Effect and mechanism of gomisin D on the isoproterenol induced myocardial injury in H9C2 cells and mice.

We established myocardial injury models in vivo and in vitro to investigate the cardioprotective effect of gomisin D obtained from Schisandra chinensis. Gomisin D significantly inhibited isoproterenol-induced apoptosis and hypertrophy in H9C2 cells. Gomisin D decreased serum BNP, ANP, CK-MB, cTn-T levels and histopathological alterations, and inhibited myocardial hypertrophy in mice. In mechanisms research, gomisin D reversed ISO-induced accumulation of intracellular ROS and Ca2+. Gomisin D further improved mitochondrial energy metabolism disorders by regulating the TCA cycle. These results demonstrated that gomisin D had a significant effect on isoproterenol-induced myocardial injury by inhibiting oxidative stress, calcium overload and improving mitochondrial energy metabolism.

[Comparison of the efficacy of TiRobot orthopaedic robot assisted F screw technique and inverted triangle parallel nail internal fixation in the treatment of unstable femoral neck fractures].

OBJECTIVE: To compare the effectiveness of TiRobot assisted F screw technique and inverted triangle parallel nail internal fixation in the treatment of unstable femoral neck fractures. METHODS: A retrospective analysis was conducted on 72 patients with unstable femoral neck fractures who were treated with percutaneous cannulated screw fixation assisted with TiRobot Orthopaedic robot from December 2019 to April 2021. Among them, 37 patients were treated with F screw internal fixation, including 16 males and 21 females, aged 47 to 64 years old with an average of （53.87±5.28） years old；According to Pauwels classification, there were 1 case of type Ⅰ, 19 cases of type Ⅱ, 17 cases of type Ⅲ；8 cases of combined medical diseases；17 cases of falling, 8 cases of traffic accident and 12 cases of falling from height；The time from injury to operation was 29 to 49 hours with average of （35.00±7.34） hours. Another 35 cases used internal fixation with an inverted triangle parallel nail, including 13 males and 22 females with an average age of 46 to 63 years old （52.36±5.05） years old；According to the Pauwels injury classification：there were 2 cases of type Ⅰ, 21 cases of type Ⅱ, 12 cases of type Ⅲ；6 cases of medical diseases, 15 cases of falling injury, 9 cases of traffic accident, 11 cases of falling injury；The time from injury to operation was 30 to 45 hours with an average of （33.00±6.83） h. The intraoperative blood loss, operation time, intraoperative fluoroscopy times, follow-up time, fracture healing time, postoperative complications were observed and compared between the two groups. The hip joint function was evaluated by Harris score at 6 months and 12 months after operation. RESULTS: There was no significant difference in operation time, intraoperative blood loss, intraoperative fluoroscopy times and other intraoperative data between two groups（P>0.05）. Both groups were followed up regularly, and the follow-up time was 12 to 16 months. The fracture healing time and Harris score of the F screw internal fixation group were better than those of the inverted triangle parallel nail internal fixation group （P<0.05）. There was 1 case of femoral neck shortening in the F screw internal fixation group, 1 case of nonunion, 1 case of nail withdrawal, and 1 case of lower extremity deep vein thrombosis in the inverted triangle internal fixation group. The incidence of complications in the F screw internal fixation group was lower than that in the inverted triangle parallel nail internal fixation group（P<0.05）. CONCLUSION: Percutaneous cannulated F screw technique using Tirobot navigation positioning system is a safe and effective treatment for patients with unstable femoral neck fractures. It can significantly shorten the fracture healing time, reduce the incidence of postoperative complications, significantly improve hip joint function, and improve the quality of life.

Zero-dimensional hybrid tin halides with stable broadband light emissions.

Considering the instability and toxicity of 3D Pb-based perovskite nanocrystals, lead-free low-dimensional organic-inorganic hybrid metal halides have attracted widespread attention as potential substitutes. Herein, two new tin-based 0D halides [H4BAPP]SnBr5·Br and [H4BAPP]SnCl5·Cl·H2O (BAPP = 1,4-bis(3-aminopropyl)piperazine) were synthesized successfully based on [SnX5]3- as an emission center. Typically, [H4BAPP]SnBr5·Br and [H4BAPP]SnCl5·Cl·H2O display broadband yellow and yellow-green light emissions originating from the radiative recombination of self-trapped excitons (STEs). The photoluminescence quantum yields (PLQYs) of the two compounds were calculated to be 19.27% and 2.36%, respectively. Furthermore, the excellent chemical and thermal stability and broadband light emissions reveal their potential application in solid-state white lighting diodes.

Integration of network pharmacology and serum medicinal chemistry to investigate the pharmacological mechanisms of QiZhuYangGan Decoction in the treatment of hepatic fibrosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Qizhuyanggan Decoction (QZD), a traditional Chinese medicine formula, is frequently utilized in clinical practice for managing hepatic fibrosis. However, the specific target and mechanism of action of QZD for hepatic fibrosis treatment remain unknown. AIM OF THE STUDY: By combining network pharmacology, serum medicinal chemistry, and experimental validation methods, our study aimed to investigate the therapeutic effects of QZD on hepatic fibrosis, the anti-hepatic fibrosis active ingredients, and the possible mechanism of anti-hepatic fibrosis action. MATERIALS AND METHODS: The study aimed to investigate the therapeutic effect of QZD on hepatic fibrosis induced by CCl4 in SD rats, as well as its mechanism of action. The rats were anesthetized intraperitoneally using 3% pentobarbital and were executed after asphyxiation with high concentrations of carbon dioxide. Several techniques were employed to evaluate the efficacy of QZD, including ELISA, Western blot, HYP reagent assay, and various pathological examinations such as HE, Masson, Sirius Red staining, and immunohistochemistry (IHC). Additionally, serum biochemical assays were conducted to assess the effect of QZD on liver injury. Network pharmacology, UPLC, molecular docking, and molecular dynamics simulation were utilized to explore the mechanism of QZD in treating hepatic fibrosis. Finally, experimental validation was performed through ELISA, IHC, RT-qPCR, and Western blot analysis. RESULT: Liver histopathology showed that QZD reduced inflammation and inhibited collagen production, and QZD significantly reduced HA and LN content to treat hepatic fibrosis. Serum biochemical analysis showed that QZD improved liver injury. Network pharmacology combined with UPLC screened six active ingredients and obtained 87 targets for the intersection of active ingredients and diseases. The enrichment analysis results indicated that the PI3K/AKT pathway might be the mechanism of action of QZD in the treatment of hepatic fibrosis, and counteracting the inflammatory response might be one of the pathways of action of QZD. Molecular docking and molecular dynamics simulations showed that the active ingredient had good binding properties with PI3K, AKT, and mTOR proteins. Western blot, ELISA, PCR, and IHC results indicated that QZD may treat hepatic fibrosis by inhibiting the PI3K/AKT/mTOR pathway and suppressing M1 macrophage polarization, while also promoting M2 macrophage polarization. CONCLUSIONS: QZD may be effective in the treatment of hepatic fibrosis by inhibiting the PI3K/AKT/mTOR signaling pathway and M1 macrophage polarization, while promoting M2 macrophage polarization. This provides a strong basis for the clinical application of QZD.

Overall quality changes and deterioration mechanism of fragrant rapeseed oils during 6-Month storage.

The strong-fragrant rapeseed oil (SFRO) is a popular rapeseed oil in China with a low refining degree only degumming with hot water, which remarkably affects its storage stability. The present study compared the overall changes of physical/chemical/nutrient quality of FROs at various temperatures, light wavelengths and headspace volumes. Results showed that red light (680 nm) had a most significant adverse effect on the overall quality of SFRO with the higher correlation coefficients to PV and TOTOX of 0.71 and 0.70, and lower correlation coefficients to chlorophyll and tocopherol of -0.95 and -0.53, respectively. Further studies revealed that red light accelerated the oxidation of fragrant rapeseed oils by degrading chlorophyll to initiate the photo-oxidation process and synthesize high amount of secondary oxidation products including aliphatic and aromatic oxidized compounds from linolenic acid. These findings provided a reference to control the deterioration of FROs by preventing the transmittance of red light.

[Establishment and Clinical Significance of Prognostic Nomogram Model for Diffuse Large B-Cell Lymphoma Based on Immunohistochemistry Markers and International Prognostic Index Scores].

OBJECTIVE: To retrospectively analyze clinical characteristics and survival time of patients with diffuse large B-cell lymphoma (DLBCL), detect prognosis-related markers, and establish a nomogram prognostic model of clinical factors combined with biomarkers. METHODS: One hundred and thirty-seven patients with DLBCL were included in this study from January 2014 to March 2019 in the First Affiliated Hospital of Nanchang University. The expression of GCET1, LMO2, BCL-6, BCL-2 and MYC protein were detected by immunohistochemistry (IHC), then the influences of these proteins on the survival and prognosis of the patients were analyzed. Univariate and multivariate Cox regression analysis were used to gradually screen the prognostic factors in nomogram model. Finally, nomogram model was established according to the result of multivariate analysis. RESULTS: The positive expression of GCET1 protein was more common in patients with Ann Arbor staging I/II (P =0.011). Compared with negative patients, patients with positive expression of LMO2 protein did not often show B symptoms (P =0.042), and could achieve better short-term curative effect (P =0.005). The overall survival (OS) time of patients with positive expression of LMO2 protein was significantly longer than those with negative expression of LMO2 protein (P =0.018), though the expression of LMO2 protein did not correlate with progression-free survival (PFS) (P >0.05). However, the expression of GCET1 protein had no significant correlation with OS and PFS. Multivariate Cox regression analysis showed that nomogram model consisted of 5 prognostic factors, including international prognostic index (IPI), LMO2 protein, BCL-2 protein, MYC protein and rituximab. The C-index applied to the nomogram model for predicting 4-year OS rate was 0.847. Moreover, the calibrated curve of 4-year OS showed that nomogram prediction had good agreement with actual prognosis. CONCLUSION: The nomogram model incorporating clinical characteristics and IHC biomarkers has good discrimination and calibration, which provides a useful tool for the risk stratification of DLBCL.

Broad immunity to SARS-CoV-2 variants of concern mediated by a SARS-CoV-2 receptor-binding domain protein vaccine.

BACKGROUND: The SARS-CoV-2 global pandemic has fuelled the generation of vaccines at an unprecedented pace and scale. However, many challenges remain, including: the emergence of vaccine-resistant mutant viruses, vaccine stability during storage and transport, waning vaccine-induced immunity, and concerns about infrequent adverse events associated with existing vaccines. METHODS: We report on a protein subunit vaccine comprising the receptor-binding domain (RBD) of the ancestral SARS-CoV-2 spike protein, dimerised with an immunoglobulin IgG1 Fc domain. These were tested in conjunction with three different adjuvants: a TLR2 agonist R4-Pam2Cys, an NKT cell agonist glycolipid α-Galactosylceramide, or MF59® squalene oil-in-water adjuvant, using mice, rats and hamsters. We also developed an RBD-human IgG1 Fc vaccine with an RBD sequence of the immuno-evasive beta variant (N501Y, E484K, K417N). These vaccines were also tested as a heterologous third dose booster in mice, following priming with whole spike vaccine. FINDINGS: Each formulation of the RBD-Fc vaccines drove strong neutralising antibody (nAb) responses and provided durable and highly protective immunity against lower and upper airway infection in mouse models of COVID-19. The 'beta variant' RBD vaccine, combined with MF59® adjuvant, induced strong protection in mice against the beta strain as well as the ancestral strain. Furthermore, when used as a heterologous third dose booster, the RBD-Fc vaccines combined with MF59® increased titres of nAb against other variants including alpha, delta, delta+, gamma, lambda, mu, and omicron BA.1, BA.2 and BA.5. INTERPRETATION: These results demonstrated that an RBD-Fc protein subunit/MF59® adjuvanted vaccine can induce high levels of broadly reactive nAbs, including when used as a booster following prior immunisation of mice with whole ancestral-strain spike vaccines. This vaccine platform offers a potential approach to augment some of the currently approved vaccines in the face of emerging variants of concern, and it has now entered a phase I clinical trial. FUNDING: This work was supported by grants from the Medical Research Future Fund (MRFF) (2005846), The Jack Ma Foundation, National Health and Medical Research Council of Australia (NHMRC; 1113293) and Singapore National Medical Research Council (MOH-COVID19RF-003). Individual researchers were supported by an NHMRC Senior Principal Research Fellowship (1117766), NHMRC Investigator Awards (2008913 and 1173871), Australian Research Council Discovery Early Career Research Award (ARC DECRA; DE210100705) and philanthropic awards from IFM investors and the A2 Milk Company.

Integrating Network Pharmacology and Experimental Validation to Explore the Pharmacological Mechanism of Astragaloside IV in Treating Bleomycin-Induced Pulmonary Fibrosis.

Purpose: Our study aims to reveal the pharmacological mechanism of Astragaloside IV in the treatment of pulmonary fibrosis(PF) through network pharmacology and experimental validation. Methods: We first determined the in vivo anti-pulmonary fibrosis effect of Astragaloside IV by HE, MASSON staining, and lung coefficients, then used network pharmacology to predict the signaling pathways and molecularly docked key pathway proteins, and finally validated the results by in vivo and in vitro experiments. Results: In in vivo experiments, we found that Astragaloside IV improved body weight (P < 0.05), increased lung coefficients (P < 0.05), and reduced lung inflammation and collagen deposition in mice with pulmonary fibrosis. The network pharmacology results showed that Astragaloside IV had 104 cross-targets with idiopathic pulmonary fibrosis, and the results of KEGG enrichment analysis indicated that cellular senescence could be an important pathway for Astragaloside IV in the treatment of pulmonary fibrosis. Astragaloside IV also bound well to senescence-associated proteins, according to molecular docking results. The results of both in vivo and in vitro experiments showed that Astragaloside IV significantly inhibited senescence protein markers such as P53, P21, and P16 and delayed cellular senescence (P < 0.05). In in vivo experiments, we also found that Astragaloside IV reduced the production of SASPs (P < 0.05), and in in vitro experiments, Astragaloside IV also reduced the production of ROS. In addition, by detecting epithelial-mesenchymal transition(EMT)-related marker protein expression, we also found that Astragaloside IV significantly inhibited the development of EMT in both in vivo and in vitro experiments (P < 0.05). Conclusion: Our research found that Astragaloside IV could alleviate bleomycin-induced PF by preventing cellular senescence and EMT.

14-3-3ζ Participates in the Phase Separation of Phosphorylated and Glycated Tau and Modulates the Physiological and Pathological Functions of Tau.

Tau plays a major role in Alzheimer's disease (AD) and several other neurodegenerative diseases. Tau undergoing liquid-liquid phase separation (LLPS) performs specific physiological functions, induces pathological processes, and contributes to neurodegeneration. Regulating Tau phase separation helps maintain physiological functions of Tau and inhibits pathological aggregation. Here, we show that the 14-3-3 zeta isoform (14-3-3ζ) participates in Tau LLPS. 14-3-3ζ can undergo co-phase separation with WT Tau, participate in and stabilize Tau droplets, and inhibit Tau droplet-driven tubulin assembly. On the other hand, 14-3-3ζ disrupts the LLPS of phosphorylated and glycated Tau, thereby inhibiting the amyloid aggregation initiated by LLPS.

Yiqi Huayu decoction alleviates bleomycin-induced pulmonary fibrosis in rats by inhibiting senescence.

Overview: In treating pulmonary fibrosis (PF), traditional Chinese medicine (TCM) has received much attention, but its mechanism is unclear. The pharmacological mechanisms of TCM can be explored through network pharmacology. However, due to its virtual screening properties, it still needs to be verified by in vitro or in vivo experiments. Therefore, we investigated the anti-PF mechanism of Yiqi Huayu Decoction (YHD) by combining network pharmacology with in vivo experiments. Methods: Firstly, we used classical bleomycin (BLM)-induced rat model of PF and administrated fibrotic rats with YHD (low-, medium-, and high-dose). We comprehensively assessed the treatment effect of YHD according to body weight, lung coefficient, lung function, and histopathologic examination. Second, we predict the potential targets by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) combined with network pharmacology. In brief, we obtained the chemical ingredients of YHD based on the UHPLC-MS/MS and TCMSP database. We collected drug targets from TCMSP, HERB, and Swiss target prediction databases based on active ingredients. Disease targets were acquired from drug libraries, Genecards, HERB, and TTD databases. The intersecting targets of drugs and disease were screened out. The STRING database can obtain protein-protein interaction (PPI) networks and hub target proteins. Molecular Complex Detection (MCODE) clustering analysis combined with enrichment analysis can explore the possible biological mechanisms of YHD. Enrichment analyses were conducted through the R package and the David database, including the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and Reactome. Then, we further validated the target genes and target proteins predicted by network pharmacology. Protein and gene expression detection by immunohistochemistry, Western blot (WB), and real-time quantitative PCR (rt-qPCR). Results: The results showed that high-dose YHD effectively attenuated BLM-induced lung injury and fibrosis in rats, as evidenced by improved lung function, relief of inflammatory response, and reduced collagen deposition. We screened nine core targets and cellular senescence pathways by UHPLC-MS/MS analysis and network pharmacology. We subsequently validated key targets of cellular senescence signaling pathways. WB and rt-qPCR indicated that high-dose YHD decreased protein and gene expression of senescence-related markers, including p53 (TP53), p21 (CDKN1A), and p16 (CDKN2A). Increased reactive oxygen species (ROS) are upstream triggers of the senescence program. The senescence-associated secretory phenotypes (SASPs), containing interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-ß1 (TGF-ß1), can further exacerbate the progression of senescence. High-dose YHD inhibited ROS production in lung tissue and consistently reduced the SASPs expression in serum. Conclusion: Our study suggests that YHD improves lung pathological injury and lung function in PF rats. This protective effect may be related to the ability of YHD to inhibit cellular senescence.

[Risk factors for acute kidney injury after hematopoietic stem cell transplantation in children: a retrospective study]. / å„¿ç«¥é€ è¡€å¹²ç»†èƒžç§»æ¤åŽæ€¥æ€§è‚¾æŸä¼¤ç›¸å ³å±é™©å› ç´ çš„å›žé¡¾æ€§ç ”ç©¶.

OBJECTIVES: To investigate the risk factors for acute kidney injury (AKI) after hematopoietic stem cell transplantation (HSCT) in children. METHODS: A retrospective analysis was performed on the medical data of 111 children who underwent HSCT from January 2018 to January 2020. A multivariate logistic regression analysis was used to identify the risk factors for AKI. The Kaplan-Meier survival analysis was used to compare the prognosis in children with different grades of AKI. RESULTS: Graft-versus-host disease (grade Ⅱ-Ⅳ) (OR=4.406, 95%CI: 1.501-12.933, P=0.007), hepatic veno-occlusive disease (OR=4.190, 95%CI: 1.191-14.740, P=0.026), and thrombotic microangiopathy (OR=10.441, 95%CI: 1.148-94.995, P=0.037) were closely associated with the development of AKI after HSCT. The children with stage Ⅲ AKI had a lower 1-year survival rate than those without AKI or with stage Ⅰ AKI or stage Ⅱ AKI (28.6%±12.1% vs 82.8%±5.2%/81.7%±7.4%/68.8%±11.6%; P<0.05). CONCLUSIONS: Children with stage Ⅲ AKI after HSCT have a higher mortality rate. Graft-versus-host disease, hepatic veno-occlusive disease, and thrombotic microangiopathy are closely associated with the development of AKI after HSCT.

Enantioselective Conjugate Addition of Alkenyl Trifluoroborates to Alkenyl-Substituted Benzimidazoles Catalyzed by Chiral Binaphthols.

The enantioselective organocatalytic conjugate alkenylation of ß-substituted alkenyl benzimidazoles afforded ß-stereogenic 2-alkyl benzimidazole derivatives in excellent enantioselectivities. Chiral binaphthols were effective catalysts for promoting the nucleophilic addition of bench-stable alkenyl trifluoroborate salts under mild conditions, expanding their applications by utilizing C=N-containing azaarenes as activating groups. The synthetic utility of this strategy is demonstrated by conversions into several useful enantiomerically enriched benzimidazole building blocks.

Astragaloside IV Ameliorates Isoprenaline-Induced Cardiac Fibrosis in Mice via Modulating Gut Microbiota and Fecal Metabolites.

Aim: Gut microbiota is of crucial importance to cardiac health. Astragaloside IV (AS-IV) is a main active ingredient of Huangqi, a traditional edible and medicinal herb that has been shown to have beneficial effects on cardiac fibrosis (CF). However, it is still uncertain whether the consumption of AS-IV alleviates cardiac fibrosis through the gut microbiota and its metabolites. Therefore, we assessed whether the anti-fibrosis effect of AS-IV is associated with changes in intestinal microbiota and fecal metabolites and if so, whether some specific gut microbes are conducive to the benefits of AS-IV. Methods: Male C57BL-6J mice were subcutaneously injected with isoprenaline (ISO) to induce cardiac fibrosis. AS-IV was administered to mice by gavage for 14 days. The effects of AS-IV on cardiac function, myocardial enzyme, cardiac weight index (CWI), and histopathology of ISO-induced CF mice were investigated. Moreover, 16S rRNA sequencing was used to establish gut-microbiota profiles. Fecal-metabolites profiles were established using the liquid chromatograph-mass spectrometry (LC-MS). Results: AS-IV treatment prevented cardiac dysfunction, ameliorated myocardial damage, histopathological changes, and cardiac fibrosis induced by ISO. AS-IV consumption increased the richness of Akkermansia, Defluviitaleaceae_UCG-011, and Rikenella. AS-IV also modulated gut metabolites in their feces. Among 141 altered gut metabolites, amino acid production was sharply changed. Furthermore, noticeable correlations were found between several specific gut microbes and altered fecal metabolites. Conclusions: An increase of Akkermansia, Defluviitaleaceae_UCG-011, and Rikenella abundance, and modulation of amino acid metabolism, may contribute to the anti-fibrosis and cardiac protective effects of Astragaloside IV.

Regeneration of meniscal avascular zone using autogenous meniscal fragments in a rabbit model.

BACKGROUND: To investigate the effects of autologous meniscus fragment (AMF) implantation on injury in the meniscal avascular zone in mature rabbits. METHODS: Adult New Zealand white rabbits were randomly divided into two groups. Massive one-piece meniscus tissue was implanted in situ as control. In the experimental group, AMF was used to repair the meniscal injury in the avascular zone. Meniscal damage was assessed by gross observation of the degree of healing and histological semi-quantitative evaluation within 12 weeks postoperatively. The healing of meniscus interface was assessed by gross observation semiquantitative scoring and microscopic examination hematoxylin and eosin (H&E) staining at 2, 4, 8, and 12 weeks after surgery. The expressions of proliferating cell nuclear antigen (PCNA), collagen type I (COL1A1), and collagen type II (COL2) were detected by immunohistochemical staining. RESULTS: The degree of healing in the AMF group showed a significant increase over time (P < 0.05); the AMF group showed higher gross scores than the control group at 4, 8, and 12 weeks after surgery (P < 0.05). The histological scores in the AMF group were significantly higher than those in the control group at 4, 8, and 12 weeks after surgery (P < 0.05). The protein expression of PCNA in the AMF group was greater than that in the control group at 2, 4, and 8 weeks after surgery (P < 0.05). In addition, compared with the control group, the protein levels of COL1A1 and COL2 were significantly upregulated at each time-point. At 2 and 4 weeks after surgery, the expression level of COL1A1 increased in both groups followed by a gradual decrease after 8 weeks (P < 0.05). At 2, 4, 8, and 12 weeks after surgery, the expression levels of COL2 showed a gradual decrease in both groups (P < 0.05). CONCLUSIONS: Our study demonstrated that the AMF method can promote the repair of rabbit meniscal injury in the avascular zone, and this method may potentially be used for clinical application.

A novel magnetic metal-organic framework absorbent for rapid detection of aflatoxins B1B2G1G2 in rice by HPLC-MS/MS.

In this study, a core-shell-structured magnetic metal-organic framework (MMOF) composite material (Fe3O4@UiO-66-NH2) was synthesized by the solvothermal method. It was employed as a new absorbent in combination with high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) for the simultaneous detection of four aflatoxins (AFs) in rice. This method could shorten the pre-processing time by exploiting the advantageous characteristics of magnetic cores. The impurity was removed quickly. The effects of extraction solution, extraction time, adsorbent types, and amount of adsorbent on the extraction rate of target compounds were optimized. Under optimized conditions, AFs were validated and showed a good linear relationship within the 0.375-20 µg kg-1 concentration range (r2 > 0.9992). The limit of detection (LOD) was 0.0188-0.1250 µg kg-1 and the limit of quantification (LOQ) was 0.0375-0.3750 µg kg-1. At three spiking levels (0.375, 2, and 10 µg kg-1), the average recovery values for the four AFs ranged from 85.1% to 111.0%. The relative standard deviation ranged from 3.4% to 7.7%. The new method proved to be simple, fast, efficient, and suitable for the determination of AFs in rice samples.

Chemical Synthesis and Antigenic Evaluation of Inner Core Oligosaccharides from Acinetobacter baumannii Lipopolysaccharide.

Acinetobacter baumannii is currently posing a serious threat to global health. Lipopolysaccharide (LPS) is a potent virulence factor of pathogenic Gram-negative bacteria. To explore the antigenic properties of A. baumannii LPS, four Kdo-containing inner core glycans from A. baumannii strain ATCC 17904 were synthesized. A flexible and divergent method based on the use of the orthogonally substituted α-Kdo-(2→5)-Kdo disaccharides was developed. Selective removal of different protecting groups in these key precursors and elongation of sugar chain via α-stereocontrolled coupling with 5,7-O-di-tert-butylsilylene or 5-O-benzoyl protected Kdo thioglycosides and 2-azido-2-deoxyglucosyl thioglycoside allowed efficient assembly of the target molecules. Glycan microarray analysis of sera from infected patients revealed that the 4,5-branched Kdo trimer was a potential antigenic epitope, which is attractive for further immunological research to develop carbohydrate vaccines against A. baumannii.

Life-threatening infections during treatment for acute lymphoblastic leukemia on the Malaysia-Singapore 2003 and 2010 clinical trials: A risk prediction model.

AIM: Life-threatening infections significantly impact the care of children undergoing therapy for acute lymphoblastic leukemia (ALL) who are at risk of severe sepsis due to both host and treatment factors. Our aim was to develop a life-threatening infection risk prediction model that would allow remote rapid triage of patients to reduce time to first dose of antibiotics and sepsis-related mortality. METHODS: A retrospective analysis of 2068 fever episodes during ALL therapy was used for model building and subsequent internal validation. RESULTS: Three hundred and seventy-seven patients were treated for ALL in two institutions with comparable critical and supportive care resources. A total of 55 patients accounted for 71 admissions to the critical care unit for sepsis that led to eight septic deaths during a 16-year study period. A retrospective analysis of risk factors for sepsis enabled us to build a model focused on 13 variables that discriminated admissions requiring critical care well: area under the receiver operating characteristic curve of .82; 95% CI .76-.87, p<.001, and Brier score of .033. Significant univariate predictors included neutropenia, presence of symptoms of abdominal pain, diarrhea, fever during induction or steroid-based phases, and the lack of any localizing source of infection at time of presentation. CONCLUSION: We have developed a risk prediction model that can reliably identify ALL patients undergoing treatment who are at a higher risk of life-threatening sepsis. Clinical applicability can potentially be extended to low-middle income settings, and its utility should be further studied in real-world settings.

[Meta-analysis of the Impact of Different Ozone Metrics on Total Mortality in China].

This study explores the effect of different ozone metrics on the total mortality risk in China. Using the CNKI, Wanfang, VIP, Web of Science, and PubMed databases, the time series studies and case crossover studies from the establishment of each database to December 31, 2020 were retrieved, and 22 eligible studies were included in this analysis. A meta-analysis was performed for the ozone metrics of O3-M1h, O3-M8h, and O3-24h. The results indicated that the increase in the total mortality risk is more closely associated with O3-M1h (RR #, 1.0052; 95%CI, 1.0031-1.0073) and is more weakly associated with O3-24h (RR #, 1.0036; 95%CI, 1.0025-1.0048) and O3-M8h (RR #, 1.0031; 95%CI, 1.0022-1.0041). A subgroup analysis of the three metrics revealed that the total mortality risk of ozone is higher in the cold season, the elderly (≥ 65) are more vulnerable to ozone pollution, and the total mortality risk in the north is higher than that in the south.

Salusin-α mitigates diabetic nephropathy via inhibition of the Akt/mTORC1/p70S6K signaling pathway in diabetic rats.

Salusin-α is a bioactive peptide that protects against atherosclerosis and hepatosteatosis. Serum salusin-α level is declined in patients suffering with renal insufficiency. However, it is still undefined whether salusin-α plays a role in diabetic nephropathy. The present study was designed to investigate the potential roles of salusin-α in diabetic renal disease. Herein, we demonstrated that the salusin-α levels in both plasma and kidney tissues from diabetic rats were obviously downregulated. Exogenous administration of salusin-α eliminated the typical characteristics of diabetic nephropathy. Salusin-α treatment decreased renal fibrosis, which was related with reduced epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells. Injection of salusin-α suppressed the production of reactive oxygen species (ROS) via attenuation of NADPH oxidase subunits protein expressions and recovery of the antioxidant system. Mechanistically, the activated Akt/mTORC1/p70S6K signaling pathway in diabetic nephropathy was counteracted by salusin-α treatment. Our results demonstrated that salusin-α exerted protective effect against diabetic nephropathy via reduced oxidative stress and fibrosis, dependent on inactivation of the Akt/mTORC1/p70S6K signaling cascade. Salusin-α may be considered as a promising target for the treatment of diabetic nephropathy.

Cytomegalovirus Latency Exacerbated Small-for-size Liver Graft Injury Through Activation of CCL19/CCR7 in Hepatic Stellate Cells.

BACKGROUND: The interplay between cytomegalovirus (CMV) latency and graft malfunction after living donor liver transplantation remains poorly defined because of the complexity of clinical confounding factors. Here, we aimed to investigate the effects of CMV latency on small-for-size graft injury and to get further insight into the pathogenic role of hepatic stellate cells (HSCs) in this process. METHODS: Rat orthotopic liver transplantation with small-for-size grafts was performed in a CMV latent model developed in immunocompetent Sprague Dawley rats using Priscott strain. Posttransplant graft injury including hepatocyte damage, stellate cell activation, and fibrogenesis was evaluated. Differential gene expression of HSCs in response to CMV latency was screened by cDNA microarray. Clinical validation was further conducted in human biopsies. RESULTS: CMV latency aggravated hepatocyte apoptosis/necrosis in the early phase and enhanced HSC expansion and graft fibrosis during the middle-late phase in small-for-size liver grafts of the rat model. cDNA microarray mining revealed CCL19/CCR7 as one of the most noteworthy pathways bridging HSC activation and liver graft injury in the presence of CMV latency. Together with CCL19 upregulation, coherent overexpression of CCR7 in accumulated HSCs was confirmed in both rat and human CMV latent recipients. Moreover, addition of CCL19 in vitro promoted HSC migration by increasing the level of matrix metalloproteinase-2. CONCLUSIONS: Our data demonstrated that CMV latency aggravated early/late phase liver graft damage and fibrogenesis via CCL19/CCR7/HSCs axis. Blockade of CMV latency-related stellate cell activation may shed light on the strategy of graft protection clinically.