Association between lactate/albumin ratio and prognosis in patients with acute myocardial infarction.

BACKGROUND: The association between the lactate/albumin ratio (L/A) as a diagnostic indicator and unfavourable clinical outcomes has been established in patients with community-acquired pneumonia, sepsis and heart failure, but the connection between L/A and all-cause mortality in patients with acute myocardial infarction (AMI) has yet to be fully understood. METHODS: This was a retrospective cohort study using MIMIC-IV (v2.2) data, with 2816 patients enrolled and all-cause mortality during hospitalization as the primary outcome. Kaplan-Meier (KM) analysis was used to compare the all-cause mortality between high-level and low-level L/A groups. Receiver operating characteristic (ROC) curve, Restricted cubic splines (RCS) and Cox proportional hazards analysis were performed to investigate the relationship between L/A ratio and in-hospital all-cause mortality. RESULTS: L/A values were significantly higher in the non-survivor groups than the survival groups (1.14 [.20] vs. .60 [.36], p < .05), and area under the ROC curve [.734 (95% confidence interval, .694-.775)] was better than other indicators. Data of COX regression analysis showed that higher L/A value supposed to be an independent risk factor for in-hospital mortality. RCS analysis showed evidence of an increasing trend and a non-linear relationship between L/A and in-hospital mortality (p-value was non-linear <.05). KM survival curves were significantly lower in the high L/A group than the low L/A group (p < .001), and the former group had an increased risk of in-hospital mortality compared with the latter one (Log Rank p < .001). CONCLUSIONS: L/A demonstrates significant independent predictive power for elevated all-cause mortality during hospitalization in patients diagnosed with AMI.

A Meta-analysis Reveals Global Change Stressors Potentially Aggravate Mercury Toxicity in Marine Biota.

Growing evidence demonstrates that global change can modulate mercury (Hg) toxicity in marine organisms; however, the consensus on such effect is lacking. Here, we conducted a meta-analysis to evaluate the effects of global change stressors on Hg biotoxicity according to the IPCC projections (RCP 8.5) for 2100, including ocean acidification (-0.4 units), warming (+4 °C), and their combination (acidification-warming). The results indicated an overall aggravating effect (ln RRΔ = -0.219) of global change on Hg toxicity in marine organisms, while the effect varied with different stressors; namely, acidification potentially alleviates Hg biotoxicity (ln RRΔ = 0.117) while warming and acidification-warming have an aggravating effect (ln RRΔ = -0.328 and -0.097, respectively). Moreover, warming increases Hg toxicity in different trophic levels, i.e., primary producers (ln RRΔ = -0.198) < herbivores (ln RRΔ = -0.320) < carnivores (ln RRΔ = -0.379), implying increasing trends of Hg biomagnification through the food web. Notably, ocean hypoxia appears to boost Hg biotoxicity, although it was not considered in our meta-analysis because of the small sample size. Given the persistent global change and combined effects of these stressors in marine environments, multigeneration and multistressor research is urgently needed to fully disclose the impacts of global change on Hg pollution and its risk.

MSC-derived exosomes mitigate cadmium-induced male reproductive injury by ameliorating DNA damage and autophagic flux.

Cadmium, an environmental toxicant, severely impairs male reproductive functions and currently lacks effective clinical treatments. Mesenchymal stem cell-derived exosomes (MSC-Exos) are increasingly recognized as a potential alternative to whole-cell therapy for tissue injury and regeneration. This study aims to investigate the protective effects of MSC-Exos against cadmium toxicity on male reproduction. Our findings reveal that MSC-Exos treatment significantly promotes spermatogenesis, improves sperm quality, and reduces germ cell apoptosis in cadmium-exposed mice. Mechanistically, MSC-Exos dramatically mitigate cadmium-induced cell apoptosis in a spermatogonia cell line (GC-1 spg) in vitro by reducing DNA damage and promoting autophagic flux. These results suggest that MSC-Exos have a protective effect on cadmium-induced germ cell apoptosis by ameliorating DNA damage and autophagy flux, demonstrating the therapeutic potential of MSC-Exos for cadmium toxicity on male reproduction.

A mAb to SIRPα downregulates the priming of naive CD4 + T cell in Primary immune thrombocytopenia.

SIRPα is a transmembrane protein that binds the protein tyrosine phosphatases SHP-1 and SHP-2 through its cytoplasmic region and is abundantly expressed on monocytes, dendritic cells, and macrophages. Studies recently showed that SIRPα is essential for priming of CD4 + T cells by DCs and for development of Th17 cell-mediated autoimmune diseases. We have now further evaluated the importance of SIRPα and that of its ligand CD47 in primary immune thrombocytopenia (ITP). In this study, we show that there was a low expression state of SIRPα on the surface of monocytes. Treatment of cells culture from ITP patients with a mAb to SIRPα that blocks the binding of SIRPα to CD47 downregulated the ITP response. The abilities of monocytes from ITP patients to stimulate an allogenic MLR were reduced. The proliferation of, and production of IL-2, by CD4 + T cells from ITP patients were inhibited, the Treg cell numbers and the production of IL-10 pairs were upregulated, and the production of TGF-ß not was inhibited, by a mAb to SIRPα. Moreover, a mAb to SIRPα, the expression of HLA-DR and CD86 were markedly inhibited and the expression of CD80 was slightly upregulated, on the surface of CD14 + monocytes from ITP patients as compared with healthy subjects. However, blockade of SIRPα increased the secretion of TLR-dependent cytokines TNF-α, IL-6 and IL-1ß by PBMCs, which may be considered as a reserve in response to danger signals. These results suggest that SIRPα on monocytes is essential for the priming of naive T cells and the development of ITP. Therefore, SIRPα is a potential therapeutic target for ITP and other autoimmune diseases.

Patients with von Willebrand disease in China: Results of an online survey.

INTRODUCTION: Little is known about the clinical characteristics of von Willebrand disease (VWD) patients in China, the impact of Covid-19 on them and their genetic mutation. AIM: To describe the clinical characteristics of a group of VWD patients in China, the impact of Covid-19 on them and their genetic mutation. METHODS: An online survey using a self-designed questionnaire was conducted among patients within a WeChat group of VWD patients in China. Data were analysed using t-test, the Chi-square test, Fisher's exact test and rank sum test. RESULTS: Data from a total of 96 patients were collected. Several important findings are yielded. Above all, type 3 patients accounted for over half of the surveyed patients. Secondly, a surprising rate (>40%) of patients had experience of being misdiagnosed. Thirdly, treatment regimens were dominated by cryoprecipitate, blood-derived FVIII and plasma, and only a small percentage of patients received prophylaxis. Fourthly, we identified 17 new von Willebrand factor (VWF) mutant genes which merit further investigation. Additionally, Covid-19 was found to pose some challenges for the patients. CONCLUSION: In China, the high rates of type 3 patients and misdiagnosis suggest that most of the VWD patients may never be diagnosed in China. When it comes to diagnosis and treatment, there is a large gap between developing countries like China and developed countries.

Comprehensive profiling of the metabolome in corn silage inoculated with or without Lactiplantibacillus plantarum using different untargeted metabolomics analyses.

Silage fermentation is a complicated biochemical process involving interactions between microbes and metabolites. However, the overall metabolome feature of ensiled forage and its response to lactic acid bacteria inoculation is poorly understood. Hence, in this study metabolome profiles of whole-plant corn silage inoculated with or without Lactiplantibacillus plantarum were characterised via solid-phase microextraction/gas chromatography/mass spectrometry (SPME-GC-MS), gas chromatography/time-of-flight mass spectrometry (GC-TOF-MS), and Liquid chromatography/Q Exactive HFX mass spectrometry (LC-QE-MS/MS) analysis. There were 2087 identified metabolites including 1143 reliably identified metabolites in fresh and ensiled whole-plant corn. After ensiling, the increased metabolites in whole-plant corn were mainly composed of organic acids, volatile organic compounds (VOC), benzene and substituted derivatives, carboxylic acids and derivatives, fatty acyls, flavonoids, indoles and derivatives, organooxygen compounds (including amines and amides), phenols, pyridines and derivatives, and steroids and steroid derivatives, which includes neurotransmitters and metabolites with aromatic, antioxidant, anti-inflammatory, and antimicrobial activities. Phenylacetaldehyde was the most abundant aromatic metabolite after ensiling. L-isoleucine and oxoproline were the major free amino acids in silage. Ensiling markedly increased the relative abundances of 3-phenyllactic acid, chrysoeriol, 6-O-acetylaustroinulin, acetylcholine, γ-aminobutyric acid, pyridoxine, and alpha-linoleic acid. Inoculation with L. plantarum remarkably changed silage VOC composition, and essential amino acids, 3-phenyllactic acid, and cinnamaldehyde compared with untreated silage. The present study does not only provide a deeper insight into metabolites of the ensiled whole-plant corn but also reveals metabolites with specific biological functions that could be much helpful in screening novel lactic acid bacteria to well ensile forages. Inoculation with L. plantarum significantly affects the metabolome in ensiled whole-plant corn.

[Analysis and evaluation on Paeoniae Radix Alba from different cultivars by UPLC-Q-TOF-MS and HPLC].

In this study, an established ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) method was combined with multivariate statistical analysis to investigate the commonality and difference of main chemical components in the medicinal parts of Paeonia lactiflora from different cultivars; in addition, a high performance liquid chromatography(HPLC) method was established to simultaneously determine the content of eight active components in Paeoniae Radix Alba. Non-targeted analysis was carried out by UPLC-Q-TOF-MS on a Waters ACQUITY UPLC BEH C_(18)(2.1 mm×100 mm, 1.7 µm) column with a gradient elution of 0.1% aqueous formic acid(A)-acetonitrile(B) as the mobile phase at a flow rate of 0.2 mL·min~(-1). The column temperature was 30 ℃, and an electrospray ionization source was used to acquire mass spectrometry data in positive and negative ion modes. According to the accurate molecular weight and fragment ion information provided by multi-stage mass spectrometry and by comparison with reference substances and literature reports, thirty-six identical components were identified in Paeoniae Radix Alba from different cultivars with positive and negative ion modes. In the negative ion mode, two groups of samples were well separated; specifically, seventeen components with significant differences in content were screened and identified, and one component unique in "Bobaishao" was obtained. Quantitative analysis was conducted by high-performance liquid chromatography(HPLC) on an Agilent HC-C_(18)(4.6 mm×250 mm, 5 µm) column with a gradient elution of 0.1% aqueous phosphoric acid(A)-acetonitrile(B) as the mobile phase at a flow rate of 1.0 mL·min~(-1). The column temperature was 30 ℃ and the detection wavelength was at 230 nm. An HPLC method was developed for the simultaneous determination of eight active components(gallic acid, oxypaeoniflorin, catechin, albiflorin, paeoniflorin, galloylpaeoniflorin, 1,2,3,4,6-O-pentagalloylglucose, benzoyl-paeoniflorin) in Paeoniae Radix Albaa from different cultivars. Satisfactory linearity was achieved within the investigated linear ranges and with fine coefficients(r>0.999 0), and the methodological investigation showed that the method had good precision, repeatability and stability. The mean recoveries were 90.61% to 101.7% with RSD of 0.12% to 3.6%(n=6). UPLC-Q-OF-MS provided a rapid and efficient qualitative analytical method for the identification of the chemical components in Paeoniae Radix Alba, and the developed HPLC method was simple, rapid and accurate, which could provide a scientific basis for the evaluation of the germplasm resources and herbal quality of Paeoniae Radix Alba from different cultivars.

A High-Performance Alginate Hydrogel Binder for Aqueous Zn-Ion Batteries.

The binder is an indispensable battery component that maintains the integrity of the electrode. Polyvinylidene fluoride (PVDF) is most commonly used as a binder in rechargeable batteries; however, it is associated with the toxic and expensive N-methyl-2-pyrrolidone organic solvent. Here, through the cross-linking of sodium alginate (SA) with metal cations, a high-performance hydrogel binder is developed that maintains the stability of MnO2 cathodes in an aqueous electrolyte. Owing to the strong adhesion, high hydrophilicity, and good mechanical stability resulting from the strong bonding of Ca2+ with SA, a commercial microsized MnO2 cathode with a Ca-SA binder delivered a capacity above 300 mAh/g at 1 C, which was larger than those of Mn-SA and Zn-SA (∼200 mAh/g) and PVDF (∼150 mAh/g) binders, and a capacity of 250 mAh/g at 3 C for over 200 cycles. These encouraging results could unlock the enormous potential of aqueous binders for practical applications in aqueous batteries.

Triamcinolone acetonide-loaded nanoparticles encapsulated by CD90+ MCSs-derived microvesicles drive anti-inflammatory properties and promote cartilage regeneration after osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a highly prevalent human degenerative joint disorder that has long plagued patients. Glucocorticoid injection into the intra-articular (IA) cavity provides potential short-term analgesia and anti-inflammatory effects, but long-term IA injections cause loss of cartilage. Synovial mesenchymal stem cells (MSCs) reportedly promote cartilage proliferation and increase cartilage content. METHODS: CD90+ MCS-derived micro-vesicle (CD90@MV)-coated nanoparticle (CD90@NP) was developed. CD90+ MCSs were extracted from human synovial tissue. Cytochalasin B (CB) relaxed the interaction between the cytoskeleton and the cell membranes of the CD90+ MCSs, stimulating CD90@MV secretion. Poly (lactic-co-glycolic acid) (PLGA) nanoparticle was coated with CD90@MV, and a model glucocorticoid, triamcinolone acetonide (TA), was encapsulated in the CD90@NP (T-CD90@NP). The chondroprotective effect of T-CD90@NP was validated in rabbit and rat OA models. RESULTS: The CD90@MV membrane proteins were similar to that of CD90+ MCSs, indicating that CD90@MV bio-activity was similar to the cartilage proliferation-inducing CD90+ MCSs. CD90@NP binding to injured primary cartilage cells was significantly stronger than to erythrocyte membrane-coated nanoparticles (RNP). In the rabbit OA model, the long-term IA treatment with T-CD90@NP showed significantly enhanced repair of damaged cartilage compared to TA and CD90+ MCS treatments. In the rat OA model, the short-term IA treatment with T-CD90@NP showed effective anti-inflammatory ability similar to that of TA treatment. Moreover, the long-term IA treatment with T-CD90@NP induced cartilage to restart the cell cycle and reduced cartilage apoptosis. T-CD90@NP promoted the regeneration of chondrocytes, reduced apoptosis via the FOXO pathway, and influenced type 2 macrophage polarization to regulate inflammation through IL-10. CONCLUSION: This study confirmed that T-CD90@NP promoted chondrocyte proliferation and anti-inflammation, improving the effects of a clinical glucocorticoid treatment plan.

A novel semiautomatic Chinese keywords instrument screening delirium based on electronic medical records.

BACKGROUND: Delirium is frequently unrecognized due to the absence of regular screening. In addition to validated bedside tools, the computer-assisted instrument based on clinical notes from electronic medical records may be useful. AIMS: To assess the psychometric properties of a Chinese-chart-based keyword instrument for semiautomatically screening delirium using Natural language processing (NLP) based on clinical notes from electronic medical records. METHODS: The patients were admitted to West China Hospital from January 2015 to December 2017. Grouping patients based on the medical notes, those with accessible physician documents but no nurse documents were classified as the physician & no-nurse (PNN) group, while those with accessible physician and nurse documents were classified as the physician & nurse (PN) group. The psychometric properties, test-retest reliability, internal consistency reliability (Cronbach's α), and criterion validity were calculated. Using receiver operating characteristic (ROC) analysis, the criterion validity of delirium was evaluated in comparison to the results of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. RESULTS: A total of 779 patients were enrolled in the study. Their ages ranged from 65 to 103 years (82.5 ± 6.5), with men accounting for 71.9% of the total. A total of 312 patients had access to only physician documents in the physician & no-nurse (PNN) group, whereas 467 patients had access to both physician and nurse documents in the physician & nurse (PN) group. All 779 patients had a Cronbach's alpha of 0.728 in terms of reliability, with 100% test-retest reliability. The area under the ROC curve (AUC) values of the delirium screening instrument for criterion validity were 0.76 (all patients, n = 779), 0.72 (PNN, n = 312), and 0.79 (PN, n = 467), respectively. CONCLUSION: A delirium screening instrument composed of Chinese keywords that can be easily and quickly obtained from electronic medical records was developed, which improved delirium detection in older people. TRIAL REGISTRATION: Not applicable.

Cloning and Functional Characterization of Two Germacrene A Oxidases Isolated from Xanthium sibiricum.

Sesquiterpene lactones (STLs) from the cocklebur Xanthium sibiricum exhibit significant anti-tumor activity. Although germacrene A oxidase (GAO), which catalyzes the production of Germacrene A acid (GAA) from germacrene A, an important precursor of germacrene-type STLs, has been reported, the remaining GAOs corresponding to various STLs' biosynthesis pathways remain unidentified. In this study, 68,199 unigenes were studied in a de novo transcriptome assembly of X. sibiricum fruits. By comparison with previously published GAO sequences, two candidate X. sibiricum GAO gene sequences, XsGAO1 (1467 bp) and XsGAO2 (1527 bp), were identified, cloned, and predicted to encode 488 and 508 amino acids, respectively. Their protein structure, motifs, sequence similarity, and phylogenetic position were similar to those of other GAO proteins. They were most strongly expressed in fruits, according to a quantitative real-time polymerase chain reaction (qRT-PCR), and both XsGAO proteins were localized in the mitochondria of tobacco leaf epidermal cells. The two XsGAO genes were cloned into the expression vector for eukaryotic expression in Saccharomyces cerevisiae, and the enzyme reaction products were detected by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) methods. The results indicated that both XsGAO1 and XsGAO2 catalyzed the two-step conversion of germacrene A (GA) to GAA, meaning they are unlike classical GAO enzymes, which catalyze a three-step conversion of GA to GAA. This cloning and functional study of two GAO genes from X. sibiricum provides a useful basis for further elucidation of the STL biosynthesis pathway in X. sibiricum.

[Multiplex PCR method for simultaneous identification of Xanthii Fructus and its adulterants].

The purpose of this study is to establish a molecular method to identify Xanthii Fructus and two adulterants, the fruits of Xanthium mongolicum and X. italicum. Xanthii Fructus is the fruit of X. sibiricum, which is a Chinese herbal medicine used clinically to treat allergic rhinitis. The fruits of X. mongolicum and X. italicum have strong morphological similarities with Xanthii Fructus, while their safety of medication cannot be guaranteed. The genomes of X. sibiricum, X. mongolicum, and X. italicum were sequenced, which generated sequences of 2.21, 2.24, and 2.54 Gb, respectively. Based on the 76 specific contigs screened out by BLASTN and Bowtie 2, the corresponding primers were designed by Primer 5.0. Three pairs of primers with stable amplification efficiency and good reproducibility were screened out to establish a multiplex PCR method based on the PCR amplification results. Further, the annealing temperature, the amount of DNA template, the number of cycles, different DNA polymerases, and different PCR thermal cyclers were optimized. Fragments of 262 bp and 458 bp from X. sibiricum, 260, 454, and 927 bp from X. mongolicum, and 260 bp and 926 bp from X. italicum were amplified under the following conditions: the annealing temperature of 52 ℃, 35 cycles, 30 ng template DNA. Then, the established method was used to detect 18 samples of X. sibiricum, 17 samples of X. mongolicum, and 12 samples of X. italicum. The results showed that all the samples had positive results, which were consistent with the morphological identification results, thus proving the stability and reliability of the established method. Combining genome sequencing technology and multiplex PCR method to identify Xanthii Fructus and its adulterants can not only obtain the difference in genetic background but also facilitate the design of reliable primers. The multiplex PCR have high specificity and repeatability, providing a new method for the molecular identification of Xanthii Fructus.

[Comparison of transcriptome of Atractylodes lancea rhizome and exploration of genes for sesquiterpenoid biosynthesis].

This study compared the transcriptome of Atractylodes lancea rhizome at different development stages and explored genes encoding the key enzymes of the sesquiterpenoid biosynthesis pathway. Specifically, Illumina NovaSeq 6000 was employed for sequencing the cDNA libraries of A. lancea rhizome samples at the growth stage(SZ), flowering stage(KH), and harvesting stage(CS), respectively. Finally, a total of 388 201 748 clean reads were obtained, and 16 925, 8 616, and 13 702 differentially expressed genes(DEGs) were identified between SZ and KH, KH and CS, and SZ and CS, separately. Among them, 53 genes were involved in the sesquiterpenoid biosynthesis pathways: 9 encoding 6 enzymes of the mevalonic acid(MVA) pathway, 15 encoding 7 enzymes of the 2-C-methyl-D-erythritol-4-phosphate(MEP) pathway, and 29 of sesquiterpenoid and triterpenoid biosynthesis pathway. Weighted gene co-expression network analysis(WGCNA) yielded 12 genes related to sesquiterpenoid biosynthesis for the SZ, 1 gene for the KH, and 1 gene for CS, and several candidate genes for sesquiterpenoid biosynthesis were discovered based on the co-expression network. This study laid a solid foundation for further research on the sesquiterpenoid biosynthesis pathway, analysis of the regulation mechanism, and mechanism for the accumulation of sesquiterpenoids in A. lancea.

Cardiac Nestin+ Mesenchymal Stromal Cells Enhance Healing of Ischemic Heart through Periostin-Mediated M2 Macrophage Polarization.

Mesenchymal stromal cells (MSCs) show potential for treating cardiovascular diseases, but their therapeutic efficacy exhibits significant heterogeneity depending on the tissue of origin. This study sought to identify an optimal source of MSCs for cardiovascular disease therapy. We demonstrated that Nestin was a suitable marker for cardiac MSCs (Nes+cMSCs), which were identified by their self-renewal ability, tri-lineage differentiation potential, and expression of MSC markers. Furthermore, compared with bone marrow-derived MSCs (Nes+bmMSCs) or saline-treated myocardial infarction (MI) controls, intramyocardial injection of Nes+cMSCs significantly improved cardiac function and decreased infarct size after acute MI (AMI) through paracrine actions, rather than transdifferentiation into cardiac cells in infarcted heart. We further revealed that Nes+cMSC treatment notably reduced pan-macrophage infiltration while inducing macrophages toward an anti-inflammatory M2 phenotype in ischemic myocardium. Interestingly, Periostin, which was highly expressed in Nes+cMSCs, could promote the polarization of M2-subtype macrophages, and knockdown or neutralization of Periostin remarkably reduced the therapeutic effects of Nes+cMSCs by decreasing M2 macrophages at lesion sites. Thus, the present work systemically shows that Nes+cMSCs have greater efficacy than do Nes+bmMSCs for cardiac healing after AMI, and that this occurs at least partly through Periostin-mediated M2 macrophage polarization.

Neutrophil-lymphocyte ratio as a predictor of delirium in older internal medicine patients: a prospective cohort study.

BACKGROUNDS: Delirium is a common neuropsychiatric syndrome in older hospitalized patients. Previous studies have suggested that inflammation and oxidative stress contribute to the pathophysiology of delirium. However, it remains unclear whether neutrophil-lymphocyte ratio (NLR), an indicator of systematic inflammation, is associated with delirium. This study aimed to investigate the value of NLR as an independent risk factor for delirium among older hospitalized patients. METHODS: We conducted a prospective study of 740 hospitalized patients aged ≥ 70 years in the geriatric ward of West China Hospital of Sichuan University. Neutrophil and lymphocyte counts were collected within 24 h after hospital admission. Delirium was assessed on admission and every 48 h thereafter. We used the receiver operating characteristic analysis to assess the ability of the NLR for predicting delirium. The optimal cut-point value of the NLR was determined based on the highest Youden index (sensitivity + specificity - 1). Patients were categorized according to the cut-point value and quartiles of NLR, respectively. We then used logistic regression to identify the unadjusted and adjusted associations between NLR as a categorical variable and delirium. RESULTS: The optimal cut-point value of NLR for predicting delirium was 3.626 (sensitivity: 75.2 %; specificity: 63.4 %; Youden index: 0.386). The incidence of delirium was significantly higher in patients with NLR > 3.626 than NLR ≤ 3.626 (24.5 % vs. 5.8 %; P < 0.001). Significantly fewer patients in the first quartile of NLR experienced delirium than in the third (4.3 % vs. 20.0 %; P < 0.001) and fourth quartiles of NLR (4.3 % vs. 24.9 %; P < 0.001). Results from the multivariable logistic regression models showed that NLR was independently associated with delirium. CONCLUSIONS: NLR is a simple and practical marker that can predict the development of delirium in older internal medicine patients.

[Germacrene-derived sesquiterpene lactones:opportunities and challenges for biosynthesis].

Sesquiterpene lactones are a kind of widely distributed natural organic compounds with anti-tumor, anti-malarial and other significant biological activities. Based on their carbocylic skeletons, sesquiterpene lactones are classified into germacranolide, guaia-nolide, xanthanolide, pseudo-guaianolide, elemonolide and eudesmanolide, etc. In recent years, with the development of various omics and synthetic biology technologies, the biosynthetic pathways of sesquiterpene lactone compounds of different structural types have gradually been resolved. Among them, the researches on germacrene-derived sesquiterpene lactones are relatively more than others. Therefore, this article focused on the germacrene-derived sesquiterpene lactone biosynthesis pathways and their key enzyme genes, which can lay the foundation for in-depth analysis of sesquiterpene lactone biosynthetic pathways, functional gene mining and heterologous synthesis of active ingredients.

The geriatric nutrition risk index versus the mini-nutritional assessment short form in predicting postoperative delirium and hospital length of stay among older non-cardiac surgical patients: a prospective cohort study.

BACKGROUNDS: Malnutrition has been shown to be associated with poor prognosis in older surgical patients. Several tools are available for detecting malnutrition. But little is known about their ability to assess risks of postoperative adverse outcomes. The study aimed to compare the ability of the Geriatric Nutritional Risk Index (GNRI) and the Mini-Nutritional Assessment Short Form (MNA-SF) in predicting postoperative delirium (POD) and length of stay (LOS) among older non-cardiac surgical patients. METHODS: Prospective study of 288 older non-cardiac surgical patients from the West China Hospital of Sichuan University. Preoperative nutritional status was assessed using the GNRI and MNA-SF, and patients were followed for the occurrence of POD and LOS. Multivariable logistic regression and linear regression analyses were used to identify predictors of these outcomes. The relative performance of the GNRI and MNA-SF as predictors of these outcomes were determined by Receiver Operating Characteristic curves (ROC) analyses and the area under the curve (AUC). RESULTS: Multivariable analysis revealed that preoperative malnutrition by the MNA-SF was significantly associated with POD. Linear regression analysis showed that preoperative low/high nutritional risk of the GNRI and malnutrition by the MNA-SF were independent predictors of prolonged LOS. Moreover, the area under the curve (AUC) of MNA-SF scores for POD was better than GNRI scores (AUC = 0.718, 95%CI: 0.64-0.80, P < 0.001 vs AUC = 0.606, 95%CI: 0.52-0.69, P = 0.019; Delong's test, P = 0.006), but the AUC of GNRI scores and MNA-SF scores have no significant difference when predicting prolonged LOS (AUC = 0.611, 95%CI: 0.54-0.69, P = 0.006 vs AUC = 0.533, 95%CI: 0.45-0.62, P = 0.421; Delong's test, P = 0.079). CONCLUSION: The MNA-SF was more effective than the GNRI at predicting the development of POD, but the two nutrition screening methods have similar performance in predicting prolonged LOS among older non-cardiac surgical patients.

Dynamic evaluation of lung involvement during coronavirus disease-2019 (COVID-19) with quantitative lung CT.

PURPOSE: To identify and quantify lung changes associated with coronavirus disease-2019 (COVID-19) with quantitative lung CT during the disease. METHODS: This retrospective study reviewed COVID-19 patients who underwent multiple chest CT scans during their disease course. Quantitative lung CT was used to determine the nature and volume of lung involvement. A semi-quantitative scoring system was also used to evaluate lung lesions. RESULTS: This study included eighteen cases (4 cases in mild type, 10 cases in moderate type, 4 cases in severe type, and without critical type cases) with confirmed COVID-19. Patients had a mean hospitalized period of 24.1 ± 7.1 days (range: 14-38 days) and underwent an average CT scans of 3.9 ± 1.6 (range: 2-8). The total volumes of lung abnormalities reached a peak of 8.8 ± 4.1 days (range: 2-14 days). The ground-glass opacity (GGO) volume percentage was higher than the consolidative opacity (CO) volume percentage on the first CT examination (Z = 2.229, P = 0.026), and there was no significant difference between the GGO volume percentage and that of CO at the peak stage (Z = - 0.628, P = 0.53). The volume percentage of lung involvement identified by AI demonstrated a strong correlation with the total CT scores at each stage (r = 0.873, P = 0.0001). CONCLUSIONS: Quantitative lung CT can automatically identify the nature of lung involvement and quantify the dynamic changes of lung lesions on CT during COVID-19. For patients who recovered from COVID-19, GGO was the predominant imaging feature on the initial CT scan, while GGO and CO were the main appearances at peak stage.

Spironolactone suppresses aldosterone-induced Kv1.5 expression by attenuating mineralocorticoid receptor-Nox1/2/4-mediated ROS generation in neonatal rat atrial myocytes.

Our previous investigation indicated that angiotensin II (Ang II) enhances the expression of Kv1.5, a promising target for the treatment of atrial fibrillation (AF), by activating reactive oxygen species (ROS)-dependent phosphorylation of Smad 2/3 (forming P-Smad 2/3) and ERK 1/2 (forming P-ERK 1/2). A recent study indicated that aldosterone (Aldo) upregulates atrial Kv1.5 protein in a rat AF model, but the mechanism remains unknown. The present study aimed to clarify the mechanism underlying Aldo-induced Kv1.5 expression and to test whether spironolactone may modulate atrial Kv1.5. Our Western blot analysis indicated that the Aldo/mineralocorticoid receptor (MR) interacts with Ang II/AT1R in upregulating Kv1.5 expression in cultured neonatal atrial myocytes (NRAMs). Blockade of MR with spironolactone and of AT1R with losartan significantly suppressed Kv1.5 expression induction by combined Aldo and Ang II treatment. Aldo increased the protein expression of Nox1, Nox2 and Nox4, but this effect was abolished by spironolactone pretreatment. The Aldo-induced upregulation of Kv1.5 was also reversed by the Src protein tyrosine kinase family inhibitor PP2, the Nox2 inhibitor gp91ds-tat and the Nox1/Nox4 inhibitor GKT137831 but not by the Rac GTPase inhibitor NSC23766. Flow cytometry showed that the Aldo-induced ROS production was inhibited by spironolactone, PP2, gp91ds-tat and GKT137831. Spironolactone suppressed the Aldo-induced protein expression phosphorylated Src (P-Src), P-Smad 2/3 and P-ERK 1/2. In conclusion, we have demonstrated that spironolactone suppresses Aldo-induced Kv1.5 expression by attenuating MR-Nox1/2/4-mediated ROS generation in NRAMs.

Inhibition of perivascular mast cell activation is involved in the atheroprotective effect of rosiglitazone in apolipoprotein E-deficient mice.

Activation of perivascular mast cells (MCs) and subsequent release of their abundant inflammatory mediators have been well documented to induce excessive inflammation and subsequent rupture of atherosclerotic plaques. Previous studies have suggested that rosiglitazone affects the stability of plaques, although the precise mechanism of action is not clearly understood. In this study, we evaluated the effects of rosiglitazone on MCs in vivo and in vitro. Apolipoprotein E-deficient (ApoE-/-) mice were fed a high-fat diet (HFD), with or without rosiglitazone supplemented in the drinking water (1.5 mg/kg/day). Compared with the HFD group, rosiglitazone did not affect blood glucose levels, but it attenuated serum levels of tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6), ameliorated plaque lipid accumulation and the expression of matrix metalloproteinases-2 and -9, increased the collagen content of plaques, and inhibited perivascular MC degranulation and chymase expression. The in vitro experiments showed that rosiglitazone treatment repressed the expression of TNFα and IL-6 induced by antigen-challenged RBL-2H3 cells in a peroxisome proliferator-activated receptor γ (PPARγ)-independent manner, which was related to the repression of protein kinase C (PKC)-ß1 activation. Combined, these results suggest that the plaque-stabilizing effect of rosiglitazone is attributable to its ability to inhibit the activation of perivascular MCs.