A new three-dimensional barium(II) coordination polymer constructed from N,N'-bis(glycinyl)pyromellitic diimide: microwave-assisted synthesis, structure, Hirshfeld surface analysis and properties.

A new three-dimensional (3D) coordination polymer, namely, poly[diaqua[µ5-2,2'-(1,3,5,7-tetraoxo-1,2,3,5,6,7-hexahydropyrrolo[3,4-f]isoindole-2,6-diyl)diacetato]barium(II)], [Ba(C14H6N2O8)(H2O)2]n, (I), has been synthesized by the microwave-irradiated reaction of Ba(NO3)2 with N,N'-bis(glycinyl)pyromellitic diimide {BGPD, namely, 2,2'-(1,3,5,7-tetraoxo-1,2,3,5,6,7-hexahydropyrrolo[3,4-f]isoindole-2,6-diyl)diacetatic acid, H2L}. The title compound was structurally characterized by single-crystal X-ray diffraction analysis and powder X-ray diffraction analysis, as well as IR spectroscopy. In the crystal structure of (I), the BaII ion is nine-coordinated by six carboxylate O atoms from five symmetry-related L2- dianions and one imide O atom, as well as two water O atoms. The coordination geometry of the central BaII ion can be described as a spherical capped square antiprism. One carboxylate group of the ligand serves as a µ3-bridge linking the BaII cations into a one-dimensional polynuclear secondary building unit (SBU). Another carboxylate group of the ligand acts as a µ2-bridge connecting the 1D SBUs, thereby forming a two-dimensional (2D) SBU. The resulting 2D SBUs are extended into a 3D framework via the pyromellitic diimide moiety of the ligand as a spacer. The 3D Ba framework can be simplified as a 5-connected hexagonal boron nitride net (bnn) topology. The intermolecular interactions in the 3D framework were further investigated by Hirshfeld surface analysis and the results show that the prominent interactions are H...O (45.1%), Ba...O (11.1%) and C...H (11.1%), as well as H...H (11.1%) contacts. The thermal stability, photoluminescence properties and UV-Vis absorption spectra of (I) were also investigated. The coordination polymer exhibits a fluorescence emission with a quantum yield of 0.071 and high thermal stability.

2D coordination polymers of cadmium(II) and zinc(II) derived from N,N'-bis(glycinyl)pyromellitic diimide: microwave-assisted synthesis, structures, spectroscopic properties and influence of metal-ion size.

Two new two-dimensional (2D) coordination polymers (CPs), namely, poly[diaqua[µ4-2,2'-(1,3,5,7-tetraoxo-1,2,3,5,6,7-hexahydropyrrolo[3,4-f]isoindole-2,6-diyl)diacetato-κ4O:O':O'':O''']cadmium(II)], [Cd(C14H6N2O8)(H2O)2]n (1), and poly[[tetraaqua[µ4-2,2'-(1,3,5,7-tetraoxo-1,2,3,5,6,7-hexahydropyrrolo[3,4-f]isoindole-2,6-diyl)diacetato-κ4O:O':O'':O'''][µ2-2,2'-(1,3,5,7-tetraoxo-1,2,3,5,6,7-hexahydropyrrolo[3,4-f]isoindole-2,6-diyl)diacetato-κ2O:O']dizinc(II)] dihydrate], {[Zn(C14H6N2O8(H2O)2]·H2O}n (2), have been synthesized by the microwave-irradiated reaction of Cd(CH3COO)2·2H2O and Zn(CH3COO)2·2H2O, respectively, with N,N'-bis(glycinyl)pyromellitic diimide {BGPD, namely, 2,2'-(1,3,5,7-tetraoxo-1,2,3,5,6,7-hexahydropyrrolo[3,4-f]isoindole-2,6-diyl)diacetic acid, H2L}. In the crystal structure of 1, the CdII ion is six-coordinated by four carboxylate O atoms from four symmetry-related L2- dianions and two coordinated water molecules, furnishing an octahedral coordination geometry. The bridging L2- dianion links four symmetry-related CdII cations into a 2D layer-like structure with a 3,4-connected bex topology. In the crystal structure of 2, the ZnII ion is five-coordinated by three carboxylate O atoms from three different L2- dianions and two coordination water molecules, furnishing a trigonal bipyramidal coordination geometry. Two crystallographically independent ligands serve as µ4- and µ2-bridges, respectively, to connect the ZnII ions, thereby forming a 2D layer with a 3,3-connected hcb topology. Crystal structure analysis reveals the presence of n→π* interactions between two carbonyl groups of the pyromellitic diimide moieties in 1 and 2. CP 1 exhibits an enhanced fluorescence emission compared with free H2L. The framework of 2 decomposes from 720 K, indicating its high thermal stability. A comparative analysis of a series of structures based on the BGPD ligand indicates that the metal-ion size has a great influence on the connection modes of the metal ions due to different steric effects, which, in turn, affects the structures of the SBUs (secondary building units) and frameworks.

Influence of a diet meal plan on pepsinogen I and II, gastrin-17, and nutritional status in gastric ulcer patients.

BACKGROUND: Gastric ulcers (GUs) have a high risk of clinical morbidity and recurrence, and further exploration is needed for the prevention, diagnosis, and treatment of the disease. AIM: To investigated the effects of a diet plan on pepsinogen (PG) I, PG II, gastrin-17 (G-17) levels and nutritional status in patients with GUs. METHODS: A total of 100 patients with GUs treated between May 2022 and May 2023 were enrolled, with 47 patients in the control group receiving routine nursing and 53 patients in the experimental group receiving dietary nursing intervention based on a diet plan. The study compared the two groups in terms of nursing efficacy, adverse events (vomiting, acid reflux, and celialgia), time to symptom improvement (burning sensation, acid reflux, and celialgia), gastric function (PG I, PG II, and G-17 levels), and nutritional status [prealbumin (PA) and albumin (ALB) levels]. RESULTS: The experimental group showed a markedly higher total effective rate of nursing, a significantly lower incidence of adverse events, and a shorter time to symptom improvement than the control group. Additionally, the experimental group's post-intervention PG I, PG II, and G-17 levels were significantly lower than pre-intervention or control group levels, whereas PA and ALB levels were significantly higher. CONCLUSION: The diet plan significantly reduced PG I, PG II, and G-17 levels in patients with GUs and significantly improved their nutritional status.

Factors Associated with Acute Pulmonary Embolism in Patients with Hypoxia After off-Pump Coronary Artery Bypass Grafting: A Case-Control Study.

Purpose: This study aims to explore the factors linked to the occurrence of acute pulmonary thromboembolism (PE) within a cohort of patients exhibiting hypoxic saturation (oxygen saturation levels falling below 93%), subsequent to undergoing off-pump coronary artery bypass grafting (OPCABG). Methods: A retrospective case-control study was conducted. A total of 296 patients met the inclusion and exclusion criteria, divided into PE group (100 cases) and non-PE group (196 cases) according to whether they had PE or not. The preoperative and postoperative information of patients were collected and statistically analyzed. Results: The results from a multivariate logistic regression analysis indicated the following factors were independently linked to PE following OPCABG: history of smoking (OR = 3.019, 95% CI, 1.437-6.634, P = 0.004), preoperative arterial oxygen partial pressure ≤78.9 mmHg (OR = 3.686, 95% CI, 1.708-8.220, P = 0.001), presence of postoperative lower extremity deep venous thrombosis (OR = 4.125, 95% CI, 1.886-9.310, P < 0.001), elevated postoperative D-dimer levels >6.76 mg/l (OR = 8.078, 95% CI, 3.749-18.217, P<0.001), postoperative NT-BNP levels (OR = 1.001, 95% CI: 1.000-1.001, P = 0.011), and elevated postoperative pulmonary arterial pressure >33.0 mmHg (OR = 10.743, 95% CI: 3.422-37.203, P < 0.001). The developed nomogram exhibited a high predictive accuracy with an area under the curve of 0.913 (95% CI: 0.878-0.948). Conclusion: When patients have a history of preoperative smoking, decreased preoperative arterial oxygen pressure, postoperative lower limb DVT, increased postoperative pulmonary artery pressure, and elevated postoperative D-Dimer and NT pro-BNP levels, it is recommended to take perioperative preventive measures, timely diagnostic evaluation, and if necessary, anticoagulant treatment. In addition, the results of this study may improve the diagnostic sensitivity of medical staff for postoperative PE in OPCABG, thereby increasing the detection rate and potentially reducing the need for excessive medical imaging procedures.

Phylogenetic and Evolutionary Comparison of Mitogenomes Reveal Adaptive Radiation of Lampriform Fishes.

Lampriform fishes (Lampriformes), which primarily inhabit deep-sea environments, are large marine fishes varying from the whole-body endothermic opah to the world's longest bony fish-giant oarfish, with species morphologies varying from long and thin to deep and compressed, making them an ideal model for studying the adaptive radiation of teleost fishes. Moreover, this group is important from a phylogenetic perspective owing to their ancient origins among teleosts. However, knowledge about the group is limited, which is, at least partially, due to the dearth of recorded molecular data. This study is the first to analyze the mitochondrial genomes of three lampriform species (Lampris incognitus, Trachipterus ishikawae, and Regalecus russelii) and infer a time-calibrated phylogeny, including 68 species among 29 orders. Our phylomitogenomic analyses support the classification of Lampriformes as monophyletic and sister to Acanthopterygii; hence, addressing the longstanding controversy regarding the phylogenetic status of Lampriformes among teleosts. Comparative mitogenomic analyses indicate that tRNA losses existed in at least five Lampriformes species, which may reveal the mitogenomic structure variation associated with adaptive radiation. However, codon usage in Lampriformes did not change significantly, and it is hypothesized that the nucleus transported the corresponding tRNA, which led to function substitutions. The positive selection analysis revealed that atp8 and cox3 were positively selected in opah, which might have co-evolved with the endothermic trait. This study provides important insights into the systematic taxonomy and adaptive evolution studies of Lampriformes species.

The Clostridium Metabolite P-Cresol Sulfate Relieves Inflammation of Primary Biliary Cholangitis by Regulating Kupffer Cells.

OBJECTIVE: To study the effect and mechanism of the Clostridium metabolite p-Cresol sulfate (PCS) in primary biliary cholangitis (PBC). METHODS: Gas chromatography-mass spectrometry (GC-MS) was used to detect differences in tyrosine, phenylalanine, tryptophan, PCS, and p-Cresyl glucuronide (PCG) between the serum of PBC patients and healthy controls. In vivo experiments, mice were divided into the normal control, PBC group, and PBC tyrosine group. GC-MS was used to detect PCS and PCG. Serum and liver inflammatory factors were compared between groups along with the polarization of liver Kupffer cells. Additionally, PCS was cultured with normal bile duct epithelial cells and Kupffer cells, respectively. PCS-stimulated Kupffer cells were co-cultured with lipopolysaccharide-injured bile duct epithelial cells to detect changes in inflammatory factors. RESULTS: Levels of tyrosine and phenylalanine were increased, but PCS level was reduced in PBC patients, with PCG showing a lower concentration distribution in both groups. PCS in PBC mice was also lower than those in normal control mice. After oral administration of tyrosine feed to PBC mice, PCS increased, liver inflammatory factors were decreased, and anti-inflammatory factors were increased. Furthermore, Kupffer cells in the liver polarized form M1 transitioned to M2. PCS can damage normal bile duct epithelial cells and suppress the immune response of Kupffer cells. But PCS protects bile duct epithelial cells damaged by LPS through Kupffer cells. CONCLUSIONS: PCS produced by Clostridium-metabolized tyrosine reduced PBC inflammation, suggesting that intervention by food, or supplementation with PCS might represent an effective clinical strategy for treating PBC.

Identifying factors affecting willingness to participate in floating population health volunteer services by Chinese volunteers based on the theory of the planned behavior expansion model.

China has the world's largest internal migrant population, called the floating population. Compared to local residents, the floating population utilizes different health services and relies heavily on health volunteer services for supplementary services. In this study, the theory of planned behavior model was used to study the willingness of volunteers to participate in floating population health volunteer services. We examined the effects of several factors on willingness to participate and found that attitude and subjective norm, but not perceived behavioral control, have significant predictive effects on willingness to participate in health volunteer services. Furthermore, altruistic values, social incentives, and personality traits not only have significant predictive effects on volunteer participation but also indirectly affect willingness through attitude and subjective norms. These findings help us understand what factors affect volunteers' willingness to provide health services to the floating population and have important implications for mobilizing volunteers for floating population health services.

The Weighted Combination of the Epworth Sleepiness Scale and the STOP-Bang Questionnaire Improved the Predictive Value of for OSAHS in Hypertensive Patients.

Purpose: Hypertension interrelated with obstructive sleep apnea hypopnea syndrome (OSAHS), worsening morbidity and mortality. It is urgent to screening OSAHS from hypertensive patients. An ideal effective questionnaire screening approach for OSAHS is lacking. In this study, we aimed to explore a new OSAHS screening method via weighted combining the current used Epworth sleepiness scale (ESS) and STOP-Bang questionnaire (SBQ) upon calculation. Patients and Methods: Three hundred and sixteen hypertensive patients with suspicion of the OSAHS were enrolled and randomized in the study into ESS, SBQ and portable respiratory polysomnography (RP) tests. The predictive value of ESS, SBQ and weighted combination were evaluated by calculating the area under curve (AUC), sensitivity and specificity, positive and negative likelihood ratio. Results: Both the two scales alone and weighted combination were closely related with apnea hypopnea index (AHI), minimum oxygen saturation and average oxygen saturation at night (P < 0.05). The AUC, sensitivity and specificity, positive predictive value (PPV) and negative predictive value (NPV) of ESS in predicting OSAHS were 79.0%, 74.8%, 75.6%, 80.1% and 57.5%, respectively. For SBQ, they were 73.6%, 67.0%, 68.6%, 65.1% and 75.2%, respectively. In contrast, the AUC, sensitivity, and specificity of the combined approach were 82.5%, 73.9% and 82.6%. Conclusion: The weighted combination of ESS and SBQ could improve the diagnostic ability of OSAHS in patients with hypertension, not only in the accuracy and sensitivity, but also for its easy procedure and accessibility and in hospital. Therefore, the weighted combination approach of ESS and SBQ is promising for OSAHS screening.

Reprogramming Microbial CO2-Metabolizing Chassis With CRISPR-Cas Systems.

Global warming is approaching an alarming level due to the anthropogenic emission of carbon dioxide (CO2). To overcome the challenge, the reliance on fossil fuels needs to be alleviated, and a significant amount of CO2 needs to be sequestrated from the atmosphere. In this endeavor, carbon-neutral and carbon-negative biotechnologies are promising ways. Especially, carbon-negative bioprocesses, based on the microbial CO2-metabolizing chassis, possess unique advantages in fixing CO2 directly for the production of fuels and value-added chemicals. In order to fully uncover the potential of CO2-metabolizing chassis, synthetic biology tools, such as CRISPR-Cas systems, have been developed and applied to engineer these microorganisms, revolutionizing carbon-negative biotechnology. Herein, we review the recent advances in the adaption of CRISPR-Cas systems, including CRISPR-Cas based genome editing and CRISPR interference/activation, in cyanobacteria, acetogens, and methanogens. We also envision future innovations via the implementation of rising CRISPR-Cas systems, such as base editing, prime editing, and transposon-mediated genome editing.

Cu(II)-Mediated aerobic oxidative synthesis of sulfonated chromeno[4,3-c]pyrazol-4(2H)-ones.

Herein, starting with propiolates and sulfonyl hydrazides, we developed a concise and facile synthesis of 2-sulfonylated chromeno [4,3-c]pyrazol-4(2H)-ones or 2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-ones via Cu(II)-promoted oxidative cascade C-C/C-N bond formation. This protocol has the advantages of atom economy and good functional group tolerance. The primary mechanism studies indicate that the reaction involves a free-radical process as well as terminal alkyne C-H activation.

Clinical predictors for nondiabetic kidney diseases in patients with type 2 diabetes mellitus: a retrospective study from 2017 to 2021.

BACKGROUND: Nondiabetic kidney disease (NDKD), which is prevalent among patients with diabetes mellitus (DM), is considerably different from diabetic kidney disease (DKD) in terms of the pathological features, treatment strategy and prognosis. Although renal biopsy is the current gold-standard diagnostic method, it cannot be routinely performed due to a range of risks. The aim of this study was to explore the predictors for differentiating NDKD from DKD to meet the urgent medical needs of patients who cannot afford kidney biopsy. METHODS: This is a retrospective study conducted by reviewing the medical records of patients with type 2 DM who underwent percutaneous renal biopsy at the Affiliated Hospital of Guizhou Medical University between January 2017 and May 2021. The demographic data, clinical data, blood test results, and pathological examination results of the patients were obtained from their medical records. Multivariate regression analysis was performed to evaluate the predictive factors for NDKD. RESULTS: A total of 244 patients were analyzed. The median age at biopsy was 55 (46, 62) years. Patients diagnosed with true DKD, those diagnosed with NDKD and those diagnosed with NDKD superimposed DKD represented 48.36% (118/244), 45.9% (112/244) and 5.74% (14/244), respectively, of the patient population. Immunoglobulin A nephropathy was the most common type of lesion in those with NDKD (59, 52.68%) and NDKD superimposed DKD (10, 71.43%). Independent predictive indicators for diagnosing NDKD included a DM duration of less than 5 years (odds ratio [OR] = 4.476; 95% confidence interval [CI]: 2.257-8.877; P < 0.001), an absence of diabetic retinopathy (OR = 4.174; 95% CI: 2.049-8.502; P < 0.001), a high RBC count (OR = 1.901; 95% CI: 1.251-2.889; P = 0.003), and a negative of urinary glucose excretion test result (OR = 2.985; 95% CI: 1.474-6.044; P = 0.002).. CONCLUSIONS: A DM duration less than 5 years, an absence of retinopathy, a high RBC count and an absence of urinary glucose excretion were independent indicators for the diagnosis of NDKD, suggesting that patients with NDKD may require a different treatment regimen than those with DKD.

Non-linear relationship between basal serum albumin concentration and cardiac arrest in critically ill patients with end-stage renal disease: a cross-sectional study.

OBJECTIVES: The aim of our study was to investigate the association between serum albumin concentration and the risk of cardiac arrest in critically ill patients with end-stage renal disease in the intensive care unit (ICU). DESIGN: This was a secondary analysis. SETTING: The Phillip electronic-ICU collaborative database from 2014 to 2015. PARTICIPANTS: This study included 4990 critically ill patients diagnosed with end-stage renal disease. PRIMARY AND SECONDARY OUTCOME MEASURES: The exposure of interest was serum albumin concentration. The outcome variable was cardiac arrest. RESULTS: A non-linear relationship was observed between serum albumin concentration and risk of cardiac arrest, with an inflection point of 3.26 g/dL after adjusting for potential confounders. The effect sizes and the CIs on the left and right sides of the inflection point were 0.88 (0.65 to 1.19) and 0.32 (0.16 to 0.64), respectively. CONCLUSIONS: Within an albumin range of 3.26-5.6 g/dL, each 1 g/dL increase in serum levels is associated with a 68% decrease of the risk of cardiac arrest in critically ill patients with end-stage renal disease.

Olfactory impact of guaiacol, ortho-vanillin, 5-methyl, and 5-formyl-vanillin as byproducts in synthetic vanillin.

To better control the quality of synthetic vanillin obtained by using the guaiacol synthesis method, the olfactory impacts of byproducts on the aroma of the synthetic vanillin samples were evaluated and their optimum concentration ranges were determined. Four byproducts (guaiacol, ortho-vanillin, 5-methyl-vanillin, and 5-formyl-vanillin) were identified by gas chromatography-mass spectrometry (GC-MS) and quantified by gas chromatography-flame ionization detection (GC-FID) in the synthetic vanillin samples with different degrees of purity. The aroma intensities (AIs) of the four byproducts obtained by gas chromatography-olfactometry (GC-O) were: guaiacol (AI: 3.5-4.0, smoke), ortho-vanillin (AI: 1.6-2.5, almond), 5-methyl-vanillin (AI: 2.5-3.3, aldehyde), and 5-formyl-vanillin (AI: 3.2-3.8, green). The aroma perceptual interactions of the four byproducts and the vanillin in the synthetic vanillin samples were determined by S-curve analysis. Guaiacol and 5-methyl-vanillin showed synergistic effects by Feller's additive model. Combined with the results of an addition experiment, when the contents of guaiacol, ortho-vanillin, 5-methyl-vanillin, and 5-formyl-vanillin were within 50, 10, 400, and 1,000 mg/kg respectively, the byproducts had no effects on the aroma quality of the synthetic vanillin samples. PRACTICAL APPLICATION: Synthetic vanillin is one of the most commonly used food additives. Currently, the purity of synthetic vanillin can reach 99.9%, but trace byproducts are still present. Continuing to improve the purity of synthetic vanillin will significantly increase its production costs. Therefore, it is necessary to determine whether the presence of these byproducts affects the aroma quality of the synthetic vanillin samples or not. If they have a negative effect on its aroma, it will be important to reduce their content. If they have no influence or positive role, there is no need to control the content of these byproducts to very low levels. This study determined the content of the byproducts produced during the synthesis of vanillin by guaiacol glyoxylic acid method, judged the perceptual interaction between the byproducts and the vanillin in the synthetic vanillin samples, and determined the optimum range within which the byproducts had no effects on the aroma quality. This study provides a theoretical basis for improving the aroma quality of synthetic vanillin while controlling the production costs.

[Preparation and in vitro evaluation of forsythoside A-loaded exosomes].

A drug delivery system of forsythoside A-loaded exosomes(FTA-Exos) with high biocompatibility and low immunogenicity was established to investigate its impact on the migration of human lung epithelial adenocarcinoma A549 cells. The exosomes from A549 cells were extracted and purified by ultra-high speed centrifugation and ultrafiltration. FTA-Exos were prepared by ultrasonic incubation, and characterized by particle size analysis, transmission electron microscopy, and Western blot assay. The uptake of FTA-Exos by A549 cells was observed under the laser confocal microscope, and the impact of FTA-Exos on the migration of A549 cells was investigated by cell scratch assay. The results showed that the average particle size of the prepared FTA-Exos was(138.90±2.37) nm, which increased slightly after drug loading. The PDI was 0.291±0.013, and the average potential was(-10.1±0.66) mV. The FTA-Exos were spheroidal in appearance as observed by transmission electron microscope, with an obvious saucer-like double-layer membrane. Western blot assay indicated that the specific proteins CD63 and Alix were both expressed in exosomes. The laser confocal microscopy suggested that FTA-Exos were taken up by A549 cells and stably maintained in the cell for 4-8 h, and the fluorescence was significantly enhanced at 4 h. The scratch assay showed that the inhibitory effect of FTA-Exos on the migration of A549 cells was significantly stronger than that of forsythoside A(P < 0.05). In conclusion, the drug delivery system of FTA-Exos established in this study had good stability, reliable preparation process, and potent inhibitory effect on the migration of A549 cells in vitro, which can provide an important reference for subsequent in-depth research and application.

Analysis of transcription factors in accessible open chromatin in the 18-trisomy syndrome based on single cell ATAC sequencing technique.

Trisomy 18 syndrome is one of the most common autosomal aneuploidy disorders. Little is known about the genetic regulation leading to the clinical phenotypes associated with the occurrence and development of trisomy 18 syndrome disorders (e.g., mental retardation, cardiac and renal abnormalities). To explore the regulatory factors that influence the phenotypes of the disease, this study used single-cell ATAC sequencing to analyze transcription factors in the accessibility chromatin regions of the single-nucleus cells of the cord blood from 18-trisomy syndrome and control subjects. A single-cell library constructed by capturing 11,611 cells identified seven major immune cell populations, and the results of cell number statistics suggested the presence of abnormalities in the immune system of 18-trisomy syndrome patients. Fourteen transcription factors (P<0.05, |FC|>1.2) were identified by analyzed accessibility chromatin regions. The relative expression levels of four of these transcription factors (TEAD1, TEAD2, TEAD4, Twist2) were confirmed using real-time quantitative fluorescence PCR. In conjunction with information from the literature, this study suggests that these four transcription factors may be associated with abnormalities in cardiac and skeletal development in patients with the 18-trisomy syndrome, thereby providing candidate molecules for mechanistic studies on the occurrence and development of the 18-trisomy syndrome phenotypes.

Kupffer Cells Regulate Natural Killer Cells Via the NK group 2, Member D (NKG2D)/Retinoic Acid Early Inducible-1 (RAE-1) Interaction and Cytokines in a Primary Biliary Cholangitis Mouse Model.

BACKGROUND Kupffer cells and natural killer (NK) cells has been identified as contributing factors in the pathogenesis of hepatitis, but the detailed mechanism of these cell types in the pathogenesis of primary biliary cholangitis (PBC) is poorly understood. MATERIAL AND METHODS In this study, polyinosinic: polycytidylic acid (poly I: C), 2-octynoic acid-bovine serum albumin (2OA-BSA) and Freund's adjuvant (FA) were injected to establish a murine PBC model, from which NK cells and Kupffer cells were extracted and isolated. The cells were then co-cultivated in a designed culture system, and then NK group 2, member D (NKG2D), retinoic acid early inducible-1 (RAE-1), F4/80, and cytokine expression levels were detected. RESULTS The results showed close crosstalk between Kupffer cells and NK cells. PBC mice showed increased surface RAE-1 protein expression and Kupffer cell cytokine secretion, which subsequently activated NK cell-mediated target cell killing via NKG2D/RAE-1 recognition, and increased inflammation. NK cell-derived interferon-γ (IFN-γ) and Kupffer cell-derived tumor necrosis factor alpha (TNF-alpha) were found to synergistically regulate inflammation. Moreover, interleukin (IL)-12 and IL-10 improved the crosstalk between NK cells and Kupffer cells. CONCLUSIONS Our findings in mice are the first to suggest the involvement of the NKG2D/RAE-1 interaction and cytokines in the synergistic effects of NK and Kupffer cells in PBC.

Metabolic activation of TM5441 in vitro and in vivo: Formation of reactive metabolites and human enzymes involved.

TM5441, a furan-containing drug, is an inhibitor of plasminogen activator inhibitor-1 (PAI-1), which can induce intrinsic apoptosis of human cancer cell lines. The aim of this study was to identify the reactive metabolites of TM5441 and to reveal the bioactivation pathways that are associated with its hepatotoxicity. The reactive metabolites were trapped by using glutathione (GSH) or N-acetyl-lysine (NAL) in rat, dog, and human liver microsomal incubation system after exposure to TM5441. Two metabolic activation pathways were disclosed. The first bioactivation pathway was dominated by Cytochrome P450 enzymes (CYP450s); TM5441 was metabolized into cis-2-butene-1,4-dial derivative dependent on NADPH, which can be trapped in the liver microsomal incubations fortified with GSH or NAL as trapping agents. Five metabolites (M1, M2, M9, M12 and M13) associated with GSH and three metabolites (M4, M7 and M14) associated with NAL were identified by liquid chromatography-high resolution mass spectrometry. The second bioactivation pathway was catalyzed by UDP-glucuronosyltransferases (UGTs); TM5441 was conjugated with glucuronide to form acyl-glucuronide (M10), which further reacted with GSH, resulting in the identification of a TM5441-S-acyl-GSH adduct (M11) in liver microsomal incubations fortified with uridine-5'-diphosphoglucuronidc acid (UDPGA) and GSH. M9, M10, M11, M12 and M13 were also detected in bile samples of rats given TM5441. Compared with rat, dog would display closer bioactivation profiles to human. The CYP450 enzyme responsible for the bioactivation of TM5441 was mainly identified as CYP3A4, using human recombinant CYP450 enzymes and specific inhibitory studies. The UGT enzymes responsible for the bioactivation of TM5441 mainly involved UGT2B7, 1A1 and 1A4. These results facilitate the understanding of the bioactivation of TM5441 and potential toxicological implications.

Genomic insights into mite phylogeny, fitness, development, and reproduction.

BACKGROUND: Predatory mites (Acari: Phytoseiidae) are the most important beneficial arthropods used in augmentative biological pest control of protected crops around the world. However, the genomes of mites are far less well understood than those of insects and the evolutionary relationships among mite and other chelicerate orders are contested, with the enigmatic origin of mites at one of the centres in discussion of the evolution of Arachnida. RESULTS: We here report the 173 Mb nuclear genome (from 51.75 Gb pairs of Illumina reads) of the predatory mite, Neoseiulus cucumeris, a biocontrol agent against pests such as mites and thrips worldwide. We identified nearly 20.6 Mb (~ 11.93% of this genome) of repetitive sequences and annotated 18,735 protein-coding genes (a typical gene 2888 bp in size); the total length of protein-coding genes was about 50.55 Mb (29.2% of this assembly). About 37% (6981) of the genes are unique to N. cucumeris based on comparison with other arachnid genomes. Our phylogenomic analysis supported the monophyly of Acari, therefore rejecting the biphyletic origin of mites advocated by other studies based on limited gene fragments or few taxa in recent years. Our transcriptomic analyses of different life stages of N. cucumeris provide new insights into genes involved in its development. Putative genes involved in vitellogenesis, regulation of oviposition, sex determination, development of legs, signal perception, detoxification and stress-resistance, and innate immune systems are identified. CONCLUSIONS: Our genomics and developmental transcriptomics analyses of N. cucumeris provide invaluable resources for further research on the development, reproduction, and fitness of this economically important mite in particular and Arachnida in general.

Identification of the Differential Effect of City-Level on the Gini Coefficient of Health Service Delivery in Online Health Community.

Inequality of health services for different specialty categories not only occurs in different areas in the world, but also happens in the online service platform. In the online health community (OHC), health services often display inequality for different specialty categories, including both online views and medical consultations for offline registered services. Moreover, how the city-level factors impact the inequality of health services in OHC is still unknown. We designed a causal inference study with data on distributions of serviced patients and online views in over 100 distinct specialty categories on one of the largest OHCs in China. To derive the causal effect of the city-levels (two levels inducing 1 and 0) on the Gini coefficient, we matched the focus cases in cities with rich healthcare resources with the potential control cities. For each of the specialty categories, we first estimated the average treatment effect of the specialty category's Gini coefficient (SCGini) with the balanced covariates. For the Gini coefficient of online views, the average treatment effect of level-1 cities is 0.573, which is 0.016 higher than that of the matched group. Similarly, for the Gini coefficient of serviced patients, the average treatment effect of level-1 cities is 0.470, which is 0.029 higher than that of the matched group. The results support the argument that the total Gini coefficient of the doctors in OHCs shows that the inequality in health services is still very serious. This study contributes to the development of a theoretically grounded understanding of the causal effect of city-level factors on the inequality of health services in an online to offline health service setting. In the future, heterogeneous results should be considered for distinct groups of doctors who provide different combinations of online contributions and online attendance.

Effects of natural ingredients on the shelf life of chicken seasoning.

The effects of the natural ingredients Angelica sinensis (AS) and Codonopsis pilosula (CP) on the shelf life of chicken seasoning were investigated. Color differences and sensory evaluation were used to indicate sensory differences. Changes in volatiles were monitored. The rate of increase in the color value a* of the AS and CP samples was lower than that in the control. Rancid flavor appeared later in the AS and CP samples than in the control. The levels of aldehydes, ketones, and alkenes increased during storage. A kinetic model was built based on the proportion of aldehydes (main marker), to predict shelf life. The predicted shelf life at room temperature was 60 days for the control, 114 days for AS, and 89 days for CP. The shelf life of chicken seasoning could be prolonged with AS and CP. This kinetic model can be used to predict the shelf life of chicken seasoning.