Explore the vast range of titles available.

BackgroundThe high levels of C reactive protein (CRP) to albumin ratio (CAR) is thought to increase the risk of poor outcomes for cancer and cardiovascular disease (CVD). However, the association between CAR and CVD in the Chinese community population has not been investigated.ObjectiveThe aim of this study was to investigate the association between CAR and CVD in the Chinese community population.MethodsA total of 62 067 participants without a history of CVD or cancer were included in this study. Kaplan-Meier survival curves were used to calculate the cumulative incidence of endpoint events in CAR quartile groups, and the results were tested by log-rank test. Fine-Gray model was used to analyse the competing risk of death. C-index, Net Reclassification Index (NRI) and Integrated Discrimination Improvement Index (IDI) of different indicators were calculated to distinguish the predictive performance of different indicators.ResultsDuring an average follow-up period of 10.3±2.1 years, 4025 participants developed CVD. In multivariable Cox regression analysis, compared with Q1 group, model 3 showed that the hazard ratio (HR) (95% confidence interval (95%CI)) of CVD in Q4 group was 1.26 (1.15 to 1.38) (p<0.01), and the HR (95% CI) per 1 SD increase was 1.06 (1.03 to 1.08) (p<0.01). The C-index, continuous NRI and IDI for predicting 10-year CVD were 73.48%, 0.1366 (0.1049 to 0.1684) (p<0.01) and 0.0002 (0.0001 to 0.0004) (p<0.01), respectively, which were higher than those of hs-CRP (C-index:0.7344, NRI:0.0711, IDI: 0.0001) and albumin (C-index:0.7339, NRI: −0.0090, IDI: 0.0000).ConclusionHigh levels of CAR can increase the risk of CVD and the predictive performance of CAR for CVD is better than that of hs-CRP or albumin alone.

The revival of interest in cancer cell metabolism in recent years has prompted the need for quantitative analytical platforms for studying metabolites from in vivo sources. We implemented a quantitative polar metabolomics profiling platform using selected reaction monitoring with a 5500 QTRAP hybrid triple quadrupole mass spectrometer that covers all major metabolic pathways. The platform uses hydrophilic interaction liquid chromatography with positive/negative ion switching to analyze 258 metabolites (289 Q1/Q3 transitions) from a single 15-min liquid chromatography–mass spectrometry acquisition with a 3-ms dwell time and a 1.55-s duty cycle time. Previous platforms use more than one experiment to profile this number of metabolites from different ionization modes. The platform is compatible with polar metabolites from any biological source, including fresh tissues, cancer cells, bodily fluids and formalin-fixed paraffin-embedded tumor tissue. Relative quantification can be achieved without using internal standards, and integrated peak areas based on total ion current can be used for statistical analyses and pathway analyses across biological sample conditions. The procedure takes ∼12 h from metabolite extraction to peak integration for a data set containing 15 total samples (∼6 h for a single sample).

The epidemiological features of the newly emerged carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-HvKP) and its potential threat to human health are currently unknown. In this study, a total of 784 bla KPC-2 -bearing CRKP strains collected from three hospitals located at different geographical locales in China during 2014-2017 were subjected to molecular typing, screening of virulence plasmid, string test and WGS (367/784 strains). The proportion of CRKP among all clinical K. pneumoniae strains increased sharply in China during 2014-2017. A large proportion (58%) of these CRKP strains were found to harbour a virulence-encoding plasmid, while only 13% of such strains exhibited a hypervirulent phenotype by string test and neutrophil assay. The lack of hypervirulent phenotype in virulent plasmid-bearing CRKP strains was found to be due to the mutation's presence on rmpA and rmpA2 genes, which rendered them non-functional, while some strains carrying wild type rmpA did not exhibit hypervirulent phenotype either suggesting that other factors might also contribute to the hypervirulence of CRKP. Phylogenetic and SNP analysis indicated that the transmission of these CRKP strains in China likely involved several major clones of ST11. Carriage of IncFII pSWU01-like, bla KPC-2 -bearing plasmid was found to be the major mechanism of carbapenem resistance in these CRKP strains. In conclusion, our data indicated that the prevalence of CRKP strains carrying the virulence plasmid has rapidly increased in China, while genetic markers were not correlated well with the hypervirulent phenotypes, which call for a better definition and screening for these truly hypervirulent CR-HvKP strains in clinical settings.

Members of the solute carrier organic anion transporting polypeptide (OATPs) family function as transporters for a large variety of amphipathic organic anions including endogenous metabolites and clinical drugs, such as bile salts, steroids, thyroid hormones, statins, antibiotics, antivirals, and anticancer drugs. OATP1B1 plays a vital role in transporting such substances into the liver for hepatic clearance. FDA and EMA recommend conducting in vitro testing of drug–drug interactions (DDIs) involving OATP1B1. However, the structure and working mechanism of OATPs still remains elusive. In this study, we determined cryo-EM structures of human OATP1B1 bound with representative endogenous metabolites (bilirubin and estrone-3-sulfate), a clinical drug (simeprevir), and a fluorescent indicator (2′,7′-dichlorofluorescein), in both outward- and inward-open states. These structures reveal major and minor substrate binding pockets and conformational changes during transport. In combination with mutagenesis studies and molecular dynamics simulations, our work comprehensively elucidates the transport mechanism of OATP1B1 and provides the structural basis for DDI predictions involving OATP1B1, which will greatly promote our understanding of OATPs.

Background Punica granatum is a fundamentally important fruit tree that has important economic, medicinal and ornamental properties. At present, there are few reports on the mitochondrial genome of pomegranate. Hence, in this study the P. granatum mitogenome was sequenced and assembled to further understanding of organization, variation, and evolution of mitogenomes of this tree species. Results The genome structure was multi-chromosomes with seven circular contigs, measuring 382,774 bp in length with a 45.91% GC content. It contained 74 genes, including 46 protein-coding genes, 25 tRNA genes, and three rRNA genes. There were 188 pairs of dispersed repeats with lengths of 30 or greater, primarily consisting of reverse complementary repeats. The mitogenome analysis identified 114SSRs and 466 RNA editing sites. Analyses of codon usage, nucleotide diversity and gene migration from chloroplast to mitochondrial were also conducted. The collinear and comparative analysis of mitochondrial structures between P. granatum and its proximal species indicated that P. granatum ‘Taishanhong’ was closely related to P. granatum ‘Qingpitian’ and Lagerstroemia indica. Phylogenetic examination based on the mitogenome also confirmed the evolutionary relationship. Conclusion The results offered crucial information on the evolutionary biology of pomegranate and highlighted ways to promote the utilization of the species’ germplasm.

The realization of compact and efficient broadband mid-infrared (MIR) lasers has enormous impacts in promoting MIR spectroscopy for various important applications. A number of well-designed waveguide platforms have been demonstrated for MIR supercontinuum and frequency comb generations based on cubic nonlinearities, but unfortunately third-order nonlinear response is inherently weak. Here, we propose and demonstrate for the first time a χ (2) micrometer waveguide platform based on birefringence phase matching for long-wavelength infrared (LWIR) laser generation with a high quantum efficiency. In a ZnGeP 2 -based waveguide platform, an octave-spanning spectrum covering 5–11 μm is generated through optical parametric generation (OPG). A quantum conversion efficiency of 74% as a new record in LWIR single-pass parametric processes is achieved. The threshold energy is measured as ~616 pJ, reduced by more than 1-order of magnitude as compared to those of MIR OPGs in bulk media. Our prototype micro-waveguide platform could be extended to other χ (2) birefringence crystals and trigger new frontiers of MIR integrated nonlinear photonics. A χ (2) nonlinear micro-waveguide platform is demonstrated based on the birefringence phase matching for simple and efficient long-wavelength infrared generation, which could trigger new frontiers of MIR integrated nonlinear photonics.

At the moment, pancreatic cancer is among the deadliest gastrointestinal diseases, and pancreatic cancer growth is a complex biological process that is based on different kinds of genes. Exosomes are extracellular vesicles containing microRNAs (miRNAs), messenger RNA (mRNA), and proteins, they act as the most prominent mediator of intercellular communication, and they regulate, instruct, and re-educate their surrounding microenvironment and target specific organs. Due to accumulative evidence proved that exosomes are involved in metastasis, cell proliferation, EMT, angiogenesis, and TME of pancreatic cancer, exosomes are crucial potential candidates to detect pancreatic cancer early. This review aims to convey the current understanding of the main functions employed by exosomes in early diagnosis and treatment of pancreatic cancer.

Wood panel surface defect detection is critical to product quality. Traditional detection methods are time-consuming and subjective, and they can lead to economic waste, while deep learning image recognition techniques offer a new approach. However, the accuracy and convergence speed of existing defect detection techniques still require improvement. In this paper, an improved algorithm based on YOLOv8n was designed for accurate detection of wood panel defects. The C-ADown method was designed to replace traditional downsampling, while preserving high-frequency features. The combination of the Dilation-wise Residual Module and multi-scale dilation attention was employed to enhance the multiscale robustness of defect detection. A hybrid encoder was added to improve localization accuracy. The loss function was optimized to improve detection accuracy and convergence speed. Compared to the base YOLOv8 version, the improved model achieved a 6.1% increase in mAP, an 8% increase in recall, and a 3.6% increase in precision, significantly enhancing the model’s detection capabilities. The GitHub link to the improved algorithm files is as follows: (https://github.com/humblefactos1/YOLOV8-CDC/tree/main.)

Our previous studies have confirmed that fluoride combined with aluminum (FA) can induce hippocampal neuron damage in the second-generation offspring (F2) of rats; however, the underlying mechanisms remain unclear. In this study, we established an F2 rat model and an NG108-15 cell model to investigate the potential modes of action. The autophagy of F2 rat hippocampal neurons and NG108-15 cells was assessed using transmission electron microscopy and immunofluorescence/immunocytochemistry kit, respectively. Hippocampal morphology was evaluated via hematoxylin-eosin (HE) staining. We measured mRNA levels of AMPK, mTOR, ULK1, and LC3 using quantitative reverse transcription PCR, and protein expressions were analyzed by Western blotting. Following treatment with rapamycin (Rap) in FA-exposed F2 rats and NG108-15 cells, a small number of primary lysosomes and autophagosomes appeared within hippocampal cells, with HE staining indicating a near-normal restoration of pyramidal cell morphology. The quantity, intensity, and volume of green fluorescent spots in the cytoplasm of NG108-15 cells increased as observed through fluorescence microscopy. The mRNA expressions of AMPK, ULK1, and LC3 were upregulated while mTOR expressions were downregulated in NG108-15 cells. Correspondingly, protein levels for AMPK, p-AMPK, ULK1, p-ULK1 along with the LC3-II/LC3-I ratio increased whereas those for mTOR, p-mTOR and p62 decreased significantly. Similar trends regarding both mRNA and protein expression were noted within the hippocampus of F2 rats as well. Activation of the AMPK/mTOR/ULK1 signaling pathway by Rap enhances FA-induced autophagy thereby mitigating neuronal damage.

Background Phosphorus plays a key role in plant adaptation to adversity and plays a positive role in the yield and quality formation of apples. Genes of the SPX domain-containing family are widely involved in the regulation of phosphorus signalling networks. However, the mechanisms controlling phosphorus deficiency are not completely understood in self-rooted apple stock. Results In this study, 26 members of the apple SPX gene family were identified by genome-wide analysis, and further divided into four subfamilies ( SPX , SPX - MFS , SPX - EXS , and SPX - RING ) based on their structural features. The chromosome distribution and gene duplications of MdSPXs were also examined. The promoter regions of MdSPXs were enriched for multiple biotic/abiotic stresses, hormone responses and typical P1BS-related elements. Analysis of the expression levels of 26 MdSPXs showed that some members were remarkably induced when subjected to low phosphate (Pi) stress, and in particular MdSPX2 , MdSPX3 , and MdPHO1.5 exhibited an intense response to low Pi stress. MdSPX2 and MdSPX3 showed significantly divergent expression levels in low Pi sensitive and insensitive apple species. Protein interaction networks were predicted for 26 MdSPX proteins. The interaction of MdPHR1 with MdSPX2, MdSPX3, MdSPX4, and MdSPX6 was demonstrated by yeast two-hybrid assay, suggesting that these proteins might be involved in the Pi-signaling pathway by interacting with MdPHR1. Conclusion This research improved the understanding of the apple SPX gene family and contribute to future biological studies of MdSPX genes in self-rooted apple stock.