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Background Intravenous immunoglobulin (IVIG)-resistant Kawasaki disease is associated with coronary artery lesion development. Purpose This study aimed to explore the factors associated with IVIG-resistance and construct and validate an interpretable machine learning (ML) prediction model in clinical practice. Methods Between December 2014 and November 2022, 602 patients were screened and risk factors for IVIG-resistance investigated. Five ML models are used to establish an optimal prediction model. The SHapley Additive exPlanations (SHAP) method was used to interpret the ML model. Results Na+, hemoglobin (Hb), C-reactive protein (CRP), and globulin were independent risk factors for IVIG-resistance. A nonlinear relationship was identified between globulin level and IVIG-resistance. The XGBoost model exhibited excellent performance, with an area under the receiver operating characteristic curve of 0.821, accuracy of 0.748, sensitivity of 0.889, and specificity of 0.683 in the testing set. The XGBoost model was interpreted globally and locally using the SHAP method. Conclusion Na+, Hb, CRP, and globulin levels were independently associated with IVIG-resistance. Our findings demonstrate that ML models can reliably predict IVIG-resistance. Moreover, use of the SHAP method to interpret the established XGBoost model's findings would provide evidence of IVIG-resistance and guide the individualized treatment of Kawasaki disease.

Abstract Cell fate decisions remain poorly understood at the molecular level. Embryogenesis provides a unique opportunity to analyze molecular details associated with cell fate decisions. Works based on model organisms have provided a conceptual framework of genes that specify cell fate control, for example, transcription factors (TFs) controlling processes from pluripotency to immunity1. How TFs specify cell fate remains poorly understood. Here we report that SALL4 relies on NuRD (nucleosome-remodeling and deacetylase complex) to interpret BMP4 signal and decide cell fate in a well-controlled in vitro system. While NuRD complex cooperates with SALL4 to convert mouse embryonic fibroblasts or MEFs to pluripotency, BMP4 diverts the same process to an alternative fate, PrE (primitive endoderm). Mechanistically, BMP4 signals the dissociation of SALL4 from NuRD physically to establish a gene regulatory network for PrE. Our results provide a conceptual framework to explore the rich landscapes of cell fate choices intrinsic to development in higher organisms involving morphogen-TF-chromatin modifier pathways.

Abstract Oracle bones (Obs) are a significant carrier of the shang dynasty civilization, primarily consisting of tortoise shells and animal bones, through the study of which we can gain a deeper understanding of the political, economic, religious, and cultural aspects of the shang dynasty. The oracle bone drill chisel (Obdc) is considered an essential non-textual material. The segmentation of Obdc assists archaeologists determine the approximate age of the Obs, which possesses considerable research value. However, the breakage of thousands of years of underground buried Obs, the blurring of the edges of the area burned by the Obdc, the different shapes, and the inconsistent number have brought challenges to the accurate segmentation of the Obdc. In this article, we propose a group convolutional attention and pvt dual-branch network (GCA-PVT-Net) for Obdc segmentation. To our knowledge, this paper is the first to research the automatic segmentation of Obdc. It is a hybrid Convolutional neural network (CNN) and Transformer framework. The work offers the following contributions: (1) The Obdc images are labeled based on the delineation criteria of different drill chisel (DC) shapes to create the Obdc dataset. (2) A convolutional attention module (CAM) is proposed as both an encoder and decoder. The feature extraction process, which effectively integrates global and local information, ensures better modeling of long-term correlations in images while preserving details. (3) A channel feature aggregation module (CFAM) is designed to enhance the effective integration of channel features, enabling feature fusion across various branches and at different levels. (4) The edge deep supervision strategy is applied to smooth the jagged edge of the predicted images at the decoder’s end. Extensive experiments on the Obdc dataset show that GCA-PVT-Net outperforms other state-of-the-art (SOTA) methods. The comparative experimental results show that the edge accuracy and segmentation accuracy of the model reach the top 1.

Abstract Cell fate is likely regulated by a common machinery, while components of this machine remain to be identified. Here we report the design and testing of engineered cell fate controller NanogBiD, fusing BiD or BRG1 interacting domain of SS18 with Nanog. NanogBiD promotes mouse somatic cell reprogramming efficiently in contrast to the ineffective native protein under multiple testing conditions. Mechanistic studies further reveal that it facilitates cell fate transition by recruiting the intended Brg/Brahma-associated factor (BAF) complex to modulate chromatin accessibility and reorganize cell state specific enhancers known to be occupied by canonical Nanog, resulting in precocious activation of multiple genes including Sall4, miR-302, Dppa5a and Sox15 towards pluripotency. Although we have yet to test our approach in other species, our findings suggest that engineered chromatin regulators may provide much needed tools to engineer cell fate in the cells as drugs era.

Abstract Dark matter density can be significantly enhanced by the supermassive black hole at the galactic center, leading to a structure called dark matter spike. Dark matter spike may change the spacetime properties of black holes that constitute deviations from GR black holes. Based on these interesting background, we construct a set of solutions of black holes in a dark matter spike under the Newtonian approximation and full relativity. Combining the mass model of M87, we study the quasinormal modes of black holes in the scalar field and axial gravitational perturbation, then compared them with Schwarzschild black hole. Besides, the impacts of dark matter on the quasinormal mode of black holes have been studied in depth. In particular, in the axial gravitational perturbation, our results show that the impacts of dark matter spike on the quasinormal mode of black holes can reach up to $$10^{-4}$$ 10 - 4 . These new features from quasinormal mode of black holes under the Newtonian approximation and full relativity may provide some help for the establishment of the final dark matter model, and provide a new thought for the indirect detection of dark matter.

Abstract The Internet of Things (IoT) is an extensive system of interrelated devices equipped with sensors to monitor and track real world objects, spanning several verticals, covering many different industries. The IoT's promise is capturing interest as its value in healthcare continues to grow, as it can overlay on top of challenges dealing with the rising burden of chronic disease management and an aging population. To address difficulties associated with IoT-enabled healthcare, we propose a secure routing protocol that combines a fuzzy logic system and the Whale Optimization Algorithm (WOA) hierarchically. The suggested method consists of two primary approaches: the fuzzy trust strategy and the WOA-inspired clustering methodology. The first methodology plays a critical role in determining the trustworthiness of connected IoT equipment. Furthermore, a WOA-based clustering framework is implemented. A fitness function assesses the likelihood of IoT devices acting as cluster heads. This formula considers factors such as centrality, range of communication, hop count, remaining energy, and trustworthiness. Compared with other algorithms, the proposed method outperformed them in terms of network lifespan, energy usage, and packet delivery ratio by 47%, 58%, and 17.7%, respectively.

Abstract Background The interplay between atrial fibrillation (AF) and obesity on mortality in critically ill patients warrants detailed exploration, given their individual impacts on patient prognosis. This study aimed to assess the associations between AF, obesity, and 1-year mortality in a critically ill population. Methods Utilizing data from the Medical Information Mart for Intensive Care (MIMIC)-IV database, we conducted a retrospective analysis of adult patients admitted to the intensive care unit. The primary endpoint was 1-year mortality, analyzed through Cox regression with hazard ratio (HR) and Kaplan-Meier survival methods. Results The study included 25,654 patients (median age 67.0 years, 40.6% female), with 39.0% having AF and 36.1% being obese. Multivariate COX regression analysis revealed that AF was associated with a 14.7% increase in the risk of 1-year mortality (p

Abstract Analyzing the genetic diversity and selection characteristics of sheep (Ovis aries) holds significant value in understanding their environmental adaptability, enhancing breeding efficiency, and achieving effective conservation and rational utilization of genetic resources. In this study, we utilized Illumina Ovine SNP 50 K BeadChip data from four indigenous sheep breeds from the southern margin of the Taklamakan Desert (Duolang sheep: n = 36, Hetian sheep: n = 74, Kunlun sheep: n = 27, Qira black sheep: n = 178) and three foreign meat sheep breeds (Poll Dorset sheep: n = 105, Suffolk sheep: n = 153, Texel sheep: n = 150) to investigate the population structure, genetic diversity, and genomic signals of positive selection within the indigenous sheep. According to the Principal component analysis (PCA), the Neighbor-Joining tree (NJ tree), and Admixture, we revealed distinct clustering patterns of these seven sheep breeds based on their geographical distribution. Then used Cross Population Extended Haplotype Homozygosity (XP-EHH), Fixation Index (FST), and Integrated Haplotype Score (iHS), we identified a collective set of 32 overlapping genes under positive selection across four indigenous sheep breeds. These genes are associated with wool follicle development and wool traits, desert environmental adaptability, disease resistance, reproduction, and high-altitude adaptability. This study reveals the population structure and genomic selection characteristics in the extreme desert environments of native sheep breeds from the southern edge of the Taklimakan Desert, providing new insights into the conservation and sustainable use of indigenous sheep genetic resources in extreme environments. Additionally, these findings offer valuable genetic resources for sheep and other mammals to adapt to global climate change.

Bevacizumab is a common strategy for the treatment of recurrent glioblastoma. Survival status is a crucial issue for patients with recurrent glioblastoma, and the apparent diffusion coefficient (ADC) values of the lower Gaussian curve have been reported to have the potential to predict prognosis in recurrent glioblastoma. In the present study, we aimed to clarify the survival prediction of ADC values in patients with recurrent glioblastoma receiving bevacizumab treatment through a systematic review and meta-analysis of randomized clinical trials, comparing ADC values higher than the cut-off values with those lower than the cut-off values to determine which type of ADC values can be associated with significant survival benefits. Different survival indicators were analyzed, including overall survival (OS) and progression-free survival (PFS). Ten studies with a total of 782 patients with recurrent glioblastoma were included. The focused outcomes were OS and PFS. Our results showed that ADC values lower than the cut-off values were associated with significant benefits for OS status compared with ADC values higher than the cut-off values. Similar significant benefits were observed for PFS. The meta-analysis results suggest that ADC values lower than the cut-off values might be associated with significant benefits for OS and PFS when compared with ADC values higher than the cut-off values. However, bias in relation to the different stages of recurrent glioblastoma and different types, doses, and regimens of bevacizumab should not be ignored.

Abstract Background Atherogenic index of plasma (AIP) is a non-traditional lipid parameter that can reflect the burden of atherosclerosis. A lipid profile resembling atherosclerosis emerged during pregnancy. Although lipid metabolism is pivotal in diabetes pathogenesis, there is no evidence linking AIP to gestational diabetes mellitus (GDM). Therefore, our objective was to explore the relationship between AIP and GDM and assess AIP's predictive capability for GDM. Methods This was a secondary analysis based on data from a prospective cohort study in Korea involving 585 single pregnant women. AIP was calculated as log10 (TG/HDL). We examined the relationship between AIP and GDM using logistic regression models, curve fitting, sensitivity analyses, and subgroup analyses. Receiver operating characteristic (ROC) analysis was also used to determine the ability of AIP to predict GDM. Results The average age of the participants was 32.06 ± 3.76 years. The AIP was 0.24 ± 0.20 on average. The GDM incidence was 6.15%. After adjustment for potentially confounding variables, AIP showed a positive linear relationship with GDM (P for non-linearity: 0.801, OR 1.58, 95% CI 1.27–1.97). The robustness of the connection between AIP and GDM was demonstrated by sensitivity analyses and subgroup analyses. An area under the ROC curve of 0.7879 (95% CI 0.7087–0.8671) indicates that AIP is an excellent predictor of GDM. With a specificity of 75.41% and sensitivity of 72.22%, the ideal AIP cut-off value for identifying GDM was 0.3557. Conclusions This study revealed that the AIP at 10–14 weeks of gestation was independently and positively correlated with GDM risk. AIP could serve as an early screening and monitoring tool for pregnant women at high risk of GDM, thereby optimizing GDM prevention strategies. Trial registration ClinicalTrials.gov registration no. NCT02276144. Graphical abstract

Abstract Pluripotent stem cells have the potential to generate embryo models that can recapitulate developmental processes in vitro. Large animals such as pigs may also benefit from stem-cell-based embryo models for improving breeding. Here, we report the generation of blastoids from porcine embryonic stem cells (pESCs). We first develop a culture medium 4FIXY to derive pESCs. We develop a 3D two-step differentiation strategy to generate porcine blastoids from the pESCs. The resulting blastoids exhibit similar morphology, size, cell lineage composition, and single-cell transcriptome characteristics to blastocysts. These porcine blastoids survive and expand for more than two weeks in vitro under two different culture conditions. Large animal blastoids such as those derived from pESCs may enable in vitro modeling of early embryogenesis and improve livestock species’ breeding practices.

Abstract Intravenous immunoglobulin (IVIG) resistance in Kawasaki disease (KD) was associated with coronary artery lesions. Neutrophil percentage-to-albumin ratio (NPAR) is an index of mortality in several inflammatory diseases. This study focused on the association of NPAR with IVIG- resistance in KD. Clinical and laboratory data of 438 children with KD before IVIG treatment were retrospectively analyzed. Notably, high NPAR was associated with older age, high WBC, NP, ALT, total bilirubin and CRP, as well as with high the incidence of IVIG-resistance, and with low hemoglobin (Hb), PLT, ALB and sodium levels. NPAR (OR: 2.366, 95% CI: 1.46–3.897, p = 0.001) and Hb (OR: 0.967, 95% CI: 0.944–0.989, p = 0.004) were independent risk factors for IVIG-resistance. NPAR showed linear relation with IVIG-resistance (p for nonlinear = 0.711) and the nonlinear correlation was found between IVIG-resistance and Hb (p for nonlinear = 0.002). The predictive performance of NPAR was superior to Beijing model (z = 2.193, p = 0.028), and not inferior to Chongqing model (z = 0.983, p = 0.326) and the combination of NPAR and Hb (z = 1.912, p = 0.056). These findings revealed that NPAR is a reliable predictor of IVIG-resistance.

With the urgent need of energy saving and consumption reduction in today's world, the topic of increasing the energy conversion efficiency of ventilation fans has been attracted a lot of attentions, it has become a key issue in the field of ventilation. The understanding on the evolution mechanism of irreversible energy loss in impeller is the premise and basis for realizing the efficient energy conversion of ventilation fans. At present, the irreversible energy loss mechanism in impeller is still lack of research. Therefore, the internal flow field of the contra-rotating axial fan at different flowrates is obtained by numerical simulation and experimental methods. A theoretical model of irreversible energy loss in impeller of ventilation fans is established based on entropy production theory, and the relationship between the irreversible energy loss in impeller and the flow field parameters is clarified. A quantitative analysis is conducted on different types of energy loss in impeller, and the spatial evolution law and causes of energy loss are clarified by combining with the flow characteristics in impeller. The results show that the entropy production method is reliable in calculating the irreversible energy loss in impeller. Direct viscous dissipation loss and wall friction loss are important components of energy loss, while turbulent dissipation is the main cause of energy loss, accounting for 60% to 80% of the total energy loss. For the front impeller, the energy loss caused by turbulent dissipation reaches the minimum at 1.0 QBEP, while the energy loss of the rear impeller increases with the decrease of flowrate. The energy loss is mainly concentrated in the region of Span=0.6−1.0, reaching 70% of the total energy loss at optimal flow condition. The spiral vortex caused by blade tip leakage flow and overflow of blade leading edge, backflow in impeller, flow separation at blade pressure and suction surface, and blade trailing edge wake will cause energy loss. The high energy loss region caused by flow separation and wake is relatively small, and the energy loss is relatively limited. However, the vortex and backflow significantly affect the flow in impeller, ultimately leading to a significant energy loss in the region near the blade tip. The research results can provide a reference for the evaluation of irreversible energy loss of ventilation fans.

Cholemic nephropathy （CN） is a disease with renal dysfunction as a major manifestation in patients with advanced chronic liver disease complicated with severe jaundice. Currently no effective non-invasive diagnostic modality is available for CN. Renal biopsy has been a gold standard for its clinical diagnosis. Furthermore, it is frequently misdiagnosed or confused with hepatorenal syndrome so that patient prognosis remains poor. The overall objective of clinical management is lowering a high level of bilirubin and blunting renal injury. If drug therapy fails, artificial liver systems may be employed for improving renal function. The underlying pathological mechanisms of CN have not been fully elucidated. However, recent studies implied that the development of disease was correlated closely with abnormal renal transporters, oxidative stress and inflammatory responses. Based upon previous studies, the authors summarized the latest researches on CN through focusing upon clinical diagnosis, potential pathogenesis and therapeutic strategies for providing theoretical rationales for advanced researches and clinical interventions of CN.

Abstract Azole antifungal drugs are commonly used to treat vulvovaginal candidiasis (VVC). The nephrotoxicity and developmental toxicity of azole drugs have not been systematically analyzed in the real world. We used the FDA Adverse Event Reporting System (FAERS) to investigate the adverse events (AEs) associated with imidazole therapy for VVC. FAERS data (from quarter 1 2004 to quarter 3 2022) were retrieved using OpenVigil 2.1, and AEs were retrieved and standardized according to the Medical Dictionary for Regulatory Activities (MedDRA). In the top 10 System Organ Class (SOC), all four drugs have been found to have kidney and urinary system diseases and pregnancy. We found significant signals, including clotrimazole [bladder transitional cell carcinoma, (report odds ratio, ROR = 291.66)], [fetal death, (ROR = 10.28)], ketoconazole[nephrogenic anemia (ROR = 22.1)], [premature rupture of membranes (ROR = 22.91 46.45, 11, 3)], Miconazole[hematuria (ROR = 19.03)], [neonatal sepsis (ROR = 123.71)], [spontaneous abortion (ROR = 5.98)], Econazole [acute kidney injury (ROR = 4.41)], [spontaneous abortion (ROR = 19.62)]. We also discovered new adverse reactions that were not reported. Therefore, when using imidazole drugs for treatment, it is necessary to closely monitor the patient's renal function, pay attention to the developmental toxicity of the fetus during pregnancy, and be aware of potential adverse reactions that may occur.

Abstract Background The aim of the study was to investigate the muscle differences in children with osteogenesis imperfecta (OI) using opportunistic low-dose chest CT and to compare different methods for the segmentation of muscle in children. Methods This single center retrospective study enrolled children with OI and controls undergoing opportunistic low-dose chest CT obtained during the COVID pandemic. From the CT images, muscle size (cross-sectional area) and density (mean Hounsfield Units [HU]) of the trunk muscles were measured at the mid-T4 and the mid-T10 level using two methods, the fixed thresholds and the Gaussian mixture model. The Bland-Altman method was also used to compute the strength of agreement between two methods. Comparison of muscle results between OI and controls were analyzed with Student t tests. Results 20 children with OI (mean age, 9.1 ± 3.3 years, 15 males) and 40 age- and sex-matched controls were enrolled. Mean differences between two methods were good. Children with OI had lower T4 and T10 muscle density than controls measured by the fixed thresholds (41.2 HU vs. 48.0 HU, p

Abstract Magnetoelectric materials, which encompass coupled magnetic and electric polarizabilities within a single phase, hold great promises for magnetic controlled electronic components or electric-field controlled spintronics. However, the realization of ideal magnetoelectric materials remains tough due to the inborn competion between ferroelectricity and magnetism in both levels of symmetry and electronic structure. Herein, we introduce a methodology for constructing single phase paramagnetic ferroelectric molecule [TMCM][FeCl4], which shows low-magnetic-field magnetoelectricity at room temperature. By applying a low magnetic field (≤1 kOe), the halogen Cl‧‧‧Cl distance and the volume of [FeCl4]− anions could be manipulated. This structural change causes a characteristic magnetostriction hysteresis, resulting in a substantial deformation of ~10−4 along the a-axis under an in-plane magnetic field of 2 kOe. The magnetostrictive effect is further qualitatively simulated by density functional theory calculations. Furthermore, this mechanical deformation significantly dampens the ferroelectric polarization by directly influencing the overall dipole configuration. As a result, it induces a remarkable α 31 component (~89 mV Oe−1 cm−1) of the magnetoelectric tensor. And the magnetoelectric coupling, characterized by the change of polarization, reaches ~12% under 40 kOe magnetic field. Our results exemplify a design methodology that enables the creation of room-temperature magnetoelectrics by leveraging the potent effects of magnetostriction.

Abstract Background Sleep health and obesity may affect the risk of female infertility. However, few studies focused on the interaction of obesity and sleep health on the female infertility risk. This study aimed to evaluate the combined impact of trouble sleeping / sleep duration and overweight/obesity/ abdominal obesity on the risk of female infertility. Methods The data for this cross-sectional study was obtained from National Health and Nutritional Examination Survey, which provided information on trouble sleeping, sleep duration, overweight/obesity, abdominal obesity, and confounding factors. Adopted weighted univariate and multivariate logistic regression models to explore the relationship between trouble sleeping, sleep duration, overweight/obesity, abdominal obesity, and the risk of infertility, respectively, and the combined effect of trouble sleeping and overweight/obesity, trouble sleeping and abdominal obesity, sleep duration and overweight/obesity, sleep duration and abdominal obesity, on the female infertility risk. Results This study included a total of 1,577 women, and 191 were diagnosed with infertility. Women with infertility had a higher proportion of people with overweight/obesity, abdominal obesity, sleep duration ≤ 7 h and trouble sleeping than those with non-infertility. The result indicated that trouble sleeping [odds ratio (OR) = 2.25, 95% confidence intervals (CI): 1.49–3.39], sleep duration ≤ 7 h (OR = 1.59, 95% CI: 1.03–2.48), and the combined impact of abdominal obesity and trouble sleeping (OR = 2.18, 95% CI: 1.28–3.72), abdominal obesity and sleep duration ≤ 7 h (OR = 2.00, 95% CI: 1.17–3.40), overweight/obesity and trouble sleeping (OR = 2.29, 95% CI: 1.24–4.26), and overweight/obesity and sleep duration ≤ 7 h (OR = 1.88, 95% CI: 1.01–3.49) were associated with increased odds of infertility, respectively. Conclusion There was combined effects of trouble sleeping/sleep duration ≤ 7 h and overweight/obesity/ abdominal obesity on increased odds of female infertility.

Coastal wetlands are hotspots for nitrogen (N) cycling, and crab burrowing is known to transform N in intertidal marsh soils. However, the underlying mechanisms remain unclear. This study conducted field experiments and used indoor control test devices to investigate the seasonal response of nitrogen to crab disturbance at the sediment–water interface in coastal tidal flat wetlands. The results showed that crab disturbance exhibited significant seasonality with large seasonal differences in cave density and depth. Due to crab disturbance, nitrogen fluxes at the sediment–water interface were much greater in the box with crabs than in the box without crabs. In summer, NH4+-N showed a positive flux from the sediment to the overlying water, but NO2−-N and NO3−-N showed positive fluxes from the sediment to the overlying water only in early stages. In winter, NH4+-N showed a positive flux from the sediment to the overlying water, but NO2−-N and NO3−-N both exhibited positive and negative fluxes. These results indicated that the presence of crab burrows can cause the aerobic layer to move downward by approximately 8–15 cm in summer and directly promote nitrification at the sediment surface.

The energy storage features on natural convection in Casson fluids are investigated in this work using the finite element method. By measuring cylinders and wavy surfaces, we may examine flow patterns and the effectiveness of heat transmission systems. We study the variation of the mass and heat transfer rates as a function of the cylinder geometry. To approximately determine velocities and temperatures, the Ladyzhenskaya-Babuška—Brezzi (LBB)-stable element is employed. Following this discretization, the resulting discrete nonlinear system is linearized using Newton's method and subsequently solved using PARDISO. Fractional applications in Casson fluid analysis reveal insights into energy storage effects, employing finite element methods to explore flow patterns, heat transmission efficiency, and geometric variations while observing the impact of parameters such as Rayleigh, Hartmann, and Lewis numbers on fluid behavior and thermal properties. The preceding research has verified the accuracy of the numerical results. According to the results, concentration gradients and other modifications to liquids become more noticeable as the Rayleigh number grows. Convective heat transmission is reduced as the Ha is raised. When the Le grows, the deformation Nuavg and Shavgalso increase. Reducing the beta makes the isotherms more stable and less affected by the motion of the fluid.

Nicotinamide adenine dinucleotide (NAD+) is a central and pleiotropic metabolite involved in cellular energy metabolism, cell signaling, DNA repair, and protein modifications. Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Metabolic stress and aging directly affect the cardiovascular system. Compelling data suggest that NAD + levels decrease with age, obesity, and hypertension, which are all notable risk factors for CVD. In addition, the therapeutic elevation of NAD + levels reduces chronic low-grade inflammation, reactivates autophagy and mitochondrial biogenesis, and enhances oxidative metabolism in vascular cells of humans and rodents with vascular disorders. In preclinical models, NAD + boosting can also expand the health span, prevent metabolic syndrome, and decrease blood pressure. Moreover, NAD + storage by genetic, pharmacological, or natural dietary NAD + -increasing strategies has recently been shown to be effective in improving the pathophysiology of cardiac and vascular health in different animal models, and human health. Here, we review and discuss NAD + -related mechanisms pivotal for vascular health and summarize recent experimental evidence in NAD + research directly related to vascular disease, including atherosclerosis, and coronary artery disease. Finally, we comparatively assess distinct NAD + precursors for their clinical efficacy and the efficiency of NAD + elevation in the treatment of major CVD. These findings may provide ideas for new therapeutic strategies to prevent and treat CVD in the clinic.

Abstract Background Pudendal neuralgia is a chronic and debilitating condition. Its prevalence ranges from 5 to 26%. Currently, therapeutic approaches to treat pudendal neuralgia include patient education, medication management, psychological and physical therapy, and procedural interventions, such as nerve block, trigger point injections, and surgery. Drug therapy has a limited effect on pain relief. A pudendal nerve block may cause a significant decrease in pain scores for a short time; however, its efficacy significantly decreases over time. In contrast, pudendal nerve pulsed radiofrequency can provide pain relief for 3 months, and ganglion impar block has been widely used for treating chronic perineal pain and chronic coccygodynia. This study aimed to determine the efficacy and safety of monotherapy (pudendal nerve pulsed radiofrequency) and combination therapy (pudendal nerve pulsed radiofrequency plus ganglion impar block) in patients with pudendal neuralgia. Methods This randomized, controlled clinical trial will include 84 patients with pudendal neuralgia who failed to respond to drug or physical therapy. Patients will be randomly assigned into one of the two groups: mono or combined treatment groups. The primary outcome will be a change in pain intensity measured using the visual analog scale. The secondary outcomes will include a Self-Rating Anxiety Scale score, Self-Rating Depression Scale score, the use of oral analgesics, the Medical Outcomes Study Health Survey Short Form-36 Item score, and the occurrence of adverse effects. The study results will be analyzed using intention-to-treat and per-protocol analyses. Primary and secondary outcomes will be evaluated between the mono and combined treatment groups. Subgroup analyses will be conducted based on the initial ailment, age, and baseline pain intensity. The safety of the treatment will be assessed by monitoring adverse events, which will be compared between the two groups. Discussion This study protocol describes a randomized, controlled clinical trial to determine the efficacy and safety of mono and combination therapies in patients with pudendal neuralgia. The study results will provide valuable information on the potential benefits of this combination therapy and contribute to the development of more effective and safer treatments for patients with pudendal neuralgia. Trial registration Chinese Clinical Trial Registry (ChiCTR2200061800).

Abstract Optimizing short‐term load forecasting performance is a challenge due to the randomness of nonlinear power load and variability of system operation mode. The existing methods generally ignore how to reasonably and effectively combine the complementary advantages among them and fail to capture enough internal information from load data, resulting in accuracy reduction. To achieve accurate and efficient short‐term load forecasting, an integral implementation framework is proposed based on convolutional neural network (CNN), gated recurrent unit (GRU) and channel attention mechanism. CNN and GRU are first combined to fully extract the highly complicated dynamic characteristics and learn time compliance relationships of load sequence. Based on CNN‐GRU network, the channel attention mechanism is introduced to further reduce the loss of historical information and enhance the impact of important characteristics. Then, the overall framework of short‐term load forecasting based on CNN‐GRU‐Attention network is proposed, and the coupling relationship between each stage is revealed. Finally, the developed framework is implemented on realistic load dataset of distribution networks, and the experimental results verify the effectiveness of the proposed method. Compared with the state‐of‐the‐art models, the CNN‐GRU‐Attention model outperforms in different evaluation metrics.

Abstract Nuclear condensates have been shown to regulate cell fate control, but its role in oncogenic transformation remains largely unknown. Here we show acquisition of oncogenic potential by nuclear condensate remodeling. The proto-oncogene SS18 and its oncogenic fusion SS18-SSX1 can both form condensates, but with drastically different properties and impact on 3D genome architecture. The oncogenic condensates, not wild type ones, readily exclude HDAC1 and 2 complexes, thus, allowing aberrant accumulation of H3K27ac on chromatin loci, leading to oncogenic expression of key target genes. These results provide the first case for condensate remodeling as a transforming event to generate oncogene and such condensates can be targeted for therapy. One sentence summary: Expulsion of HDACs complexes leads to oncogenic transformation.

Abstract In-depth comprehension and modulation of the electronic structure of the active metal sites is crucial to enhance their intrinsic activity of electrocatalytic oxygen evolution reaction (OER) toward anion exchange membrane water electrolyzers (AEMWEs). Here, we elaborate a series of amorphous metal oxide catalysts (FeCrOx, CoCrOx and NiCrOx) with high performance AEMWEs by high-valent chromium dopant. We discover that the positive effect of the transition from low to high valence of the Co site on the adsorption energy of the intermediate and the lower oxidation barrier is the key factor for its increased activity by synchrotron radiation in-situ techniques. Particularly, the CoCrOx anode catalyst achieves the high current density of 1.5 A cm−2 at 2.1 V and maintains for over 120 h with attenuation less than 4.9 mV h−1 in AEMWE testing. Such exceptional performance demonstrates a promising prospect for industrial application and providing general guidelines for the design of high-efficiency AEMWEs systems.

Abstract Engineering atom-scale sites are crucial to the mitigation of polysulfide shuttle, promotion of sulfur redox, and regulation of lithium deposition in lithium–sulfur batteries. Herein, a homonuclear copper dual-atom catalyst with a proximal distance of 3.5 Å is developed for lithium–sulfur batteries, wherein two adjacent copper atoms are linked by a pair of symmetrical chlorine bridge bonds. Benefiting from the proximal copper atoms and their unique coordination, the copper dual-atom catalyst with the increased active interface concentration synchronously guide the evolutions of sulfur and lithium species. Such a delicate design breaks through the activity limitation of mononuclear metal center and represents a catalyst concept for lithium–sulfur battery realm. Therefore, a remarkable areal capacity of 7.8 mA h cm−2 is achieved under the scenario of sulfur content of 60 wt.%, mass loading of 7.7 mg cm−2 and electrolyte dosage of 4.8 μL mg−1.

Abstract Background Transforming growth factor-β (TGF-β) is a cytokine with multiple functions, including cell growth regulation, extracellular matrix production, angiogenesis homeostasis adjustment and et al. TGF-β pathway activation promotes tumor metastasis/progression and mediates epithelial-mesenchymal transmission suppressing immunosurveillance in advanced tumors. GFH018, a small molecule inhibitor blocking TGF-β signal transduction, inhibits the progression and/or metastasis of advanced cancers. This first-in-human study evaluated the safety, tolerability, pharmacokinetics (PK), and efficacy of GFH018 monotherapy in patients with advanced solid tumors. Methods This phase I, open-label, multicenter study used a modified 3+3 dose escalation and expansion design. Adult patients with advanced solid tumors failing the standard of care were enrolled. Starting at 5 mg, eight dose levels up to 85 mg were evaluated. Patients received GFH018 BID (14d-on/14d-off) starting on the 4th day after a single dose on cycle 1, day 1. Subsequent cycles were defined as 28 days. The study also explored the safety of 85 mg BID 7d-on/7d-off. Adverse events were graded using NCI criteria for adverse events (NCI-CTCAE v5.0). PK was analyzed using a noncompartmental method. Efficacy was evaluated using RECIST 1.1. Blood samples were collected for biomarker analysis. Results Fifty patients were enrolled and received at least one dose of GFH018. No dose-limiting toxicity occurred, and the maximum tolerated dose was not reached. Forty-three patients (86.0%) had at least one treatment-related adverse event (TRAE), and three patients (6.0%) had ≥ G3 TRAEs. The most common TRAEs (any grade/grade ≥3) were AST increased (18%/0%), proteinuria (14%/2%), anemia (14%/2%), and ALT increased (12%/0%). No significant cardiotoxicity or bleeding was observed. GFH018 PK was linear and dose-independent, with a mean half-life of 2.25–8.60 h from 5 – 85 mg. Nine patients (18.0%) achieved stable disease, and one patient with thymic carcinoma achieved tumor shrinkage, with the maximum target lesion decreased by 18.4%. Serum TGF-β1 levels were not associated with clinical responses. The comprehensive recommended dose for Phase II was defined as 85 mg BID 14d-on/14d-off. Conclusions GFH018 monotherapy presented a favorable safety profile without cardiac toxicity or bleeding. Modest efficacy warrants further studies, including combination strategies. Trial registration ClinicalTrial. gov ( https://www.clinicaltrials.gov/ ), NCT05051241. Registered on 2021-09-02.

Abstract Background The objective was to investigate the efficacy of different doses of levothyroxine therapy among pregnant women exhibiting high-normal thyroid stimulating hormone levels and positive thyroid peroxidase antibodies throughout the first half of pregnancy. Methods Pregnant women exhibiting high-normal thyroid stimulating hormone levels and thyroid peroxidase antibodies positivity throughout the initial half of pregnancy were selected from January 2021 to September 2023. Based on the different doses of levothyroxine, the pregnant women were categorized into the nonintervention group (G0, 122 women), 25 µg levothyroxine intervention group (G25, 69 women), and 50 µg levothyroxine intervention group (G50, 58 women). Serum parameters, gastrointestinal symptoms, small intestinal bacterial overgrowth (SIBO), maternal and neonatal outcomes were compared after the intervention among the three groups. Results After the intervention, in the G25 and G50 groups, the thyroid stimulating hormone, triglyceride and low-density lipoprotein levels were notably less in contrast to those in the G0 group (P

Objective Dual‐plate fixation was thought to be the gold standard for treating complicated bicondylar tibial plateau fractures, yet it was found to be hard to accommodate the posterior column in three‐column fractures. Currently, column‐specific fixation is becoming more and more recognized, but no comprehensive investigation has been performed to back it up. Therefore, the objective of this study was to validate the importance of posterior column fixation in the three‐column tibial fractures by a finite element (FE) analysis and clinical study. Methods In FE analysis, three models were developed: the longitudinal triple‐plate group (LTPG), the oblique triple‐plate group (OTPG), and the dual‐plate group (DPG). Three loading scenarios were simulated. The distribution of the displacement and the equivalent von Mises stress (VMS) in each structure was calculated. The comparative measurements including the maximum posterior column collapse (MPCC), the maximum total displacement of the model (MTD), the maximum VMS of cortical posterior column (MPC‐VMS), and the maximum VMS located on each group of plates and screws (MPS‐VMS). The clinical study evaluated the indicators between the groups with or without the posterior plate, including operation time, blood loss volume, full‐weight bearing period, Hospital for Special Surgery Knee Scoring system (HSS), Rasmussen score, and common postoperative complications. Results In the FE analysis, the MPCC, the MPC‐VMS, and the MTD were detected in much lower amounts in LTPG and OTPG than in DPG. In comparison with DPG, the LTPG and OTPG had larger MPS‐VMS. In the clinical study, 35 cases were included. In the triple‐plate (14) and dual‐plate (21) groups, the operation took 115.6 min and 100.5 min (p

This study investigates the application of Ultrasonic Pulse Velocity (UPV) for crack depth estimation in cylindrical structures, focusing on two approaches: reference measurement and dual measurement. It addresses the challenge of applying UPV to curved surfaces, a scenario less studied than that of flat surfaces. The paper details the modification of UPV methodologies to account for curvature, presenting analytic solutions and numerical validations for both approaches. The findings reveal that curvature-adjusted equations yield accurate crack depth estimations, enhancing the reliability of UPV in diverse structural contexts. The study contributes to safer and more effective structural health monitoring, particularly in cylindrical infrastructures like columns and foundations.

Abstract In the evolving landscape of smart libraries, this research pioneers an IoT-based low-cost architecture utilizing Software-Defined Networking (SDN). The increasing demand for more efficient and economical solutions in library management, particularly in the realm of RFID-based processes such as authentication, property circulation, and book loans, underscores the significance of this study. Leveraging the collaborative potential of IoT and SDN technologies, our proposed system introduces a fresh perspective to tackle these challenges and advance intelligent library management. In response to the evolving landscape of smart libraries, our research presents an Internet of Things (IoT)-based low-cost architecture utilizing SDN. The exploration of this architectural paradigm arises from a recognized gap in the existing literature, pointing towards the necessity for more efficient and cost-effective solutions in managing library processes. Our proposed algorithm integrates IoT and SDN technologies to intelligently oversee various library activities, specifically targeting RFID-based processes such as authentication, property circulation management, and book loan management. The system's architecture, encompasses components like the data center, SDN controllers, RFID tags, tag readers, and other network sensors. By leveraging the synergy between RFID and SDN, our innovative approach reduces the need for constant operator supervision in libraries. The scalability and software-oriented nature of the architecture cater to extensive library environments. Our study includes a two-phase investigation, combining practical implementation in a small-scale library with a simulation environment using MATLAB 2021. This research not only fills a crucial gap in current knowledge but also lays the foundation for future advancements in the integration of IoT and SDN technologies for intelligent library management.

Abstract This paper presents a detailed scattering analysis of a hollow-core plasmonic-shell cylindrical wire to design an efficient, compact, narrowband, and reconfigurable optical absorber. The shell is formed by a thin graphene material, investigated in its epsilon-near-zero (ENZ) plasmonic region. Compared to the graphene plasmonic resonances in the terahertz(THz)/far-infrared (FIR) frequencies, the ENZ plasmonic resonances offer a blue shift in the operating frequency of the second-order plasmonic resonances by increasing the geometrical dimensions. This feature is successfully used to design efficient optical wave absorbers with absorption cross-sections much larger than geometrical and scattering cross-sections. The observed blue shift in the resonance spectrum, which is the key point of the design, is further verified by defining each particle with its polarizability and fulfilling the resonant scattering condition in the framework of Mie’s theory. Furthermore, graphene relaxation time and chemical potential can be used to manipulate the absorption rate. Observed resonances have narrow widths, achieved with simple geometry. To consider more practical scenarios, the one-dimensional arrangement of the cylindrical elements as a dense and sparse array is also considered and the design key point regarding graphene quality is revealed. The quality factor of the sparse array resonance is 2272.8 and it demands high-quality graphene material in design. It is also observed that due to the use of small particles in the design, the near-field and cooperative effects are not visible in the absorption cross-section of the array and a clear single peak is attained. This polarization-insensitive absorber can tolerate a wide range of incident angles with an absorption rate above 90%.

Abstract This study aimed to investigate the effects of ammonia addition on ethylene counter-flow diffusion flames with different diluents on the fuel or oxidizer side, using kinetic analyses. A special emphasis was put on assessing the coupled chemical effects of NH3 and CO2 on C2H4 combustion chemistry. The chemical effects could be evaluated by comparing fictitious inert NH3 or CO2 with normal active NH3 or CO2. The results revealed that the addition of NH3 decreased the mole fractions and production rates of key soot precursors, such as acetylene, propynyl, and benzene. When CO2 was used as the dilution gas, the coupled chemical effects of NH3 and CO2 were affected by the chemical effects of CO2 to varying degrees. With the oxidizer-side CO2 addition, the coupled chemical effects of NH3 and CO2 reduced the mole fractions of H, O, OH radicals, acetylene, propynyl, and benzene, while the effects differed from the fuel-side CO2 addition. The coupled chemical effects of NH3 and CO2 also promoted the formation of aldehyde contaminants, such as acetaldehyde, to some extent, particularly with CO2 addition on the oxidizer side.

A central question in neural tissue engineering is how the tissue-engineered nerve (TEN) translates detailed transcriptional signals associated with peripheral nerve regeneration into meaningful biological processes. Here, we report a skin-derived precursor-induced Schwann cell (SKP-SC)-mediated chitosan/silk fibroin-fabricated tissue-engineered nerve graft (SKP–SCs-TEN) that can promote sciatic nerve regeneration and functional restoration nearly to the levels achieved by autologous nerve grafts according to behavioral, histological, and electrophysiological evidence. For achieving better effect of neuroregeneration, this is the first time to jointly apply a dynamic perfusion bioreactor and the ascorbic acid to stimulate the SKP-SCs secretion of extracellular matrix (ECM). To overcome the limitation of traditional tissue-engineered nerve grafts, jointly utilizing SKP-SCs and their ECM components were motivated by the thought of prolongating the effect of support cells and their bioactive cues that promote peripheral nerve regeneration. To further explore the regulatory model of gene expression and the related molecular mechanisms involved in tissue engineering-aided peripheral nerve regeneration, we performed a cDNA microarray analysis of gene expression profiling, a comprehensive bioinformatics analysis and a validation study on the grafted segments and dorsal root ganglia tissues. A wealth of transcriptomic and bioinformatics data has revealed complex molecular networks and orchestrated functional regulation that may be responsible for the effects of SKP-SCs-TEN on promoting peripheral nerve regeneration. Our work provides new insights into transcriptomic features and patterns of molecular regulation in nerve functional recovery aided by SKP-SCs-TEN that sheds light on the broader possibilities for novel repair strategies of peripheral nerve injury.

Abstract Cholestasis, a chronic liver condition, disrupts bile acid homeostasis and complicates drug disposition, posing significant challenges in medicating cholestatic patients. Drug metabolism enzymes and transporters (DMETs) are pivotal in drug clearance. Research indicates that cholestasis leads to alterations in both hepatic and extrahepatic DMETs, with changes in expression and function documented in rodents and humans. This review synthesizes the modifications in key drug disposition components within cholestasis, focusing on cytochrome P450 (CYP450), drug transporters, and their substrates. Additionally, we briefly discuss certain drugs that have demonstrated efficacy in restoring DMET expression in cholestatic conditions. Ultimately, these insights necessitate a reevaluation of drug selection and dosing guidelines for patients with cholestasis.

Tetrodotoxin (TTX) is a highly potent and widely distributed ion-channel marine neurotoxin; it has no specific antidote and poses a great risk to human health. Therefore, detecting and quantifying TTX to effectively implement prevention strategies is important for food safety. The development of novel and highly sensitive, highly specific, rapid, and simple techniques for trace TTX detection has attracted widespread attention. This review summarizes the latest advances in the detection and quantitative analysis of TTX, covering detection methods based on biological and cellular sensors, immunoassays and immunosensors, aptamers, and liquid chromatography-mass spectrometry. It further discusses the advantages and applications of various detection technologies developed for TTX and focuses on the frontier areas and development directions of TTX detection, providing relevant information for further investigations.

To uncover the security aspects of the Water-Energy-Food-Nexus (WEFN) and develop innovative methods for evaluating its security, we initially utilize the coefficient of variation-cumulative information contribution rate (COV-CICR) model to select assessment metrics. This approach ensures a well-suited set of indicators for assessing the security of the WEFN. Subsequently, the WEFN security assessment model is developed by utilizing a random forest model that has been fine-tuned with the aquila optimizer. To illustrate this model's application, we use the example of the Hongxinglong branch of China's Beidahuang Farming Group Co., Ltd. The study conducted a detailed analysis of the spatiotemporal variations in the security of the WEFN (Water-Energy-Food Nexus) system across 12 subsidiary farms. Furthermore, it identified key driving factors and elucidated their mechanisms by accounting for data fluctuations. The research included calculating the contribution index of these key driving factors to accurately determine the dominant factors under varying conditions. The results indicate that over time, the WEFN security level in the study trended upward. From 2002–2008, the WEFN security level slowly increased. From 2009–2018, WEFN security remained stable. From 2018–2021, the security level rapidly accelerated. Spatially, the WEFN security in the southern region is lower than that in the northern region, while the central region’s security remained stable. The primary controlling factors for WEFN security also vary at different scales. In comparison to the BP, RF, and PSO-RF models, the AO-RF model demonstrates outstanding advantages in terms of fitting performance, reliability, reasonableness, and stability. This fully supports the applicability of the AO-RF model in WEFN security assessment. The research findings enrich the integrated application of intelligent optimization and machine learning in WEFN studies, introduce a novel analytical model for WEFN security drivers, and expand our understanding of the new mechanisms underlying WEFN security operations.