Search

Hyperlipidemia is a major risk factor for erectile dysfunction (ED). Oxidative stress and phenotypic modulation of corpus cavernosum smooth muscle cells (CCSMCs) are the key pathological factors of ED. N-acetylcysteine (NAC) can inhibit oxidative stress; however, whether NAC can alleviate pathological variations in the corpus cavernosum and promote erectile function recovery in hyperlipidemic rats remains unclear. A hyperlipidemia model was established using 27 eight-week-old male Sprague–Dawley (SD) rats fed a high-fat and high-cholesterol diet (hyperlipidemic rats, HR). In addition, 9 male SD rats were fed a normal diet to serve as controls (NC). HR rats were divided into three groups: HR, HR+normal saline (NS), and HR+NAC (n = 9 for each group; NS or NAC intraperitoneal injections were administered daily for 16 weeks). Subsequently, the lipid profiles, erectile function, oxidative stress, phenotypic modulation markers of CCSMCs, and tissue histology were analyzed. The experimental results revealed that erectile function was significantly impaired in the HR and HR + NS groups, but enhanced in the HR + NAC group. Abnormal lipid levels, over-activated oxidative stress, and multi-organ lesions observed in the HR and HR + NS groups were improved in the HR + NAC group. Moreover, the HR group showed significant phenotypic modulation of CCSMCs, which was also inhibited by NAC treatment. This report focuses on the therapeutic effect of NAC in restoring erectile function using a hyperlipidemic rat model by preventing CCSMC phenotypic modulation and attenuating oxidative stress.

Constructing a functional hybrid coating appears to be a promising strategy for addressing the poor corrosion resistance and insufficient endothelialization of Mg-based stents. Nevertheless, the steps for preparing composite coatings are usually complicated and time-consuming. Herein, a novel composite coating, composed of bioactive magnesium thioctic acid (MTA) layer formed by deposition and corrosion-resistant magnesium hydroxide (Mg(OH)2) layer grown in situ, is simply fabricated on ZE21B alloys via one-step electrodeposition. Scanning electron microscopy (SEM) shows that the electrodeposited coating has a compact and uniform structure. And the high adhesion of the MTA/Mg(OH)2 hybrid coating is also confirmed by the micro-scratch test. Electrochemical test, scanning kelvin probe (SKP), and hydrogen evolution measurement indicate that the hybrid coating effectively reduces the degradation rate of Mg substrates. Haemocompatibility experiment and cell culture trial detect that the composite coating is of fine biocompatibility. Finally, the preparation mechanism of MTA/Mg(OH)2 hybrid coatings is discussed and proposed. This coating shows a great potential application for cardiovascular stents.

BackgroundPolycyclic aromatic hydrocarbons (PAHs), one of the main components of fine particulate matter (PM2.5), have a certain impact on ambient air quality, and long-term exposure to PAHs may pose potential health risks to human beings. ObjectiveTo identify the distribution characteristics and sources of PAHs in atmospheric PM2.5 in a district of Taizhou City from 2019 to 2021, and to evaluate the health risks of PAHs to the population in the area through the inhalation pathway. MethodsFrom 2019 to 2021, air PM2.5 sampling was carried out at a state-controlled surveillance point in a district of Taizhou City for 7 consecutive days on the 10th-16th of each month, the sampling time was 24 h·d−1, and the sampling flow rate was 100 L·min−1. PM2.5 mass concentration was calculated by gravimetric method. A total of 16 PAHs were determined by ultrasonic extraction-liquid chromatography. Kruskal-Wallis H test was used to compare the distribution charac teristics of PAHs concentrations by years and seasons, characteristic ratio and principal component analysis (PCA) was used to analyze their sources, and a lifetime carcinogenic risk (ILCR) model was used to assess the health risk of PAHs. ResultsFrom 2019 to 2021, the annual average concentrations [M (P25, P75)] of ∑PAHs in atmospheric PM2.5 in the selected district of Taizhou City were 6.52 (2.46, 10.59), 8.52 (4.56, 12.29), and 3.72 (1.51, 7.11) ng·m−3, respectively, and the annual benzo[a]pyrene (BaP) excess rates (national limit: 1 ng·m−3) were 27.38% (23/84), 47.62% (40/84), and 19.04% (16/84), respectively, both presenting 2020> 2019 > 2021 (P

BackgroundExposure to diisononyl phthalate (DINP), an endocrine disruptor associated with metabolic diseases and widely used in plastic products, has been linked to the development of several adverse health outcomes in the liver, including non-alcoholic fatty liver disease (NAFLD). ObjectiveTo investigate the effects and the possible molecular mechanisms of DINP exposure on lipid metabolism in human hepatocellular carcinoma cells (HepG2 cells). MethodsFirst, HepG2 cells were treated with DINP at three time spots (24, 48, and 72 h) and eleven doses (0, 0.003, 0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30, and 100 mmol·L−1). Cell viability were detected using cell counting kit 8 (CCK8). Intracellular lipid deposition was determined by oil red O staining and lipid content detection, and triglyceride (TG) and cholesterol (TC) were further detected. Finally, the mRNA expression levels were detected by fluorescence quantitative PCR, including fatty acid synthesis related genes [acetyl-CoA carboxylase alpha (Accα), fatty acid synthase (Fasn), malonyl-CoA decarboxylase (Mlycd), and sterol regulatory element binding protein 1 (Srebp1)] and β-oxidation related genes [peroxisome proliferator activated receptor alpha (Pparα), AMP-activated protein kinase (Ampk), carnitine palmitoyltransferase 1A (Cpt-1a), transcription factor A, mitochondrial (Tfam), nuclear respiratory factor 1 (Nrf1), and peroxisome proliferator-activated receptor gamma and coactivator 1 alpha (Pgc1-α)]. ResultsCompared with the control group (0 mmol·L−1), the no observed adverse effect levels (NOAEL) of HepG2 cell viability were 0.3, 0.1, and 0.1 mmol·L−1 after 24, 48, and 72 h exposure to DINP, respectively, and the corresponding lowest observed adverse effect levels (LOAEL) were 1, 0.3, and 0.3 mmol·L−1, respectively (P

Abstract Background Porcine epidemic diarrhea (PED) is an infectious disease of the digestive tract caused by the porcine epidemic diarrhea virus (PEDV), characterized by vomiting, severe diarrhea, and high mortality rates in piglets. In recent years, the distribution of this disease in China has remarkably increased, and its pathogenicity has also increased. PEDV has been identified as the main cause of viral diarrhea in piglets. This study aimed to understand the genetic evolution and diversity of PEDV to provide a theoretical basis for the development of new vaccines and the prevention and treatment of PED. Methods A PEDV strain was isolated from the small intestine of a diarrheal piglet using Vero cells. The virus was identified using reverse transcription-polymerase chain reaction (RT-PCR), indirect immunofluorescence assay (IFA), and transmission electron microscopy. The whole genome sequence was sequenced, phylogenetic analysis was conducted using MEGA (version 7.0), and recombination analysis was performed using RDP4 and SimPlot. The S protein amino acid sequence was aligned using Cluster X (version 2.0), and the S protein was modeled using SWISS-MODEL to compare differences in structure and antigenicity. Finally, the piglets were inoculated with PEDV to evaluate its pathogenicity in newborn piglets. Result PEDV strain CH/HLJ/18 was isolated. CH/HLJ/18 shared 89.4–99.2% homology with 52 reference strains of PEDV belonging to the GII-a subgroup. It was a recombinant strain of PEDV BJ-2011-1 and PEDV CH_hubei_2016 with a breakpoint located in ORF1b. Unique amino acid deletions and mutations were observed in the CH/HLJ/18 S protein. The piglets then developed severe watery diarrhea and died within 7 d of inoculation with CH/HLJ/18, suggesting that CH/HLJ/18 was highly pathogenic to newborn piglets. Conclusion A highly pathogenic recombinant PEDV GII-a strain, CH/HLJ/18, was identified in China, with unique deletion and mutation of amino acids in the S protein that may lead to changes in protein structure and antigenicity. These results will be crucial for understanding the prevalence and variation of PEDV and for preventing and controlling PED.

As a soft computing method, applying fuzzy cognitive map (FCM) to time series prediction has become a timely issue pursued by numerous researchers. Although many FCM construction methods have emerged, most of them exhibit obvious limitations in weight learning especially for long-term or complex time series. Either the weight calculation is computationally expensive, or it cannot achieve gratifying accuracy. In this paper, a new method for constructing FCM is proposed which extracts concepts from data by exploiting triangular membership function, and the weights of high-order FCM are subtly obtained by transforming the learning problem of FCM into a convex optimization problem with constraints. Since then, FCM with optimized weights is used to represent fuzzy logical relationships of time series and implement prediction further. Fifteen benchmark time series,such as Soybean Price time series, Yahoo stock time series, Condition monitoring of hydraulic systems time series etc. are applied to verify prediction performance of the proposed method. Accordingly, experiment results show that the proposed numerical prediction method of time series is effective and can acquire better prediction accuracy with lower computation time than other recent advanced methods. In addition, the influence of parameters of the method is analyzed individually.

Edge computing plays a crucial role in the field of the Internet of Vehicles (IoV), meeting the resource and latency requirements of time-sensitive vehicle applications. However, the emergence of numerous compute-intensive and latency-sensitive applications, such as augmented reality and autonomous driving, has led to a situation where traditional edge computing architectures cannot meet the increasing application demands of the IoV. This paper extends the paradigm of vehicular edge computing to a collaborative cloud-edge cluster resource provisioning framework. Integrating compute resources from multiple Edge Service Providers (ESP) and the cloud enables horizontal and vertical collaborative computation offloading among service nodes. To facilitate resource sharing among different ESPs, we introduce a dynamic pricing model and utilize software-defined networking (SDN) to tackle this scenario’s complex resource management challenges. Furthermore, with the optimization objectives of minimizing task computation latency and maximizing the profits of ESPs, we establish a mathematical model. Before resource allocation, we employ a clustering algorithm to determine initial offloading decisions, reducing the dimensionality of the action space. Subsequently, we employ the Double Deep Q-Network (DDQN) algorithm to achieve a rational allocation of compute resources. Simulation results demonstrate that compared to the Deep Q-Network (DQN) algorithm and greedy strategy, the proposed approach reduces latency by 18.18% and 34.85%, respectively, while increasing the profits of edge service providers by 16.25% and 33.33%, respectively.

Abstract Background The human pancreas is composed of specialized cell types producing hormones and enzymes critical to human health. These specialized functions are the result of cell type-specific transcriptional programs which manifest in cell-specific gene expression. Understanding these programs is essential to developing therapies for pancreatic disorders. Transcription in the human pancreas has been widely studied by single-cell RNA technologies, however the diversity of protocols and analysis methods hinders their interpretability in the aggregate. Results In this work, we perform a meta-analysis of pancreatic single-cell RNA sequencing data. We present a database for reference transcriptome abundances and cell-type specificity metrics. This database facilitates the identification and definition of marker genes within the pancreas. Additionally, we introduce a versatile tool which is freely available as an R package, and should permit integration into existing workflows. Our tool accepts count data files generated by widely-used single-cell gene expression platforms in their original format, eliminating an additional pre-formatting step. Although we designed it to calculate expression specificity of pancreas cell types, our tool is agnostic to the biological source of count data, extending its applicability to other biological systems. Conclusions Our findings enhance the current understanding of expression specificity within the pancreas, surpassing previous work in terms of scope and detail. Furthermore, our database and tool enable researchers to perform similar calculations in diverse biological systems, expanding the applicability of marker gene identification and facilitating comparative analyses.

Abstract For the current stellar spectral simulation can not realize the stellar color temperature information with large dynamic range simulation, this paper proposes a broad spectrum high-resolution subdivision and spatial beam zoning modulation combined with a large dynamic range of stellar radiation information simulation method, designed a kind of imaging and non-imaging stellar radiation information simulation optical system, using an optical system to achieve multi-color temperature spectrum and large dynamic range stellar simulation. The experimental results show that the designed system can simultaneously achieve the spectral simulation accuracy (single point evaluation) better than ± 7% in the range of spectral 450–1000 nm and color temperature 3000–11,000 K; on the premise of ensuring the spectral simulation accuracy, the magnitude simulation range reaches 0 to + 12 Mv, and the magnitude simulation accuracy is better than ± 0.05 Mv; Accurate simulation of stellar spectral information and energy large dynamic range tuning is realized, and the system is extended. The system function has been extended to realize the switching of broadband and narrowband modes, The half-peak width of the narrowband output beam is better than 4.1 nm, which extends the application of the spectral simulation technology and provides the theoretical and technical basis for the ground calibration of the development of the high-precision stellar radiation information ground simulation system.

Abstract Raising photoelectric conversion efficiency and enhancing heat management are two critical concerns for silicon-based solar cells. In this work, efficient Yb3+ infrared emissions from both quantum cutting and upconversion were demonstrated by adjusting Er3+ and Yb3+ concentrations, and thermo-manage-applicable temperature sensing based on the luminescence intensity ratio of two super-low thermal quenching levels was discovered in an Er3+/Yb3+ co-doped tungstate system. The quantum cutting mechanism was clearly decrypted as a two-step energy transfer process from Er3+ to Yb3+. The two-step energy transfer efficiencies, the radiative and nonradiative transition rates of all interested 4 f levels of Er3+ in NaY(WO4)2 were confirmed in the framework of Föster-Dexter theory, Judd-Ofelt theory, and energy gap law, and based on these obtained efficiencies and rates the quantum cutting efficiency was furthermore determined to be as high as 173% in NaY(WO4)2: 5 mol% Er3+/50 mol% Yb3+ sample. Strong and nearly pure infrared upconversion emission of Yb3+ under 1550 nm excitation was achieved in Er3+/Yb3+ co-doped NaY(WO4)2 by adjusting Yb3+ doping concentrations. The Yb3+ induced infrared upconversion emission enhancement was attributed to the efficient energy transfer 4I11/2 (Er3+) + 2F7/2 (Yb3+) → 4I15/2 (Er3+) + 2F5/2 (Yb3+) and large nonradiative relaxation rate of 4I9/2. Analysis on the temperature sensing indicated that the NaY(WO4)2:Er3+/Yb3+ serves well the solar cells as thermos-managing material. Moreover, it was confirmed that the fluorescence thermal quenching of 2H11/2/4S3/2 was caused by the nonradiative relaxation of 4S3/2. All the obtained results suggest that NaY(WO4)2:Er3+/Yb3+ is an excellent material for silicon-based solar cells to improve photoelectric conversion efficiency and thermal management.

Underwater images super-resolution (SR) is a challenging task due to underwater images usually contain severely blurred details, color distortion, and low contrast. Although numerous deep learning-based methods have been developed to solve these problems, these methods suffer from huge model parameters and computations. To address this gap, we propose a frequency-domain enhanced attention network (FEAN), supported by a series of frequency-enhanced attention modules (FEAM), for accurate underwater SR. Specifically, we start by utilizing a Gaussian filter to decompose the features into high and low frequencies and pass them to the FEAM. Then, in the high-frequency path, we propose a multi-scale attention enhancement block (MAEB) to extract rich image texture information. While in the low-frequency path, we perform a simple convolutional operation to realize the brightness and contrast adjustment of the image. Further, we devise a channel attention fusion block (CAFB) to integrate the enhanced high and low-frequency features to further strengthen the powerful representational capability of the network. Finally, we employ two convolutions to further modulate the features on the high-frequency path for effective color bias correction and detail enhancement. Experimental results show that our FEAN performs better than other underwater SR methods on the USR-248 dataset, with PSNR values of 29.97 dB, 26.23 dB, and 23.99 dB, corresponding to $\times 2$ , $\times 4$ , and $\times 8$ scale factors.

Abstract Background The rising prevalence of opportunistic infections (OIs) in inflammatory bowel disease (IBD) in conjunction with the use of biologics/immunosuppressive agents has garnered attention. However, there is a dearth of research on OIs in Mainland China. This study seeks to evaluate the national ratio trend of OIs in IBD and elucidate the influence of economic and climate factors on IBD patients with OIs and their outcomes. Methods The nationwide data was obtained from the Inpatient medical record home page via the Health Statistics and Information Reporting System (HSRS). Patients diagnosed with IBD were enlisted for participation, and their demographic and clinical information, encompassing infection type, surgical procedures, and expenses, were gathered. The National Bureau of Statistics provided data on monthly sunshine exposure hours and yearly Gross Domestic Product (GDP). Results Findings indicate that between 2014 and 2019, a total of 381,752 patients with IBD were admitted to hospitals, with 364,249 patients lacking OIs and 17,503 patients presenting with OIs. The annual proportion of OIs exhibited an upward trend, rising from 3.54% in 2014 to 4.81% in 2019. There was a significant correlation observed between individuals who identified as male, those who visited hospitals in southern regions, or those originating from areas with lower GDP or shorter sunshine exposure hours, and a higher incidence of OIs. Among patients diagnosed with either Crohn’s disease (CD) or ulcerative colitis (UC), Clostridium difficile was found to be the most prevalent infection, followed by Epstein-Barr virus and cytomegalovirus. Furthermore, the occurrence of OIs was found to be associated with an increased rate of surgical interventions in UC patients. Conclusions The rising prevalence of OIs among hospitalized patients with IBD necessitates heightened attention towards mitigating associated risk factors, particularly among IBD patients residing in less developed regions or experiencing limited exposure to sunlight. This approach aims to minimize hospital stays and associated costs.

In this work, static immersion and gravimetric methods were used to study the corrosion behavior of three common stainless steels and four Ni-based alloys in a NaCl–MgCl2–KCl mixed molten salt under vacuum atmosphere. The corrosion test was conducted at 700 °C, with a maximum exposure time of 100 h. Corrosion behavior was determined by measuring the mass loss of the sample at different time intervals and the corrosion rates at 100 h. The microstructure of the alloy was analyzed by scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), atomic force microscope (AFM), and X-ray diffraction (XRD). The results showed that stainless steels were generally more severely corroded than Ni-based alloys. 304 stainless steel and In800H exhibited the worst corrosion resistance, whereas Ni-based alloy In625 had the best corrosion resistance. Fe and Cr were dissolved in the molten chloride salts and reacted with the molten chloride salts. Mo played a positive role in suppressing the corrosion of the alloys in molten chloride salts by inhibiting the outward diffusion of the elements.

In the remote sensing field, deep learning-based methods have become mainstream for remote sensing image object detection in recent years. However, traditional methods, such as convolutional neural networks (CNNs), mainly ignore the dependencies between features, failing to capture the spatial relationships and relative positions of objects, which affects the detection performance of dense objects, especially small-size objects. To this end, a high-order feature association network (HOFA-Net) for dense object detection in remote sensing has been proposed to better capture the interdependencies between features of channel and spatial dimensions, yielding more distinguishable features. First, we employ CNNs to learn high-level but low-resolution features of objects. To capture feature interdependencies while retaining crucial information, we design a feature association module based on size adaptation nonlocal. This module partitions the low-resolution and high-level features into local regions and utilizes nonlocal residual connections to capture the local contextual information of objects. In addition, we introduce a high-order feature association (HFA) module designed to learn nonlinear feature correlations and interdependencies within the features. In addition, a covariance normalization acceleration strategy is introduced to accelerate computation. Experimental results on two public remote sensing datasets, including the DOTA dataset and the Tiny Person dataset, demonstrate the superiority and effectiveness of the proposed method through comparative experiments.

Coronavirus disease 2019 (COVID-19), a severely spreading pandemic, has dramatically brought physiological and economical burdens to people. Although the injectable vaccines have some achievements for coronavirus defense, they still generate accompanied pain, untoward reaction and cannot take part in mucosal immunity. Inhalable vaccines, as a safe, facile and efficient strategy, have been presented to protect body from virus by inducing robust mucosal immunity. Here, we give a perspective of an inhalable COVID-19 vaccine composed of lung-derived exosomes (a type of virus-like particle) conjugated with viral receptor-binding domain. The lung-derived exosomes act as carriers, such inhalable particles successfully reach at lung and reveal wider distribution and longer retention on respiratory mucosa. In addition, such vaccines induce the high production of specific antibodies and T cells in lung, significantly protecting host against coronavirus invasion. It is conceived that inhalable virus-like particles with long-term stability wound open a new avenue for vaccines delivery and further achieve vaccine popularization to against with COVID-19 pandemic.

Abstract Quasi-continuous wave (QCW) laser has a very broad application in the industrial field, especially in additive manufacturing, surface treatment, laser cutting, laser cleaning, and laser drilling. Compared with the unidirectional fiber laser, the bidirectional output can be achieved two ports high power output with only one resonator, which can greatly reduce the industrial cost. However, there are few researches on QCW fiber lasers with bidirectional output. Here, we optimized and demonstrated a bidirectional output QCW laser with output power of 2 × 4.5 kW based on a double-clad ytterbium-doped fiber with a core/cladding diameter of 25/400 μm. The peak power at both ends reached 4515 W and 4694 W, respectively. The Raman suppression ratio at both ends of A and B is about 12 dB, and the beam quality factor M 2 is about 1.37 and 1.42, respectively. The corresponding optical-to-optical efficiency is 79%. To the best of our knowledge, this is the highest peak power of QCW laser with near-single-mode beam quality in a bidirectional structure laser.

Abstract Background Rhein can significantly delay the progression of chronic nephropathy. However, its mechanism of action has not been adequately elaborated, which hinders its extensive clinical application. In this work, the effects of rhein on models of TGF-β-induced NRK-49F cellular fibrosis and rat renal ischemia–reperfusion fibrosis were evaluated using metabolomics and western blotting. Methods The metabolic profiles of NRK-49F cells and rat urine, serum, and kidney tissues in the control, model, and rhein groups were investigated using UPLC-QTOF-MS. The levels of p-P65, p-IKK, p-AKT, p-P38, p-JNK and AP-1 in NRK-49F cells were measured using western blotting and immunofluorescence methods. Molecular docking and network pharmacology methods were employed to explore the relationship between the potential targets of rhein and key proteins in the NF-κB and MAPK signaling pathways. Results Various potential metabolites, including sphingolipids, ceramides, phosphatidylcholine, and lysophosphatidylcholine,14-hydroxy-E4-neuroprostane E, and 5-HPETE, were present in the cell, tissue, urine, and serum samples; however, few metabolites matches exactly among the four type of biological samples. These differential metabolites can effectively differentiated between the control, model, and rhein groups. Pathway enrichment analysis of differential metabolites unveiled that sphingolipid metabolism, arachidonic acid metabolism, and glycerophospholipid metabolism were closely related to nephropathy. Phosphorylation levels of AKT, IKK, P65 and AP-1 in NRK-49F cells was reduced by rhein treatment. Network pharmacology and molecular docking showed that the potential targets of rhein might regulated the expression of MAPK and AKT in the NF-κB and MAPK signaling pathways. Conclusion In brief, rhein might delays the progression of chronic nephropathy via the metabolic pathways, NF-κB and MAPKs signaling pathways, which provides the foundation for its development and clinical application.

Abstract Background Recent studies demonstrated that elevated osmolarity could induce adipocyte dedifferentiation, representing an appealing procedure to generate multipotent stem cells. Here we aim to elucidate the molecular mechanisms that underlie osmotic induction of adipocyte reprogramming. Methods To induce dedifferentiation, the 3T3-L1 or SVF adipocytes were cultured under the hypertonic pressure in 2% PEG 300 medium. Adipocyte dedifferentiation was monitored by aspect ratio measurement, Oil Red staining and qPCR to examine the morphology, lipid droplets, and specific genes of adipocytes, respectively. The osteogenic and chondrogenic re-differentiation capacities of dedifferentiated adipocytes were also examined. To investigate the mechanisms of the osmotic stress-induced dedifferentiation, extracellular vesicles (EVs) were collected from the reprograming cells, followed by proteomic and functional analyses. In addition, qPCR, ELISA, and TNF-α neutralizing antibody (20 ng/ml) was applied to examine the activation and effects of the TNF-α signaling. Furthermore, we also analyzed the Wnt signaling by assessing the activation of β-catenin and applying BML-284, an agonist of β-catenin. Results Hypertonic treatment induced dedifferentiation of both 3T3-L1 and the primary stromal vascular fraction (SVF) adipocytes, characterized by morphological and functional changes. Proteomic profiling revealed that hypertonicity induced extracellular vesicles (EVs) containing mitochondrial molecules including NDUFA9 and VDAC. Functionally, the mitochondrial EVs (MEVs) stimulated TNF-α signaling that activates Wnt-β-catenin signaling and adipocyte dedifferentiation. Neutralizing TNF-α inhibited hypertonic dedifferentiation of adipocytes. In addition, direct activation of Wnt-β-catenin signaling using BML-284 could efficiently induce adipocyte dedifferentiation while circumventing the apoptotic effect of the hypertonic treatment. Conclusions Hypertonicity prompts the adipocytes to release MEVs, which in turn enhances the secretion of TNF-α as a pro-inflammatory cytokine during the stress response. Importantly, TNF-α is essential for the activation of the Wnt/β-catenin signaling that drives adipocyte dedifferentiation. A caveat of the hypertonic treatment is apoptosis, which could be circumvented by direct activation of the Wnt/β-catenin signaling using BML-284.

Abstract Background More than half of patients with tuberous sclerosis complex (TSC) suffer from drug-resistant epilepsy (DRE), and resection surgery is the most effective way to control intractable epilepsy. Precise preoperative localization of epileptogenic tubers among all cortical tubers determines the surgical outcomes and patient prognosis. Models for preoperatively predicting epileptogenic tubers using 18F-FDG PET images are still lacking, however. We developed noninvasive predictive models for clinicians to predict the epileptogenic tubers and the outcome (seizure freedom or no seizure freedom) of cortical tubers based on 18F-FDG PET images. Methods Forty-three consecutive TSC patients with DRE were enrolled, and 235 cortical tubers were selected as the training set. Quantitative indices of cortical tubers on 18F-FDG PET were extracted, and logistic regression analysis was performed to select those with the most important predictive capacity. Machine learning models, including logistic regression (LR), linear discriminant analysis (LDA), and artificial neural network (ANN) models, were established based on the selected predictive indices to identify epileptogenic tubers from multiple cortical tubers. A discriminating nomogram was constructed and found to be clinically practical according to decision curve analysis (DCA) and clinical impact curve (CIC). Furthermore, testing sets were created based on new PET images of 32 tubers from 7 patients, and follow-up outcome data from the cortical tubers were collected 1, 3, and 5 years after the operation to verify the reliability of the predictive model. The predictive performance was determined by using receiver operating characteristic (ROC) analysis. Results PET quantitative indices including SUVmean, SUVmax, volume, total lesion glycolysis (TLG), third quartile, upper adjacent and standard added metabolism activity (SAM) were associated with the epileptogenic tubers. The SUVmean, SUVmax, volume and TLG values were different between epileptogenic and non-epileptogenic tubers and were associated with the clinical characteristics of epileptogenic tubers. The LR model achieved the better performance in predicting epileptogenic tubers (AUC = 0.7706; 95% CI 0.70–0.83) than the LDA (AUC = 0.7506; 95% CI 0.68–0.82) and ANN models (AUC = 0.7425; 95% CI 0.67–0.82) and also demonstrated good calibration (Hosmer‒Lemeshow goodness-of-fit p value = 0.7). In addition, DCA and CIC confirmed the clinical utility of the nomogram constructed to predict epileptogenic tubers based on quantitative indices. Intriguingly, the LR model exhibited good performance in predicting epileptogenic tubers in the testing set (AUC = 0.8502; 95% CI 0.71–0.99) and the long-term outcomes of cortical tubers (1-year outcomes: AUC = 0.7805, 95% CI 0.71–0.85; 3-year outcomes: AUC = 0.8066, 95% CI 0.74–0.87; 5-year outcomes: AUC = 0.8172, 95% CI 0.75–0.87). Conclusions The 18F-FDG PET image-based LR model can be used to noninvasively identify epileptogenic tubers and predict the long-term outcomes of cortical tubers in TSC patients.

Abstract Background Lupus mesenteric vasculitis (LMV) as initial presentation is rare, especially in childhood-onset systemic lupus erythematosus (cSLE). It is a critical complication of lupus. At present, the research on cSLE with LMV as the initial presentation is few. The aim of this study was to analyze the clinical characteristics and prognosis of cSLE with LMV in the Chinese population, compared with non-LMV cSLE. Methods A retrospective case-controlled study was conducted on 55 cSLE patients between July 2018 and July 2021. The clinical data, laboratory findings, imaging, treatment, and follow-up data were collected and compared between the two groups of cSLE with LMV and non-LMV. Non-LMV cSLE patients were matched according to the age and sex of LMV patients. Results A total of 11 cSLE patients with LMV as the LMV group and 44 cSLE patients without LMV as the non-LMV group were included. The average age of onset was 12.55 ± 1.57 years old, the male-to-female ratio was 2:9, and high disease activity was observed in the LMV group. Abdominal pain was most common in LMV. Compared with the non-LMV, the percentage of abdominal pain, vomiting, abdominal distension, and diarrhea was higher, and gastrointestinal tract, serous cavity, kidney, and lung damage were higher in the LMV group (P

Abstract Unraveling the intricate relationship between mechanical factors and brain activity is a pivotal endeavor, yet the underlying mechanistic model of signaling pathways in brain mechanotransduction remains enigmatic. To bridge this gap, we introduced an in situ multi-scale platform, through which we delineate comprehensive brain biomechanical traits in white matter (WM), grey-white matter junctions (GW junction), and the pons across human brain tissue from four distinct donors. We investigate the three-dimensional expression patterns of Piezo1, Piezo2, and TMEM150C, while also examining their associated histological features and mechanotransduction signaling networks, particularly focusing on the YAP/β-catenin axis. Our results showed that the biomechanical characteristics (including stiffness, spring term, and equilibrium stress) associated with Piezo1 vary depending on the specific region. Moving beyond Piezo1, our result demonstrated the significant positive correlations between Piezo2 expression and stiffness in the WM. Meanwhile, the expression of Piezo2 and TMEM150C was shown to be correlated to viscoelastic properties in the pons and WM. Given the heterogeneity of brain tissue, we investigated the three-dimensional expression of Piezo1, Piezo2, and TMEM150C. Our results suggested that three mechanosensitive proteins remained consistent across different vertical planes within the tissue sections. Our findings not only establish Piezo1, Piezo2, and TMEM150C as pivotal mechanosensors that regulate the region-specific mechanotransduction activities but also unveil the paradigm connecting brain mechanical properties and mechanotransduction activities and the variations between individuals.

Abstract Background Significant lower genital tract (LGT) dysbiosis and an associated lower rate of clinical pregnancy after in vitro fertilization–frozen embryo transfer (IVF-FET) among polycystic ovary syndrome (PCOS) patients have been previously reported by our group. We aimed to assess whether transvaginal Lactobacillus supplementation can reverse LGT dysbiosis and further improve perinatal outcomes in PCOS patients after IVF-FET. Methods/design This is a protocol for a multicenter, open-label, randomized controlled trial in China. Women diagnosed with PCOS who are undergoing IVF-FET treatment will be recruited. Allocation to the intervention/control arms at a ratio of 1:1 will be executed by an electronic randomization system. Participants in the intervention arm will receive the live Lactobacillus capsule vaginally for 10 consecutive days before embryo transfer, while those in the control arm will receive standard individualized care. The primary outcomes will be the clinical pregnancy rate, implantation rate, and live birth rate. 16S rRNA sequencing and liquid chromatography–mass spectrometry will be conducted to evaluate the LGT microbiome and systemic metabonomics before and after the intervention. A sample of 260 participants will provide 95% power to detect a 20% increase in the rate of clinical pregnancy (α = 0.025, one-tailed test, 15% dropout rate). A total of 300 participants will be recruited. Discussion This is the first large and multicenter randomized controlled trial aimed at assessing the efficacy of transvaginal Lactobacillus supplementation on restoring the LGT microbiome and improving perinatal outcomes in PCOS patients after IVF-FET. This pragmatic trial is promising for increasing the rates of clinical pregnancy and live birth in PCOS patients after IVF-FET. Ethics and dissemination Ethical review approval was obtained from the Medical Research Ethics Committees of the International Peace Maternity and Child Health Hospital of Shanghai Jiao Tong University (15 October 2020, GKLW 2020-29). To maximize dissemination, these findings will be reported in open access publications in journals with high impact, and oral and poster conference presentations will be performed. Trial registration ChiCTR ChiCTR2000036460. Registered on 13 September 2020, https://www.chictr.org.cn/showproj.html?proj=59549 .

Identifying the characteristics of coal fine development and production can guide the exploration and development of coalbed methane (CBM). In this paper, drilling coring, logging information, drainage and production data, and coal fine samples from CBM wells were collected in Shizhuang area, Qinshui Basin, China. Based on logging interpretation, laser particle size analysis and mass fraction testing, the development characteristics of coal fine and its impact on production were systematically analyzed. The results show that the primary coal fine in the study area can be divided into five areas: complex coal fine development, coal fine at the bottom of the coal seam, no coal fine, less coal fine, and coal fine at the top and bottom of the coal seam. The output coal fine particle size distribution ranges from 0.4 μm to 3 300 μm, and the concentrated coal fine mass fraction ranges from 0 to 0.5. The development characteristics of coal fine affect the initial pulverized production time of CBM wells. The complex area generally produces coal fine for the first time before the occurrence of gas. The undeveloped areas and less developed areas generally produce coal fine for the first time after the occurrence of gas. Affected by the development of coal fine near the wellbore, the coal fine produced in the drainage and depressurization stage is mainly composed of medium and coarse particles, and the coal fine mass fraction is not high. Affected by the drainage intensity and the development characteristics of coal fine, the coal fine produced in the production and deflation stage is dominated by medium and fine particles, and the coal fine mass fraction is high and fluctuates greatly. In the stable gas production stage, CBM wells mainly produce primary coal fine and secondary coal fine produced by fracturing engineering in distal fractures. The coal fine particles and the mass fraction fluctuation are small. The output of coal fine in the gas production decay stage is small.

Abstract Various external factors that interfere with traffic flow, such as weather conditions, traffic accidents, incidents, and Points of Interest (POIs), need to be considered in performing traffic forecasting tasks. However, the current research methods encounter difficulties in effectively incorporating these factors with traffic characteristics and efficiently updating them, which leads to a lack of dynamics and interpretability. Moreover, capturing temporal dependence and spatial dependence separately and sequentially can result in issues, such as information loss and model errors. To address these challenges, we present a Knowledge Representation learning-actuated spatial–temporal graph neural network (KR-STGNN) for traffic flow prediction. We combine the knowledge embedding with the traffic features via Gated Feature Fusion Module (GFFM), and dynamically update the traffic features adaptively according to the importance of external factors. To conduct the co-capture of spatial–temporal dependencies, we subsequently propose a spatial–temporal feature synchronous capture module (ST-FSCM) combining dilation causal convolution with GRU. Experimental results on a real-world traffic data set demonstrate that KR-STGNN has superior forecasting performances over diverse prediction horizons, especially for short-term prediction. The ablation and perturbation analysis experiments further validate the effectiveness and robustness of the designed method.

The aim of the study was to evaluate the potential diagnostic and prognostic value of gene, Poly A-Binding Protein Interacting Protein 2B (PAIP2B) in pancreatic cancer. We used the gene expression data and clinical information of pancreatic adenocarcinoma patients from The Cancer Genome Atlas database and Gene Expression Omnibus database to analyze the expression of PAIP2B in pancreatic cancer samples, and validated the expression of PAIP2B in tumor tissue, using bioinformatics technology to explore the prognostic value of PAIP2B and its possible biological function. A significantly lower level of PAIP2B was observed in pancreatic cancer patients than in controls, and validated by immunohistochemistry. PAIP2B reduced the proliferation and invasion of cancer cells and had a significantly high expression in early stage. Patients with lower levels of PAIP2B had a significantly shorter median survival time than those with higher levels. DNA demethylation played an important role in PAIP2B expression. In addition, PAIP2B expression was significantly associated with the tumor-infiltrating immune cells, especially T cells CD8, T cells CD4 memory resting, macrophages M0, and dendritic cells resting. Our study also found that PAIP2B regulated miRNA function leading to disease progression in pancreatic cancer patients. Our study explored the potential value of PAIP2B as a biological link between prognosis and pancreatic cancer, and provided reference for the follow-up study on the role of PAIP2B in pancreatic cancer.

Abstract The collaborations between industry, university, and research institutes have become more relevant with the trend of knowledge commercialization, while whether there exists a “superstar” in R&D alliance networks, who played a key role in the diffusion and transfer of technology and knowledge, remains unexplored. Based on R&D activities information of joint patents in China, this study applied two-mode network analysis to understand the R&D alliance network of the industry-university-research institute (IUR) collaboration. Three types of networks, collaboration networks, knowledge networks, and inter-organizational technology networks among IUR are developed, and their evolution process is analyzed at different levels, including overall structure, individual characteristics, and temporal evolution among IUR. The results show that no permanent superstar is being the dominant position. Distinct modes have been emerging in different periods: in the formation period, the mode is U-R, I-U, U, R, I; in the growth period, the mode is I-R, I-U, I-U-R; in the mature period, the mode is I-U-R. In addition, different technology classes were aggregated in different periods. This paper attempts to provide countermeasures and recommendations for enterprises, universities, and research institutions to enable the success of their collaborations.

Abstract Endometriosis, a prevalent condition, has long been recognized as a chronic and debilitating ailment affecting an estimated 1790 million women worldwide. Observational studies have established a correlation between endometriosis and ovarian cancer. Thus, we endeavored to employ Two-Sample Mendelian Randomization, utilizing summary statistics from a Genome-Wide Association Study of endometriosis and epithelial ovarian cancer, with genetic markers serving as proxies for epithelial ovarian cancer. The analysis revealed a significant correlation between these entities, with an odds ratio (OR) of 1.23 (95% CI 1.11–1.36). Upon histotype-specific examination, robust evidence emerged for an association of endometriosis with the risk of endometrioid carcinoma (OR 1.49, 95% CI 1.24–1.81), clear cell carcinoma (OR 2.56, 95% CI 1.75–3.73), and low malignant potential tumors (OR 1.28, 95% CI 1.08–1.53). These findings provide a theoretical framework for prospective investigations aimed at enhancing the potential therapeutic efficacy of managing endometriosis in averting the onset and progression of ovarian cancer.

Abstract Background The association between chemotherapy-induced leukopenia (CIL) and survival for patients with early breast cancer (EBC) is not known. We investigated the relationship between different grades of CIL and survival in patients with EBC receiving adjuvant chemotherapy. Methods A total of 442 patients with EBC receiving a regimen containing an anthracycline (A) and taxane (T) were included into our analysis. Survival analyses were undertaken using Kaplan–Meier curves. The P-value was calculated using the log rank test. Subgroup analysis was conducted to investigate the correlation of CIL grade and survival based on the clinicopathological characteristics of patients. Afterwards, univariate and multivariate analyses screened out independent prognostic factors to construct a prognostic model, the robustness of which was verified. Results Patients with EBC who experienced grade 2–4 (“moderate” and “severe”) CIL were associated with longer overall survival (OS) than those with grade 0–1 (mild) CIL (P = 0.021). Compared with patients with mild CIL, OS was longer in patients with severe CIL (P = 0.029). Patients who suffered from moderate CIL tended to have longer OS than those with mild CIL (P = 0.082). Nevertheless, there was no distinguishable difference in OS between moderate- or severe-CIL groups. Subgroup analysis revealed that patients with moderate CIL had longer OS than those with mild CIL among patients who were premenstrual, or with human epidermal growth factor receptor 2-positive (HER2+), > 3 lymph nodes with metastases, a tumor diameter > 5 cm. A prognostic model based on menstrual status, N stage, and CIL grade showed satisfactory robustness. Conclusion The grade of CIL was strongly associated with the prognosis among patients with EBC who received a regimen containing both anthracyclines and taxanes. Patients with a “moderate” CIL grade tended to have better survival outcomes.

Abstract The monitoring of physiological parameters is a crucial topic in promoting human health and an indispensable approach for assessing physiological status and diagnosing diseases. Particularly, it holds significant value for patients who require long-term monitoring or with underlying cardiovascular disease. To this end, Visual Contactless Physiological Monitoring (VCPM) is capable of using videos recorded by a consumer camera to monitor blood volume pulse (BVP) signal, heart rate (HR), respiratory rate (RR), oxygen saturation (SpO2) and blood pressure (BP). Recently, deep learning-based pipelines have attracted numerous scholars and achieved unprecedented development. Although VCPM is still an emerging digital medical technology and presents many challenges and opportunities, it has the potential to revolutionize clinical medicine, digital health, telemedicine as well as other areas. The VCPM technology presents a viable solution that can be integrated into these systems for measuring vital parameters during video consultation, owing to its merits of contactless measurement, cost-effectiveness, user-friendly passive monitoring and the sole requirement of an off-the-shelf camera. In fact, the studies of VCPM technologies have been rocketing recently, particularly AI-based approaches, but few are employed in clinical settings. Here we provide a comprehensive overview of the applications, challenges, and prospects of VCPM from the perspective of clinical settings and AI technologies for the first time. The thorough exploration and analysis of clinical scenarios will provide profound guidance for the research and development of VCPM technologies in clinical settings.

Abstract Free heme is released from hemoproteins during hemolysis or ischemia reperfusion injury and can be pro‐inflammatory. Most studies on nephrotoxicity of hemolysis‐derived proteins focus on free hemoglobin (fHb) with heme as a prosthetic group. Measurement of heme in its free, non‐protein bound, form is challenging and not commonly used in clinical routine diagnostics. In contrast to fHb, the role of free heme in acute kidney injury (AKI) after cardiopulmonary bypass (CPB) surgery is unknown. Using an apo‐horseradish peroxidase‐based assay, we identified free heme during CPB surgery as predictor of AKI in patients undergoing cardiac valve replacement (n = 37). Free heme levels during CPB surgery correlated with depletion of hemopexin (Hx), a heme scavenger‐protein. In mice, the impact of high levels of circulating free heme on the development of AKI following transient renal ischemia and the therapeutic potential of Hx were investigated. C57BL/6 mice were subjected to bilateral renal ischemia/reperfusion injury for 15 min which did not cause AKI. However, additional administration of free heme in this model promoted overt AKI with reduced renal function, increased renal inflammation, and reduced renal perfusion on functional magnetic resonance imaging. Hx treatment attenuated AKI. Free heme administration to sham operated control mice did not cause AKI. In conclusion, free heme is a predictor of AKI in CPB surgery patients and promotes AKI in transient renal ischemia. Depletion of Hx in CPB surgery patients and attenuation of AKI by Hx in the in vivo model encourage further research on Hx therapy in patients with increased free heme levels during CPB surgery.

To evaluate the perioperative and functional outcomes of holmium laser enucleation of the prostate (HoLEP) among patients with and without prior transurethral prostate surgery. we performed a systematic search of the Cochrane Library, PubMed, Embase, Web of Science and Scopus databases for articles evaluating the effectiveness of salvage HoLEP (S-HoLEP) versus primary HoLEP (P-HoLEP) until January 2023. Nine studies involving 6044 patients were included for both quantitative and qualitative analysis. Compared with P-HoLEP, S-HoLEP used more energy (weighted mean difference = 14.27 KJ; 95% CI = 4.75–23.79; P = 0.003) and had an increased incidence of postoperative clot retention (odds ratio = 2.12; 95% CI = 1.25–3.59; P = 0.005) and urethral stricture (OR = 1.99; 95% CI = 1.04–3.8; P = 0.04). However, the International Prostate Symptom Score at the sixth month of follow-up was significantly lower for S-HoLEP than for P-HoLEP (WMD = −0.80; 95% CI = −1.38 to −0.22; P = 0.007). There was no significant difference between S-HoLEP and P-HoLEP in terms of operative time, enucleation time, enucleation efficiency, morcellation time, resected weight, catheterisation time, hospital stay duration, quality of life, maximum urinary flow rate, postvoid residual and intraoperative and postoperative overall complications. compared with P-HoLEP, S-HoLEP is still a feasible and effective method for treating residual benign prostatic hyperplasia, with only a slight increase in the probability of energy utilisation, clot retention and urethral stricture. Despite these minor discrepancies, the overall beneficial effects of the two modalities on symptom resolution is noteworthy.

Abstract Background Neoporphyra haitanensis, a major marine crop native to southern China, grows in the harsh intertidal habitats of rocky coasts. The thallus can tolerate fluctuating and extreme environmental stresses, for example, repeated desiccation/rehydration due to the turning tides. It is also a typical model system for investigating stress tolerance mechanisms in intertidal seaweed. The basic leucine zipper (bZIP) transcription factors play important roles in the regulation of plants’ responses to environmental stress stimuli. However, little information is available regarding the bZIP family in the marine crop Nh. haitanensis. Results We identified 19 bZIP genes in the Nh. haitanensis genome and described their conserved domains. Based on phylogenetic analysis, these 19 NhhbZIP genes, distributed unevenly on the 11 superscaffolds, were divided into four groups. In each group, there were analogous exon/intron numbers and motif compositions, along with diverse exon lengths. Cross-species collinearity analysis indicated that 17 and 9 NhhbZIP genes were orthologous to bZIP genes in Neopyropia yezoensis and Porphyra umbilicalis, respectively. Evidence from RNA sequencing (RNA-seq) data showed that the majority of NhhbZIP genes (73.68%) exhibited transcript abundance in all treatments. Furthermore, genes NN 2, 4 and 5 showed significantly altered expression in response to moderate dehydration, severe dehydration, and rehydration, respectively. Gene co-expression network analysis of the representative genes was carried out, followed by gene set enrichment analysis. Two NhhbZIP genes collectively responding to dehydration and rehydration and their co-expressing genes mainly participated in DNA repair, DNA metabolic process, and regulation of helicase activity. Two specific NhhbZIP genes responding to severe dehydration and their corresponding network genes were mainly involved in macromolecule modification, cellular catabolic process, and transmembrane transport. Three specific NhhbZIP genes responding to rehydration and their co-expression gene networks were mainly involved in the regulation of the cell cycle process and defense response. Conclusions This study provides new insights into the structural composition, evolution, and function of the NhhbZIP gene family. Our results will help us to further study the functions of bZIP genes in response to dehydration and rehydration in Nh. haitanensis and improve Nh. haitanensis in southern China.

Abstract Background The lack of access to physical therapists in developing countries and rural areas poses a significant challenge in supervising postsurgical rehabilitation, potentially impeding desirable outcomes following surgical interventions. For this reason, this study aims to evaluate the feasibility, safety, and effectiveness of utilizing a digital rehabilitation program based on computer vision and augmented reality in comparison with traditional care for patients who will undergo isolated meniscus repair, since to date, there is no literature on this topic. Methods This study intends to enroll two groups of participants, each to be provided with informed consent before undergoing randomization into either the experimental or control group. The experimental group will undergo a digital rehabilitation program utilizing computer vision and augmented reality (AR) technology following their surgical procedure, while the control group will receive conventional care, involving in-clinic physical therapy sessions weekly. Both groups will adhere to a standardized rehabilitation protocol over a six-month duration. Follow-up assessments will be conducted at various intervals, including preoperatively, and at 2 weeks, 6 weeks, 12 weeks, and 24 weeks postoperatively. Imaging assessments and return-to-play evaluations will be conducted during the final follow-up. Clinical functionality will be assessed based on improvements in International Knee Documentation Committee (IKDC) and Visual Analog Scale (VAS) scores. Registration number ChiCTR2300070582.

In order to clarify the characteristic compounds and establish the authenticity evaluation method of heptapleurum honey, high-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry (HPLC-Q/TOF-MS/MS) was used to qualitative and quantitative analysis of characteristic compounds in heptapleurum honey. Five compounds were identified including 4-(1'-cyclodiethyl ether-3'-butanediol)-3,5,5-trimethyl-2-cyclohexenone (Unedone B), 3,4,5-trimethoxy cinnamyl alcohol, 4-(1'2'-dihydroxy-3'epoxypropane) -3,5,5-2-cyclohexenone (Unedone C), trans, trans abscisic acid, and cis, trans abscisic acid. Notably, 3,4,5-trimethoxy cinnamyl alcohol was first found in honey, and it could be a marker of heptapleurum honey. Moreover, 10 raw heptapleurum honey samples with different geographic origins were collected to establish HPLC fingerprint. The authenticity of six commercial heptapleurum honey samples were evaluated by combining characteristic compound with HPLC fingerprint. The results demonstrated that three brands of sample were genuine pure heptapleurum honey, two brands of sample might be mixed with other honeys. A brand sample did not contain characteristic compound and were significantly different with the standard fingerprints of heptapleurum honey. It was inferred that the sample was not heptapleurum honey. This study provides theoretical reference for the authenticity evaluation of heptapleurum honey.

An intelligent single radar image de-raining method based on unsupervised self-attention generative adversarial networks is proposed to improve the accuracy of wave height parameter inversion results. The method builds a trainable end-to-end de-raining model with an unsupervised cycle-consistent adversarial network as an AI framework, which does not require pairs of rain-contaminated and corresponding ground-truth rain-free images for training. The model is trained by feeding rain-contaminated and clean radar images in an unpaired manner, and the atmospheric scattering model parameters are not required as a prior condition. Additionally, a self-attention mechanism is introduced into the model, allowing it to focus on rain clutter when processing radar images. This combines global and local rain clutter context information to output more accurate and clear de-raining radar images. The proposed method is validated by applying it to actual field test data, which shows that compared with the wave height derived from the original rain-contaminated data, the root-mean-square error is reduced by 0.11 m and the correlation coefficient of the wave height is increased by 14% using the de-raining method. These results demonstrate that the method effectively reduces the impact of rain on the accuracy of wave height parameter estimation from marine X-band radar images.

Pesticides are agricultural inputs that can significantly reduce yield losses, regulate plant growth, effectively liberate agricultural productivity, and improve food security. The availability of pesticides in economies worldwide is ensured by redistribution through international trade, with different economies playing different roles in this process. In this study, we measured and ranked the importance of economies using nine node metrics. We found that the clustering coefficient was negatively correlated with the other eight node metrics, whereas the other eight node metrics were positively correlated with each other and could be grouped into three communities (betweenness; in-degree, PageRank, authority, and in-closeness; out-degree, hub, and out-closeness). We further investigated the structural robustness of international pesticide trade networks proxied by large component size under three types of shocks to economies (node removal in descending, random, and ascending orders). The results showed that, except for the clustering coefficient, international pesticide trade networks are relatively robust under shocks to economies in ascending order but fragile under shocks to economies in descending order. By contrast, removing nodes with a clustering coefficient in ascending and descending order yielded similar robustness curves. Moreover, the structural robustness related to large component size evolved over time and exhibited an inverse U-shaped pattern.

AbstractContext Atopic dermatitis (AD) is a common inflammatory skin disease characterized with hyperactivation of type 2 T helper (Th2) immune responses. Icariin is a flavonoid glucoside with anti-inflammatory activities, which has been used to treat multiple diseases.Objective The present study investigates the underlying mechanisms by which icariin regulates Th2 responses and AD development.Materials and methods BALB/c mice were induced by DNFB to establish AD models, and injected with or without 10 mg/kg icariin for 2 weeks (i.p., daily). CD4+T cells were induced by Th2 condition to simulate AD in vitro, and also treated with or without 100 µM icariin.Results Icariin ameliorated AD-like skin lesion, manifested as a significant decrease in dermatitis scores (from 8.00 ± 1.00 to 3.67 ± 0.58), serum IgE levels (from 3119.15 ± 241.81 to 948.55 ± 182.51 ng/mL), epidermal thickness (from 93.86 ± 4.61 to 42.67 ± 2.48 µm) and infiltration of mast cells (from 60.67 ± 3.21 cells to 36.00 ± 2.65 cells). Also, icariin inactivated NLRP3 inflammasome, inhibited Th2 skewing, reduced lncRNA MALAT1 expression, but elevated miR-124-3p expression in vivo and in vitro. MALAT1 increased NLRP3 expression through targeting miR-124-3p. Knockdown of MALAT1 repressed NLRP3 inflammasome activation and mitigated Th1/Th2 imbalance in Th2-conditioned CD4+T cells, whereas both MALAT1 overexpression and miR-124-3p inhibition ablated the inhibitory effects of icariin on Th2 immune responses.Discussion and conclusions The findings further improve our understanding of the mechanism by which icariin affects AD progression, and highlights the potential of icariin in the treatment of AD.

AbstractSorafenib (SRF) presents undesirable effects in clinical treatment, due to the lack of targeting, poor water solubility, and obvious side effects. In this study, we constructed a novel nanodrug carrier system for accurate and efficient delivery of SRF, improving its therapeutic effects and achieving tumor-specific imaging. The hollow mesoporous MnO2 (H-MnO2) nanoparticles equipped with target substance aptamers (APT) on the surface were used to load SRF for the first time. The resulting H-MnO2-SRF-APT could specifically bound to glypican-3 (GPC3) receptors on the surface of hepatocellular carcinoma (HCC), rapidly undergoing subsequent degradation under decreased pH conditions in the tumor microenvironment (TME) and releasing the loaded SRF. In this process, Mn2+ ions were used for T1-weighted magnetic resonance imaging simultaneously. The in vitro cell experiments indicated that H-MnO2-SRF-APT showed much more effects on the inhibition in the proliferation of Huh7 and HepG2 HCC cells than that of the non-targeted H-MnO2-SRF and free SRF. Besides, the in vivo results further confirmed that H-MnO2-SRF-APT could effectively inhibit the growth of xenograft tumors Huh7 in the naked mouse with good biosafety. In conclusion, H-MnO2-SRF-APT could significantly enhance the therapeutic effect of SRF and is expected to be a new way of diagnosis and treatment of HCC.

Abstract Ischaemia of the heart and limbs attributable to compromised blood supply is a major cause of mortality and morbidity. The mechanisms of functional angiogenesis remain poorly understood, however. Here we show that FNIP1 plays a critical role in controlling skeletal muscle functional angiogenesis, a process pivotal for muscle revascularization during ischemia. Muscle FNIP1 expression is down-regulated by exercise. Genetic overexpression of FNIP1 in myofiber causes limited angiogenesis in mice, whereas its myofiber-specific ablation markedly promotes the formation of functional blood vessels. Interestingly, the increased muscle angiogenesis is independent of AMPK but due to enhanced macrophage recruitment in FNIP1-depleted muscles. Mechanistically, myofiber FNIP1 deficiency induces PGC-1α to activate chemokine gene transcription, thereby driving macrophage recruitment and muscle angiogenesis program. Furthermore, in a mouse hindlimb ischemia model of peripheral artery disease, the loss of myofiber FNIP1 significantly improved the recovery of blood flow. Thus, these results reveal a pivotal role of FNIP1 as a negative regulator of functional angiogenesis in muscle, offering insight into potential therapeutic strategies for ischemic diseases.

Abstract The blood proteome holds great promise for precision medicine but poses substantial challenges due to the low abundance of most plasma proteins and the vast dynamic range of the plasma proteome. Here we address these challenges with NUcleic acid Linked Immuno-Sandwich Assay (NULISA™), which improves the sensitivity of traditional proximity ligation assays by ~10,000-fold to attomolar level, by suppressing assay background via a dual capture and release mechanism built into oligonucleotide-conjugated antibodies. Highly multiplexed quantification of both low- and high-abundance proteins spanning a wide dynamic range is achieved by attenuating signals from abundant targets with unconjugated antibodies and next-generation sequencing of barcoded reporter DNA. A 200-plex NULISA containing 124 cytokines and chemokines and other proteins demonstrates superior sensitivity to a proximity extension assay in detecting biologically important low-abundance biomarkers in patients with autoimmune diseases and COVID-19. Fully automated NULISA makes broad and in-depth proteomic analysis easily accessible for research and diagnostic applications.

Abstract The current study evaluated the effect of SGLT-2 inhibitor, dapagliflozin, on left ventricular remodeling in patients with type 2 diabetes and HFrEF. 60 patients were randomized (1:1) to receive dapagliflozin 10 mg once daily, or placebo double blind for 1 year. Patients underwent transthoracic echocardiography and doppler evaluation prior to dapagliflozin initiation and at 1 year. At 1year, adjusted mean difference versus placebo in change from baseline in LVEF was 2.5% (95% CI: 1.00–4.06, P = 0.002). Adjusted mean difference versus placebo in change from baseline in LVED volume was − 6.0ml (95% CI: -8.07 -−3.87, P

Abstract Extracellular vesicles (EVs) are nanoscale vesicles derived from cells that mediate intercellular communication by transporting bioactive molecules. They play significant roles in various physiological and pathological conditions. EVs hold great potential as novel biomarkers of diseases, therapeutic agents, and drug delivery vehicles. Furthermore, EVs as novel drug delivery vehicles have demonstrated significant advantages in preclinical settings. In this review, we discussed the biogenesis and characteristics of EVs and their functions in cancer. We summarize the therapeutic applications of EVs as a natural delivery vehicles in cancer therapy. We highlight the existing challenges, illuminate vital questions, and propose recommendations to effectively address them effectively.

Abstract Background and aims Manganese (Mn) deficiency and intoxication may affect nonalcoholic fatty liver disease (NAFLD) risk differently. We aimed to explore the association between blood Mn and NAFLD in an area with high Mn exposure in drinking water. Methods We conducted a case–control study among 1407 patients with NAFLD and 1774 sex- and age-matched healthy controls in a physical examination population in Zhoushan hospital, Zhejiang province in China. We used the restricted cubic splines method to investigate the dose–response relationship. Logistic regression models were applied to determine the risk of NAFLD, and severity of NAFLD. Results The blood Mn concentration was higher in the NAFLD group than in the control group in women (16.1 ± 6.2 μg/L vs. 14.7 ± 6.4 μg/L, P = 0.022) and men (14.5 ± 6.3 μg/L vs. 13.6 ± 6.8 μg/L, P

Abstract Background The purpose of this study was to evaluate the vaginal microecology and the distribution of human papillomavirus (HPV) subtypes in patients with uterine adhesions and explore the correlation between HPV infection and vaginal microecology imbalance and the occurrence of intrauterine adhesion (IUA). Methods A total of 479 women were enrolled in the study, including 259 in the normal group and 220 in the IUA group. Vaginal microecological and HPV analyses were performed on all participants. Significant differences between the two groups were analyzed, and Spearman correlation analysis was performed. Results The incidence of IUA in patients between 31 and 40 years of age was high. The I-II degree of vaginal cleanliness in the IUA group was significantly lower than that in the normal group, and the number of III-IV degree was significantly higher than that in the normal group. Moreover, the incidences of VVC (vulvovaginal candidiasis) and vaginal disorders and infections with HPV 16 and HPV 52 subtypes were significantly higher in the IUA group than in the normal group. The incidence of high-risk HPV infection combined with vaginal disorders in the IUA group was higher than that in the normal group. Correlation analysis showed that the occurrence of IUAs was positively correlated with HPV infection and negatively correlated with PH and vaginal microecological imbalance. Conclusion The HPV infection rate and vaginal microecology disorders affect the occurrence of IUAs. For patients with IUAs, control of the HPV infection rate and the prevention of vaginal microecological disorders should be improved.

Abstract Background Prior epidemiological observational studies have duly documented a correlative link between inflammatory bowel disease (IBD) and bladder cancer (BC); however, the establishment of a definitive causal relationship has remained elusive. The principal objective of this meticulous investigation was to rigorously evaluate the causal nexus between IBD and BC, employing the robust methodology of Mendelian randomization (MR) analysis. Methods We meticulously performed both univariate and multivariate Mendelian randomization (MVMR) analyses employing publicly accessible genome-wide association study (GWAS) data. The central approach employed for our investigations was inverse variance weighting (IVW) method, while diligently scrutinizing potential sources of heterogeneity and horizontal pleiotropy via the rigorous utilization of Cochran’s Q test, the MR-PRESSO method, and MR-Egger. Results In the univariate MR analysis, no causal link was observed between genetic prediction of IBD and BC. Furthermore, both Crohn’s disease (CD) and ulcerative colitis (UC) showed no causal association with BC. The consistent association between CD and UC in the MVMR analysis supports this finding. Conclusion This study found no genetic basis for the causative association of IBD and BC. It is crucial to emphasize that further comprehensive investigations are warranted to delve into the intricate underlying mechanisms that may contribute to these associations.

For the problem of stick-slip vibration caused by hard rock formation in the process of drill bit penetrating in coal mine, and the discrete element method (DEM) was employed to study the rock cutting performance and stick-slip vibration behavior of PDC bit drilling in five typical different hardness rock strata. The result shows that the stick-slip phenomenon of the bit is more obvious with the increasing of the formation hardness, and in the ultra-hard rock layer, it slips on the rock surface and cannot be effectively drilled. The approach of increasing the rotational speed of the bit can weaken the stick-slip behavior to an extent, but it has no obvious effect on improving the drilling efficiency. The drilling performance of the bit can be improved by increasing drilling pressure, but it will also lead to more serious stick-slip vibration. The torsional impact method can effectively weaken or even inhibit the stick-slip vibration of the bit and improve the drilling performance. However, excessive torsional impact force will lead to an increase in the impact load on the bit.

Permian Wujiaping Formation in Hongxing area of eastern Sichuan is rich in high-quality shale, and multiple wells have achieved high productivity of industrial gas. It is an important replacement block for the natural gas production capacity of the Jianghan Oilfield. However, due to the complex structure and lithology, deep burial depth of the target layer, and large fluctuations in the attitude of thin reservoirs, complex situations such as well leakage and collapse occuring frequently, low mechanical drilling speed, long drilling cycles, and difficulty in ensuring the drilling rate of high-quality reservoirs seriously restrict the benefit development. Based on the summary of previous data, the drilling difficulties were analyzed, the optimal design of drilling engineering was carried out, and some key rock breaking tools were selected to optimize the density and sealing performance of drilling fluid. The "three opening" wellbore structure with three different diameters, "irregular tooth PDC and mixed drill bits + high torque equal wall thickness screw + reinforced parameter drilling", simple pressure control by a rotary control head, and low density and strong sealing drilling fluid technology for "both leakage and collapse treatment" were formed. We have established a geological engineering integrated guidance technology based on "vertical depth prediction, segmented slope control, and five charts and one table", and proposed the direction for further improvement. The on-site application shows that: (1) the "three opening" wellbore structure with three different diameters meets the safety drilling requirements in Hongxing area, laying the foundation for drilling speed increase. The parameter drilling was enhanced by high-performance PDC, and the mechanical drilling speed of each opening is significantly improved. The drilling speed of the third opening section in the Permian formation increased by 15%, and the horizontal section increased by 22%; (2) The density reduction and nano sealing drilling fluid technology effectively reduced the number and time of complex treatments, and the time for complex treatments was reduced by 20.5% compared to the early implementation of wells; (3) The penetration rate of high-quality reservoirs significantly increased to 93.27%, an increase of 19.85% compared to the previous period.

【Objective】It aims to preliminarily reveal the effect of dietary supplementation with porcine Lactobacillus reuteri LR1 on the expression of intestinal extracellular matrix (ECM) in weaned piglets, providing references for the promotion and application of porcine LR1 in animal husbandry.【Method】One hundred and forty-four Duroc-Landrace-Yorkshire crossbred weaned piglets with similar body weights at 21 days of age were selected and randomly divided into three treatment groups, which were fed a basal diet (control group, CON group), a basal diet supplemented with 75 mg/kg of aureomycin and 100 mg/kg of quinol (antibiotic group, AO group), and a basal diet supplemented with 5×1010 CFU/kg of porcine L. reuteri LR1 (porcine L. reuteri LR1 group, LR1 group), respectively, and each treatment group was divided into 8 pens for feeding, with 6 pigs in each pen. The experiment lasted for 42 days. On the 43rd day, one piglet from each group was randomly selected for slaughter, and samples of the duodenum (proximal), jejunum (middle), and ileum (distal) were taken for the detection of extracellular matrix related indicators such as intestinal collagen, fibronectin, tenascin and related regulatory factors.【Result】Masson staining observations showed that collagen fibers in the duodenum, jejunum and ileum all extended from the lower to the upper layers of the intestinal mucosa. Compared with the CON group, the collagen volume fraction of the duodenum decreased significantly in both the LR1 and AO groups (P < 0.05), and the collagen volume fraction of the ileum also decreased significantly in the LR1 group (P < 0.05). TMT high-throughput proteomics results showed that the ECM-receptor interaction pathway was one of the major differential protein-enriched pathways, and the expression of its differential proteins, COL1A2, COL4A2, COL6A1, ITGA1, and other ECM molecules, was significantly lower in the LR1 group than that in the CON group (P < 0.05). In addition, the gene expression of COL1A2, COL3A1 and ITGβ2 in jejunum and ileum of LR1 and AO groups was significantly reduced compared with the CON group (P < 0.05), and the gene expression of COL4A2, COL5A1, COL6A1, FN1, TNC, ITGα1 in jejunum, and ITGα1 in ileum was also significantly reduced in the LR1 group (P < 0.05), but there were no significant effect on COL4A2, COL5A1, COL6A1, FN1 and TNC in ileum. Compared with the CON group (P < 0.05), in the ileum of the LR1 and AO groups, the contents of Collagen Ⅰ, Collagen Ⅱ, Collagen Ⅲ, Collagen Ⅳ, Collagen Ⅴ and Collagen Ⅵ significantly decreased; the gene expression of ileal cellular regulatory factors SEC6A1 and PDE4D in LR1 group significantly decreased (P < 0.05). Compared with the AO group (P < 0.05), the gene expression of the extracellular regulator MMP2 was significantly lower in the LR1 group (P < 0.05); and the gene expression of the intracellular regulator SEC6A1 and cytokine TGF-β significantly decreased in the LR1 group.【Conclusion】Addition of porcine L. reuteri LR1 to the diet could modulate ECM remodeling by reducing gene expression of ECM regulators SEC6A1, PDE4D and other genes.