colloidal properties, structures, rheological properties, and chemical composition location of CNPs were analyzed during 15 min to 5 h lamb soup stewing. With the increasing stewing time, the particle size and absolute value of the zeta potential of CNPs increased, indicating that CNPs became more stable. As the stewing time increased, the blue-shifted Fourier transform infrared spectroscopy absorption peaks and the red-shifted fluorescence spectroscopy absorption peaks certificated the structural changes in CNPs. And α-helix and ß-turn content decreased, while ß-sheet and random coil content increased in processing, potentially resulting in the opening CNPs structures. In addition, our findings revealed that proteins were encapsulated within the lipids in the inner part, while carbohydrates were dispersed in the outermost layers of the CNPs with a phospholipid bilayer.

Regulation of B-1 cell numbers and B cell-mediated antibody production by Inpp4b.

T and B lymphocytes are crucial players in cellular and humoral immune responses. The development, activation and differentiation of T and B lymphocytes are regulated by the best characterized PI3K-PI (3,4,5) P3-AKT phosphoinositide signalling pathway. As a branch of the phosphoinositide signalling pathway, the lipid phosphatase INPP4B inhibits AKT activation through degrading the phosphoinositide signalling messenger PI (3,4) P2. However, the role of Inpp4b in T and B lymphocytes remains elusive. Here, we reported that Inpp4b was highly expressed in human and murine T- and B-1 lymphocytes. Despite its higher expression in T lymphocytes, neither T cell development and homeostasis nor in vitro T cell activation and CD4+ T cell differentiation were altered upon loss of Inpp4b. Interestingly, combined direct phenotype analysis of Inpp4b conventional knockout mice and adoptive transfer studies revealed that ablation of Inpp4b intrinsically reduced peritoneal B-1 cells rather B-2 cells. Moreover, Inpp4b deficiency led to impaired thymus independent (TI) and thymus dependent (TD) antigens-induced antibody production. Further in vitro analysis revealed that CD40-mediated B cell proliferation was impaired upon ablation of Inpp4b. Our findings reveal that Inpp4b is required in regulating B-1 cell numbers and B cell-mediated antibody production.

Investigation of the Correlation between Cuff Inflatable Hypertension and the Difference in Interarm Diastolic Pressure Induced by Single Arm Ischemia.

The correlation between cuff inflatable hypertension and the difference in interarm diastolic pressure induced by single arm ischemia is investigated. A total of 126 patients undergoing coronary angiography in our hospital from January 2020 to January 2021 are selected and divided into the non-pseudohypertension (non-PHT) group (64 cases) and the PHT group (62 cases) according to the difference between systolic blood pressure and diastolic blood pressure measured directly and indirectly. The patients are subjected to the beam arm ischemia test and blood pressure measurement. The diastolic pressure differences between the patients before and after the beam arm are analyzed, and endothelial function and imaging indicators are compared. The risk factors for PHT are analyzed by binary logistic regression, and the diagnostic efficacy of diastolic blood pressure difference interarms (DBPI-r) for PHT patients is analyzed by receiver operating characteristic (ROC) curve. The experimental results show that the diastolic pressure difference induced by single arm ischemia can be used in the diagnosis of cuff inflatable hypertension.

Identification of novel B-1 transitional progenitors by B-1 lymphocyte fate-mapping transgenic mouse model Bhlhe41 dTomato-Cre.

B-1 lymphocytes exhibit specialized roles in host defense against multiple pathogens. Despite the fact that CD19+CD93+B220lo/- B cells have been identified as B-1 progenitors, the definition for B-1 progenitors remains to be elucidated as CD19+CD93+B220+ B cells are capable to give rise to B-1 cells. Given that transcription factor Bhlhe41 is highly and preferentially expressed in B-1 cells and regulates B-1a cell development, we generated a transgenic mouse model, Bhlhe41dTomato-Cre , for fate mapping and functional analysis of B-1 cells. Bhlhe41dTomato-Cre mice efficiently traced Bhlhe41 expression, which was mainly restricted to B-1 cells in B-cell lineage. We showed an efficient and specific Cre-mediated DNA recombination in adult B-1 cells and neonatal B-1 progenitors rather than B-2 cells by flow cytometric analysis of Bhlhe41 dTomato-Cre/+ Rosa26 EYFP mice. Treatment of Bhlhe41 dTomato-Cre/+ Rosa26 iDTR mice with diphtheria toxin revealed a robust efficacy of B-1 cell depletion. Interestingly, using Bhlhe41 dTomato-Cre mice, we demonstrated that neonatal B-1 progenitors (CD19+CD93+B220lo/-) expressed Bhlhe41 and were identical to well-defined transitional B-1a progenitors (CD19+CD93+B220lo/-CD5+), which only gave rise to peritoneal B-1a cells. Moreover, we identified a novel population of neonatal splenic CD19hidTomato+B220hiCD43loCD5lo B cells, which differentiated to peritoneal B-1a and B-1b cells. Bhlhe41 deficiency impaired the balance between CD19hidTomato+B220lo/-CD5hi and CD19hidTomato+B220hiCD5lo cells. Hence, we identified neonatal CD19hidTomato+B220hiCD43loCD5lo B cells as novel transitional B-1 progenitors. Bhlhe41 dTomato-Cre/+ mouse can be used for fate mapping and functional studies of B-1 cells in host-immune responses.

Induction of the apoptosis, degranulation and IL-13 production of human basophils by butyrate and propionate via suppression of histone deacetylation.

Allergic diseases are caused by dysregulated Th2 immune responses involving multiple effector cells including basophils. Short chain fatty acids (SCFAs), mainly acetate, propionate and butyrate, exert immunomodulatory functions via activation of its receptors GPR41 and GPR43, and inhibition of the histone deacetylases (HDACs) activity. In allergic diseases, SCFAs suppress the activity of mast cells, eosinophils and type 2 innate lymphoid cells (ILC2) but enhance the function of Th2 cells. Here, we aimed to elucidate the function of SCFAs on human basophils. Human basophils were purified from healthy donors by flow cytometric sorting. The surface proteins, apoptosis and degranulation of basophils were analyzed by flow cytometric analysis. The mRNA expression was assayed using real-time PCR. Interleukin 4 (IL-4) and IL-13 were measured by ELISA. Histone acetylation was examined by western blot. GPR41 was expressed by basophils and was enhanced by IL-3. Acetate induced intracellular calcium influx in basophils which was suppressed by blocking GPR41. Propionate and butyrate, but not acetate, induced the expression of CD69 and IL-13. In addition, propionate and butyrate enhanced IgE-mediated basophil degranulation but inhibited basophil survival and IL-4 secretion. Propionate and butyrate induced histone acetylation of basophils and suppression of HDACs activity mimicked the effects of propionate and butyrate on human basophils. Our findings demonstrate that propionate and butyrate may play a complex role in regulating basophil apoptosis, activation and degranulation via inhibiting HDACs activity. The in vivo effects of SCFAs on the regulation of basophil-associated allergic diseases need to be further explored.

Effects of different aberrations in the CRLF2 gene on the biological characteristics and drug sensitivities of Nalm6 cells.

INTRODUCTION: To investigate the effects and mechanism of action of upregulated CRLF2 expression resulting from different aberrations in the CRLF2 gene (CRLF2, CRLF2 + IK6, P2RY8-CRLF2 and CRLF2 F232C) in the B cell ALL cell line Nalm6. METHODS: Cell proliferation was measured using cell counting kit-8. Transcriptome sequencing technology (RNA-seq) was used to compare changes in gene expression resulting from different aberrations in CRLF2. High-throughput drug sensitivity testing was used to determine the drug sensitivity of cells. RESULTS: All four aberrations in CRLF2 upregulated CRLF2 expression and promoted the proliferation of Nalm6 cells. The RNA-seq results showed the upregulation of genes in the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway and the downregulation of genes in the cell cycle pathway in the CRLF2 F232C-overexpressing cells. Western blotting showed that the expression of p-STAT5 protein was significantly higher in the CRLF2 F232C-overexpressing cells. Cells with aberrations in CRLF2 were more resistant to cyclophosphamide and drugs commonly used during treatment than cells in the vector group. The half-maximal inhibitory concentration (IC50 or GI50 ) of dexamethasone was significantly higher in the CRLF2 F232C-overexpressing cell line. CONCLUSIONS: The overexpression of CRLF2, CRLF2 + IK6, P2RY8-CRLF2 and CRLF2 F232C promotes the proliferation of Nalm6 cells, activates the JAK/STAT signalling pathway and leads to a reduction in sensitivity towards various chemotherapeutic drugs.

iTRAQ-Based Phosphoproteomic Analysis of Toxoplasma gondii Tachyzoites Provides Insight Into the Role of Phosphorylation for its Invasion and Egress.

The invasion and egress are two key steps in lytic cycle vital to the propagation of Toxoplasma gondii infection, and phosphorylation is believed to play important roles in these processes. However, the phosphoproteome of T. gondii at these two stages has not been characterized. In this study, we profiled the phosphoproteome of tachyzoites at the stages of "just invading" (JI) and "prior to egress" (PE) based on iTRAQ quantitative analysis, in which a total of 46 phosphopeptides, 42 phosphorylation sites, and 38 phosphoproteins were detected. In the comparison of PE vs. JI, 10 phosphoproteins were detected with their phosphorylation level significantly changed, and four of them were demonstrated to be significantly down-regulated at the transcriptional level. Bioinformatic analysis of these identified phosphoproteins suggested that phosphorylation-mediated modulation of protein function was employed to regulate the pathway of toxoplasmosis and metabolism and cellular processes correlated with tachyzoite's binding, location, and metabolism, and thus play vital roles in the parasite lytic cycle. Moreover, cytoskeletal network (CN)-associated Inner Membrane Complex (IMC1, IMC4, IMC6 and IMC12), Intravascular Network (IVN)-related GRAs (GRA2, GRA3, GRA7 and GRA12), and Parasitophorous Vacuole Membrane (PVM)-localized ROP5 were shown to be enriched at the central nodes in the protein interaction network generated by bioinformatic analysis, in which the phosphorylation level of IMC4, GRA2, GRA3, and GRA12 were found to be significantly regulated. This study revealed the main cellular processes and key phosphoproteins crucial for the invasion and egress of T. gondii, which will provide new insights into the developmental biology of T. gondii in vitro and contribute to the understanding of pathogen-host interaction from the parasite perspective.

Interleukin 3-induced GITR promotes the activation of human basophils.

Human basophils regulate allergic reactions by secreting histamine, interleukin 4 (IL-4) and IL-13 through key surface receptors FcεRI as well as IL-3R, which are constitutively expressed on basophils. IL-3/IL-3R signaling axis plays key roles in regulating the development and activation of basophils. We and others have shown that IL-3-induced surface receptors e.g. ST2, IL-17RB and IL-2 receptors regulate the biology of basophils. However, the expression and function of IL-3-induced surface proteins on human basophils remain to be elucidated. We in this study aimed to identify new basophil activation regulators by transcriptomic analysis of IL-3-stimulated basophils. Gene expression microarray analysis of IL-3-treated basophils revealed 2050 differentially expressed genes, of which 323 genes encoded surface proteins including GITR. We identified that GITR was preferentially induced by IL-3 rather than anti-IgE, IL-33, fMLP and C5a. IL-3-induced GITR was suppressed by inhibitors targeting JAK2, PI3K and MEK1/2. Stimulation of IL-3-treated basophils by GITR enhanced the expression of IL-4 and IL-13. Moreover, IgE-mediated degranulation was enhanced by GITRL in the presence of IL-3. This transcriptomic analysis of IL-3-activated basophils helps to identify novel activation regulator. IL-3-induced GITR promoted the activation of basophils, adding new evidence supporting GITR as an important player in Th2-associated immune responses.

Bioavailability of heavy metals in contaminated soil as affected by different mass ratios of biochars.

The biochars are efficient adsorbent of heavy metals. However, the type of biochar species determines the effectiveness of biochars for immobilization of heavy metals. In this experiment, we mixed different biochars in variable mass ratios and evaluated their effects on plant growth and bioavailability of heavy metals. The results revealed that amendment of single and mixed biochars has increased pH, EC, available P and K of soil. The straw block biochar with maize straw biochar at a mass ratio of 1:2 (SDM) has significantly decreased Pb and Cu concentration in soil. The straw block biochar with maize straw biochar at a mass ratio of 2:1 (DSM) has highly increased the dry biomass of Chinese cabbage than single biochar or control, whereas plant physiological properties were mostly not affected. It is concluded that peanut shell biochar with maize straw biochar at a mass ratio of 2:1 (DPS) and DSM have significantly decreased Pb, Zn and Cu concentration in plants. The single peanut shell biochar has significantly decreased the plant Cd concentration. The ability of transport of heavy metals in Chinese cabbage was in the sequence of Cd > Zn > Cu > Pb. The mixing of different biochars has decreased the concentration of heavy metals in plants more effectively than single biochar.

Interleukin 2 regulates the activation of human basophils.

Basophils are important effector cells in allergic disorders and anti-parasitic immune response. A number of activators including interleukin 3 (IL-3) and IgE have been identified in the regulation of human basophils expressing mediators such as histamine and leukotriene C4 (LTC4) and cytokines, including IL-4 and IL-13. Human basophils express high levels of IL-2 receptors. However, the function of the IL-2 pathway in basophils remains unknown. Here, we identified that IL-2 induced the activation of human basophils in vitro to express a variety of inflammatory cytokines and chemokines including IL-5, IL-13, GM-CSF and CCL-17. This effect by IL-2 is confirmed by an upstream regulator analysis using Ingenuity pathway analysis. Of note, one of the top regulated cytokines, IL-5, was for the first time identified to be induced by IL-2 in human basophils rather than IL-3 or anti-IgE. Immunofluorescence analysis of skin specimens from bullous pemphigoid and eczema revealed that infiltrating basophils in skin lesions widely expressed IL-5 and GM-CSF. Together, our findings reveal IL-2 as a novel regulator of human basophils. This adds a new layer to support the importance of basophils in allergic disorders.

Negative life events and major depressive disorder among HIV-positive individuals in Guangdong, China: A cross-sectional study.

HIV-positive individuals encounter a number of negative life events (NLEs). This cross-sectional study aimed to evaluate the association between NLEs and major depressive disorder (MDD) among HIV-positive individuals in Guangdong, China, about which little is known.HIV-positive individuals were recruited from the Centers for Disease Prevention and Control of Guangzhou, Zhongshan, and Yangjiang from September 2007 to September 2008. Data on NLEs were collected using a questionnaire. The Structured Clinical Interview for DSM-IV-TR Axis I Disorders-Patient Edition (SCID-I/P) based on the DSM-IV criteria was used to diagnose MDD. Multiple logistic regression analyses were conducted to evaluate the association between NLEs and MDD.Among the 339 participants, 306 (90.27%) reported that one or more NLEs had ever occurred. Participants who reported NLEs that included HIV infection, financial problems, AIDS diagnosis, HIV/AIDS discrimination, conflict with spouse or lover, conflict with other family members, problems in childbearing, and conflict with nonfamily were at a higher risk of MDD. Participants who reported more NLEs in the last year had a higher risk of MDD (OR = 2.86, 95%CI: 1.76-4.65) than individuals who reported fewer NLEs. Individuals with higher chronic stress scores had a higher risk of MDD (OR = 4.36, 95%CI: 2.44-7.78) than individuals with lower chronic stress scores. However, acute stress was not associated with MDD.NLEs were common among HIV-positive individuals. MDD was associated with a greater number of NLEs and the increased chronic stress caused by the NLEs. Interventions should be tailored to those who reported NLEs to help reduce the risk of MDD and increase the quality of life among HIV-positive individuals.

Prevalence of and factors associated with major depressive disorder among HIV-positive individuals in Guangdong, China.

BACKGROUND: People living with HIV may suffer from mental disorders. We aimed to explore the prevalence of and factors associated with major depressive disorder (MDD) among HIV-positive individuals in Guangdong, China, about which little is known. METHODS: A cross-sectional study was conducted to recruit HIV-positive individuals from the Centers for Disease Prevention and Control of Guangzhou, Zhongshan, and Yangjiang from September 2007 to September 2008. Data were collected by questionnaires. MDD was diagnosed and assessed by two psychiatrists using the Structured Clinical Interview for DSM-IV-TR Axis I Disorders-Patient Edition (SCID-I/P) based on the DSM-IV criteria. Multiple logistic regression analyses were conducted to explore the factors associated with MDD. RESULTS: The prevalences of lifetime MDD and current MDD among the 339 included participants were 22.71% (95% confidence interval [CI]: 18.25-27.17%) and 12.09% (95%CI: 8.62%-15.57%), respectively. The results of multiple logistic regression showed that patients with AIDS had a higher risk of lifetime MDD (odds ratio [OR] = 2.69, 95%CI: 1.38-5.26) and current MDD (OR = 3.51, 95%CI: 1.59-7.75) than HIV-infected individuals. Participants with more number of negative life events were more likely to have lifetime MDD (OR = 2.33, 95%CI: 1.34-4.06) and current MDD (OR = 3.77, 95%CI: 1.76-8.09) than individuals with fewer negative life events. Individuals with higher score of social support were less likely to have lifetime MDD (OR = 0.45, 95%CI: 0.26-0.80) and current MDD (OR = 0.46, 95%CI: 0.21-0.97) than individuals with less social support. CONCLUSIONS: The prevalence of MDD was high among HIV-positive individuals in China. AIDS diagnosis, decreased social support, and an increased number of negative life events were risk factors for MDD.

Chinese C allele carriers of the ERCC5 rs1047768 polymorphism are more sensitive to platinum-based chemotherapy: a meta-analysis.

It is suspected that ERCC5 rs1047768 and rs17655 polymorphisms influence the response to platinum-based chemotherapy. This meta-analysis was performed to summarize the scattered evidence regarding the association between these two polymorphisms and sensitivity to platinum-based treatment. Thirteen studies were included after a comprehensive literature search. The pooled odds ratios and 95% confidence intervals suggested that the C allele of the ERCC5 rs1047768 polymorphism is associated with elevated sensitivity to platinating agents, especially for Chinese patients. However, no difference among rs17655 genotypes could be detected.

Influence of the ABCB1 polymorphisms on the response to Taxane-containing chemotherapy: a systematic review and meta-analysis.

PURPOSE: Multidrug resistance mediated by ABCB1 has been perceived to be one of the obstacles for cancer chemotherapy. This meta-analysis was performed to verify the effect of the ABCB1 rs1045642 and rs1128503 polymorphisms on the response to Taxane-containing chemotherapy. METHODS: Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were employed to evaluate the impact of these two ABCB1 polymorphisms. R scripts were developed to perform the meta-analysis. RESULTS: A total of nine articles (including nine studies for rs1045642 and five for rs1128503) were collected in our systematic review. However, our meta-analysis showed no significant effect of these two ABCB1 polymorphisms on the response to Taxane-containing regimens. CONCLUSIONS: This study highlights the unsuitability of relying on the ABCB1 rs1045642 and rs1128503 polymorphisms as therapeutic response biomarkers of Taxane-containing chemotherapy. Further polycentric studies in larger and multiracial populations are needed to validate the conclusions.

The complete chloroplast genome of Primulina and two novel strategies for development of high polymorphic loci for population genetic and phylogenetic studies.

BACKGROUND: Primulina Hance is an emerging model for studying evolutionary divergence, adaptation and speciation of the karst flora. However, phylogenetic relationships within the genus have not been resolved due to low variation detected in the cpDNA regions. Chloroplast genomes can provide important information for phylogenetic and population genetic studies. Recent advances in next-generation sequencing (NGS) techniques greatly facilitate sequencing whole chloroplast genomes for multiple individuals. Consequently, novel strategies for development of highly polymorphic loci for population genetic and phylogenetic studies based on NGS data are needed. METHODS: For development of high polymorphic loci for population genetic and phylogenetic studies, two novel strategies are proposed here. The first protocol develops lineage-specific highly variable markers from the true high variation regions (Con_Seas) across whole cp genomes, instead of traditional noncoding regions. The pipeline has been integrated into a single perl script, and named "Con_Sea_Identification_and_PIC_Calculation". The second method assembles chloroplast fragments (poTs) and sub-super-marker (CpContigs) through our "SACRing" pipeline. This approach can fundamentally alter the strategies used in phylogenetic and population genetic studies based on cp markers, facilitating a transition from traditional Sanger sequencing to RAD-Seq. Both of these scripts are available at https://github.com/scbgfengchao/ . RESULTS: Three complete Primulina chloroplast genomes were assembled from genome survey data, and then two novel strategies were developed to yield highly polymorphic markers. For experimental evaluation of the first protocol, a set of Primulina species were used for PCR amplification. The results showed that these newly developed markers are more variable than traditional ones, and seem to be a better choice for phylogenetic and population studies in Primulin a. The second method was also successfully applied in population genetic studies of 21 individuals from three natural populations of Primulina. CONCLUSIONS: These two novel strategies may provide a pathway for similar research in other non-model species. The newly developed high polymorphic loci in this study will promote further the phylogenetic and population genetic studies in Primulina and other genera of the family Gesneriaceae.

[Biocatalytic desymmetric hydrolysis of 3-(4-chlorophenyl)-glutaronitrile to the key precursor of optically pure baclofen].

We produced (S)-4-cyano-3-(4-chlorophenyl)-butyrate by highly stereoselective biocatalyst in this study. A nitrilase-producing strain, named Gibberella intermedia WX12, was isolated by 3-(4-chlorophenyl)-glutaronitrile as substrate in the screening with phenol-sodium hypochlorite method. The fermentation conditions and catalytic properties of this strain were investigated. The preferred carbon and nitrogen sources for nitrilase production were lactose (30 g/L) and peptone (20 g/L). After being cultivated for 96 h, the cells were collected for use in biotransformation. The hydrolysis of 3-(4-chlorophenyl)-glutaronitrile was performed at 30 degrees C in phosphate buffer (pH 8.0, 50 mmol/L) for 24 h to give (S)-4-cyano-3-(4-chlorophenyl)-butyric acid with 90% yield and > 99% of ee, which can be used for the synthesis of (R)- and (S)-baclofen. The configuration of product was determined by chemically converting it to baclofen and comparison with the authentic sample by chiral HPLC analysis.