Comparison between sepsis-induced coagulopathy and sepsis-associated coagulopathy criteria in identifying sepsis-associated disseminated intravascular coagulation.

BACKGROUND: Disseminated intravascular coagulation (DIC) is associated with increased mortality in sepsis patients. In this study, we aimed to assess the clinical ability of sepsis-induced coagulopathy (SIC) and sepsis-associated coagulopathy (SAC) criteria in identifying overt-DIC and pre-DIC status in sepsis patients. METHODS: Data from 419 sepsis patients were retrospectively collected from July 2018 to December 2022. The performances of the SIC and SAC were assessed to identify overt-DIC on days 1, 3, 7, or 14. The SIC status or SIC score on day 1, the SAC status or SAC score on day 1, and the sum of the SIC or SAC scores on days 1 and 3 were compared in terms of their ability to identify pre-DIC. The SIC or SAC status on day 1 was evaluated as a pre-DIC indicator for anticoagulant initiation. RESULTS: On day 1, the incidences of coagulopathy according to overt-DIC, SIC and SAC criteria were 11.7%, 22.0% and 31.5%, respectively. The specificity of SIC for identifying overt-DIC was significantly higher than that of the SAC criteria from day 1 to day 14 (P<0.05). On day 1, the SIC score with a cut-off value > 3 had a significantly higher sensitivity (72.00%) and area under the curve (AUC) (0.69) in identifying pre-DIC than did the SIC or SAC status (sensitivity: SIC status 44.00%, SAC status 52.00%; AUC: SIC status 0.62, SAC status 0.61). The sum of the SIC scores on days 1 and 3 had a higher AUC value for identifying the pre-DIC state than that of SAC (0.79 vs. 0.69, P<0.001). Favorable effects of anticoagulant therapy were observed in SIC (adjusted hazard ratio [HR]=0.216, 95% confidence interval [95% CI]: 0.060-0.783, P=0.018) and SAC (adjusted HR=0.146, 95% CI: 0.041-0.513, P=0.003). CONCLUSION: The SIC and SAC seem to be valuable for predicting overt-DIC. The sum of SIC scores on days 1 and 3 has the potential to help identify pre-DIC.

Low-Dose Colchicine Ameliorates Doxorubicin Cardiotoxicity Via Promoting Autolysosome Degradation.

BACKGROUND: The only clinically approved drug that reduces doxorubicin cardiotoxicity is dexrazoxane, but its application is limited due to the risk of secondary malignancies. So, exploring alternative effective molecules to attenuate its cardiotoxicity is crucial. Colchicine is a safe and well-tolerated drug that helps reduce the production of reactive oxygen species. High doses of colchicine have been reported to block the fusion of autophagosomes and lysosomes in cancer cells. However, the impact of colchicine on the autophagy activity within cardiomyocytes remains inadequately elucidated. Recent studies have highlighted the beneficial effects of colchicine on patients with pericarditis, postprocedural atrial fibrillation, and coronary artery disease. It remains ambiguous how colchicine regulates autophagic flux in doxorubicin-induced heart failure. METHODS AND RESULTS: Doxorubicin was administered to establish models of heart failure both in vivo and in vitro. Prior studies have reported that doxorubicin impeded the breakdown of autophagic vacuoles, resulting in damaged mitochondria and the accumulation of reactive oxygen species. Following the administration of a low dose of colchicine (0.1 mg/kg, daily), significant improvements were observed in heart function (left ventricular ejection fraction: doxorubicin group versus treatment group=43.75%±3.614% versus 57.07%±2.968%, P=0.0373). In terms of mechanism, a low dose of colchicine facilitated the degradation of autolysosomes, thereby mitigating doxorubicin-induced cardiotoxicity. CONCLUSIONS: Our research has shown that a low dose of colchicine is pivotal in restoring the autophagy activity, thereby attenuating the cardiotoxicity induced by doxorubicin. Consequently, colchicine emerges as a promising therapeutic candidate to improve doxorubicin cardiotoxicity.

FGF13 deficiency ameliorates calcium signaling abnormality in heart failure by regulating microtubule stability.

Calcium signaling abnormality in cardiomyocytes, as a key mechanism, is closely associated with developing heart failure. Fibroblast growth factor 13 (FGF13) demonstrates important regulatory roles in the heart, but its association with cardiac calcium signaling in heart failure remains unknown. This study aimed to investigate the role and mechanism of FGF13 on calcium mishandling in heart failure. Mice underwent transaortic constriction to establish a heart failure model, which showed decreased ejection fraction, fractional shortening, and contractility. FGF13 deficiency alleviated cardiac dysfunction. Heart failure reduces calcium transients in cardiomyocytes, which were alleviated by FGF13 deficiency. Meanwhile, FGF13 deficiency restored decreased Cav1.2 and Serca2α expression and activity in heart failure. Furthermore, FGF13 interacted with microtubules in the heart, and FGF13 deficiency inhibited the increase of microtubule stability during heart failure. Finally, in isoproterenol-stimulated FGF13 knockdown neonatal rat ventricular myocytes (NRVMs), wildtype FGF13 overexpression, but not FGF13 mutant, which lost the binding site of microtubules, promoted calcium transient abnormality aggravation and Cav1.2 downregulation compared with FGF13 knockdown group. Generally, FGF13 deficiency improves abnormal calcium signaling by inhibiting the increased microtubule stability in heart failure, indicating the important role of FGF13 in cardiac calcium homeostasis and providing new avenues for heart failure prevention and treatment.

Knowledge mapping and global trends of drug hypersensitivity from 2013 to 2023: A bibliometric analysis.

BACKGROUND: Drug hypersensitivity is a major global public health issue with a significant increase in prevalence in populations. Here, we provide a deep insight into the frontier hotspot and future direction in the field of drug hypersensitivity. METHODS: A knowledge map is portrayed based on publications related to drug hypersensitivity from Web of Science Core Collection using CiteSpace. Co-occurrence relationships of countries, institutes, authors, journals, references, and keywords are constructed. According to the co-occurrence relationships, hotspots and future trends are overviewed. RESULTS: The United States ranked first in the world and China with the second highest publications was the only developing country. Torres, Mayorga, and Blanca were highly productive authors. Harvard University was the institution with the most research publications. Keywords co-occurrence analysis suggested applications in emerging causes, potential mechanisms, and clinical diagnosis as the research hotspots and development frontiers. CONCLUSION: Research on drug hypersensitivity is in a rapid development stage and an emerging trend in reports of anaphylaxis to polyethylene glycols is identified. Developing algorithms for understanding the standardization process of culprit drugs, clinical manifestations, and diagnostic methods will be the focus of future direction. In addition, a better understanding of the mechanisms to culprit drugs with immunological precise phenotypic definitions and high-throughput platforms is needed.

Ginsenoside Rb1 attenuates doxorubicin induced cardiotoxicity by suppressing autophagy and ferroptosis.

Ginsenoside Rb1 (Rb1), an active component isolated from traditional Chinese medicine Ginseng, is beneficial to many cardiovascular diseases. However, whether it can protect against doxorubicin induced cardiotoxicity (DIC) is not clear yet. In this study, we aimed to investigate the role of Rb1 in DIC. Mice were injected with a single dose of doxorubicin (20 mg/kg) to induce acute cardiotoxicity. Rb1 was given daily gavage to mice for 7 days. Changes in cardiac function, myocardium histopathology, oxidative stress, cardiomyocyte mitochondrion morphology were studied to evaluate Rb1's function on DIC. Meanwhile, RNA-seq analysis was performed to explore the potential underline molecular mechanism involved in Rb1's function on DIC. We found that Rb1 treatment can improve survival rate and body weight in Dox treated mice group. Rb1 can attenuate Dox induced cardiac dysfunction and myocardium hypertrophy and interstitial fibrosis. The oxidative stress increase and cardiomyocyte mitochondrion injury were improved by Rb1 treatment. Mechanism study found that Rb1's beneficial role in DIC is through suppressing of autophagy and ferroptosis. This study shown that Ginsenoside Rb1 can protect against DIC by regulating autophagy and ferroptosis.

A metal-organic framework signaling probe-mediated immunosensor for the economical and rapid determination of enrofloxacin in milk.

Ensuring the safety of animal-derived foods requires the reliable and swift identification of enrofloxacin residues to monitor the presence of antibiotics. In this regard, we synthesized, tuned, and investigated the optical properties of a bimetallic metal-organic framework (Ce/Zr-UiO 66). The investigation was facilitated by employing a polydopamine-coated pipette tip with high adsorption efficiency, serving as an immunoreactive carrier. Subsequently, an immunofunctionalized variant of Ce/Zr-UiO 66, referred to as Ce/Zr-UiO 66@ Bovine serum albumin-enrofloxacin, was developed as an optical probe for the rapid and sensitive identification of enrofloxacin across a variety of samples. The method can accurately detect enrofloxacin at concentrations as low as 0.12 ng/mL, with a determination time of under 15 min; furthermore, it demonstrates exceptional efficacy when applied to food, environmental, and clinical samples. The implementation of this methodology offers a valuable means for cost-effective, rapid, and on-site enrofloxacin determination.

Dual-Track Multifunctional Bimetallic Metal-Organic Frameworks for Antibiotic Enrichment and Detection.

The improper use and overuse of antibiotics have led to significant burdens and detrimental effects on the environment, food supply, and human health. Herein, a magnetic solid-phase extraction program and an optical immunosensor based on bimetallic Ce/Zr-UiO 66 for the detection of antibiotics are developed. A magnetic Fe3O4@SiO2@Ce/Zr-UiO 66 metal-organic framework (MOF) is prepared to extract and enrich chloramphenicol from fish, wastewater, and urine samples, and a horseradish peroxidase (HRP)-Ce/Zr-UiO 66@bovine serum protein-chloramphenicol probe is used for the sensitive detection of chloramphenicol based on the dual-effect catalysis of Ce and HRP. In this manner, the application of Ce/Zr-UiO 66 in integrating sample pretreatment and antibiotic detection is systematically investigated and the associated mechanisms are explored. It is concluded that Ce/Zr-UiO 66 is a versatile dual-track material exhibiting high enrichment efficiency (6.37 mg g-1) and high sensitivity (limit of detection of 51.3 pg mL-1) for chloramphenicol detection and serving as a multifunctional MOF for safeguarding public health and hygiene.

Multilayered Fe3O4@(ZIF-8)3 combined with a computer-vision-enhanced immunosensor for chloramphenicol enrichment and detection.

The misuse and overuse of chloramphenicol poses severe threats to food safety and human health. In this work, we developed a magnetic solid-phase extraction (MSPE) pretreatment material coated with a multilayered metal-organic framework (MOF), Fe3O4 @ (ZIF-8)3, for the separation and enrichment of chloramphenicol from fish. Furthermore, we designed an artificial-intelligence-enhanced single microsphere immunosensor. The inherent ultra-high porosity of the MOF and the multilayer assembly strategy allowed for efficient chloramphenicol enrichment (4.51 mg/g within 20 min). Notably, Fe3O4 @ (ZIF-8)3 exhibits a 39.20% increase in adsorption capacity compared to Fe3O4 @ZIF-8. Leveraging the remarkable decoding abilities of artificial intelligence, we achieved the highly sensitive detection of chloramphenicol using a straightforward procedure without the need for specialized equipment, obtaining a notably low detection limit of 46.42 pM. Furthermore, the assay was successfully employed to detect chloramphenicol in fish samples with high accuracy. The developed immunosensor offers a robust point-of-care testing tool for safeguarding food safety and public health.

DUSP22 Ameliorates Endothelial-to-Mesenchymal Transition in HUVECs through Smad2/3 and MAPK Signaling Pathways.

Endothelial-to-mesenchymal transition (EndMT) is the process by which endothelial cells lose their endothelial properties and acquire mesenchymal characteristics. Dual-specific protein phosphatase 22 (DUSP22) inactivates various protein kinases and transcription factors by dephosphorylating serine/threonine residues: hence, it plays a key role in many diseases. The aim of this study was to explore the functional role of DUSP22 in EndMT. In the transforming growth factor-ß-induced EndMT model in human umbilical vein endothelial cells (HUVECs), we observed a downregulation of DUSP22 expression. This DUSP22 deficiency could aggravate EndMT. Conversely, the overexpression of DUSP22 could ameliorate EndMT. We used signaling pathway inhibitors to verify our results and found that DUSP22 could regulate EndMT through the smad2/3 and the mitogen-activated protein kinase (MAPK) signaling pathways. In summary, DUSP22 ameliorates EndMT in HUVECs in vitro through the smad2/3 and MAPK signaling pathways.

Cancer burden attributable to risk factors, 1990-2019: A comparative risk assessment.

An up-to-date comprehensive assessment of the cancer burden attributable to risk factors is essential for cancer prevention. We analyzed the population attributable fraction (PAF) of cancer disability-adjusted life years (DALYs) attributable to 11 level 2 risk factors using data from the Global Burden and Disease Study (GBD) 2019. We highlighted that almost half of the cancer DALYs can be preventable by modifying relevant risk factors. The attributable cancer DALYs increased by 60.42%-105.0 million from 1990 to 2019. Tobacco, dietary risks, alcohol use, high body-mass index, and air pollution were the top five risk factors. The PAFs attributable to high fasting plasma glucose, high body-mass index, and low physical activity have increased worldwide from 1990 to 2019. Unsafe sex was the leading risk factor for women before age of 54. Tailored prevention programs targeted at specific populations should be scaled up to reduce the cancer burden in the future.

Phosphorylated CPI-17 and MLC2 as Biomarkers of Coronary Artery Spasm-Induced Sudden Cardiac Death.

Coronary artery spasm (CAS) plays an important role in the pathogeneses of various ischemic heart diseases and has gradually become a common cause of life-threatening arrhythmia. The specific molecular mechanism of CAS has not been fully elucidated, nor are there any specific diagnostic markers for the condition. Therefore, this study aimed to examine the specific molecular mechanism underlying CAS, and screen for potential diagnostic markers. To this end, we successfully constructed a rat CAS model and achieved in vitro culture of a human coronary-artery smooth-muscle cell (hCASMC) contraction model. Possible molecular mechanisms by which protein kinase C (PKC) regulated CAS through the C kinase-potentiated protein phosphatase 1 inhibitor of 17 kDa (CPI-17)/myosin II regulatory light chain (MLC2) pathway were studied in vivo and in vitro to screen for potential molecular markers of CAS. We performed hematoxylin and eosin staining, myocardial zymogram, and transmission electron microscopy to determine myocardial and coronary artery injury in CAS rats. Then, using immunohistochemical staining, immunofluorescence staining, and Western blotting, we further demonstrated a potential molecular mechanism by which PKC regulated CAS via the CPI-17/MLC2 pathway. The results showed that membrane translocation of PKCα occurred in the coronary arteries of CAS rats. CPI-17/MLC2 signaling was observably activated in coronary arteries undergoing CAS. In addition, in vitro treatment of hCASMCs with angiotensin II (Ang II) increased PKCα membrane translocation while consistently activating CPI-17/MLC2 signaling. Conversely, GF-109203X and calphostin C, specific inhibitors of PKC, inactivated CPI-17/MLC2 signaling. We also collected the coronary artery tissues from deceased subjects suspected to have died of CAS and measured their levels of phosphorylated CPI-17 (p-CPI-17) and MLC2 (p-MLC2). Immunohistochemical staining was positive for p-CPI-17 and p-MLC2 in the tissues of these subjects. These findings suggest that PKCα induced CAS through the CPI-17/MLC2 pathway; therefore, p-CPI-17 and p-MLC2 could be used as potential markers for CAS. Our data provide novel evidence that therapeutic strategies against PKC or CPI-17/MLC2 signaling might be promising in the treatment of CAS.

Visualization Analysis of Artificial Intelligence Literature in Forensic Research.

OBJECTIVES: To analyze the literature on artificial intelligence in forensic research from 2012 to 2022 in the Web of Science Core Collection Database, to explore research hotspots and developmental trends. METHODS: A total of 736 articles on artificial intelligence in forensic medicine in the Web of Science Core Collection Database from 2012 to 2022 were visualized and analyzed through the literature measuring tool CiteSpace. The authors, institution, country (region), title, journal, keywords, cited references and other information of relevant literatures were analyzed. RESULTS: A total of 736 articles published in 220 journals by 355 authors from 289 institutions in 69 countries (regions) were identified, with the number of articles published showing an increasing trend year by year. Among them, the United States had the highest number of publications and China ranked the second. Academy of Forensic Science had the highest number of publications among the institutions. Forensic Science International, Journal of Forensic Sciences, International Journal of Legal Medicine ranked high in publication and citation frequency. Through the analysis of keywords, it was found that the research hotspots of artificial intelligence in the forensic field mainly focused on the use of artificial intelligence technology for sex and age estimation, cause of death analysis, postmortem interval estimation, individual identification and so on. CONCLUSIONS: It is necessary to pay attention to international and institutional cooperation and to strengthen the cross-disciplinary research. Exploring the combination of advanced artificial intelligence technologies with forensic research will be a hotspot and direction for future research.

The effects of restraint stress on ceramide metabolism disorders in the rat liver: the role of CerS6 in hepatocyte injury.

BACKGROUND: Stress is implicated in various pathological conditions leading to liver injury. Existing evidence suggests that excessive stress can induce mitochondrial damage in hepatocytes, yet the underlying mechanism remains unclear. Ceramide synthase 6 (CerS6)-derived C16:0 ceramide is recognised as a lipotoxic substance capable of causing mitochondrial damage. However, the role of CerS6 in stress has received insufficient attention. This study aimed to explore the involvement of CerS6 in stress-induced hepatic damage and its associated mechanisms. METHODS: The rat restraint stress model and a corticosterone (CORT)-induced hepatocyte stress model were employed for in vivo and in vitro experimental analyses, respectively. Changes in mitochondrial damage and ceramide metabolism in hepatocytes induced by stress were evaluated. The impact of CORT on mitochondrial damage and ceramide metabolism in hepatocytes was assessed following CerS6 knockdown. Mitochondria were isolated using a commercial kit, and ceramides in liver tissue and hepatocytes were detected by LC-MS/MS. RESULTS: In comparison to the control group, rats subjected to one week of restraint exhibited elevated serum CORT levels. The liver displayed significant signs of mitochondrial damage, accompanied by increased CerS6 and mitochondrial C16:0 ceramide, along with activation of the AMPK/p38 MAPK pathway. In vitro studies demonstrated that CORT treatment of hepatocytes resulted in mitochondrial damage, concomitant with elevated CerS6 and mitochondrial C16:0 ceramide. Furthermore, CORT induced sequential phosphorylation of AMPK and p38 MAPK proteins, and inhibition of the p38 MAPK pathway using SB203580 mitigated the CORT-induced elevation in CerS6 protein. Knocking down CerS6 in hepatocytes inhibited both the increase in C16:0 ceramide and the release of mitochondrial cytochrome c induced by CORT. CONCLUSIONS: CerS6-associated C16:0 ceramide plays a mediating role in stress-induced mitochondrial damage in hepatocytes. The molecular mechanism is linked to CORT-induced activation of the AMPK/p38 MAPK pathway, leading to upregulated CerS6.

Norepinephrine-Activated p38 MAPK Pathway Mediates Stress-Induced Cytotoxic Edema of Basolateral Amygdala Astrocytes.

The amygdala is a core region in the limbic system that is highly sensitive to stress. Astrocytes are key players in stress disorders such as anxiety and depression. However, the effects of stress on the morphology and function of amygdala astrocytes and its potential mechanisms remain largely unknown. Hence, we performed in vivo and in vitro experiments using a restraint stress (RS) rat model and stress-induced astrocyte culture, respectively. Our data show that norepinephrine (NE) content increased, cytotoxic edema occurred, and aquaporin-4 (AQP4) expression was up-regulated in the basolateral amygdala (BLA) obtained from RS rats. Additionally, the p38 mitogen-activated protein kinase (MAPK) pathway was also observed to be significantly activated in the BLA of rats subjected to RS. The administration of NE to in vitro astrocytes increased the AQP4 level and induced cell edema. Furthermore, p38 MAPK signaling was activated. The NE inhibitor alpha-methyl-p-tyrosine (AMPT) alleviated cytotoxic edema in astrocytes, inhibited AQP4 expression, and inactivated the p38 MAPK pathway in RS rats. Meanwhile, in the in vitro experiment, the p38 MAPK signaling inhibitor SB203580 reversed NE-induced cytotoxic edema and down-regulated the expression of AQP4 in astrocytes. Briefly, NE-induced activation of the p38 MAPK pathway mediated cytotoxic edema in BLA astrocytes from RS rats. Thus, our data provide novel evidence that NE-induced p38 MAPK pathway activation may be one of the mechanisms leading to cytotoxic edema in BLA under stress conditions, which also could enable the development of an effective therapeutic strategy against cytotoxic edema in BLA under stress and provide new ideas for the treatment of neuropsychiatric diseases.

Magnetocardiography-based coronary artery disease severity assessment and localization using spatiotemporal features.

Objective.This study aimed to develop an automatic and accurate method for severity assessment and localization of coronary artery disease (CAD) based on an optically pumped magnetometer magnetocardiography (MCG) system.Approach.We proposed spatiotemporal features based on the MCG one-dimensional signals, including amplitude, correlation, local binary pattern, and shape features. To estimate the severity of CAD, we classified the stenosis as absence or mild, moderate, or severe cases and extracted a subset of features suitable for assessment. To localize CAD, we classified CAD groups according to the location of the stenosis, including the left anterior descending artery (LAD), left circumflex artery (LCX), and right coronary artery (RCA), and separately extracted a subset of features suitable for determining the three CAD locations.Main results.For CAD severity assessment, a support vector machine (SVM) achieved the best result, with an accuracy of 75.1%, precision of 73.9%, sensitivity of 67.0%, specificity of 88.8%, F1-score of 69.8%, and area under the curve of 0.876. The highest accuracy and corresponding model for determining locations LAD, LCX, and RCA were 94.3% for the SVM, 84.4% for a discriminant analysis model, and 84.9% for the discriminant analysis model.Significance. The developed method enables the implementation of an automated system for severity assessment and localization of CAD. The amplitude and correlation features were key factors for severity assessment and localization. The proposed machine learning method can provide clinicians with an automatic and accurate diagnostic tool for interpreting MCG data related to CAD, possibly promoting clinical acceptance.

Characterization of global research trends and prospects on sudden coronary death: A literature visualization analysis.

Background: Sudden coronary death is a major global public health issue that has a significant impact on both individuals and society. Nowadays, scholars are active in sudden coronary death all over the world. However, no relevant bibliometric studies have been published. Here, we aim to gain a better understanding the current state of research and to explore potential new research directions through bibliometric analysis. Methods: Articles and reviews on sudden coronary death from 2012 to 2023 were retrieved from the Web of Science Core Collection (WoSCC). The topic search was conducted using the following keywords: ((("sudden cardiac death" OR "sudden death") AND (coronary OR "myocardial infarction")) OR "sudden coronary death"). Knowledge maps of authors, countries, institutions, journals, keywords, and citations were conducted by CiteSpace. Publication dynamics, hotspots, and frontiers were analyzed independently by authors. Results: A total of 2914 articles were identified from January 1, 2012 to June 20, 2023. The USA (n = 972) contributed the greatest absolute productivity and UK (centrality = 0.13) built a robust global collaboration. Harvard University was the institution with the highest number of publications (n = 143). Huikuri HV and Junttila MJ were the most published authors who devoted to searching for biomarkers of sudden coronary death. American Journal of Cardiology was the journal with the most publications, and Circulation was the most cited journal. Left ventricular ejection fraction, society, inflammation, and fractional flow reserve became novel burst words that lasted until 2023. Research on etiology and pathology, role of early risk factors in risk stratification, potential predictive biomarkers and novel measurement methods for the prevention and management of sudden coronary death were identified as the research hotspots and frontiers. Conclusion: Our knowledge and understanding of sudden coronary death have significantly improved. Ongoing efforts should focus on the various etiologies and pathologies of sudden coronary death. Furthermore, a novel sudden coronary death risk model, large-scale population studies, and the rational use of multiple indicators to individualize the assessment of sudden coronary death and other risk factors are other emerging research trends.

Artificial Intelligence-Based Imaging Transcoding System for Multiplex Screening of Viable Foodborne Pathogens.

Multiplex detection of viable foodborne pathogens is critical for food safety and public health, yet current assays suffer trade-offs between cost, assay complexity, sensitivities, and the specificity between live and dead bacteria. We herein developed a sensing method using artificial intelligence transcoding (SMART) for rapid, sensitive, and multiplex profiling of foodborne pathogens. The assay utilizes the programmable polystyrene (PS) microspheres to encode different pathogens, inducing subsequent visible signals under conventional microscopy that can be analyzed using a customized, artificial intelligence-computer vision, which was trained to decode the intrinsic properties of PS microspheres to reveal the numbers and types of pathogens. Our approach enabled the rapid and simultaneous detection of multiple bacteria from egg samples of <102 CFU/mL without DNA amplification and showed strong consistency with the standard microbiologic and genotypic methods. We adopted our assay through phage-guided targeting to enable the discrimination between live and dead bacteria.

GLOBAL SIGNATURES OF THE MICROBIOME AND METABOLOME DURING HOSPITALIZATION OF SEPTIC PATIENTS.

ABSTRACT: Background: The gut plays an important role in the development of sepsis and acts as one of the possible drivers of multiple-organ dysfunction syndrome. This study aimed to explore the dynamic alterations in the gut microbiota and its metabolites in septic patients at different stages of intensive care unit (ICU) admission. Methods: In this prospective observational study, a total of 109 fecal samples from 23 septic patients, 16 nonseptic ICU patients and 10 healthy controls were analyzed. 16S rRNA gene sequencing and ultra-performance liquid chromatography coupled to tandem mass spectrometry targeted metabolomics were used for microbiota and metabolome analysis. A prediction model combining the Sequential Organ Failure Assessment score, Klebsiella , taurocholic acid, and butyric acid was used to predict the prognosis of sepsis. Results: The diversity and dominant species of the gut microbiota of septic patients were significantly disturbed. The proportions of normal gut microbiota, such as Firmicutes on the phylum level, as well as Faecalibacterium, Subdoligranulum , Ruminococcus , Agathobacter , and Blautia on the genus level, were decreased at different stages of ICU admission, while the proportions of potential pathogenic bacteria, such as Proteobacteria on the phylum level, and Enterococcus and Stenotrophomonas on the genus level were significantly increased. In addition, the amount of short-chain fatty acids and secondary bile acids decreased in septic patients, while that of the primary bile acids increased markedly. Bacterial richness and diversity were lower in the nonsurviving patients than those in the surviving patients in the later stage of ICU admission. In the nomogram model, the higher abundance of Klebsiella , concentration of taurocholic acid, and Sequential Organ Failure Assessment score, combined with a lower butyric acid concentration, could predict a higher probability of death from sepsis. Conclusions: Our study indicated that the dynamical alterations of gut microbiota and its metabolites were associated with the prognosis of the sepsis. Based on these alterations and clinical indicators, a nomogram model to predict the prognosis of septic patients was performed.

Mobile and Self-Sustained Data Storage in an Extremophile Genomic DNA.

DNA has been pursued as a novel biomaterial for digital data storage. While large-scale data storage and random access have been achieved in DNA oligonucleotide pools, repeated data accessing requires constant data replenishment, and these implementations are confined in professional facilities. Here, a mobile data storage system in the genome of the extremophile Halomonas bluephagenesis, which enables dual-mode storage, dynamic data maintenance, rapid readout, and robust recovery. The system relies on two key components: A versatile genetic toolbox for the integration of 10-100 kb scale synthetic DNA into H. bluephagenesis genome and an efficient error correction coding scheme targeting noisy nanopore sequencing reads. The storage and repeated retrieval of 5 KB data under non-laboratory conditions are demonstrated. The work highlights the potential of DNA data storage in domestic and field scenarios, and expands its application domain from archival data to frequently accessed data.

Water/fat separation for self-navigated diffusion-weighted multishot echo-planar imaging.

The purpose of this study was to develop a self-navigation strategy to improve scan efficiency and image quality of water/fat-separated, diffusion-weighted multishot echo-planar imaging (ms-EPI). This is accomplished by acquiring chemical shift-encoded diffusion-weighted data and using an appropriate water-fat and diffusion-encoded signal model to enable reconstruction directly from k-space data. Multishot EPI provides reduced geometric distortion and improved signal-to-noise ratio in diffusion-weighted imaging compared with single-shot approaches. Multishot acquisitions require corrections for physiological motion-induced shot-to-shot phase errors using either extra navigators or self-navigation principles. In addition, proper fat suppression is important, especially in regions with large B0 inhomogeneity. This makes the use of chemical shift encoding attractive. However, when combined with ms-EPI, shot-to-shot phase navigation can be challenging because of the spatial displacement of fat signals along the phase-encoding direction. In this work, a new model-based, self-navigated water/fat separation reconstruction algorithm is proposed. Experiments in legs and in the head-neck region of 10 subjects were performed to validate the algorithm. The results are compared with an image-based, two-dimensional (2D) navigated water/fat separation approach for ms-EPI and with a conventional fat saturation approach. Compared with the 2D navigated method, the use of self-navigation reduced the shot duration time by 30%-35%. The proposed algorithm provided improved diffusion-weighted water images in both leg and head-neck regions compared with the 2D navigator-based approach. The proposed algorithm also produced better fat suppression compared with the conventional fat saturation technique in the B0 inhomogeneous regions. In conclusion, the proposed self-navigated reconstruction algorithm can produce superior water-only diffusion-weighted EPI images with less artefacts compared with the existing methods.