Threshold effect of physical exercise on its association to diabetes mellitus in short sleep population: evidence from a nationwide study.

Background: The prevalence of diabetes mellitus (DM) is a significant public health concern, especially among individuals with short sleep duration. Understanding the relationship between physical exercise and DM in this population is crucial for developing effective prevention strategies. However, the presence of a potential threshold effect of exercise on DM risk remains unclear. Methods: Using data from the National Health and Nutrition Examination Survey (NHANES) spanning from 2007 to 2018, this population-based study investigated the association between physical exercise and DM in individuals with short sleep duration (no more than 7 hours per night). Weighted logistic regression analyses were conducted, adjusting for demographic and lifestyle factors. Additionally, a two-piecewise linear regression model was employed to identify any threshold effect of exercise on DM risk. Results: This study included 15,092 participants identified with short sleep duration. Demographic characteristics stratified by DM status indicate higher prevalence among certain groups, such as middle-aged and older adults, males, and non-Hispanic Whites. The analysis revealed an inverse association between exercise levels and DM prevalence among the short sleep population. In the fully adjusted model, individuals engaging in sufficient exercise (> 600 MET-minutes/week) exhibited significantly reduced odds of developing DM [OR (95% CI): 0.624(0.527,0.738), p < 0.001]. Furthermore, the segmented regression model identified an inflection point at 2000 MET-minutes/week, below which a significant correlation between exercise and DM was observed. Conclusions: This study provides evidence of a threshold effect of physical exercise on its association with DM in individuals with short sleep duration. Tailored exercise interventions targeting this population may help mitigate DM risk and improve overall health outcomes. Further research is warranted to validate these findings and explore optimal exercise thresholds for DM prevention strategies.

A Fast and Accurate Mapping Method for an OPGW Tower Based on Hybrid Distributed Optical Fiber Sensing.

The combination of the dark fiber in existing Optical Fiber Composite Overhead Ground Wire (OPGW) with Distributed Optical Fiber Sensing (DOFS) technology can be used to enable online monitoring and provide early warnings of anomalies in high-voltage transmission lines. Accurate mapping of the optical cable length to the geographic coordinates of actual towers is a key factor in achieving this goal. This paper discusses the principle of using a DOFS system for transmission line tower positioning and presents four available positioning features. To overcome the limitations of single physical parameter positioning, this paper presents a self-developed hybrid DOFS that simultaneously captures Rayleigh backscattering and Brillouin scattering signals. Several physical parameters, including temperature, strain, and vibration, are acquired synchronously. Through hybrid multi-parameter analysis, the rapid and accurate positioning of OPGW line towers is achieved. Experimental results have shown that the proposed method, based on the hybrid DOFS system, can locate up to 82 towers, while the traditional method could only identify 12. The hybrid system was able to complete 80% of the tension towers in 40 h. This paper presents a novel multi-parameter localization method that has the potential to significantly improve the efficiency and reliability of grid operation and maintenance.

Kidney fibrosis molecular mechanisms Spp1 influences fibroblast activity through transforming growth factor beta smad signaling.

Kidney fibrosis marks a critical phase in chronic kidney disease with its molecular intricacies yet to be fully understood. This study's deep dive into single-cell sequencing data of renal tissue during fibrosis pinpoints the pivotal role of fibroblasts and myofibroblasts in the fibrotic transformation. Through identifying distinct cell populations and conducting transcriptomic analysis, Spp1 emerged as a key gene associated with renal fibrosis. The study's experimental findings further confirm Spp1's vital function in promoting fibroblast to myofibroblast differentiation via the TGF-ß/Smad signaling pathway, underscoring its contribution to fibrosis progression. The suppression of Spp1 expression notably hindered this differentiation process, spotlighting Spp1 as a promising therapeutic target for halting renal fibrosis. This condensed summary encapsulates the essence and findings of the original research within the specified word limit.

A hybrid simulation method towards the gamma ray phase contrast imaging for metallic material.

A high efficiency simulation method for propagation-based phase-contrast imaging, called directional macro-wavefront (DMWF), is developed with the aim of simulating high-energy phase-contrast imaging. This method takes both Monte Carlo and wave optical propagation into consideration. Traditional wave-optics-based simulation methods for phase-contrast imaging encounter unacceptable computational complexity when high-energy radiation is used. In contrast, this method effectively addresses this issue by using macro-wavefront integration. Several simulation examples using typical parameters of inverse Compton scattering sources are presented to illustrate the excellent energy adaptability and efficiency of the DMWF method. This method provides a more efficient approach for phase-contrast imaging simulations, which will drive the advancement of high-energy phase-contrast imaging.

Pan-omics-based characterization and prediction of highly multidrug-adapted strains from an outbreak fungal species complex.

Strains from the Cryptococcus gattii species complex (CGSC) have caused the Pacific Northwest cryptococcosis outbreak, the largest cluster of life-threatening fungal infections in otherwise healthy human hosts known to date. In this study, we utilized a pan-phenome-based method to assess the fitness outcomes of CGSC strains under 31 stress conditions, providing a comprehensive overview of 2,821 phenotype-strain associations within this pathogenic clade. Phenotypic clustering analysis revealed a strong correlation between distinct types of stress phenotypes in a subset of CGSC strains, suggesting that shared determinants coordinate their adaptations to various stresses. Notably, a specific group of strains, including the outbreak isolates, exhibited a remarkable ability to adapt to all three of the most commonly used antifungal drugs for treating cryptococcosis (amphotericin B, 5-fluorocytosine, and fluconazole). By integrating pan-genomic and pan-transcriptomic analyses, we identified previously unrecognized genes that play crucial roles in conferring multidrug resistance in an outbreak strain with high multidrug adaptation. From these genes, we identified biomarkers that enable the accurate prediction of highly multidrug-adapted CGSC strains, achieving maximum accuracy and area under the curve (AUC) of 0.79 and 0.86, respectively, using machine learning algorithms. Overall, we developed a pan-omic approach to identify cryptococcal multidrug resistance determinants and predict highly multidrug-adapted CGSC strains that may pose significant clinical concern.

Development of novel imipridone derivatives with potent anti-cancer activities as human caseinolytic peptidase P (hClpP) activators.

Based on a clinically staged small molecular hClpP activator ONC201, a class of imipridone derivatives was designed and synthesized. These compounds were evaluated in a protease hydrolytic assay, as well as cell growth inhibition assays in three cancer cell lines, MIA PACA-2, HCT116, and MV4-11. A number of compounds that can more potently activate hClpP and more effectively inhibit cell growth in the three cancer cell lines than ONC201 were identified. The most potent compound, ZYZ-17, activated hClpP with an EC50 value of 0.24 µM and inhibited the growth of the three cancer cell lines with IC50 values of less than 10 nM. Mechanism studies for ZYZ-17 revealed that it potently activates cellular hClpP, efficiently induces the degradation of hClpP substrates, and robustly induces apoptosis in the three cancer cell lines. Furthermore, ZYZ-17 demonstrated a promising pharmacokinetic (PK) profile and exhibited highly potent in vivo antitumor activity in a pancreatic cancer MIA PACA-2 xenograft model in BALB/c nude mice.

Circ_0001361/miR-490-5p/IGF2 Axis Regulates the Viability and Apoptosis of Neuroblastoma Cells.

BACKGROUND: Circular RNAs (circRNAs) are involved in the neuroblastoma (NB) development. Objectie: The study aimed to determine the biological behaviors of circ_0001361 and explore its underlying mechanism in NB. METHODS: The circ_0001361, miR-490-5p, and IGF2 levels were measured using quantitative real-time polymerase chain reaction. Cellular processes were analyzed using MTT assay or fluorescence-activated cell sorting (FACS). Phosphorylated (p)-PI3K, p-AKT, Bax, and caspase-3 were tested by western blot. Dual-luciferase reporter analysis together with RNA pull-down analysis were utilized to evaluate the correlation of miR-490-5p and circ_0001361 or IGF2. RESULTS: The results in this study illustrated that an elevation of circ_0001361 levels was observed in NB. Depletion of circ_0001361 suppressed the viability but facilitated apoptosis of NB cells. Circ_0001361 sponged miR-490-5p, which targeted to regulate IGF2. Inhibition of miR-490-5p rescued the effect induced by circ_0001361 knockdown, while deletion of IGF2 rescued the effect induced by the miR-490-5p inhibitor. CONCLUSIONS: In summary, a loss of circ_0001361 inhibited NB progression via targeting the miR-490-5p/IGF2 axis, suggesting that circ_0001361 may be a novel therapeutical target of NB.

Fucoxanthin Inhibits the Proliferation and Metastasis of Human Pharyngeal Squamous Cell Carcinoma by Regulating the PI3K/Akt/mTOR Signaling Pathway.

Human pharyngeal squamous cell carcinoma (HPSCC) is the most common malignancy in the head and neck region, characterized by high mortality and a propensity for metastasis. Fucoxanthin, a carotenoid isolated from brown algae, exhibits pharmacological properties associated with the suppression of tumor proliferation and metastasis. Nevertheless, its potential to inhibit HPSCC proliferation and metastasis has not been fully elucidated. This study represents the first exploration of the inhibitory effects of fucoxanthin on two human pharyngeal squamous carcinoma cell lines (FaDu and Detroit 562), as well as the mechanisms underlying those effects. The results showed dose-dependent decreases in the proliferation, migration, and invasion of HPSCC cells after fucoxanthin treatment. Further studies indicated that fucoxanthin caused a significant reduction in the expression levels of proteins in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway, as well as the downstream proteins matrix metalloproteinase (MMP)-2 and MMP-9. Specific activators of PI3K/AKT reversed the effects of fucoxanthin on these proteins, as well as on cell proliferation and metastasis, in FaDu and Detroit 562 cells. Molecular docking assays confirmed that fucoxanthin strongly interacted with PI3K, AKT, mTOR, MMP-2, and MMP-9. Overall, fucoxanthin, a functional food component, is a potential therapeutic agent for HPSCC.

Discovery of Dehydrogenated Imipridone Derivatives as Activators of Human Caseinolytic Protease P.

Based on the founding member of imipridones, ONC201, a class of dehydrogenated imipridone derivatives was designed, synthesized, and evaluated in a series of biochemical and biological assays as human caseinolytic protease P (hClpP) activators. Mechanism studies for one of the most potent compounds, XT6, indicated that it can potently bind to both recombinant and cellular hClpP, effectively promote the formation of hClpP tetradecamer, efficiently induce the degradation of hClpP substrates, robustly upregulate the expression of ATF4, and strongly inhibit the phosphorylations of AKT and ERK. More importantly, XT6 exhibited a promising pharmacokinetic profile in rats and could penetrate the blood brain barrier. It showed highly potent in vivo antitumor activity in a MIAPACA2 cell line derived pancreatic cancer model in BALB/c nude mice.

Does vegetation greening have a positive effect on global vegetation carbon and water use efficiency?

Terrestrial ecosystems have undergone significant changes as a result of climate change, profoundly affecting global carbon and water cycling processes. Notably, the synergistic changes in vegetation carbon use efficiency (CUE) and water use efficiency (WUE) and their response to patterns of climate change over the last 40 years are unknown. Therefore, in this study, global vegetation WUE and CUE were inverted using Gross primary productivity (GPP), Net primary productivity (NPP) and total evaporation (ET) data from 1981 to 2019 to reveal their temporal and spatial patterns of change through trend analysis and stability analysis. A stepwise regression algorithm was used to reveal the potential driving law of environmental factors on vegetation WUE and CUE. The results shows that (1) From 1981 to 2019, the global vegetation WUE and CUE showed in a relatively stable state, and the trends of WUE and CUE were -0.00004/year and 0.006 g C m-2 mm-1/year, respectively; (2) the greening of vegetation was the most important cause of the changes in WUE and CUE, and the driving force of rain and heat conditions on the CUE of vegetation was smaller than that of solar radiation and soil water, the regions where CO2 is the dominant factor affecting CUE and WUE are mainly in the north temperate zone; (3) the region of synergistic growth of WUE and CUE accounts for about 31.38 % of the global terrestrial area, and this pattern of change suggests that the global vegetation carbon sink potential is huge, and the popularization of vegetation planting patterns under the synergistic growth of CUE and WUE should be strengthened. The research has shown that vegetation greening is a key factor influencing changes in the WUE and CUE of vegetation, therefore, the implementation of ecological engineering will be an important step in combating climate change.

Application value of adrenal venous sampling in the surgical treatment of primary aldosteronism.

The diagnosis of primary aldosteronism (PA) is critical for determining treatment strategies. The aim of the present study was to investigate the clinical value of preoperative adrenal venous sampling (AVS) for determining the benefit of PA surgery. Patients diagnosed with PA at Liaocheng People's Hospital (Liaocheng, China) between January 2015 and December 2020 were selected and divided into two groups: Group A underwent adrenal computed tomography (CT) only, whereas Group B underwent adrenal CT and successful AVS. Subsequently, the improvement rate of adrenal CT and adrenal CT + AVS in the treatment of PA was compared. A total of 164 patients were included, with an average age of 46.69±13.64 years. There were 62 patients in Group A and 102 in Group B. Among the patients diagnosed with unilateral lesions on adrenal CT scan, 82.61% of patients in group A and 87.72% in group B showed improvement; however, the difference was not significant (χ2=0.534, P=0.465). Among the patients diagnosed with bilateral lesions on adrenal CT images, 62.50% of patients in Group A and 91.11% of patients in Group B showed improvement (P=0.019). In conclusion, unilateral adrenal lesions detected by CT did not benefit significantly from surgical decision-making after AVS. AVS should be advised for all patients with bilateral adrenal PA who are willing to undergo adrenal surgery, which is conducive to correct lateral segmentation and improve treatment choices.

Small molecules for inflammatory bowel disease and the risk of infection and malignancy: A systematic review and meta-Analysis.

OBJECTIVES: This meta-analysis aimed to ascertain whether small molecule drugs increase the risk of infection or malignancy in adult IBD patients. METHODS: A comprehensive search of eight databases was conducted from their inception to November 2023. The risk of infections or malignancies in adult IBD patients treated with JAK inhibitors and S1P receptor modulators was compared. Fixed-effects or random-effects models were performed, and relative risk (RR) and 95 % confidence interval (CI) were calculated. RESULTS: 27 RCTs from 14 studies were included (n = 10,623). The evidence indicates that small molecule drugs increase the risk of any infections (RR: 1.23, 95 %CI: 1.05-1.44) and herpes zoster (RR: 2.23, 95 %CI: 1.39-3.57). Specifically, UC patients on Filgotinib and Tofacitinib, and CD patients on Upadacitinib, showed elevated risks of any infections (RR: 1.27, 95 % CI: 1.04-1.56; RR: 1.42, 95 % CI: 1.16-1.75; RR: 1.57, 95 % CI: 1.11-2.22). CD patients on Upadacitinib also had a significantly higher risk of herpes zoster (RR: 2.64, 95 %CI: 1.16-5.99). No infections were associated with S1P receptor modulators, and similarly, no malignancies were linked to small molecule drugs. CONCLUSIONS: JAK inhibitors increase the risk of any infections and herpes zoster Over a one-year follow-up period in IBD patients. Continuous monitoring of their long-term safety is necessary.

A Genetically Engineered Biomimetic Nanodecoy for the Treatment of Liver Fibrosis.

Liver fibrosis, arising from factors such as viral infections or metabolic disorders, represents an ongoing global health challenge and is a major risk factor for hepatocellular carcinoma. Unfortunately, there are no clinically approved drugs available for its treatment. Recent studies have illuminated the pivotal role of macrophage recruitment in the pathogenesis of liver fibrosis, presenting a potential therapeutic target. Therefore, it holds great promise to develop novel anti-fibrotic therapies capable of inhibiting this process. Herein, a drug-loaded biomimetic nanodecoy (CNV-C) is developed by harnessing genetically engineered cellular vesicles for the treatment of liver fibrosis. CNV-C is equipped with a C-C motif chemokine receptor 2 (CCR2)-overexpressed surface, enabling it to selectively neutralize elevated levels of C-C motif chemokine ligand 2 (CCL2), thereby reducing macrophage infiltration and the subsequent production of the fibrogenic cytokine transforming growth factor ß (TGF-ß). Moreover, curcumin, an anti-fibrotic agent, is loaded into CNV-C and delivered to the liver, facilitating its efficacy in suppressing the activation of hepatic stellate cells by blocking the downstream TGF-ß/Smad signaling. This combinational therapy ultimately culminates in the alleviation of liver fibrosis in a mouse model induced by carbon tetrachloride. Collectively, the findings provide groundbreaking proof-of-concept for employing genetically modified nanodecoys to manage liver fibrosis, which may usher in a new era of anti-fibrotic treatments.

Frontiers in Operations: Valuing Nursing Productivity in Emergency Departments.

Problem definition: We quantify the increase in productivity in emergency departments (ED) from increasing nurse staff. We then estimate the associated revenue gains for the hospital and the associated welfare gains for society. Academic/practical relevance: The United States is over a decade into the worst nursing shortage crisis in history, fueled by chronic under-investment. To demonstrate to hospital managers and policymakers the benefits of investing in nursing, we clarify the positive downstream effects of doing so in the ED setting. Methodology: We use a high-resolution data set of patient visits to the ED of a major U.S. academic hospital. Time-dependent hazard estimation methods (nonparametric and parametric) are used to study how the realtime service speed of a patient varies with the state of the ED, including the time-varying workloads of the assigned nurse. A counterfactual simulation is used to estimate the gains from increasing nurse staff in the ED. Results: We find that lightening a nurse's workload by one patient is associated with a 14% service speedup for every patient under the nurse's care. Simulation studies suggest that adding one more nurse to the busiest 12-hour shift of each day can shorten stays and avert $160,000 in lost patient wages per 10,000 visits. The reduction in service times also frees up capacity for treating more patients and generate $470,000 in additional net revenues for the hospital per 10,000 visits. Extensive sensitivity analyses suggest that our key message-investing in nursing will more than pay for itself-is likely to hold across a wide range of EDs. Managerial implications: In determining whether to invest in more nursing resources, hospital managers need to look beyond whether payer reimbursements alone are sufficient to cover the upfront costs, to also account for the resulting downstream benefits.

Efficacy, kinetics, inactivation mechanism and application of cold plasma in inactivating Alicyclobacillus acidoterrestris spores.

As spores of Alicyclobacillus acidoterrestris can survive traditional pasteurization, this organism has been suggested as a target bacterium in the fruit juice industry. This study aimed to investigate the inactivation effect of cold plasma on A. acidoterrestris spores and the mechanism behind the inactivation. The inactivation effect was detected by the plate count method and described by kinetic models. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), the detection of dipicolinic acid (DPA) release and heat resistance detection, the detection and scavenging experiment of reactive species, and cryo-scanning electron microscopy were used to explore the mechanism of cold plasma inactivation of A. acidoterrestris. The results showed that cold plasma can effectively inactivate A. acidoterrestris spores in saline with a 3.0 ± 0.3 and 4.4 ± 0.8 log reduction in CFU/mL, for 9 and 18 min, respectively. The higher the voltage and the longer the treatment time, the stronger the overall inactivation effect. However, a lower gas flow rate may increase the probability of spore contact with reactive species, resulting in better inactivation results. The biphasic model fits the survival curves better than the Weibull model. SEM and TEM revealed that cold plasma treatment can cause varying degrees of damage to the morphology and structure of A. acidoterrestris spores, with at least 50 % sustaining severe morphological and structural damage. The DPA release and heat resistance detection showed that A. acidoterrestris spores did not germinate but died directly during the cold plasma treatment. 1O2 plays the most important role in the inactivation, while O3, H2O2 and NO3- may also be responsible for inactivation. Cold plasma treatment for 1 min reduced A. acidoterrestris spores in apple juice by 0.4 ± 0.0 log, comparable to a 12-min heat treatment at 95 °C. However, as the treatment time increased, the survival curve exhibited a significant tailing phenomenon, which was most likely caused by the various compounds in apple juice that can react with reactive species and exert a physical shielding effect on spores. Higher input power and higher gas flow rate resulted in more complete inactivation of A. acidoterrestris spores in apple juice. What's more, the high inactivation efficiency in saline indicates the cold plasma device provides a promising alternative for controlling A. acidoterrestris spores during apple washing. Overall, our study provides adequate data support and a theoretical basis for using cold plasma to inactivate A. acidoterrestris spores in the food industry.

Modulating Surface Architecture and Electronic Conductivity of Li-rich Manganese-Based Cathode.

Li-rich manganese-based cathode (LRMC) has attracted intense attention to developing advanced lithium-ion batteries with high energy density. However, LRMC is still plagued by poor cyclic stability, undesired rate capacity, and irreversible oxygen release. To address these issues, herein, a feasible polyvinylidene fluoride (PVDF)-assisted interface modification strategy is proposed for modulating the surface architecture and electronic conductivity of LRMC by intruding the F-doped carbon coating, spinel structure, and oxygen vacancy on the LRMC, which can greatly enhance the cyclic stability and rate capacity, and restrain the oxygen release for LRMC. As a result, the modified material delivers satisfactory cyclic performance with a capacity retention of 90.22% after 200 cycles at 1 C, an enhanced rate capacity of 153.58 mAh g-1 at 5 C and 126.32 mAh g-1 at 10 C, and an elevated initial Coulombic efficiency of 85.63%. Moreover, the thermal stability, electronic conductivity, and structure stability of LRMC are also significantly improved by the PVDF-assisted interface modification strategy. Therefore, the strategy of simultaneously modulating the surface architecture and the electronic conductivity of LRMC provides a valuable idea to improve the comprehensive electrochemical performance of LRMC, which offers a promising reference for designing LRMC with high electrochemical performance.