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Proteomic, cellular and biochemical analysis of the stress protein NUPR1 reveals that it binds to PARP1 into the nucleus and inhibits PARP1 activity in vitro. Mutations on residues Ala33 or Thr68 of NUPR1 or treatment with its inhibitor ZZW-115 inhibits this effect. PARylation induced by 5-fluorouracil (5-FU) treatment is strongly enhanced by ZZW-115 and associated with a decrease of NAD+/NADH ratio and rescued by the PARP inhibitor olaparib. Cell death induced by ZZW-115 treatment of pancreas cancer-derived cells is rescued by olaparib and improved with PARG inhibitor PDD00017273. The mitochondrial catastrophe induced by ZZW-115 treatment or by genetic inactivation of NUPR1 is associated to a hyperPARylation of the mitochondria, disorganization of the mitochondrial network, mitochondrial membrane potential decrease, and with increase of superoxide production, intracellular level of reactive oxygen species (ROS) and cytosolic levels of Ca2+. These features are rescued by olaparib or NAD+ precursor nicotinamide mononucleotide in a dose-dependent manner and partially by antioxidants treatments. In conclusion, inactivation of NUPR1 induces a hyperPARylation, which in turn, induces a mitochondrial catastrophe and consequently a cell death through a non-canonical Parthanatos, since apoptosis inducing-factor (AIF) is not translocated out of the mitochondria.Correct species identification is crucial for ensuring the quality, safety, and efficacy of herbal medicine. Market research indicates that Curculigo glabrescens Rhizoma (CGR) was the major counterfeit of the medicine Curculigo orchioides Rhizoma (COR). To accurately discriminate COR and CGR remains a challenge, and it becomes even more difficult when the herbs have been heavily processed into a powder. In this work, combined with high performance liquid chromatography analysis, a novel component in CGR was discovered, and two stable isotopes (N%, C%, δ15N, δ13C) and nineteen mineral elements were determined along with multivariate statistical analysis to distinguish the authentic COR samples and counterfeit CGR samples. The results showed that there were significant differences between the mean value of N%, δ15N and δ13C according to the botanical origins. In addition, these two species can be differentiated by principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) analysis. A linear discriminant analysis (LDA) model with a good classification rate (100%) and cross-validation rate (100%) was established. Hence, stable isotope and mineral element contents combined with chemometrics analysis could be considered as an effective and reliable method for discriminating the source species of COR and CGR.The successful implementation of pharmacogenetics (PGx) into clinical practice requires patient genomic data to be shared between stakeholders in multiple settings. This creates a number of barriers to widespread adoption of PGx, including privacy concerns related to the storage and movement of identifiable genomic data. Informatic solutions that support secure and equitable data access for genomic data are therefore important to PGx. Here we propose a methodology that uses smart contracts implemented on a blockchain-based framework, PGxChain, to address this issue. The design requirements for PGxChain were identified through a systematic literature review, identifying technical challenges and barriers impeding the clinical implementation of pharmacogenomics. These requirements included security and privacy, accessibility, interoperability, traceability and legal compliance. A proof-of-concept implementation based on Ethereum was then developed that met the design requirements. PGxChain's performance was examined using Hyperledger Caliper for latency, throughput, and transaction success rate. The findings clearly indicate that blockchain technology offers considerable potential to advance pharmacogenetic data sharing, particularly with regard to PGx data security and privacy, large-scale accessibility of PGx data, PGx data interoperability between multiple health care providers and compliance with data-sharing laws and regulations.Burkholderia pseudomallei is a Gram-negative intracellular bacterium that causes melioidosis, a life-threatening disease. The interaction of B. pseudomallei with its host is complicated, and cellular response to B. pseudomallei infection is still largely unknown. In this study, we aimed to determine host-cell responses to B. pseudomallei at the proteomics level. We performed proteomic profiling of B. pseudomallei HNBP001-infected mouse macrophage RAW264.7 cells to characterize the cellular response dynamics during infection. Western blot analysis was utilized for the validation of changes in protein expression. click here Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted using the clusterProfiler R package. Compared with the negative control (NC) group, 811 common proteins varied over time, with a cut-off level of two fold change and an adjusted P-value less than 0.05. The bioinformatics analysis revealed that the proteins significantly changed in the B. pseudomallei HNBP001 infection group (Bp group) were enriched in glycometabolism pathways, including glycolysis, fructose and mannose metabolism, pentose phosphate pathway, galactose metabolism, and carbon metabolism. Western blot analysis verified three selected proteins involved in glycometabolism pathways, namely PGM1, PKM, and PGK1 were increase over time post the infection. Furthermore, in vitro functional analysis revealed an increased glucose uptake and decreased ATP production and O-GlcNAcylation in the Bp group compared with control group, suggesting that B. pseudomallei HNBP001 infection induces changes in glycometabolism in RAW264.7 cells. These results indicate that glycometabolism pathways change in RAW264.7 cells post B. pseudomallei HNBP001 infection, providing important insights into the intimate interaction between B. pseudomallei and macrophages.Chinese herbal medicine (CHM) has been used for arthritis in China and elsewhere across the world. However, knowledge about the prevalence and profile of middle-aged and older women who used CHM for arthritis in China is limited. This study aims to identify potentially important insights into the factors associated with CHM use amongst middle-aged and older women with arthritis in China. Data were drawn from the China Health and Retirement Longitudinal Study (CHARLS), a population-based survey of Chinese adults aged 45 years or older, comprising 10,833 Chinese women who completed a questionnaire in 2015. Stepwise multiple logistic regression modeling was conducted to determine the key factors (demographic, health condition, and health services use) predicting the use of CHM for the treatment of arthritis. Results revealed that 17.2% of women with arthritis were taking CHM for their arthritic symptoms. Women with arthritis who used CHM were more likely to experience finger pain (OR = 1.70), had difficulty in stooping, kneeling, crouching (OR = 1.40), visited a Traditional Chinese hospital (OR = 2.22), consulted massage therapists (OR = 2.06) and/or had experienced a fall (OR = 1.41). The prevalence of CHM use is high amongst middle-aged and older Chinese women with arthritis. Given the high risk of functional disability and impaired mental health, further research is needed to explore the potential health benefits of CHM for women with arthritis in order to help facilitate the efficacious and safe use of CHM alongside conventional medical care.Understanding the impact of long-term exposure of microorganisms to space is critical in understanding how these exposures impact the evolution and adaptation of microbial life under space conditions. In this work we subjected Nostoc sp. CCCryo 231-06, a cyanobacterium capable of living under many different ecological conditions, and also surviving in extreme ones, to a 23-month stay at the International Space Station (the Biology and Mars Experiment, BIOMEX, on the EXPOSE-R2 platform) and returned it to Earth for single-cell genome analysis. We used microfluidic technology and single cell sequencing to identify the changes that occurred in the whole genome of single Nostoc cells. The variant profile showed that biofilm and photosystem associated loci were the most altered, with an increased variant rate of synonymous base pair substitutions. The cause(s) of these non-random alterations and their implications to the evolutionary potential of single bacterial cells under long-term cosmic exposure warrants further investigation.Nanocrystalline structured variants of commercially available alloys have shown potential for boosting the mechanical properties of these materials, leading to a reduction in waste and thereby retaining feasible supply chains. One approach towards achieving these nanostructures resides in frictional treatments on manufactured parts, leading to differential refinement of the surface structure as compared to the bulk material. In this work the machining method is considered to be a testing platform for the formation and study of frictional nanostructured steel, assembly of which is stabilized by fast cooling of the produced chip. Analysis of the mechanical properties has shown extraordinary results at the surface, over 2000 MPa of strength on AISI1045 steel, more than three times the strength of the base material, demonstrating at the same time a reduction of 15% in the elastic modulus. The microscopic analysis suggests a reassembly of the elements in a new lattice of carbon supersaturated nano-ferrite.Recent advances in tissue engineering and biofabrication technology have yielded a plethora of biological tissues. Among these, engineering of bioartificial muscle stands out for its exceptional versatility and its wide range of applications. From the food industry to the technology sector and medicine, the development of this tissue has the potential to affect many different industries at once. However, to date, the biofabrication of cultured meat, biorobotic systems, and bioartificial muscle implants are still considered in isolation by individual peer groups. To establish common ground and share advances, this review outlines application-specific requirements for muscle tissue generation and provides a comprehensive overview of commonly used biofabrication strategies and current application trends. By solving the individual challenges and merging various expertise, synergetic leaps of innovation that inspire each other can be expected in all three industries in the future.Clarifying the generalizability of deep-learning-based surgical-instrument segmentation networks in diverse surgical environments is important in recognizing the challenges of overfitting in surgical-device development. This study comprehensively evaluated deep neural network generalizability for surgical instrument segmentation using 5238 images randomly extracted from 128 intraoperative videos. The video dataset contained 112 laparoscopic colorectal resection, 5 laparoscopic distal gastrectomy, 5 laparoscopic cholecystectomy, and 6 laparoscopic partial hepatectomy cases. Deep-learning-based surgical-instrument segmentation was performed for test sets with (1) the same conditions as the training set; (2) the same recognition target surgical instrument and surgery type but different laparoscopic recording systems; (3) the same laparoscopic recording system and surgery type but slightly different recognition target laparoscopic surgical forceps; (4) the same laparoscopic recording system and recognition target surgical instrument but different surgery types.