Pyroptosis inhibitors MCC950 and VX-765 mitigate myocardial injury by alleviating oxidative stress, inflammation, and apoptosis in acute myocardial hypoxia.

Acute myocardial infarction (AMI) is a prevalent cardiovascular disease with high morbidity and mortality rates worldwide. Pyroptosis is an inflammatory form of programmed cell death that has been linked to various pathological conditions. However, its exact contribution to the onset and progression of heart injury in AMI has not yet fully elucidated. Herein, we established mouse AMI model by ligating the left anterior descending artery and performed transcriptome analysis during the early phase of AMI. Mouse HL-1 and human AC-16 cardiomyocytes were subjected to hypoxia to simulate ischemic injury in vitro. Our results revealed a significant activation of the inflammatory response at 3 h post-ligation, as confirmed by RNA sequencing. We identified the occurrence of NLRP3 inflammasome-mediated pyroptosis in the cardiac tissues of human cases with AMI, as well as in mouse models of AMI and hypoxia-induced cardiomyocytes, using immunohistochemistry staining and Western blotting assays. Concurrently, pharmacological inhibition of NLRP3 inflammasome-mediated pyroptosis with MCC950 and VX-765 effectively decreased hypoxia-induced cardiomyocytes injury, while mitigating myocardial oxidative stress, apoptosis and inflammation caused by hypoxia. Moreover, the circulating levels of gasdermin D (GSDMD), the pyroptosis executor, were remarkably elevated in the plasma of mice with early AMI and in the supernatant of hypoxia-exposed cardiomyocytes in a time-dependent manner using ELISA and Western blotting. Furthermore, the change in circulating GSDMD positively correlated with Creatine Kinase-MB (CK-MB) in the plasma of early-stage AMI mouse. In summary, these findings indicated a critical role for NLRP3 inflammasome-mediated pyroptosis in the progression of AMI, the administration of MCC950 and VX-765 may be attractive candidate therapeutic approaches for cardiac injury caused by acute hypoxia or even AMI. Additionally, the circulating GSDMD exhibits potential as a newly diagnostic biomarker for AMI.

Characterizing identity by descent segments in Chinese interpopulation unrelated individual pairs.

Identity by descent (IBD) segments, uninterrupted DNA segments derived from the same ancestral chromosomes, are widely used as indicators of relationships in genetics. A great deal of research focuses on IBD segments between related pairs, while the statistical analyses of segments in irrelevant individuals are rare. In this study, we investigated the basic informative features of IBD segments in unrelated pairs in Chinese populations from the 1000 Genome Project. A total of 5922 IBD segments in Chinese interpopulation unrelated individual pairs were detected via IBIS and the average length of IBD was 3.71 Mb in length. It was found that 17.86% of unrelated pairs shared at least one IBD segment in the Chinese cohort. Furthermore, a total of 49 chromosomal regions where IBD segments clustered in high abundance were identified, which might be sharing hotspots in the human genome. Such regions could also be observed in other ancestry populations, which implies that similar IBD backgrounds also exist. Altogether, these results demonstrated the distribution of common background IBD segments, which helps improve the accuracy in pedigree studies based on IBD analysis.

Development of a 39 MM-InDel multiplex assay for the forensic application.

Insertion/deletion polymorphisms (InDels) are a category of highly prevalent markers in the human genome, characterized by their distinctive attributes, including short amplicon sizes and low mutation rates, which have shown great potential in forensic applications. Multi-allelic InDel and multi-InDel markers, collectively abbreviated as MM-InDels, were developed to enhance polymorphism by the introduction of novel alleles. Nevertheless, the relatively low mutation rates of InDels, coupled with the founder effect, result in distinct allele frequency distributions among populations. The divergent characteristics of InDels in different populations also pose challenges to the establishment of universally efficient InDel multiplex assays. To enhance the system efficiency of the InDel assay and its applicability across diverse populations, 39 MM-InDels with high polymorphism in five different ancestry superpopulations were selected from the 1000 Genomes Project dataset and combined with an amelogenin gender marker to construct a multiplex assay (named MMIDplex). The combined power of discrimination and the cumulative probability of exclusion of 39 MM-InDels were 1 - 1.3 × 10-23 and 1 - 9.83 × 10-6 in the Chinese Han population, and larger than 1-10-19 and 1-10-4 in the reference populations, relatively. These results demonstrate that the MMIDplex assay has the potential to obtain sufficient power for individual identification and paternity test in global populations.

4 mC site recognition algorithm based on pruned pre-trained DNABert-Pruning model and fused artificial feature encoding.

DNA 4 mC plays a crucial role in the genetic expression process of organisms. However, existing deep learning algorithms have shortcomings in the ability to represent DNA sequence features. In this paper, we propose a 4 mC site identification algorithm, DNABert-4mC, based on a fusion of the pruned pre-training DNABert-Pruning model and artificial feature encoding to identify 4 mC sites. The algorithm prunes and compresses the DNABert model, resulting in the pruned pre-training model DNABert-Pruning. This model reduces the number of parameters and removes redundancy from output features, yielding more precise feature representations while upholding accuracy.Simultaneously, the algorithm constructs an artificial feature encoding module to assist the DNABert-Pruning model in feature representation, effectively supplementing the information that is missing from the pre-trained features. The algorithm also introduces the AFF-4mC fusion strategy, which combines artificial feature encoding with the DNABert-Pruning model, to improve the feature representation capability of DNA sequences in multi-semantic spaces and better extract 4 mC sites and the distribution of nucleotide importance within the sequence. In experiments on six independent test sets, the DNABert-4mC algorithm achieved an average AUC value of 93.81%, outperforming seven other advanced algorithms with improvements of 2.05%, 5.02%, 11.32%, 5.90%, 12.02%, 2.42% and 2.34%, respectively.

Improving the geographical origin classification of Radix glycyrrhizae (licorice) through hyperspectral imaging assisted by U-Net fine structure recognition.

Radix glycyrrhizae (licorice) is extensively employed in traditional Chinese medicine, and serves as a crucial raw material in industries such as food and cosmetics. The quality of licorice from different origins varies greatly, so classification of its geographical origin is particularly important. This study proposes a technique for fine structure recognition and segmentation of hyperspectral images of licorice using deep learning U-Net neural networks to segment the tissue structure patterns (phloem, xylem, and pith). Firstly, the three partitions were separately labeled using the Labelme tool, which was utilized to train the U-Net model. Secondly, the obtained optimal U-Net model was applied to predict three partitions of all samples. Lastly, various machine learning models (LDA, SVM, and PLS-DA) were trained based on segmented hyperspectral data. In addition, a threshold method and a circumcircle method were applied to segment licorice hyperspectral images for comparison. The results revealed that compared with the threshold segmentation method (which yielded SVM classifier accuracies of 99.17%, 91.15%, and 92.50% on the training set, validation set, and test set, respectively), the U-Net segmentation method significantly enhanced the accuracy of origin classification (99.06%, 94.72% and 96.07%). Conversely, the circumcircle segmentation method did not effectively improve the accuracy of origin classification (99.65%, 91.16% and 92.13%). By integrating Raman imaging of licorice, it can be inferred that the U-Net model, designed for region segmentation based on the inherent tissue structure of licorice, can effectively improve the accuracy origin classification, which has positive significance in the development of intelligence and information technology of Chinese medicine quality control.

C-H Bond Activation by a Seven-Coordinate Bipyridine-Bipyrazole Ruthenium(IV) Oxo Complex.

Ruthenium-oxo species with high coordination numbers have long been proposed as active intermediates in catalytic oxidation chemistry. By employing a tetradentate bipyridine-bipyrazole ligand, we herein reported the synthesis of a seven-coordinate (CN7) ruthenium(IV) oxo complex, [RuIV(tpz)(pic)2(O)]2+ (RuIVO) (tpz = 6,6'-di(1H-pyrazol-1-yl)-2,2'-bipyridine, pic = 4-picoline), which exhibits high activity toward the oxidation of alkylaromatic hydrocarbons. The large kinetic isotope effects (KIE) for the oxidation of DHA/DHA-d4 (KIE = 10.3 ± 0.1) and xanthene/xanthene-d2 (KIE = 17.2 ± 0.1), as well as the linear relationship between log (rate constants) and bond dissociation energies of alkylaromatics, confirmed a mechanism of hydrogen atom abstraction.

Reliability and validity assessment of the Chinese version of the Intrahospital Transport Safety Scale (IHTSS) in intensive care units.

BACKGROUND: Intrahospital transport of critically ill patients is a common practice in intensive care units (ICUs), where patients' safety is constantly challenged in high-intensity and dynamic environments. While Intrahospital Transport Safety Scale (IHTSS) is widely used internationally to evaluate the intrahospital transport safety, it has not been introduced in China. OBJECTIVES: This study aimed to assess the reliability and validity of the Chinese version of the IHTSS scale among critical care nurses in China. METHODS: A cross-sectional study was conducted using a cluster sampling method. A total of 544 critical care nurses from 25 ICUs in 10 tertiary hospitals were recruited. We employed exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) to examine the questionnaire's underlying factor structure, ensuring construct validity. Additionally, internal consistency was assessed using Cronbach's alpha coefficient, test-retest reliability, and corrected item-total correlation. RESULTS: The Chinese version of the scale displayed robust psychometric properties, with a Cronbach's α coefficient of 0.976, a split-half reliability of 0.906, and a test-retest reliability of 0.856. EFA revealed a robust four-factor model that accounted for 75.970% of the variance, with the factor loadings of the items ranging from 0.433 to 0.951. CFA indicated a strong model fit, with a chi-square to degrees of freedom ratio (CMIN/DF) of 2.765, comparative fit index (CFI) of 0.943, incremental fit index (IFI) of 0.943, and goodness-of-fit index (GFI) of 0.845, supporting the efficacy of the four-factor model in assessing intrahospital transport safety for critically ill patients. CONCLUSION: The Chinese version of the IHTSS demonstrated favourable reliability and validity among critical care nurses in China, making it a suitable tool for measuring the level of intrahospital transport safety for critically ill patients.

Development of a multiplex panel with 31 multi-allelic InDels for forensic DNA typing.

Insertion/Deletion (InDel) polymorphic genetic markers are abundant in human genomes. Diallelic InDel markers have been widely studied for forensic purposes, yet the low polymorphic information content limits their application and current InDel panels remain to be improved. In this study, multi-allelic InDels located out of low complexity sequence regions were selected in the datasets from East Asian populations, and a multiplex amplification system containing 31 multi-allelic InDel markers and the Amelogenin marker (FA-HID32plex) was constructed and optimized. The preliminary study on sensitivity, species specificity, inhibitor tolerance, mixture resolution, and the detection of degraded samples demonstrates that the FA-HID32plex is highly sensitive, specific, and robust for traces and degraded samples. The combined power of discrimination (CPD) of 31 multi-allelic InDel markers was 0.999 999 999 999 999 999 85, and the cumulative probability of exclusion (CPE) was 0.999 920 in a Chinese Han population, which indicates a high discrimination power. Altogether, the FA-HID32plex panel could provide reliable supplements or stand-alone information in individual identification and paternity testing, especially for challenging samples.

Structure and Reactivity of a Seven-Coordinate Ruthenium Iodosylbenzene Complex.

Seven-coordinate (CN7) ruthenium-oxo species have attracted much attention as highly reactive intermediates in both organic and water oxidation. Apart from metal-oxo, other metal-oxidant adducts, such as metal-iodosylarenes, have also recently emerged as active oxidants. We reported herein the first example of a CN7 Ru-iodosylbenzene complex, [RuIV(bdpm)(pic)2(O)I(Cl)Ph]+ (H2bdpm = [2,2'-bipyridine]-6,6'-diylbis(diphenylmethanol); pic = 4-picoline). The X-ray crystal structure of this complex shows that it adopts a distorted pentagonal bipyramidal geometry with Ru-O(I) and O-I distances of 2.0451(39) and 1.9946(40) Å, respectively. This complex is highly reactive, and it readily undergoes O-atom transfer (OAT) and C-H bond activation reactions with various organic substrates. This work should provide insights for the development of new highly reactive oxidizing agents based on CN7 geometry.

Oxidation of Hypophosphorous Acid by a Ruthenium(VI) Nitrido Complex in Aqueous Acidic Solution. Evidence for a Proton-Coupled N-Atom Transfer Mechanism.

The oxidation of hypophosphorous acid (H3PO2) by a ruthenium(VI) nitrido complex, [(L)RuVI(N)(OH2)]+ (RuVIN; L = N,N'-bis(salicylidene)-o-cyclohexyldiamine dianion), has been studied in aqueous acidic solutions at pH 0-2.50. The reaction has the following stoichiometry: 2[(L)RuVI(N)(OH2)]+ + 3H3PO2 + H2O → 2[(L)RuIII(NH2P(OH)2)(OH2)]+ + H3PO3. The pseudo-first-order rate constant, kobs, depends linearly on [H3PO2], and the second-order rate constant k2 depends on [H+] according to the relationship k2 = k[H+]/([H+] + Ka), where k is the rate constant for the oxidation of H3PO2 molecule and Ka is the dissociation constant of H3PO2. At 298.0 K and I = 1.0 M, k = (2.04 ± 0.19) × 10-2 M-1 s-1 and Ka = (6.38 ± 0.63) × 10-2 M. A kinetic isotope effect (KIE) of 2.9 ± 0.1 was obtained when kinetic studies were carried out with D3PO2 at pH 1.16, suggesting P-H bond cleavage in the rate-determining step. On the other hand, when the kinetics were determined in D2O, an inverse KIE of 0.21 ± 0.03 (H3PO2 in H2O vs H3PO2 in D2O) was found. On the basis of experimental results and DFT calculations, the proposed mechanism involves an acid-catalyzed tautomerization of H2P(O)(OH) to HP(OH)2; the latter molecule is the reacting species which reacts with RuVIN via a proton-coupled N-atom transfer pathway.

Evaluation of one-step RT-PCR multiplex assay for body fluid identification.

The discrimination of body fluid stains provides crucial evidence during the investigation of criminal cases. Previous studies have demonstrated the practical value of mRNA profiling in body fluid identification. Conventional strategy of mRNA profiling entails reverse transcription and PCR amplification in two separate procedures with different buffer systems. In this study, we subjected the one-step multiplex reverse transcription PCR strategy to mRNA profiling with the inclusion of the same 18 tissue-specific biomarkers in the F18plex system targeting peripheral blood, menstrual blood, vaginal secretion, saliva, semen, and urine. The Qiagen OneStep RT-PCR kit and Titanium One-Step RT-PCR kit were applied to multiplex construction, while reproducible profiling results were obtained with both kits. Compared to the F18plex system, similar expression profiles of biomarkers were obtained in targeted tissues, while expected cross-reaction was observed in non-targeted body fluids. However, CYP2B7P1 and SPINK5 were detected in menstrual blood samples, which was not observed using the F18plex system. Full-profiling results were obtained in all samples using 0.1 ng peripheral blood and semen RNA, and 1 ng menstrual blood, vaginal secretion, saliva, and urine RNA. In conclusion, the application of one-step mRNA profiling strategy could be a reliable and economical method for the simplified, specific, and simultaneous analysis of tissue-specific biomarkers for the discrimination of body fluid origin.

Effectiveness of a Mobile Device-Based Resilience Training Program in Reducing Depressive Symptoms and Enhancing Resilience and Quality of Life in Parents of Children With Cancer: Randomized Controlled Trial.

BACKGROUND: Caring for children with cancer can be a stressful experience for parents and may have negative effects on their physical and psychological well-being. Although evidence has shown that resilience is associated with positive psychological well-being, few interventions have been specifically designed to enhance the resilience of parents of children with cancer. OBJECTIVE: The aim of this study is to examine the effectiveness of a mobile device-based resilience training program in reducing depressive symptoms and enhancing resilience and quality of life (QoL) in parents of children with cancer. METHODS: Parents of children diagnosed with cancer were recruited from the pediatric oncology wards of 3 tertiary hospitals in China. The participants were randomly assigned to either the experimental group (52/103, 50.5%) to undergo an 8-week mobile device-based resilience training program or to the control group (51/103, 49.5%) to receive an 8-week program of placebo information. The study outcomes included resilience, depressive symptoms, and QoL, as measured by the Connor-Davidson Resilience Scale, the Self-Rating Depression Scale, and the Short Form of the 6-Dimension Health Survey, respectively. All data were collected at baseline and at 2 and 6 months of follow-up. The data analysis followed the intention-to-treat principle. A generalized estimating equation was used to examine the effects of the intervention. RESULTS: The participants were mostly female (72/103, 69.9%), and their mean age was 33.6 (SD 5.2) years. The participants in the experimental group showed significantly higher levels of resilience (mean 67.96, SD 15.8 vs mean 58.27, SD 19.0; P<.001) and lower levels of depressive symptoms (mean 40.17, SD 9.9 vs mean 46.04, SD 10.9; P<.001) than those in the control group at 6 months of follow-up. The intervention showed statistically significant effects in improving resilience (ß=6.082; P=.01) and decreasing depressive symptoms (ß=-2.772; P=.04) relative to the control group. The QoL score in the experimental group was higher than that in the control group at 6 months of follow-up (mean 0.79, SD 0.2 vs mean 0.76, SD 0.3; P=.07); however, no statistically significant intervention effect was detected (ß=.020; P=.38). CONCLUSIONS: The mobile device-based resilience training program effectively enhanced resilience and alleviated depressive symptoms in parents of children with cancer. It is highly recommended that health care professionals incorporate this resilience training program when providing psychological care to parents of children with cancer. TRIAL REGISTRATION: Clinical.Trials.gov NCT04038242; http://clinicaltrials.gov/ct2/show/NCT04038242.

Application of ITO Method in Determination of Special Half-Sibling Relationship.

OBJECTIVES: To identify whether the relationship between Zhang A, Zhang B, Zhang C and Zhang X is the half-sibling relationship whose mother is sister (hereinafter referred to as the special half-sibling relationship) or the common first cousin relationship and discuss the application of ITO method in discriminating the special kinship. METHODS: DNA was extracted from blood stain of four identified individuals, PowerPlex® 21 System and AGCU 21+1 STR kit were used to detect autosomal STR genetic markers. Investigator® Argus X-12 QS kit was used to detect the X chromosome STR genetic markers, the special half-sibling index (SHSI) and first cousin index (FCI) and their likelihood ratio (LR) were calculated by ITO method. RESULTS: The LR results of SHSI to FCI, which were calculated based on autosomal STR genotyping and the analysis of X-STR genotyping results suggested that the relationship between Zhang A, Zhang B, Zhang C and Zhang X was inclined to be a special half-sibling relationship. CONCLUSIONS: For the identification of special kinship, it is necessary to comprehensively apply various genetic markers according to the case. After the conclusion that shared alleles cannot be excluded from the analysis, ITO method can be further used to establish discriminant assumptions according to the specific case to obtain objective and reliable identification opinions.

Novel regulation of miR-34a-5p and HOTAIR by the combination of berberine and gefitinib leading to inhibition of EMT in human lung cancer.

HOTAIR is an important carcinogenic lncRNA and involves in tumorigenesis, and invasion. MiR-34a-5p functions as a tumour suppressor. However, the underlying mechanism of HOTAIR regulation especially in association with miR-34a-5p in non-small-cell lung cancer (NSCLC) has not been explored. Herein, we performed series of in vitro experiments, including viability, migration, invasion, apoptosis and in vivo xenograft model, and identified that HOTAIR was remarkably elevated in NSCLC cells. Enforced HOTAIR expression promoted migration and invasion, while depleted HOTAIR diminished the ability of migration and invasion of NSCLC cells. We also observed that miR-34a-5p was dramatically inhibited in NSCLC cells and the binding correlation between HOTAIR and miR-34a-5p was confirmed by dual-luciferase reporter and RNA immunoprecipitation assays. We also showed that induction of miR-34a-5p and reduction of HOTAIR, and the interaction between miR-34a-5p and HOTAIR resulted in the suppression of epithelial-mesenchymal transition (EMT) as illustrated by induction of key epithelial markers E-cadherin expression, reduction of vimentin and EMT-inducing transcription factor snail. Excessive expression of snail resisted miR-34a-5p-inhibited cell growth. Snail binds to E-cadherin promoter and regulates E-cadherin expression. There was a synergy in combination of berberine and gefinitib in this process. Similar findings were also observed in a tumour xenograft model. Collectively, this is the first report demonstrating reciprocal interaction of miR-34a-5p- and HOTAIR-mediated regulation of snail resulting in inhibition of EMT process by the combination of berberine and gefitinib suggesting that regulation of miR-34a-5p- and HOTAIR-mediated inhibition of EMT may provide novel treatment paradigms for lung cancer.

Genetic analysis of tri-allelic patterns at the CODIS STR loci.

In the routine of autosomal STR genotyping for forensic aims, tri-allelic patterns could be occasionally observed at a single locus in phenotypically normal individuals. Two predominant types of tri-allelic variants have been nominated. Uneven intensities of three alleles are normally considered as the Type 1 pattern, and balanced height of three alleles are considered as the Type 2 pattern. In this study, the prevalence of tri-allelic patterns at the CODIS STR loci was investigated in global populations based on previous reports. The frequencies of the Type 1 and Type 2 pattern manifest a correlation with the germline mutation rates at the CODIS STR loci. The irregular high frequencies of the Type 2 pattern at TPOX with low germline mutation rates could attribute to the stable inheritance of genomic rearrangement from ancestral origin. Furthermore, results from genetic pattern analysis show that only a single allele from STRs with the Type 1 pattern could be transmitted from parents to offsprings, while a single allele and a combination of two alleles from STRs with the Type 2 pattern present an equal opportunity of transmission from parents to offsprings. Altogether, these results provide a genetic portrait of STRs with tri-allelic patterns, which will help the genetic interpretation of tri-allelic patterns in forensic practice.

Genetic analysis of type 2 tri-allelic pattern at TPOX locus in the Chinese Han population.

Tri-allelic patterns can occasionally be observed during the profiling of short tandem repeats (STRs) in routine forensic practice. In previous studies, the Type 2 tri-allelic pattern at TPOX has been widely studied in African and Brazilian populations. In this study, we investigated the incidence, rearrangement, and inheritance of the Type 2 tri-allelic pattern at the TPOX locus in a Chinese Han population. The frequency of the Type 2 pattern at TPOX was approximately 0.0189%, and the major extra allele was allele 11 in the Chinese Han population. Two major allelic combinations, 8/11 and 11/12, were observed, which are different from the configuration of that in both African and Brazilian populations. Tight linkage between alleles 11 and 12 was observed in the majority of the Type 2 pattern at TPOX in the Chinese Han population, while the location of the extra copy on chromosome 2 was validated, which shows an identical ancestral origin. The excess allelic combination 8/11 implies a homogeneous origin and tight linkage relationship. However, the rearrangement in the Type 2 pattern with the 8/11 allelic combination remained unknown. Altogether, these results show the configuration of the Type 2 tri-allelic pattern at the TPOX locus in the Chinese Han population, which will assist in the understanding of the Type 2 tri-allelic pattern at the TPOX locus in the global population.

Trace Fe Incorporation into Ni-(oxy)hydroxide Stabilizes Ni3+ Sites for Anodic Oxygen Evolution: A Double Thin-Layer Study.

Iron incorporation is essential for the record activity of NiFe-(oxy)hydroxides to oxygen evolution reaction (OER), but the details of how Fe affects catalysis remain under active investigation. In this work, we present a double thin-layer strategy for finding unique and solid evidence for the role of Fe in the OER mechanism. A thin-layer catalyst of a few nanometers of thickness was deposited on a Ni substrate and a thin-layer electrolyte of 0.1 mm thickness was created using a thin-layer spectroelectrochemical cell. The OER activity, the catalyst composition, and the electrolyte species were investigated together as a function of the Fe deposition time. The results show that trace Fe incorporation favors the formation of ß-NiOOH in the thin-layer catalyst and effectively suppresses the dissolution of NiOOH into the electrolyte. The results of double-potential step chronoabsorptometry and cyclic voltabsorptometry demonstrate the potential-dependent formation of a Ni3+ intermediate in the electrolyte and, more importantly, the dissolution suppression effect due to Fe incorporation. These findings link the role of Fe in OER catalysis to the increased insolubility of Ni3+ active sites and highlight the importance of paying close attention to the active-site stability of an electrocatalyst impaired by the electrolyte at a reaction potential.

Oxyberberine, a novel gut microbiota-mediated metabolite of berberine, possesses superior anti-colitis effect: Impact on intestinal epithelial barrier, gut microbiota profile and TLR4-MyD88-NF-κB pathway.

Berberine (BBR), a naturally-occurring isoquinoline alkaloid isolated from several Chinese herbal medicines, has been widely used for the treatment of dysentery and colitis. However, its blood concentration was less than 1 %, and intestinal microflora-mediated metabolites of BBR were considered to be the important material basis for the bioactivities of BBR. Here, we investigated the anti-colitis activity and potential mechanism of oxyberberine (OBB), a novel gut microbiota metabolite of BBR, in DSS-induced colitis mice. Balb/C mice treated with 3 % DSS in drinking water to induce acute colitis were orally administrated with OBB once daily for 8 days. Clinical symptoms were analyzed, and biological samples were collected for microscopic, immune-inflammation, intestinal barrier function, and gut microbiota analysis. Results showed that OBB significantly attenuated DSS-induced clinical manifestations, colon shortening and histological injury in the mice with colitis, which achieved similar therapeutic effect to azathioprine (AZA) and was superior to BBR. Furthermore, OBB remarkably ameliorated colonic inflammatory response and intestinal epithelial barrier dysfunction. OBB appreciably inhibited TLR4-MyD88-NF-κB signaling pathway through down-regulating the protein expressions of TLR4 and MyD88, inhibiting the phosphorylation of IκBα, and the translocation of NF-κB p65 from cytoplasm to nucleus. Moreover, OBB markedly modulated the gut dysbiosis induced by DSS and restored the dysbacteria to normal level. Taken together, the result for the first time revealed that OBB effectively improved DSS-induced experimental colitis, at least partly through maintaining the colonic integrity, inhibiting inflammation response, and modulating gut microflora profile.

C-terminus of heat shock protein 60 can activate macrophages by lectin-like oxidized low-density lipoprotein receptor 1.

Immune responses against antigens generally require an efficient activation of antigen-presenting cells (APCs). Currently, the targeting of vaccine antigens to APCs has emerged as a promising strategy for boosting vaccine immunogenicity. Here, we reported that the C-terminus of heat shock protein 60 (HSP60C) can activate mouse peritoneal macrophages to secret a series of cytokines, and phosphorylation of p38 mitogen-activated protein kinase (MAPK) and NF-κB p65 was involved in the pathway. We showed that the activation effect of HSP60C on macrophages was independent of toll-like receptor (TLR) 4 and the TLR-associated myeloide differentiation factor 88 (MyD88). Knockdown of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) reduced the activation of HSP60C-induced macrophage p38 MAPK, NF-κB p65 and cytokine secretion to some extent. Finally, we found that HSP60C up-regulated the expression of LOX-1 on macrophages and ovalbumin (OVA) model antigen fused with HSP60C markedly enhanced OVA-specific IgG responses. Thus, our results unravel a novel LOX-1-dependent pathway by which HSP60C can effectively activate macrophages and APCs targeting based on LOX-1 interaction is a promising approach to improve vaccines.

Generation and Reactivity of a One-Electron-Oxidized Manganese(V) Imido Complex with a Tetraamido Macrocyclic Ligand.

The synthesis and X-ray structure of a new manganese(V) mesitylimido complex with a tetraamido macrocyclic ligand (TAML), [MnV (TAML)(N-Mes)]- (1), are reported. Compound 1 is oxidized by [(p-BrC6 H4 )3 N]+. [SbCl6 ]- and the resulting MnVI species readily undergoes H-atom transfer and nitrene transfer reactions.