Considering microplastic characteristics in ecological risk assessment: A case study for China.

Microplastics (MPs) pose a significant global concern, requiring a multifaceted approach to their risk assessment procedures, especially concerning their characteristics in the environment. The Horqin Left Middle Banner in Northeast China was chosen for the research region to investigate the abundance, composition, distribution, and ecological impact of MPs in surface agricultural soils. The concentrations of MPs ranged from 300 to 12800 items/kg, with a median concentration of 1550 items/kg (average = 1994 items/kg). The normal-sized MPs (500-5000 µm) had a higher relative abundance than small MPs (<500 µm). MPs were mainly derived from textiles and packaging and were affected by atmospheric transportation. Rayon and PET fibers were the main polymers identified. Furthermore, the potential environmental risks posed by the fundamental characteristics (abundance, chemical composition, and size) of MPs were quantified using multiple risk assessment models. The conditional fragmentation model indicated a propensity for MPs to degrade into smaller particles. Ecological risk assessments using pollution load index, pollution hazard index, and potential ecological risk index models revealed varying levels of risk. This study conducted a comprehensive assessment of the ecological risks of MPs based on their environmental characteristics, emphasizing the importance of considering multiple factors in the risk assessment process. ENVIRONMENT IMPLICATION: This study investigates the occurrence, distribution, and ecological risk of microplastics (MPs) in agricultural soils of the Northeast Plain of China, a major food production area. MPs are persistent organic pollutants that can pose threats to soil health, crop quality, and food security. By analyzing the composition, size, and source of MPs, as well as their fragmentation and stability in soil, this study provides valuable data for assessing the environmental risk of MPs in agricultural regions. The study also suggests strategies for mitigating MPs pollution and protecting soil ecosystems.

A perspective of spatial variability and ecological risks of antibiotics in the agricultural-pastoral ecotone soils in eastern Inner Mongolia.

Antibiotics have garnered growing attention as pharmaceuticals ubiquitously present in human society. Within the soil environment, antibiotics exhibit a propensity for high environmental persistence, thereby posing a potential threat to the ecosystem. However, research on antibiotics in agricultural-pastoral ecotone soils is scarce. This study investigates the occurrence, distribution and risk of 11 common antibiotics in agricultural soils of the agro-pastoral transition zone in Horqin Left Middle Banner, eastern Inner Mongolia. The total concentration varies from not detectable to 609.62 µg/kg. Tetracyclines are the dominant antibiotic, with a higher detection frequency than Macrolides and Sulfonamides. The detection rates of the three types of antibiotics differ significantly. The study also finds that soil properties (organic matter content, pH, bulk density, clay, cation exchange capacity have no significant correlation with antibiotics in soil. Moreover, spatial regression analysis reveals that population density is the primary factor influencing the spatial distribution of antibiotics in soil. Ecological risk assessment shows that clarithromycin and erythromycin are the two most harmful factors in the ecological risk of agricultural soil.

A Personal Healthcare Knowledge Graph Framework for Diagnosis of Pelvic Masses Diseases.

A Personal Health Knowledge Graph (PHKG) facilitates the efficient integration of potential diagnostic clues from patients' electronic health records with medical knowledge, establishing diagnostic reasoning paths and ensuring accurate, individually interpretable results in the diagnosis of pelvic masses.

Does a Digital Health Application Could Be the Supplement to the Influenza Surveillance System?

Epidemics of seasonal influenza is a major public health concern in china. Historical percentage of influenza-like illness (ILI%) from CDC and health enquiry data from a health-related application were collected, when combining the real-time ILI-related search queries with one-week ago's ILI%, it was able to predict the trend of ILI correctly and timely. Digital health application is potentializing a supplement to the traditional influenza surveillance systems in China.

Integrating environmental carry capacity based on pesticide risk assessment in soil management: A case study for China.

Pesticides are widely used in agriculture and can pose risks to soil health and environmental quality. This study assessed the occurrence, distribution, ecological risk, and environmental carrying capacity of 56 currently used pesticides and three metabolites in agricultural soils of Horqin Left Middle Banner, a typical Northeast China agricultural area. 29 pesticides were detected, with atrazine, clothianidin, and propiconazole the most common. Clothianidin and difenoconazole were high-risk to non-target organisms according to risk-toxicity exposure ratio and risk quotient approaches. This study provides a comprehensive and improvement framework for pesticide soil environmental carrying capacity (SECC) assessment and soil quality protection early warning. The SECC model showed no pesticides surpassed the soil carrying capacity threshold under the current application pattern. Five pesticides (clothianidin, difenoconazole, propiconazole, atrazine, and imidacloprid) may reach the threshold within 10 years, requiring pesticide reduction and soil quality monitoring. An early warning system based on SECC values and cumulative amounts of pesticides predicted that clothianidin may exceed the threshold within 0.1 years. These pesticides should be prioritized for management and regulation to prevent soil environmental degradation. The findings can help inform policymakers and stakeholders on pesticide management and sustainable agricultural development in Horqin Left Middle Banner and similar regions.

Uptake, Translocation, and Terminal Residue of Chlorantraniliprole and Difenoconazole in Rice: Effect of the Mixed-Application with Adjuvant.

Plant oil adjuvants are widely used to improve the utilization rate of pesticides. In this study, the uptake, translocation, and terminal residue of chlorantraniliprole and difenoconazole spraying with plant oil adjuvant in rice (Oryza sativa L.) were evaluated. After being mixed with the tank-mixed plant oil adjuvant, the cuticular wax of rice leaf was destroyed, which decreased the hydrophobicity of the rice leaf and facilitated the wetting, spreading, and penetration of pesticides onto the rice leaf. Additionally, the adjuvant promoted the translocation of difenoconazole from leaves to stems, but had little effect on the translocation of difenoconazole from leaves to roots, while inhibiting chlorantraniliprole translocation. Although adjuvant increased the initial deposition of chlorantraniliprole and difenoconazole on rice, the terminal residue was not significantly affected. The findings can promote the safe use of chlorantraniliprole and difenoconazole in rice production, especially when used with plant oil adjuvants. In the future, studies on more rice cultivars will be necessary to determine the generality of the conclusions.

Macrophage-mediated tumor-targeted delivery of engineered Salmonella typhi murium VNP20009 in anti-PD1 therapy against melanoma.

Bacterial antitumor therapy has great application potential given its unique characteristics, including genetic manipulation, tumor targeting specificity and immune system modulation. However, the nonnegligible side effects and limited efficacy of clinical treatment limit their biomedical applications. Engineered bacteria for therapeutic applications ideally need to avoid their accumulation in normal organs and possess potent antitumor activity. Here, we show that macrophage-mediated tumor-targeted delivery of Salmonella typhimurium VNP20009 can effectively reduce the toxicity caused by administrating VNP20009 alone in a melanoma mouse model. This benefits from tumor-induced chemotaxis for macrophages combined with their slow release of loaded strains. Inspired by changes in the tumor microenvironment, including a decrease in intratumoral dysfunctional CD8+ T cells and an increase in PDL1 on the tumor cell surface, macrophages were loaded with the engineered strain VNP-PD1nb, which can express and secrete anti-PD1 nanoantibodies after they are released from macrophages. This novel triple-combined immunotherapy significantly inhibited melanoma tumors by reactivating the tumor microenvironment by increasing immune cell infiltration, inhibiting tumor cell proliferation, remodeling TAMs to an M1-like phenotype and prominently activating CD8+ T cells. These data suggest that novel combination immunotherapy is expected to be a breakthrough relative to single immunotherapy.

Bacteria-mediated tumor-targeted delivery of tumstatin (54-132) significantly suppresses tumor growth in mouse model by inhibiting angiogenesis and promoting apoptosis.

Tumor growth is an angiogenesis-dependent process and accompanied by the formation of hypoxic areas. Tumstatin is a tumor-specific angiogenesis inhibitor that suppresses the proliferation and induces the apoptosis of tumorous vascular endothelial cells. VNP20009, an attenuated Salmonella typhimurium strain, preferentially accumulates in the hypoxic areas of solid tumors. In this study, a novel Salmonella-mediated targeted expression system of tumstatin (VNP-Tum5) was developed under the control of the hypoxia-induced J23100 promoter to obtain anti-tumor efficacy in mice. Treatment with VNP-Tum5 effectively suppressed tumor growth and prolonged survival in the mouse model of B16F10 melanoma. VNP-Tum5 exhibited a higher efficacy in inhibiting the proliferation and inducing the necrosis and apoptosis of B16F10 cells in vitro and in vivo compared with VNP (control). VNP-Tum5 significantly inhibited the proliferation and migration of mouse umbilical vascular endothelial cells to impede angiogenesis. VNP-Tum5 downregulated the expression of anti-vascular endothelial growth factor A, platelet endothelial cell adhesion molecule-1, phosphorylated phosphoinositide 3 kinase, and phosphorylated protein kinase B and upregulated the expression of cleaved-caspase 3 in tumor tissues. This study is the first to use tumstatin-transformed VNP20009 as a tumor-targeted system for treatment of melanoma by combining anti-tumor and anti-angiogenic effects.

Bacterially mediated drug delivery and therapeutics: Strategies and advancements.

It was already clinically apparent 150 years ago that bacterial therapy could alleviate diseases. Recently, a burgeoning number of researchers have been using bacterial regimens filled with microbial therapeutic leads to diagnose and treat a wide range of disorders and diseases, including cancers, inflammatory diseases, metabolic disorders and viral infections. Some bacteria that were designed to have low toxicity and high efficiency in drug delivery have been used to treat diseases successfully, especially in tumor therapy in animal models or clinical trials, thanks to the progress of genetic engineering and synthetic bioengineering. Therefore, genetically engineered bacteria can serve as efficient drug delivery vehicles, carrying nucleic acids or genetic circuits that encode and regulate therapeutic payloads. In this review, we summarize the development and applications of this approach. Strategies for genetically modifying strains are described in detail, along with their objectives. We also describe some controlled strategies for drug delivery and release using these modified strains as carriers. Furthermore, we discuss treatment methods for various types of diseases using engineered bacteria. Tumors are discussed as the most representative example, and other diseases are also briefly described. Finally, we discuss the challenges and prospects of drug delivery systems based on these bacteria.

Houston Methodist Variant Viewer: An Application to Support Clinical Laboratory Interpretation of Next-generation Sequencing Data for Cancer.

INTRODUCTION: Next-generation-sequencing (NGS) is increasingly used in clinical and research protocols for patients with cancer. NGS assays are routinely used in clinical laboratories to detect mutations bearing on cancer diagnosis, prognosis and personalized therapy. A typical assay may interrogate 50 or more gene targets that encompass many thousands of possible gene variants. Analysis of NGS data in cancer is a labor-intensive process that can become overwhelming to the molecular pathologist or research scientist. Although commercial tools for NGS data analysis and interpretation are available, they are often costly, lack key functionality or cannot be customized by the end user. METHODS: To facilitate NGS data analysis in our clinical molecular diagnostics laboratory, we created a custom bioinformatics tool termed Houston Methodist Variant Viewer (HMVV). HMVV is a Java-based solution that integrates sequencing instrument output, bioinformatics analysis, storage resources and end user interface. RESULTS: Compared to the predicate method used in our clinical laboratory, HMVV markedly simplifies the bioinformatics workflow for the molecular technologist and facilitates the variant review by the molecular pathologist. Importantly, HMVV reduces time spent researching the biological significance of the variants detected, standardizes the online resources used to perform the variant investigation and assists generation of the annotated report for the electronic medical record. HMVV also maintains a searchable variant database, including the variant annotations generated by the pathologist, which is useful for downstream quality improvement and research projects. CONCLUSIONS: HMVV is a clinical grade, low-cost, feature-rich, highly customizable platform that we have made available for continued development by the pathology informatics community.

p53 binding sites in normal and cancer cells are characterized by distinct chromatin context.

The tumor suppressor protein p53 interacts with DNA in a sequence-dependent manner. Thousands of p53 binding sites have been mapped genome-wide in normal and cancer cells. However, the way p53 selectively binds its cognate sites in different types of cells is not fully understood. Here, we performed a comprehensive analysis of 25 published p53 cistromes and identified 3,551 and 6,039 'high-confidence' binding sites in normal and cancer cells, respectively. Our analysis revealed 2 distinct epigenetic features underlying p53-DNA interactions in vivo. First, p53 binding sites are associated with transcriptionally active histone marks (H3K4me3 and H3K36me3) in normal-cell chromatin, but with repressive histone marks (H3K27me3) in cancer-cell chromatin. Second, p53 binding sites in cancer cells are characterized by a lower level of DNA methylation than their counterparts in normal cells, probably related to global hypomethylation in cancers. Intriguingly, regardless of the cell type, p53 sites are highly enriched in the endogenous retroviral elements of the ERV1 family, highlighting the importance of this repeat family in shaping the transcriptional network of p53. Moreover, the p53 sites exhibit an unusual combination of chromatin patterns: high nucleosome occupancy and, at the same time, high sensitivity to DNase I. Our results suggest that p53 can access its target sites in a chromatin environment that is non-permissive to most DNA-binding transcription factors, which may allow p53 to act as a pioneer transcription factor in the context of chromatin.

Cyclic AMP (cAMP) Receptor Protein-cAMP Complex Regulates Heparosan Production in Escherichia coli Strain Nissle 1917.

Heparosan serves as the starting carbon backbone for the chemoenzymatic synthesis of heparin, a widely used clinical anticoagulant drug. The availability of heparosan is a significant concern for the cost-effective synthesis of bioengineered heparin. The carbon source is known as the pivotal factor affecting heparosan production. However, the mechanism by which carbon sources control the biosynthesis of heparosan is unclear. In this study, we found that the biosynthesis of heparosan was influenced by different carbon sources. Glucose inhibits the biosynthesis of heparosan, while the addition of either fructose or mannose increases the yield of heparosan. Further study demonstrated that the cyclic AMP (cAMP)-cAMP receptor protein (CRP) complex binds to the upstream region of the region 3 promoter and stimulates the transcription of the gene cluster for heparosan biosynthesis. Site-directed mutagenesis of the CRP binding site abolished its capability of binding CRP and eliminated the stimulative effect on transcription. (1)H nuclear magnetic resonance (NMR) analysis was further performed to determine the Escherichia coli strain Nissle 1917 (EcN) heparosan structure and quantify extracellular heparosan production. Our results add to the understanding of the regulation of heparosan biosynthesis and may contribute to the study of other exopolysaccharide-producing strains.

Hydrolysis of by-product adenosine diphosphate from 3'-phosphoadenosine-5'-phosphosulfate preparation using Nudix hydrolase NudJ.

3'-Phosphoadenosine-5'-phosphosulfate (PAPS) is the obligate cosubstrate and source of the sulfonate group in the chemoenzymatic synthesis of heparin, a clinically used anticoagulant drug. Previously, we have developed a method to synthesize PAPS with Escherichia coli crude extracts, which include three overexpressed enzymes and a fourth unidentified protein. The unknown protein degrades adenosine diphosphate (ADP), the by-product of PAPS synthesis reaction. To further understand and control the process of in vitro enzymatic PAPS synthesis, we decide to identify the fourth protein and develop a defined method to synthesize PAPS using purified enzymes. Here, we show that the purified Nudix hydrolase NudJ degrades ADP at high efficiency and serves as the fourth enzyme in PAPS synthesis. Under the defined condition of PAPS synthesis, all of the 10-mM ADP is hydrolyzed to form adenosine monophosphate (AMP) in a 15-min reaction. ADP is a better substrate for NudJ than adenosine triphosphate (ATP). Most importantly, the purified NudJ does not cleave the product PAPS. The removal of ADP makes the PAPS peak more separable from other components in the chromatographic purification process. This developed enzymatic approach of PAPS production will contribute to the chemoenzymatic synthesis of heparin.

Enantioselective DNA condensation induced by heptameric lanthanum helical supramolecular enantiomers.

DNA condensation induced by a pair of heptameric La(III) helical enantiomers M-[La7(S-L)6(CO3)(NO3)6(OCH3)(CH3OH)7]·2CH3OH·5H2O and P-[La7(R-L)6(CO3)(NO3)6(OCH3)(CH3OH)5(H2O)2]·2CH3OH·4H2O (M-La and P-La, L=2-(2-hydroxybenzylamino)-3-carbamoylpropanoic acid) has been investigated by UV/vis spectroscopy, fluorescence spectroscopy, CD spectroscopy, EMSA, RALS, DLS, and SEM. The enantiomers M-La and P-La could induce CT-DNA condensation at a low concentration as observed in UV/vis spectroscopy. DNA condensates possessed globular nanoparticles with nearly homogeneous sizes in solid state determined by SEM (ca. 250 nm for M-La and ca. 200 nm for P-La). The enantiomers bound to DNA through electrostatic attraction and hydrogen bond interactions in a major groove, and rapidly condensed free DNA into its compact state. DNA decompaction has been acquired by using EDTA as disassembly agent, and analyzed by UV/vis spectroscopy, CD spectroscopy and EMSA. Moreover, the enantiomers M-La and P-La displayed discernible discrimination in DNA interaction and DNA condensation, as well as DNA decondensation. Our study suggested that lanthanum(III) enantiomers M-La and P-La were efficient DNA packaging agents with potential applications in gene delivery.

Dinuclear nickel(II) triple-stranded supramolecular cylinders: syntheses, characterization and G-quadruplexes binding properties.

Three dinuclear nickel triple-stranded supramolecular cylinders [Ni2(L1)3][ClO4]4 (1), [Ni2(L2)3][ClO4]4 (2) and [Ni2(L3)3][ClO4]4 (3) with bis(pyridylimine) Schiff base containing triphenyl groups in the spacers as ligands were synthesized and characterized. The human telomeric G-quadruplexes binding properties of cylinders 1-3 were evaluated by means of UV-Vis spectroscopy, circular dichroism (CD) spectroscopy and fluorescence resonance energy transfer (FRET) melting assay. UV-Vis studies revealed that the supramolecular cylinders 1-3 could bind to G-quadruplex DNA with high binding constants (Kb values ranging from 0.11-2.2×10(6) M(-1)). FRET melting studies indicated that the cylinders 1-3 had much stronger stabilizing effect on G-quadruplex DNA (ΔTm up to 24.5°C) than the traditional cylinder Ni2L3(4+) just containing diphenylmethane spacers (ΔTm=10.6 °C). Meanwhile, cylinders 1-3 were found to have a modest degree of selectivity for the quadruplex DNA versus duplex DNA in competition FRET assays. Moreover, CD spectroscopy revealed that complex 1 could induce G-quadruplex formation in the absence of metal ions solution and convert antiparallel G-quadruplex into hybrid structure in Na(+) solution. These results provided a new insight into the development of supramolecular cylinders as potential anticancer drugs targeting G-quadruplex DNA.

Hexa-kis-(µ2-4-amino-3,5-dimethyl-4H-1,2,4-triazole)hexa-aqua-tricobalt(II) naphthalene-1,5-disulfonate tetra-chloride.

In the centrosymmetric trinuclear cation of the title compound, [Co3(C4H(8)N4)6(H2O)6](C10H6O6S2)Cl4, the three Co(II) atoms are bridged by six triazole mol-ecules via the N atoms in the 1,2-positions. The central Co(II) atom, lying on an inversion center, is coordinated by six triazole N atoms while the terminal Co(II) atoms are coordinated by three triazole N atoms and three water O atoms in a distorted octa-hedral geometry. The naphthalene-disulfonate anion is also centrosymmetric. The four chloride counter anions are half-occupied; the H atoms of the amino groups show an occupancy of 2/3. O-H⋯Cl, O-H⋯O and N-H⋯O hydrogen bonds link the complex cations and the chloride and naphthalene-1,5-disulfonate anions.

A new type of entangled coordination network: coexistence of polythreading and polyknotting involved molecular braids.

A fascinating polythreaded coordination network formed by 1D crankshaft shaped chains threading into a 2D undulated sheet in a one-over/one-under interweaving fashion was reported, in which the 2D layer exhibits an unusual polyknotted entanglement containing triple-stranded molecular braids.

Is tongxinluo more effective than isosorbide dinitrate in treating angina pectoris? A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Tongxinluo (TXL), consisting of 12 Chinese Materia Medica items catalogued in the Chinese Pharmacopoeia, is commercially available in China, South Korea, and Russia. Hundreds of randomized clinical trials (RCTs) on TXL in treating cardiovascular diseases were conducted and published in China. This study provides a comprehensive Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant systematic review with sensitivity and subgroup analyses to evaluate the evidence about whether TXL is more effective than isosorbide dinitrate (ISDN) in treating ischemic heart disease, particularly angina pectoris. METHODS: RCTs published between 1996 and 2010 on TXL versus ISDN in treating angina pectoris for at least 4 weeks were retrieved from eight bibliographical databases (e.g., MEDLINE,(®) PubMed, Chinese National Knowledge Infrastructure, Cochrane Library, and WanFang Data). The quality of RCTs was assessed with the Jadad scale. Meta-analysis was performed to estimate the overall effects based on symptomatic and electrocardiographic (ECG) improvements. Subgroup analysis, sensitivity analysis, and meta-regression were conducted on the study characteristics of RCTs. RESULTS: Twenty (20) RCTs with a total of 1936 participants were included after eligibility assessment. The Jadad score of all included studies was 2. The means of summary odds ratios (ORs) for comparing TXL and nitrates were 3.30 (95% confidence interval [CI] 2.37-4.58) by symptoms (n=20) and 2.38 (95% CI 1.846-3.09) by ECG (n=18). There was a significant correlation of ORs between symptoms and ECG (ρ=0.77 and p=0.00026). Subgroup analysis, sensitivity analysis, and meta-regression found no significant difference in overall effects among all study characteristics except the years of publication (p=0.0409). CONCLUSIONS: The meta-analysis of 20 eligible RCTs demonstrates moderate evidence that TXL is more effective than ISDN for treating angina pectoris. This result warrants further RCTs of multicenters/countries, larger sample sizes, and higher quality.