ABSTRACT
Background: Hypertension is highly prevalent among patients undergoing hemodialysis, with a significant proportion experiencing poorly controlled blood pressure (BP). Digital BP management in this population has been underused. Objective: This study aimed to explore the efficacy of a web-based home BP monitoring (HBPM) program in improving predialysis BP control and enhancing knowledge, perception, and adherence to HBPM among patients with hypertension undergoing hemodialysis. Methods: A multicenter, open-label, randomized controlled trial was conducted at 2 hemodialysis units. Patients were randomly allocated in a 1:1 ratio to either the web-based HBPM program as the intervention group or to usual care as the control group over a 6-month period. The primary outcomes were the predialysis BP control rate, defined as less than 140/90 mm Hg, and the predialysis systolic and diastolic BP, assessed from baseline to the 6-month follow-up. Secondary outcomes included patient knowledge, perception, and adherence to HBPM, evaluated using the HBPM Knowledge Questionnaire, HBPM Perception Scale, and HBPM Adherence Scale, respectively. A generalized estimating equations analysis was used to analyze the primary outcomes in the intention-to-treat analysis. Results: Of the 165 patients enrolled in the program (n=84, 50.9% in the web-based HBPM group and n=81, 49.1% in the control group), 145 (87.9%) completed the follow-up assessment. During the follow-up period, 11 instances of hypotension occurred in 9 patients in the web-based HBPM group, compared to 15 instances in 14 patients in the control group. The predialysis BP control rate increased from 30% (25/84) to 48% (40/84) in the web-based HBPM group after the 6-month intervention, whereas in the control group, it decreased from 37% (30/81) to 25% (20/81; χ22=16.82, P<.001; odds ratio 5.11, 95% CI 2.14-12.23, P<.001). The web-based HBPM group demonstrated a significant reduction after the 6-month intervention in the predialysis systolic BP (t163=2.46, P=.02; ß=-6.09, 95 % CI -10.94 to -1.24, P=.01) and the predialysis diastolic BP (t163=3.20, P=.002; ß=-4.93, 95% CI -7.93 to -1.93, P=.001). Scores on the HBPM Knowledge Questionnaire (t163=-9.18, P<.001), HBPM Perception Scale (t163=-10.65, P<.001), and HBPM Adherence Scale (t163=-8.04, P<.001) were significantly higher after 6 months of intervention. Conclusions: The implementation of a web-based HBPM program can enhance predialysis BP control and the knowledge, perception, and adherence to HBPM among patients undergoing hemodialysis. This web-based HBPM program should be promoted in appropriate clinical settings.
Subject(s)
Blood Pressure Monitoring, Ambulatory , Hypertension , Renal Dialysis , Humans , Male , Female , Middle Aged , Aged , Renal Dialysis/methods , Blood Pressure Monitoring, Ambulatory/methods , Blood Pressure Monitoring, Ambulatory/instrumentation , Hypertension/psychology , Hypertension/therapy , Hypertension/complications , Internet , Surveys and Questionnaires , AdultABSTRACT
Optogenetics-based integrated photoelectrodes with high spatiotemporal resolution play an important role in studying complex neural activities. However, the photostimulation artifacts caused by the high level of integration and the high impedance of metal recording electrodes still hinder the application of photoelectrodes for optogenetic studies of neural circuits. In this study, a neural optrode fabricated on sapphire GaN material was proposed, and 4 µLEDs and 14 recording microelectrodes were monolithically integrated on a shank. Poly(3,4-ethylenedioxythiophene)/polystyrenesulfonate and multiwalled carbon nanotubes (PEDOT:PSS-MWCNT) and poly(3,4-ethylenedioxythiophene) and graphene oxide (PEDOT-GO) composite films were deposited on the surface of the recording microelectrode by electrochemical deposition. The results demonstrate that compared with the gold microelectrode, the impedances of both composite films reduced by more than 98%, and the noise amplitudes decreased by 70.73 and 87.15%, respectively, when exposed to light stimulation. Adjusting the high and low levels, we further reduced the noise amplitude by 48.3%. These results indicate that modifying the electrode surface by a polymer composite film can effectively enhance the performance of the microelectrode and further promote the application of the optrode in the field of neuroscience.
ABSTRACT
Carbapenems and colistin are vital antimicrobials used to treat Enterobacteriaceae-caused infections. The present study aimed to characterize the coexistence mechanism of carbapenem and colistin resistance in an Escherichia coli isolated from retail chicken meat. A total of 4 E. coli isolates co-harboring carbapenem resistance gene blaNDM (2 E. coli isolates with blaNDM-5 and 2 with blaNDM-9) and colistin resistance gene mcr-1. Antimicrobial susceptibility testing exhibited that all the 4 E. coli strains had multidrug resistance profile and consistent with the resistance genes they carried. MLST showed that 3 E. coli isolates belonged to a pathogenic E. coli lineage ST354, which is closely associated with human infections and pose a serious threat to public health. Whole genome sequencing (WGS) showed that 4 mcr-1-positive plasmids with sizes of 60.4 kb to 67.4 kb all belonged to the IncI2 type. A total of 5 blaNDM-harboring plasmids ranged from 99.0 kb to 138.3 kb, among which 4 plasmids belonged to unknow type and only pCS5L-NDM belonged to IncFIA/IncFIB group of hybrid plasmids, a novel carrier for blaNDM. Comparative analysis exhibited that the mcr-1 or blaNDM-carrying plasmids of E. coli strains from chicken meat showed high identity with that from Enterobacteriaceae of human origin, which indicated the risk of mcr-1 or blaNDM dissemination from retail meat to human. The simultaneous occurrence of mcr-1 and blaNDM in E. coli emphasizes the significant of antimicrobial resistance surveillance in retail meat.
ABSTRACT
The Pedestrian Collision Avoidance System (PCAS) of Intelligent Vehicle (IV) can be effective in preventing the occurrence of traffic accidents. However, the complicated operation environments introduce great challenges to the camera used by the PCAS. Therefore, the camera based PCAS should be fully tested and evaluated before deployment. The traditional simulation test for the camera based PCAS attempted to use geometric or physical simulation models, which have low reality and are suitable for the primary stage of the PCAS development. Camera-in-the-Loop (CIL) test is one of Hardware-in-the-Loop methods that embeds the real camera hardware into the virtual simulation system to test the camera. CIL can utilize the real hardware response while overcoming the common simulation weakness of fidelity. In this paper, we construct a CIL test platform, and propose the CIL based test scenarios generation and scenario parameter impact evaluation method for PCAS. First, we construct the CIL test platform whose image quality and functional confidence are both validated to prove CIL credibility. Second, the PCAS under the test is analyzed and the corresponding test scenario parameters are designed. In order to accelerate the test scenario generation, a Greedy Based Combination test method (GBC) based on the CIL is proposed. The Chi-square analysis and two-factor of variance analysis verification methods are used to analyze the influence of individual and multiple scenario parameters on the PCAS performance. The experiment results show that the GBC improves the test speed by 12 times compared to the traversal test, and the frequency ratio of each scenario parameter is no more than 3% different from that of the traversal test. Also, GBC has an equivalent ability to find the PCAS collision scenarios parameter combination to the traversal test.
ABSTRACT
Physical unclonable functions (PUFs) have emerged as an unprecedented solution for modern information security and anticounterfeiting by virtue of their inherent unclonable nature derived from distinctive, randomly generated physical patterns that defy replication. However, the creation of traceable optical PUF tags remains a formidable challenge. Here, we demonstrate a traceable PUF system whose unclonability arises from the random distribution of diamonds and the random intensity of the narrow emission from germanium vacancies (GeV) within the diamonds. Tamper-resistant PUF labels can be manufactured on diverse and intricate structural surfaces by blending diamond particles into polydimethylsiloxane (PDMS) and strategically depositing them onto the surface of objects. The resulting PUF codes exhibit essentially perfect uniformity, uniqueness, reproducibility, and substantial encoding capacity, making them applicable as a private key to fulfill the customization demands of circulating commodities. Through integration of a digitized "challenge-response" protocol, a traceable and highly secure PUF system can be established, which is seamlessly compatible with contemporary digital information technology. Thus, the GeV-PUF system holds significant promise for applications in data security and blockchain anticounterfeiting, providing robust and adaptive solutions to address the dynamic demands of these domains.
ABSTRACT
The ineffectiveness of cisplatin therapy in treating colorectal cancer (CRC) is attributed to an increase of resistance. It's necessary to investigate adjunctive agents capable of enhancing drug efficacy. Previous studies have shown that ropivacaine inhibit the growth of various cancer cells, but its impact on cisplatin resistance in tumors is not well understood. This study was to illustrate the impact and mechanism of ropivacaine enhanced cisplatin-sensitivity of CRC. Cisplatin alone treatment resulted in the elevation of reactive oxygen species (ROS) and intracellular Fe2+ levels, as well as a reduction in mitochondrial membrane potential (MMP) in cisplatin-sensitive LOVO cells, while these effects were mitigated in the cisplatin-resistant LOVO/DDP cells. The co-administration of ropivacaine with cisplatin inhibited cell viability and cell migration, decreased MMP, and promoted ROS accumulation and apoptosis in both LOVO cells and LOVO/DDP cells. And they upregulated the levels of ferroptosis makers and downregulated the expression of anti-ferroptosis proteins. However, this effect was reversed by ferroptosis inhibitor ferrostatin-1 or liproxstatin-1. Furthermore, we o demonstrated that the co-administration of ropivacaine and cisplatin resulted in a decrease in SIRT1 expression, and SIRT1 knockdown in LOVO/DDP cells enhanced the ferroptosis and the anti-tumor properties of ropivacaine, while also inhibiting the activation of the Nrf2/Keap1 pathway. The above results suggested that ropivacaine increased the sensitivity of CRC cells to cisplatin by promoting ferroptosis through the inhibition of SIRT1 expression, which proposes a therapeutic approach for overcoming cisplatin resistance in CRC.
Subject(s)
Antineoplastic Agents , Cisplatin , Colorectal Neoplasms , Ferroptosis , NF-E2-Related Factor 2 , Reactive Oxygen Species , Ropivacaine , Signal Transduction , Sirtuin 1 , Humans , Ropivacaine/pharmacology , Ferroptosis/drug effects , Cisplatin/pharmacology , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Signal Transduction/drug effects , NF-E2-Related Factor 2/metabolism , Sirtuin 1/metabolism , Sirtuin 1/genetics , Cell Line, Tumor , Reactive Oxygen Species/metabolism , Antineoplastic Agents/pharmacology , Membrane Potential, Mitochondrial/drug effects , Cell Movement/drug effects , Cell Survival/drug effects , Drug Resistance, Neoplasm/drug effects , Apoptosis/drug effectsABSTRACT
INTRODUCTION: Antithrombotic therapy prevents adverse ischemic events following acute ischemic stroke (AIS). Intravenous tirofiban provides desirable antiplatelet effects, especially in patients who are vulnerable to neurological deterioration (ND). AIM: The aim of the study was to test the hypothesis that intravenous administration of tirofiban, initiated within 24 h of ictus and continued for consecutive 72 h, would be more effective than aspirin in reducing the risk of ND within 72 h of enrollment among patients with potentially atherothrombotic ischemic stroke. METHODS: The Safety and Efficacy of Tirofiban in Preventing Neurological Deterioration in Acute Ischemic Stroke (TREND) trial is an investigator-initiated, multicenter, prospective, randomized, open-label, masked endpoint study. Its eligibility criteria included AIS secondary to potential atherosclerosis, a National Institutes of Health Stroke Scale (NIHSS) score ranging from 4 to 20 points, ineligibility for recanalization therapy, and administration within 24 h postsymptom onset. Randomization was performed at a 1:1 ratio to allocate 420 patients into two groups to receive an intravenous tirofiban bridge to oral antiplatelet drugs or direct oral antiplatelet drugs. OUTCOMES: The primary outcome is the proportion of patients with a ≥4-point increase in NIHSS score within 72 h of intervention compared to the score at enrollment. The key secondary outcomes include changes in NIHSS score, modified Rankin scale (mRS) score at 90 days, and dichotomized mRS scores (0-2 vs. 3-6 and 0-1 vs. 2-6) at 90 days. The safety variables are symptomatic intracerebral hemorrhage, any intracerebral hemorrhage, and systemic hemorrhage within 72 h after randomization and 90-day mortality. CONCLUSIONS: The TREND trial may identify the suitability of intravenous tirofiban as a routine clinical strategy to prevent ND in patients with AIS within 24 h of the onset of symptoms. TRIAL REGISTRATION: http://www.clinicaltrials.gov (identifier: NCT04491695).
ABSTRACT
BACKGROUND: Moyamoya disease (MMD) is a significant cause of childhood stroke and transient ischemic attacks (TIAs). This study aimed to assess the safety and efficacy of remote ischemic conditioning (RIC) in children with MMD. METHODS: In a single-center pilot study, 46 MMD patients aged 4 to 14 years, with no history of reconstructive surgery, were randomly assigned to receive either RIC or sham RIC treatment twice daily for a year. The primary outcome measured was the cumulative incidence of major adverse cerebrovascular events (MACEs). Secondary outcomes included ischemic stroke, recurrent TIA, hemorrhagic stroke, revascularization rates, and clinical improvement assessed using the patient global impression of change (PGIC) scale during follow-up. RIC-related adverse events were also recorded, and cerebral hemodynamics were evaluated using transcranial Doppler. RESULTS: All 46 patients completed the final follow-up (23 each in the RIC and sham RIC groups). No severe adverse events associated with RIC were observed. Kaplan-Meier analysis indicated a significant reduction in MACEs frequency after RIC treatment [log-rank test (Mantel-Cox), P = 0.021]. At 3-year follow-up, two (4.35%) patients had an ischemic stroke, four (8.70%) experienced TIAs, and two (4.35%) underwent revascularization as the qualifying MACEs. The clinical improvement rate in the RIC group was higher than the sham RIC group on the PGIC scale (65.2% vs. 26.1%, P < 0.01). No statistical difference in cerebral hemodynamics post-treatment was observed. CONCLUSIONS: RIC is a safe and effective adjunct therapy for asymptomatic children with MMD. This was largely due to the reduced incidence of ischemic cerebrovascular events.
ABSTRACT
Time series is a typical data type in numerous domains; however, labeling large amounts of time series data can be costly and time-consuming. Learning effective representation from unlabeled time series data is a challenging task. Contrastive learning stands out as a promising method to acquire representations of unlabeled time series data. Therefore, we propose a self-supervised time-series representation learning framework via Time-Frequency Fusion Contrasting (TF-FC) to learn time-series representation from unlabeled data. Specifically, TF-FC combines time-domain augmentation with frequency-domain augmentation to generate the diverse samples. For time-domain augmentation, the raw time series data pass through the time-domain augmentation bank (such as jitter, scaling, permutation, and masking) and get time-domain augmentation data. For frequency-domain augmentation, first, the raw time series undergoes conversion into frequency domain data following Fast Fourier Transform (FFT) analysis. Then, the frequency data passes through the frequency-domain augmentation bank (such as low pass filter, remove frequency, add frequency, and phase shift) and gets frequency-domain augmentation data. The fusion method of time-domain augmentation data and frequency-domain augmentation data is kernel PCA, which is useful for extracting nonlinear features in high-dimensional spaces. By capturing both the time and frequency domains of the time series, the proposed approach is able to extract more informative features from the data, enhancing the model's capacity to distinguish between different time series. To verify the effectiveness of the TF-FC method, we conducted experiments on four time series domain datasets (i.e., SleepEEG, HAR, Gesture, and Epilepsy). Experimental results show that TF-FC significantly improves in recognition accuracy compared with other SOTA methods.
ABSTRACT
Stroke can lead to cardiac complications such as arrhythmia, myocardial injury, and cardiac dysfunction, collectively termed stroke-heart syndrome (SHS). These cardiac alterations typically peak within 72 h of stroke onset and can have long-term effects on cardiac function. Post-stroke cardiac complications seriously affect prognosis and are the second most frequent cause of death in patients with stroke. Although traditional vascular risk factors contribute to SHS, other potential mechanisms indirectly induced by stroke have also been recognized. Accumulating clinical and experimental evidence has emphasized the role of central autonomic network disorders and inflammation as key pathophysiological mechanisms of SHS. Therefore, an assessment of post-stroke cardiac dysautonomia is necessary. Currently, the development of treatment strategies for SHS is a vital but challenging task. Identifying potential key mediators and signaling pathways of SHS is essential for developing therapeutic targets. Therapies targeting pathophysiological mechanisms may be promising. Remote ischemic conditioning exerts protective effects through humoral, nerve, and immune-inflammatory regulatory mechanisms, potentially preventing the development of SHS. In the future, well-designed trials are required to verify its clinical efficacy. This comprehensive review provides valuable insights for future research.
Subject(s)
Stroke , Humans , Stroke/therapy , Stroke/complications , Stroke/physiopathology , Heart Diseases/etiology , Heart Diseases/physiopathology , Heart Diseases/therapy , SyndromeABSTRACT
Mixed phenotype acute leukemia (MPAL) is a type of acute leukemia in which encompasses mixed features of myeloid, T-lymphoid, and/or B-lymphoid differentiation. Philadelphia chromosome-positive (Ph+) MPAL is a rare subgroup with a poor prognosis and accounts for ï¼1% of adult acute leukemia. Until now, there is still no consensus on how to best treat Ph+ MPAL. Here, we report a 62-year-old male with Ph+ (atypical e13a2 BCR-ABL1 fusion protein) MPAL. This patient presented with recurrent and intense bone pain due to bone marrow necrosis (BMN). Besides, he did not achieve a complete remission for the first two chemotherapies, until he received flumatinib combined with hyper-CVAD (B) (a dose-intensive regimen include methotrexate and cytarabine). To our knowledge, this is the first report to describe the coexistence of BMN and atypical e13a2 BCR-ABL1 transcripts in patients with MPAL. This finding will bring new understandings in the diagnosis and treatment of Ph+ MPAL.
Subject(s)
Bone Marrow , Fusion Proteins, bcr-abl , Necrosis , Humans , Male , Middle Aged , Fusion Proteins, bcr-abl/genetics , Bone Marrow/pathology , Leukemia, Biphenotypic, Acute/genetics , Leukemia, Biphenotypic, Acute/pathology , Leukemia, Biphenotypic, Acute/drug therapyABSTRACT
PURPOSE: This study investigates the prognostic value of skeletal muscle index (SMI) and skeletal muscle radiodensity (SMD) measured by chest CT in relation to all-cause and cardiovascular disease (CVD) mortality among hemodialysis (HD) patients. METHODS: A retrospective study was conducted from January 2015 to December 2021 involving HD patients at a dialysis center. Chest CT scans at the twelfth thoracic vertebra level (T12) were analyzed to assess SMI and SMD. Sex-specific cut-off values for two metrics were determined using maximally selected rank statistics. Hazard ratios (HRs) were calculated to evaluate the associations of SMI and SMD with mortality. The discrimination of prognostic models was also compared. RESULTS: The study included 603 patients with a median age of 58 years. Of these, 187 (31.0%) patients with SMI < 30.00 cm2/m2 (male) or < 25.04 cm2/m2 (female) and 192 (31.8%) patients with SMD < 32.25 HU (male) or < 30.64 HU (female) were categorized as lower SMI and SMD, respectively. Over a median follow-up of 3.8 years, 144 deaths occurred. Multivariate Cox regression analysis showed that lower SMI and SMD were independently associated with all-cause mortality (SMI: HR = 1.47, 95% CI 1.03-2.10; SMD: HR = 1.75, 95% CI 1.20-2.54) and CVD mortality (SMI: HR = 1.74, 95% CI 1.03-2.94; SMD: HR = 1.72, 95% CI 1.02-2.95). Adding SMI and SMD to the established risk model improved the C-index from 0.82 to 0.87 (P < 0.001). Decision curve analysis showed that the prognostic model incorporating both SMI and SMD offered the highest net benefit for predicting all-cause mortality. CONCLUSIONS: Muscle metrics derived from CT scans at T12 level provide valuable prognostic information which could enhance the role of chest CT in muscle assessment among HD patients.
ABSTRACT
The recent theory-driven discovery of a class of clathrate hydrides (e.g., CaH6, YH6, YH9, and LaH10) with superconducting critical temperatures (Tc) well above 200 K has opened the prospects for "hot" superconductivity above room temperature under pressure. Recent efforts focus on the search for superconductors among ternary hydrides that accommodate more diverse material types and configurations compared to binary hydrides. Through extensive computational searches, we report the prediction of a unique class of thermodynamically stable clathrate hydrides structures consisting of two previously unreported H24 and H30 hydrogen clathrate cages at megabar pressures. Among these phases, LaSc2H24 shows potential hot superconductivity at the thermodynamically stable pressure range of 167 to 300 GPa, with calculated Tcs up to 331 K at 250 GPa and 316 K at 167 GPa when the important effects of anharmonicity are included. The very high critical temperatures are attributed to an unusually large hydrogen-derived density of states at the Fermi level arising from the newly reported peculiar H30 as well as H24 cages in the structure. Our predicted introduction of Sc in the La-H system is expected to facilitate future design and realization of hot superconductors in ternary clathrate superhydrides.
ABSTRACT
Our study aimed to construct a predictive model for identifying instances of futile recanalization in patients with anterior circulation occlusion acute ischemic stroke (AIS) who achieved complete reperfusion following endovascular therapy. We included 173 AIS patients who attained complete reperfusion, as indicated by a Modified Thrombolysis in Cerebral Infarction (mTICI) scale score of 3. Our approach involved a thorough analysis of clinical factors, imaging biomarkers, and potential no-reflow biomarkers through both univariate and multivariate analyses to identify predictors of futile recanalization. The comprehensive model includes clinical factors such as age, presence of diabetes, admission NIHSS score, and the number of stent retriever passes; imaging biomarkers like poor collaterals; and potential no-reflow biomarkers, notably disrupted blood-brain barrier (OR 4.321, 95% CI 1.794-10.405; p = 0.001), neutrophil-to-lymphocyte ratio (NLR; OR 1.095, 95% CI 1.009-1.188; p = 0.030), and D-dimer (OR 1.134, 95% CI 1.017-1.266; p = 0.024). The model demonstrated high predictive accuracy, with a C-index of 0.901 (95% CI 0.855-0.947) and 0.911 (95% CI 0.863-0.954) in the original and bootstrapping validation samples, respectively. Notably, the comprehensive model showed significantly improved predictive performance over models that did not include no-reflow biomarkers, evidenced by an integrated discrimination improvement of 8.86% (95% CI 4.34%-13.39%; p < 0.001) and a categorized reclassification improvement of 18.38% (95% CI 3.53%-33.23%; p = 0.015). This model, which leverages the potential of no-reflow biomarkers, could be especially beneficial in healthcare settings with limited resources. It provides a valuable tool for predicting futile recanalization, thereby informing clinical decision-making. Future research could explore further refinements to this model and its application in diverse clinical settings.
ABSTRACT
Direct ethanol fuel cells (DEFCs), which have been widely recognized as nontoxic and green energy conversion devices, show attractive application prospects for liquid hydrogen-carriers, due to the higher specific energy and lower toxicity of ethanol. Pt-based catalysts are widely used in DEFCs, while their poor poisoning resistance highlights the importance of composition and structure optimization. Herein, we synthesized a series of reduced graphene oxide supported ternary alloy AuxPt1-xCu3/rGO (x = 0-1) catalysts with excellent ethanol oxidation performance and a composition-dependent volcano plot trend of the ordering degree was observed and rationalized. The highest Pt-normalized mass activity of Au0.8Pt0.2Cu3/rGO is attributed to the optimized CO binding energy according to DFT calculations. This work not only provides an efficient EOR catalyst based on ordered alloys AuxPt1-xCu3 (x = 0-1), but also offers valuable insight into the role of a third metal in tuning the structure and function of alloys.
ABSTRACT
Skeletal growth, modeling, and remodeling are regulated by various molecules, one of them being the recently identified osteoanabolic factor WNT1. We have previously reported that WNT1 transcriptionally activates the expression of Omd, encoding Osteomodulin (OMD), in a murine mesenchymal cell line, which potentially explained the skeletal fragility of mice with mutational WNT1 inactivation, since OMD has been shown to regulate type I collagen fibril formation in vitro. In this study we confirmed the strong induction of Omd expression in a genome-wide expression analysis of transfected cells, and we obtained further evidence for Omd being a direct target gene of WNT1. To assess the in vivo relevance of this regulation, we crossed Omd-deficient mice with a mouse line harboring an inducible, osteoblast-specific Wnt1 transgene. After induction of Wnt1 expression for 1 or 3 weeks, the osteoanabolic potency of WNT1 was not impaired despite the Omd deficiency. Since current knowledge regarding the in vivo physiological function of OMD is limited, we next focused on skeletal phenotyping of wild-type and Omd-deficient littermates, in the absence of a Wnt1 transgene. Here we did not observe an impact of Omd deficiency on trabecular bone parameters by histomorphometry and µCT either. Importantly, however, male and female Omd-deficient mice at the ages of 12 and 24 weeks displayed a slender bone phenotype with significantly smaller long bones in the transversal dimension, while the longitudinal bone growth remained unaffected. Although mechanical testing revealed no significant changes explained by impaired bone material properties, atomic force microscopy of the femoral bone surface of Omd-deficient mice revealed moderate changes at the nanostructural level, indicating altered regulation of collagen fibril formation and aggregation. Taken together, our data demonstrate that, although OMD is dispensable for the osteoanabolic effect of WNT1, its deficiency in mice specifically modulates transversal cortical bone morphology.
We explored the physiological relevance of the protein Osteomodulin (OMD) that we previously found to be induced by the osteoanabolic molecule WNT1. While other studies have shown that OMD is involved in the regulation of collagen fibril formation in vitro, its function in vivo has not been investigated. We confirmed that OMD is directly regulated by WNT1 but surprisingly, when we bred mice lacking OMD with mice engineered to highly express WNT1, we found that the osteoanabolic effect of WNT1 was unaffected by the absence of OMD. Interestingly, mice lacking OMD did show differences in the shape of their bones, particularly in their width, despite no significant changes in bone density or length. Investigation of the bone matrix of mice lacking OMD at the nanostructural level indicated moderate differences in the organization of collagen fibrils. This study provided further insights into the effect of WNT1 on bone metabolism and highlighted a specific function of OMD in skeletal morphology.
Subject(s)
Cortical Bone , Wnt1 Protein , Animals , Cortical Bone/metabolism , Cortical Bone/pathology , Cortical Bone/diagnostic imaging , Mice , Wnt1 Protein/metabolism , Wnt1 Protein/genetics , Organ Size , Female , Male , Osteoblasts/metabolism , Osteoblasts/pathology , Gene Expression Regulation , X-Ray MicrotomographyABSTRACT
The Finkel-Biskis-Jinkins Osteosarcoma (c-Fos; encoded by FOS) plays an important role in several cardiovascular diseases, including atherosclerosis and stroke. However, the relationship between FOS and venous thromboembolism (VTE) remains unknown. We identified differentially expressed genes in Gene Expression Omnibus dataset, GSE48000, comprising VTE patients and healthy individuals, and analysed them using CIBERSORT and weighted co-expression network analysis (WGCNA). FOS and CD46 expressions were significantly downregulated (FOS p = 2.26E-05, CD64 p = 8.83E-05) and strongly linked to neutrophil activity in VTE. We used GSE19151 and performed PCR to confirm that FOS and CD46 had diagnostic potential for VTE; however, only FOS showed differential expression by PCR and ELISA in whole blood samples. Moreover, we found that hsa-miR-144 which regulates FOS expression was significantly upregulated in VTE. Furthermore, FOS expression was significantly downregulated in neutrophils of VTE patients (p = 0.03). RNA sequencing performed on whole blood samples of VTE patients showed that FOS exerted its effects in VTE via the leptin-mediated adipokine signalling pathway. Our results suggest that FOS and related genes or proteins can outperform traditional clinical markers and may be used as diagnostic biomarkers for VTE.
Subject(s)
Computational Biology , MicroRNAs , Neutrophils , Proto-Oncogene Proteins c-fos , Venous Thromboembolism , Female , Humans , Male , Biomarkers/blood , Biomarkers/metabolism , Gene Expression Profiling , Gene Expression Regulation , Gene Regulatory Networks , MicroRNAs/genetics , MicroRNAs/blood , MicroRNAs/metabolism , Neutrophils/metabolism , Proto-Oncogene Proteins c-fos/genetics , Proto-Oncogene Proteins c-fos/metabolism , Venous Thromboembolism/blood , Venous Thromboembolism/genetics , Venous Thromboembolism/metabolismABSTRACT
Campylobacter jejuni is recognized as a significant foodborne pathogen, and recent studies have indicated a rising trend of aminoglycosides resistance gene aph(2â³)-If among C. jejuni isolates from food-producing animals in China. However, systematic information about aph(2â³)-If-positive C. jejuni from food-producing animals and other sources worldwide based on whole-genome analysis remains a knowledge gap. In this study, we aimed to analyze the worldwide distribution, genetic environment and phylogenetic tree of aph(2â³)-If by utilizing Whole Genome Sequencing (WGS) data obtained, coupled with information in the GenBank database. A total of 160C. jejuni isolates in the GenBank database and 14C. jejuni isolates in our laboratory carrying aph(2â³)-If gene were performed for further analysis. WGS analysis revealed the global distribution of aph(2â³)-If among C. jejuni from 6 countries. Multilocus Sequence Typing(MLST) results indicated that 70 STs were involved in the dissemination of aph(2â³)-If, with ST10086 being the predominant ST. Whole-genome Multilocus Sequence Typing(wg-MLST) analysis according to times, countries, and origins of C. jejuni isolation further demonstrated a close relationship between aph(2â³)-If carrying C. jejuni isolates from farm and food. The findings also revealed the existence of 32 distinct types of genetic environments surrounding aph(2â³)-If among these isolates. Notably, Type 30, characterized by the arrangement ISsag10-deoD-ant(9)-hp-hp-aph(2â³)-If, emerged as the predominant genetic environment. In conclusion, our analysis provides the inaugural perspective on the worldwide distribution of aph(2â³)-If. This resistance gene demonstrates horizontal transferability and regional diffusion in a clonal pattern. The close association observed among aph(2â³)-If-positive C. jejuni strains isolated from poultry, food, and clinical environments underscores the potential for zoonotic transmission from these isolates.
Subject(s)
Aminoglycosides , Anti-Bacterial Agents , Campylobacter Infections , Campylobacter jejuni , Drug Resistance, Bacterial , Multilocus Sequence Typing , Phylogeny , Campylobacter jejuni/genetics , Campylobacter jejuni/drug effects , Drug Resistance, Bacterial/genetics , Aminoglycosides/pharmacology , Animals , Anti-Bacterial Agents/pharmacology , Campylobacter Infections/microbiology , Campylobacter Infections/veterinary , Campylobacter Infections/epidemiology , Whole Genome Sequencing , Humans , Prevalence , China , Food Microbiology , Microbial Sensitivity TestsABSTRACT
Driven by the good developmental potential and favorable environment at this stage, Ganoderma lucidum is recognized as a precious large fungus with medicinal and nutritional health care values. Among them, polysaccharides, triterpenoids, oligosaccharides, trace elements, etc. are important bioactive components in G. lucidum. These bioactive components will have an impact on gut flora, thus alleviating diseases such as hyperglycemia, hyperlipidemia and obesity caused by gut flora disorder. While numerous studies have demonstrated the ability of G. lucidum and its active components to regulate gut flora, a systematic review of this mechanism is currently lacking. The purpose of this paper is to summarize the regulatory effects of G. lucidum and its active components on gut flora in cardiovascular, gastrointestinal and renal metabolic diseases, and summarize the research progress of G. lucidum active components in improving related diseases by regulating gut flora. Additionally, review delves into the principle by which G. lucidum and its active components can treat or assist treat diseases by regulating gut flora. The research progress of G. lucidum in intestinal tract and its potential in medicine, health food and clinical application were fully explored for researchers.