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Abstract Background Accurately classifying primary bone tumors is crucial for guiding therapeutic decisions. The National Comprehensive Cancer Network guidelines recommend multimodal images to provide different perspectives for the comprehensive evaluation of primary bone tumors. However, in clinical practice, most patients’ medical multimodal images are often incomplete. This study aimed to build a deep learning model using patients’ incomplete multimodal images from X-ray, CT, and MRI alongside clinical characteristics to classify primary bone tumors as benign, intermediate, or malignant. Methods In this retrospective study, a total of 1305 patients with histopathologically confirmed primary bone tumors (internal dataset, n = 1043; external dataset, n = 262) were included from two centers between January 2010 and December 2022. We proposed a Primary Bone Tumor Classification Transformer Network (PBTC-TransNet) fusion model to classify primary bone tumors. Areas under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity were calculated to evaluate the model’s classification performance. Results The PBTC-TransNet fusion model achieved satisfactory micro-average AUCs of 0.847 (95% CI: 0.832, 0.862) and 0.782 (95% CI: 0.749, 0.817) on the internal and external test sets. For the classification of benign, intermediate, and malignant primary bone tumors, the model respectively achieved AUCs of 0.827/0.727, 0.740/0.662, and 0.815/0.745 on the internal/external test sets. Furthermore, across all patient subgroups stratified by the distribution of imaging modalities, the PBTC-TransNet fusion model gained micro-average AUCs ranging from 0.700 to 0.909 and 0.640 to 0.847 on the internal and external test sets, respectively. The model showed the highest micro-average AUC of 0.909, accuracy of 84.3%, micro-average sensitivity of 84.3%, and micro-average specificity of 92.1% in those with only X-rays on the internal test set. On the external test set, the PBTC-TransNet fusion model gained the highest micro-average AUC of 0.847 for patients with X-ray + CT. Conclusions We successfully developed and externally validated the transformer-based PBTC-Transnet fusion model for the effective classification of primary bone tumors. This model, rooted in incomplete multimodal images and clinical characteristics, effectively mirrors real-life clinical scenarios, thus enhancing its strong clinical practicability.

Abstract Multi-sequence magnetic resonance imaging is crucial in accurately identifying knee abnormalities but requires substantial expertise from radiologists to interpret. Here, we introduce a deep learning model incorporating co-plane attention across image sequences to classify knee abnormalities. To assess the effectiveness of our model, we collected the largest multi-sequence knee magnetic resonance imaging dataset involving the most comprehensive range of abnormalities, comprising 1748 subjects and 12 types of abnormalities. Our model achieved an overall area under the receiver operating characteristic curve score of 0.812. It achieved an average accuracy of 0.78, outperforming junior radiologists (accuracy 0.65) and remains competitive with senior radiologists (accuracy 0.80). Notably, with the assistance of model output, the diagnosis accuracy of all radiologists was improved significantly (p

Abstract Objective To develop a deep learning (DL) model for segmenting fat metaplasia (FM) on sacroiliac joint (SIJ) MRI and further develop a DL model for classifying axial spondyloarthritis (axSpA) and non-axSpA. Materials and methods This study retrospectively collected 706 patients with FM who underwent SIJ MRI from center 1 (462 axSpA and 186 non-axSpA) and center 2 (37 axSpA and 21 non-axSpA). Patients from center 1 were divided into the training, validation, and internal test sets (n = 455, 64, and 129). Patients from center 2 were used as the external test set. We developed a UNet-based model to segment FM. Based on segmentation results, a classification model was built to distinguish axSpA and non-axSpA. Dice Similarity Coefficients (DSC) and area under the curve (AUC) were used for model evaluation. Radiologists’ performance without and with model assistance was compared to assess the clinical utility of the models. Results Our segmentation model achieved satisfactory DSC of 81.86% ± 1.55% and 85.44% ± 6.09% on the internal cross-validation and external test sets. The classification model yielded AUCs of 0.876 (95% CI: 0.811–0.942) and 0.799 (95% CI: 0.696–0.902) on the internal and external test sets, respectively. With model assistance, segmentation performance was improved for the radiological resident (DSC, 75.70% vs. 82.87%, p 0.05). Conclusions DL is a novel method for automatic and accurate segmentation of FM on SIJ MRI and can effectively increase radiologist’s performance, which might assist in improving diagnosis and progression of axSpA. Critical relevance statement DL models allowed automatic and accurate segmentation of FM on sacroiliac joint MRI, which might facilitate quantitative analysis of FM and have the potential to improve diagnosis and prognosis of axSpA. Key points • Deep learning was used for automatic segmentation of fat metaplasia on MRI. • UNet-based models achieved automatic and accurate segmentation of fat metaplasia. • Automatic segmentation facilitates quantitative analysis of fat metaplasia to improve diagnosis and prognosis of axial spondyloarthritis. Graphical Abstract

Abstract Objectives The objective of this study is to evaluate the value of S100‐A8 protein as a diagnostic marker for spinal tuberculosis and to explore its role in the potential pathogenesis of spinal tuberculosis (STB). Methods The peripheral blood of 100 spinal tuberculosis patients admitted to the General Hospital of Ningxia Medical University from September 2018 to June 2021 were collected as the observation group, and the peripheral blood of 30 healthy medical examiners were collected as the control group. Three samples from the observation group and three samples from the control group were selected for proteomics detection and screening of differential proteins. Kyoto Encyclopedia of Genes (KEGG) was used to enrich and analyze related signaling pathways to confirm the target protein. The serum expression levels of the target proteins were determined and compared between the two groups using enzyme‐linked immunosorbent assay (ELISA). Statistical methods were used to evaluate the value of target protein as a diagnostic marker for STB. A macrophage model of Mycobacterium tuberculosis infection was constructed and S100‐A8 small interfering RNA was used to investigate the molecular mechanism of the target protein. Results S100‐A8 protein has the value of diagnosing spinal tuberculosis (AUC = 0.931, p

Ferroptosis is a newly discovered form of programmed cell death triggered by intracellular iron overload, which leads to the accumulation of lipid peroxides in various cells. It has been implicated in the pathogenesis and progression of various diseases, including tumors, neurological disorders, and cardiovascular diseases. The intricate mechanism underlying ferroptosis involves an imbalance between the oxidation and antioxidant systems, disturbances in iron metabolism, membrane lipid peroxidation, and dysregulation of amino acid metabolism. We highlight the key molecular mechanisms governing iron overload and ferroptosis, and discuss potential molecular pathways linking ferroptosis with arrhythmias.

Internet of Things (IoT) is an important technology employed in a variety of different applications, such as transportation, healthcare, and manufacturing. In recent years, the number of IoT devices deployed globally has been increasing at a rapid pace and is estimated to reach 20 billion by the end of 2025. In modern industry, IoT plays a pivotal role by monitoring the condition of industrial machines and, consequently, improving the efficiency of industrial processes. To optimize the efficiency of industrial IoT applications, various Artificial Intelligence (AI) techniques have been adopted, leading to a new computing paradigm, namely, Industrial Artificial Intelligence of Things (i.e. Industrial AIoT). In this paper, we describe the challenges to tackle and the opportunities to explore in Industrial AIoT. Specifically, we first review the use of state-of-the-art AI methods in Industrial AIoT applications, with a focus on Deep Learning (DL) and Machine Learning (ML) techniques. Thereafter, we present a series of important applications of Industrial AIoT. The key challenges associated with the implementation of Industrial AIoT applications are also discussed. In addition, the societal and economic impacts of Industrial AIoT are briefly described. Finally, we outline the future research directions in Industrial AIoT, which should be further investigated to fully utilize the potential of this innovative technology.

Berberine hydrochloride (BH) extracted from Coptis chinensis (CC) and Matrine (MT) separated from Sophora flavescens (SF) are alkaloids with potent anti-bacterial, anti-inflammatory, and anti-tumor effects. Motivated by the clinical practice of using CC and SF together, we aimed to demonstrate that the synergistic application of the natural compounds BH and MT could enhance therapeutic effects and minimize side effects. Two types of liposomes, liposomes containing only BH (BH-LP) and liposomes containing both BH and MT (BH-MT-LP), were successfully prepared via the reverse evaporation method. The liposome preparation process was optimized by single-factor screening and the Box–Behnken experimental design method. The results showed that the liposomes had particle sizes in the range of 222.7 to 235.4 nm, polydispersity indicated in the range of 11.8% to 23.3%, and zeta potentials in the range of −35.9 to −31.1 mv. BH-MT-LP showed superior anti-tumor activity against MDA-MB-231, HepG-2, and HGC-27 cells in vitro. The incorporation of MT effectively promoted the anti-tumor effect of BH, while the controlled release from liposomes further enhanced the therapeutic efficacy of BH. Furthermore, based on the flow cytometry results, we speculated that BH-MT-LP might promote apoptosis by blocking the G1 phase of cells and inducing cell death. In conclusion, BH-MT-LP provides evidence for the combined use of natural compounds as a stable, safe, and practical drug delivery system for the treatment of potential cancers. Meanwhile, the successful preparation for BH-MT-LP also provides a new approach to the combined use of traditional Chinese medicine ingredients.

A universal recombinant adenovirus type-5 (Ad5) vaccine against COVID19 (Ad-US) was constructed, and immunogenicity and broad-spectrum of Ad5-US were evaluated with both intranasal and intramuscular immunization routes. The humoral immune response of Ad5-US in serum and bronchoalveolar lavage fluid were evaluated by the enzyme-linked immunosorbent assay (ELISA), recombinant vesicular stomatitis virus based pseudovirus neutralization assay, and angiotensin-converting enzyme-2 (ACE2) -binding inhibition assay. The cellular immune response and Th1/Th2 biased immune response of Ad5-US were evaluated by the IFN-γ ELISpot assay, intracellular cytokine staining, and Meso Scale Discovery (MSD) profiling of Th1/Th2 cytokines. Intramuscular priming followed by an intranasal booster with Ad5-US elicited the broad-spectrum and high levels of IgG, IgA, pseudovirus neutralizing antibody (PNAb), and Th1-skewing of the T-cell response. Overall, the adenovirus type-5 vectored universal SARS-CoV-2 vaccine Ad5-US was successfully constructed, and Ad5-US was highly immunogenic and broad spectrum. Intramuscular priming followed by an intranasal booster with Ad5-US induced the high and broad spectrum systemic immune responses and local mucosal immune responses.

The leading cause of composite restoration failure is recurrent marginal decay. The margin between the composite and tooth is initially sealed by a low-viscosity adhesive, but chemical, physical, and mechanical stresses work synergistically and simultaneously to degrade the adhesive, destroying the interfacial seal and providing an ideal environment for bacteria to proliferate. Our group has been developing self-strengthening adhesives with improved chemical and mechanical characteristics. This paper reports a self-strengthening adhesive formulation that resists hydrolysis-mediated degradation by providing intrinsic reinforcement of the polymer network through synergistic stimulation of free-radical polymerization, sol-gel reaction, and hydrophobicity. Hydrophobic resin formulation (NE1) was developed using HEMA/BisGMA 28/55w/w and 15 wt% MPS. Control (NC1) contained HEMA/BisGMA 28/55 w/w and 15 wt% MES. The polymerization kinetics, water sorption, leachates, and dynamic mechanical properties of the resin samples were investigated. The NC1 and NE1 samples showed comparable polymerization kinetics, degrees of conversion and water sorption. In contrast, NC1 showed significantly higher levels of HEMA and BisGMA leachate, indicating faster degradation in ethanol. At day 3, cumulative HEMA leachate for NC1 was ten times greater than NE1 (p

Electrical storms (ESs) following percutaneous coronary intervention (PCI) in acute myocardial infarction (AMI) patients pose a significant challenge, affecting prognostic outcomes and increasing mortality. This meta-analysis synthesized data from 11 studies involving 9,666 AMI patients to identify risk factors associated with ES following PCI. Our findings revealed an average ES incidence of 7.70%, with identified risk factors including low thrombolysis in myocardial infarction (TIMI) flow grades (0-1), elevated cardiac troponin I levels, persistent hypotension, reperfusion arrhythmias, the right coronary artery being the infarct-related artery, increased diameter of the infarct-related artery, renal dysfunction, elevated creatine kinase-MB, and bradycardia. Notably, the use of β-blockers was found to significantly reduce the risk of ES. The study underscores the importance of early identification and management of these risk factors in AMI patients undergoing PCI to prevent the occurrence of ES, highlighting the protective role of β-blockers. This research provides a foundation for future strategies aimed at reducing the incidence and improving the prognosis of ES in this patient population.

Cardiac fibrosis is a serious health problem because it is a common pathological change in almost all forms of cardiovascular diseases. Cardiac fibrosis is characterized by the transdifferentiation of cardiac fibroblasts (CFs) into cardiac myofibroblasts and the excessive deposition of extracellular matrix (ECM) components produced by activated myofibroblasts, which leads to fibrotic scar formation and subsequent cardiac dysfunction. However, there are currently few effective therapeutic strategies protecting against fibrogenesis. This lack is largely because the molecular mechanisms of cardiac fibrosis remain unclear despite extensive research. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling cascade is an extensively present intracellular signal transduction pathway and can regulate a wide range of biological processes, including cell proliferation, migration, differentiation, apoptosis, and immune response. Various upstream mediators such as cytokines, growth factors and hormones can initiate signal transmission via this pathway and play corresponding regulatory roles. STAT3 is a crucial player of the JAK/STAT pathway and its activation is related to inflammation, malignant tumors and autoimmune illnesses. Recently, the JAK/STAT3 signaling has been in the spotlight for its role in the occurrence and development of cardiac fibrosis and its activation can promote the proliferation and activation of CFs and the production of ECM proteins, thus leading to cardiac fibrosis. In this manuscript, we discuss the structure, transactivation and regulation of the JAK/STAT3 signaling pathway and review recent progress on the role of this pathway in cardiac fibrosis. Moreover, we summarize the current challenges and opportunities of targeting the JAK/STAT3 signaling for the treatment of fibrosis. In summary, the information presented in this article is critical for comprehending the role of the JAK/STAT3 pathway in cardiac fibrosis, and will also contribute to future research aimed at the development of effective anti-fibrotic therapeutic strategies targeting the JAK/STAT3 signaling.

Background: Randomized controlled trials (RCTs) are often considered the gold standard and the cornerstone for clinical practice. However, bibliometric studies on worldwide RCTs of ophthalmology published in the 21st century have not been reported in detail yet. This study aims to perform a bibliometric study and visualization analysis of worldwide ophthalmologic RCTs in the 21st century. Methods: Global ophthalmologic RCTs from 2000 to 2022 were searched in the Web of Science Core Collection. The number of publications, country/region, institution, author, journal, and research hotspots of RCTs were analyzed using HistCite, VOSviewer, CiteSpace, and Excel software. Results: 2366 institutions and 90 journals from 83 countries/regions participated in the publication of 1769 global ophthalmologic RCTs, with the United States leading in the number of volumes and research field, and the Moorfields Eye Hospital contributing to the most publications. Ophthalmology received the greatest number of publications and co-citations. Jeffrey S. Heier owned the most publications and Jost B. Jonas owned the most co-citations. The knowledge foundations of global ophthalmologic RCTs were mainly retinopathy, glaucoma, dry eye disease (DED), and cataracts, and anti-vascular endothelial growth factor (VEGF) therapy (ranibizumab), topical ocular hypotensive medication, laser trabeculoplasty. Anti-VEGF therapy for age-related macular degeneration (AMD), DME (diabetic macular edema), and DED, the use of new diagnostic tools, and myopia were the hottest research highlights. Anti-VEGF therapy, prompt laser, triamcinolone, and verteporfin photodynamic therapy for AMD, DME, and CNV (choroidal neovascularization), DED, myopia, and open-angle glaucoma were the research hotspots with the longest duration. The future research hotspots might be DED and the prevention and control of myopia. Conclusions: Overall, the number of global ophthalmologic RCTs in the 21st century was keeping growing, there was an imbalance between the regions and institutions, and more efforts are required to raise the quantity, quality, and global impact of high-quality clinical evidence in developing countries/regions.

Multi-seam mining in gully region has resulted in serious and complex chain disasters, including fissure development, mountain landslides, river blockage, and intensified water inflow. To prevent and control landslides and water inrush disasters, it is crucial to explore the characteristics and laws of overlying strata failure under the coupling effect of gully terrain and repeated mining in coal seams. This study focuses on the mining of multiseam in the gully terrain of Xiqu Coal Mine. The comprehensive analysis method, integrating surface exploration, InSAR dynamic observation, rainfall-runoff analysis, and numerical simulation, is used to analyze the entire process of spatial expansion of overlying strata failure and surface subsidence caused by downward mining of multiseam in the gully region. The results reveal that after the critical mining of the lower coal seam in the gully region, the lower strata beneath the key stratum in interlayered formations are prone to develop cutting failure and vertical fissure, with tensile cracking being the dominant mode of failure. The proportion of shear fractures in the overburden above the key stratum increases significantly, and the gully slope is prone to shear slip under the effects of mining subsidence and gravity. The connection phenomenon between the downward fractures of the slope and the upward fractures of the overburden can even occur. In addition, if the accumulation formed by mountain landslides due to repeated mining blocks the river channel and forms a barrier lake during the flood season, there is a risk of underground water inflow. To prevent such disasters, high-precision terrain synthesized by UAV tilt photogrammetry is used to simulate the rainfall inundation range and time percentage of different durations in Fanshigou watershed during the “100-year return period” rainstorm in Shanxi Province. The research proposes a comprehensive prevention and control method of surface runoff water disaster based on fissure development and surface inundation range, which provides support for gully water disaster prevention and risk assessment in Fanshigou small watershed. This study can serve as a useful reference for the prevention and control of surface geological disasters and the protection of water resources under the condition of multiseam mining in gully regions.

Atherosclerotic cardiovascular disease (ASCVD) frequently results in sudden death and poses a serious threat to public health worldwide. The drugs approved for the prevention and treatment of ASCVD are usually used in combination but are inefficient owing to their side effects and single therapeutic targets. Therefore, the use of natural products in developing drugs for the prevention and treatment of ASCVD has received great scholarly attention. Andrographolide (AG) is a diterpenoid lactone compound extracted from Andrographis paniculata. In addition to its use in conditions such as sore throat, AG can be used to prevent and treat ASCVD. It is different from drugs that are commonly used in the prevention and treatment of ASCVD and can not only treat obesity, diabetes, hyperlipidaemia and ASCVD but also inhibit the pathological process of atherosclerosis (AS) including lipid accumulation, inflammation, oxidative stress and cellular abnormalities by regulating various targets and pathways. However, the pharmacological mechanisms of AG underlying the prevention and treatment of ASCVD have not been corroborated, which may hinder its clinical development and application. Therefore, this review summarizes the physiological and pathological mechanisms underlying the development of ASCVD and the in vivo and in vitro pharmacological effects of AG on the relative risk factors of AS and ASCVD. The findings support the use of the old pharmacological compound (‘old bottle’) as a novel drug (‘novel wine’) for the prevention and treatment of ASCVD. Additionally, this review summarizes studies on the availability as well as pharmaceutical and pharmacokinetic properties of AG, aiming to provide more information regarding the clinical application and further research and development of AG.

Dioscorea cirrhosa L. (D. cirrhosa) tuber is a traditional medicinal plant that is abundant in various pharmacological substances. Although diosgenin is commonly found in many Dioscoreaceae plants, its presence in D. cirrhosa remained uncertain. To address this, HPLC-MS/MS analysis was conducted and 13 diosgenin metabolites were identified in D. cirrhosa tuber. Furthermore, we utilized transcriptome data to identify 21 key enzymes and 43 unigenes that are involved in diosgenin biosynthesis, leading to a proposed pathway for diosgenin biosynthesis in D. cirrhosa. A total of 3,365 unigenes belonging to 82 transcription factor (TF) families were annotated, including MYB, AP2/ERF, bZIP, bHLH, WRKY, NAC, C2H2, C3H, SNF2 and Aux/IAA. Correlation analysis revealed that 22 TFs are strongly associated with diosgenin biosynthesis genes (—r2— > 0.9, P

Abstract Background Parkinson’s disease (PD) is the second most common neurodegenerative disease. The pathologic characteristic feature is the loss of dopaminergic neurons in the substantia nigra (SN). However, the biochemical mechanisms are unclear. A large number of studies have shown that oxidative damage is the primary cause of PD. Hence, antioxidants could become a suitable option to treat PD. The thioredoxin (Trx) system represents a useful, potentially disease-relevant oxidation–reduction system. Thioredoxin reductase 1 (TR1) is a significant component of the Trx system. Methods The overexpression lentivirus (LV) or LV-TR1 in the TR1-A53T model of PD by the stereotactic brain, and successful overexpression of LV or LV-TR1 in the MPP+-induced cellular model by LV or LV-TR1 transfection. Results We confirmed that interleukin-7 mRNA levels increased in MPP+ compared to that in the control and MPP+-TR1 groups using quantitative polymerase chain reaction. The γ-H2AX level was increased in the Tg-A53T group compared to that in the TR1-A53T group by western blotting. The expression of Na+-K+-ATP was decreased in the MPP+ group compared to that in the control and MPP+-TR1 groups by high content screening. Tg-A53T(the C57BL/6 mice transferred with mutant human a-syn); TR1-A53T(A53T mice which were injected TR1-LV 2 µl in SNc on two sides with minipump).The mice were fed for 10 months. control (the N2a cells cultivated with DMEM); MPP+(the N2a cells dealt with MPP+(1 mM) 48 h), MPP+-LV (the N2a cells over-expressed LV for 24 h then dealt with MPP+(1 mM) 48 h). MPP+-TR1(the N2a cell over-expressed TR1-LV for 24 h then dealt with MPP+(1 mM) 48 h). From the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, we confirmed that the overexpression of TR1 in SN pars compacta cells decreased oxidative stress, apoptosis, DNA damage, and inflammatory response and increased NADPH, Na+-K+-ATP, and immune response in this PD model. Conclusions Our study shows that overexpressed TR1 can be developed as a neuroprotective agent for PD. Therefore, our findings demonstrate a new targeted protein for the treatment of PD.

Urban parks are important for improving the quality of living environments. Although the impact of parks on housing prices has been well documented, the effects of the COVID-19 pandemic remain vague. This paper analyzes the housing prices of neighborhoods around Meixi Lake park in Changsha, at the initial stage of the COVID-19 pandemic in June 2020 and the stable stage of the recovery period in June 2023, which demonstrates the impacts of urban parks on property pricing and housing choice based on residential transaction data. The results indicate that urban parks are given a high priority in determining people’s choices. In June 2020, the risk of epidemic transmission and noise interference lowered the price of property that is close to public parks and recreational facilities. However, good management and social services in residential areas increase housing prices. However, when the pandemic ended, the strong demand for outdoor activities led to a price rise in the properties near Meixi Lake park. People are most likely to choose houses in a neighborhood characterized by good educational facilities and a high-quality living environment. More specially, the houses with a short distance to parks and where residents can enjoy the view of a lake or mountains are preferable to any others. A residential area adjacent to a super large park paired with a small park is the most valuable consideration for property developers and housing consumers.

Toosendanin (TSN), extracted from Melia. toosendan Sieb.et Zucc. and Melia. azedarach L., has been developed into an ascaris repellent in China. However, with the improvement of public health protection, the incidence of ascariasis has been reduced considerably, resulting in limited medical application of TSN. Therefore, it is questionable whether this old ascaris repellent can develop into a drug candidate. Modern studies have shown that TSN has strong pharmacological activities, including anti-tumor, anti-botulinum, anti-viral and anti-parasitic potentials. It also can regulate fat formation and improve inflammation. These researches indicate that TSN has great potential to be developed into a corresponding medical product. In order to better development and application of TSN, the availability, pharmacodynamics, pharmacokinetics and toxicology of TSN are summarized systematically. In addition, this review discusses shortcomings in the current researches and provides useful suggestions about how TSN developed into a drug candidate. Therefore, this paper illustrates the possibility of developing TSN as a medical product, aimed to provide directions for the clinical application and further research of TSN.

Summary: Coronary artery disease (CAD) affects millions of individuals worldwide and results in a substantial burden to healthcare systems. Although it is established that CAD affects females differently than males, differences between the sexes are not routinely accounted for. Body mass index is a known risk factor for CAD. However, more accurate metrics of body fat, including waist-to-hip circumference ratio (WHR), could be more meaningful clinically. WHR exhibits sex differences due to sex hormones, differing effects at genetic risk loci, and other factors. It is unclear if WHR is a causal factor for CAD in one or both sexes, but this information will be crucial for improving heart health. Causal inference, however, can be challenging. Large-scale cohorts with genetic data allow for Mendelian randomization, which, given certain assumptions, tests whether there is a causal relationship between an exposure and the outcome using genetic variants.We conducted sex-specific, one-sample MR analyses using two-stage least-squares regression in the UK Biobank with genetic variants robustly associated with WHR. We found evidence of a causal relationship between WHR and CAD risk in females (OR [95% CI] = 1.16 [1.06–1.26]; p value = 7.5E-4), whereas in males, we did not find evidence of a causal relationship (OR [95% CI] = 1.40 [0.98–2.01]; p value = 0.063). Results were supported by two additional MR approaches (using a genetic risk score and two-sample MR using the inverse variance weighted approach).We encourage future work assessing sex-specific effects using causal inference techniques to better understand factors contributing to complex disease risk.

Abstract Background Hemiarthroplasty following tumor resection of the distal femur in children provides a chance to preserve the proximal tibial physis for limb elongation. Based on three-dimensional (3D) printing technology, the uncemented unipolar prosthesis with joint stability reinforced structures (JSRSs) was custom-designed for our cases. This study aimed to describe the design and assess the short-term outcomes of this refined prosthetic hemiarthroplasty. Methods Seven patients (four females and three males) received 3D-printed customized uncemented unipolar prosthesis for hemiarthroplasty after removal of the distal femur, from September 2019 to October 2020 at our Orthopedics department. The limb function, growth of the preserved proximal tibial physis, joint stability, and limb length discrepancy (LLD) were assessed. Complications were recorded. Results Six patients survived with no evidence of metastasis or local recurrence at the last follow-up, and one patient died of lung metastasis at 19 months postoperatively. Follow-up ranged from 19 to 32 months, with an average of 26 months. Elongation of the tibia was observed in all cases. At the last follow-up, four patients exhibited equal growth length compared with the healthy contralateral tibia. LLD ranged from 0.8 to 1.6 cm with a mean of 1.3 cm. The average knee range of motion was 95.3° of flexion and 4.5° of extension. All patients achieved satisfactory postoperative limb function with a mean MSTS score of 25.8. The results of the drawer, Lachman, and pivot shift tests were negative in all patients. During follow-up, painless joint space narrowing was observed in two patients. The screw for ligament fixation loosened in one of the seven patients at 17 months postoperatively. No subluxation of the joint, angular deformity, or breakage of the implant was detected in the remaining patients. Conclusions 3D-printed customized uncemented unipolar prosthesis with JSRS would be a good choice for reconstructing tumorous defect in the distal femur in children.

The flat glass industry is a typical industry with high energy consumption and extensive carbon emission. The carbon emission of flat glass industry in China ranks first in the same industry in the world. At present, there are few researches on carbon emission prediction for industrial enterprises, especially for the flat glass industry, due to lack of monitoring data. This paper selects electricity consumption as the influencing factor of carbon emission. This paper firstly preprocesses the electricity consumption data according to the China greenhouse gas emission standard. Next, this paper selects a correlation variable to fit the historical data of the flat glass industry based on Support Vector Regression (SVR). Finally, it obtains the parameters of the basic form of the electricity consumption to carbon emission model of the industry. The validity of the electricity-carbon modeling method and the accuracy of the model are verified by simulation experiments. The electricity-carbon model established by the method in this paper has a high accuracy rate, and the coefficient of determination (R2) reaches 0.98, which can play an auxiliary role in the verification of carbon emissions.

Diabetes mellitus is a main risk factor for periodontitis, but until now, the underlying molecular mechanisms remain unclear. Diabetes can increase the pathogenicity of the periodontal microbiota and the inflammatory/host immune response of the periodontium. Hyperglycemia induces reactive oxygen species (ROS) production and enhances oxidative stress (OS), exacerbating periodontal tissue destruction. Furthermore, the alveolar bone resorption damage and the epigenetic changes in periodontal tissue induced by diabetes may also contribute to periodontitis. We will review the latest clinical data on the evidence of diabetes promoting the susceptibility of periodontitis from epidemiological, molecular mechanistic, and potential therapeutic targets and discuss the possible molecular mechanistic targets, focusing in particular on novel data on inflammatory/host immune response and OS. Understanding the intertwined pathogenesis of diabetes mellitus and periodontitis can explain the cross-interference between endocrine metabolic and inflammatory diseases better, provide a theoretical basis for new systemic holistic treatment, and promote interprofessional collaboration between endocrine physicians and dentists.

BackgroundAutism spectrum disorder (ASD) is a severe public health concern, and most of the children with ASD experience a substantial delay in FMS. This study aimed to investigate the effectiveness of exercise interventions in improving FMS in children with ASD, and provide evidence to support the scientific use of exercise interventions in practice.MethodsWe searched seven online databases (PubMed, Scopus, Web of Science, Embase, EBSCO, Clinical Trials, and The Cochrane Library) from inception to May 20, 2022. We included randomized control trials of exercise interventions for FMS in children with ASD. The methodological quality of the included studies was assessed using the Physiotherapy Evidence Database Scale. Stata 14.0 software was used for meta-analysis, forest plotting, subgroup analysis, heterogeneity analysis, and meta-regression.ResultsThirteen studies underwent systematic review (541 participants), of which 10 underwent meta-analysis (297 participants). Overall, exercise interventions significantly improved overall FMS in children with ASD. Regarding the three categories of FMS, exercise interventions significantly improved LMS (SMD = 1.07; 95% CI 0.73 to 1.41, p < 0.001), OCS (SMD = 0.79; 95% CI 0.32 to 1.26, p = 0.001), and SS (SMD = 0.72; 95% CI 0.45 to 0.98, p < 0.0001).Conclusionexercise interventions can effectively improve the FMS of children with ASD. The effects on LMS are considered as large effect sizes, while the effects on OCS and SS are considered as moderate effect sizes. These findings can inform clinical practice.Systematic review registrationhttps://inplasy.com/inplasy-2022-12-0013/.

BackgroundThe role of specific unsaturated fatty acids (FAs) in the development of overweight/obesity remains unclear in the general population. Here, we aimed to explore the associations of different types of unsaturated FAs with overweight/obesity risk among the Chinese population.MethodsEight thousand seven hundred forty-two subjects free of overweight/obesity at entry in the China Health and Nutrition Survey (CHNS) were followed up until 2015. Dietary unsaturated FAs were assessed by 3-day 24-h recalls with a weighing method in each wave. Cox regression models were used to obtain the hazard ratios (HRs) and 95% confidence intervals (CIs) for overweight/obesity risk associated with unsaturated FAs.ResultsDuring a median follow-up of 7 years, 2,753 subjects (1,350 males and 1,403 females) developed overweight/obesity. Consuming more monounsaturated FAs (MUFAs) was associated with a lower risk of overweight/obesity (highest vs. lowest quartile: HR 0.80, 95% CI 0.67–0.96; P-trend = 0.010). Similar inverse associations were observed for plant-MUFAs (HRQ4vsQ1 0.83, 95% CI: 0.73–0.94; P-trend = 0.003) and animal-MUFAs (HRQ4vsQ1 0.77, 95% CI: 0.64–0.94; P-trend = 0.004), total dietary oleic acid (OA) (HRQ4vsQ1 0.66, 95% CI: 0.55–0.79; P-trend

Vaccination is the most effective and economical way to prevent meningococcal meningitis. In the past few decades, with widespread use of meningococcal vaccines, the incidence of meningococcal meningitis has dropped significantly. There are some vaccines available in Chinese markets, of which mainly included groups A, C, W, and Y monovalent and multivalent polysaccharide meningococcal vaccines (MPV), group A and C polysaccharide meningococcal conjugated vaccines (MPCV-AC), and meningococcal groups A and C and haemophilus b conjugate vaccine (MPCV-AC-hib). With the nearly 50 years of development of meningococcal vaccines in China, significant achievements have been made in vaccine production, quality control, and related research, but the burden of meningococcal disease is still underestimated; the meningococcal vaccine immunization strategy has not been perfected; meningococcal vaccines from different manufacturers have inconsistent immunization procedures and no group B meningococcal vaccines are available in the market. Therefore, it is suggested that meningococcal monitoring methods should be continuously improved and research on meningococcal disease burden should be carried out for facilitating the improvement of meningococcal vaccine immunization procedures and strategy. Furthermore, considering the serogroup highly variable and antigen drift characteristics of Neisseria meningitides, a vaccine with longer immunity and better protection effect should be developed by using genetic recombination and other technologies.

Abstract Crowdfunding is an innovative strategy for financing a new business venture from the general public instead of seeking funds in traditional ways, such as issuing bonds or bank lending. This study aims to identify the determinants affecting the success of a crowdfunding campaign and how different measurements for crowdfunding success, different crowdfunding models, and the selection of subdivided determinants influence the determinants’ impacts on crowdfunding success. We set the disciplines in the search strategy to select studies related to crowdfunding success. Ultimately, 94 empirical papers are selected to reveal the different findings for the determinants of crowdfunding success; based on this information, we construct an integrated framework for future research. There has been much research on project- and creator-related factors; however, many of these factors have inconsistent relationships with crowdfunding success due to varying measurements of success. In particular, different measurements used within the same study for determinants or crowdfunding success may also produce inconsistent results. In addition, different crowdfunding models of a project have been found to induce additional findings. Our review of the determinants of crowdfunding success and the definitions of the determinants, as well as the proposed integrated framework, can help focus future work on relatively new or unique determinants rarely addressed in the existing literature. This work provides practical implications for both theory and practice, and directions for future research.

In order to give better play to the reuse value of pilose antler waste, the chemical components and pharmacological activities of the waste were studied. Pilose antler medicinal materials were treated according to the production process of pilose antler oral liquid standard (Ministry of Health Standard: WS3-B-2232-96). Then the waste produced in the production of pilose antler oral liquid was reextracted by water extraction and alcohol precipitation. Ultrahigh performance liquid chromatography quadrupole electrostatic field orbital trap high resolution mass spectrometry (UPLC-Q-Orbitrap HRMS), bicinchoninic acid (BCA) and phenol-sulfuric acid methods were used to study the chemical components of the extract. The antioxidant capacity of the extract was evaluated by three ways including free radical scavenging test of 1,1-diphenyl-2-trinitrophenylhydrazine (DPPH), 2,2-diazo-bis (3-ethyl-benzothiazole-6-sulfonic acid) diammonium salt (ABTS) and Ferric ion reducing antioxidant power (FRAP). Moreover, the antioxidant activity was further verified by hydrogen peroxide and glutamate cell oxidative damage model. The skin injury repairing activity of the extract was proved via mouse skin trauma model. The results showed that via water extraction and alcohol precipitation, the supernatant contained oligosaccharides, amino acids, nucleosides and other substances. The lower precipitation part was mainly protein polypeptide and polysaccharide, and the sum of the two was more than 70%. The antioxidant results showed that after water extraction and alcohol precipitation treatment, the two supernatant parts of the waste produced by oral liquid showed better antioxidant activity. Among them, the antioxidant effect of the supernatant part of pilose antler drug residue after water extraction and alcohol precipitation treatment was better, and the IC50 of DPPH and ABTS+ free radical scavenging rates were 0.82 and 2.52 mg/mL respectively, FRAP results also confirmed this, and when the concentration was 0.1 mg/mL, it could significantly (P

Abstract The temperature dependence of the low-energy magnetic excitations in the spin-triplet superconductor UTe2 was measured via inelastic neutron scattering in the normal and superconducting states. These excitations have a peak instensity at 4 meV, follow the Brillouin zone edges near the crystallographic b-axis, obey the paramagnetic structural symmetry, and track the temperature evolution of the heavy fermion bulk magnetic susceptibility. Thus, the imaginary part of the dynamic susceptibility follows the behavior of interband correlations in a hybridized Kondo lattice with an appropriate characteristic energy. These excitations are a lower-dimensional analog of phenomena observed in other Kondo lattice materials, such that their presence is not necessarily due to dominance of ferromagnetic or antiferromagnetic correlations. The onset of superconductivity alters the magnetic excitations noticeably on the same energy scales, suggesting that these changes originate from additional electronic structure modification.

Atrial fibrillation (AF) is the most common type of arrhythmia in clinical practice, and its incidence is positively correlated with risk factors that include advanced age, hypertension, diabetes, and heart failure. Although our understanding of the mechanisms that govern the occurrence and persistence of AF has been increasing rapidly, the exact mechanism of AF is still not fully understood. Autophagy is an evolutionarily highly conserved and specific physiological process in cells that has been suggested as a potential therapeutic target for several cardiovascular diseases including the pathophysiology of AF. The present article provides an updated review of the fast-progressing field of research surrounding autophagy in AF, and how regulating autophagy might be a therapeutic target to reduce the incidence of AF.

Abstract Patients with AMI usually present with the specific changes for electrocardiogram (ECG) and biomarkers of cardiac injury. Here, we present a rare case with chest pain and normal ECG and biomarkers of cardiac injury. Emergent coronary angiography revealed an occlusion of proximal left anterior descending coronary artery. The patient was diagnosed with AMI, and his symptom relieved after implantation of drug‐eluting stents. Caution should be exercised for the exclusion of AMI in patients with chest pain and both normal ECG and biomarkers of cardiac injury.

Changes in the microbial community are considered important factors affecting the yield and quality of ginseng cultivated in farmland, while the characteristics of the change in the microbial community of the soil before and after cultivation of ginseng in farmland are not well understood. Here, we aimed to fill this research gap by comparing the differences in soil nutrients and microbial communities between continuously cultivated ginseng soils for 1-, 2-, 3- and 5-year-old ginseng soils and corresponding uncultivated ginseng soils. The soil properties (pH, total soil organic carbon (TOC) content and total nitrogen (TN) content) of aged ginseng soil (3- and 5-year-old) were significantly reduced compared with those of the control soil after ginseng was cultivated in farmland. With the exception of 2-year-old ginseng, soil bacterial richness and diversity were higher in different ages of cultivated ginseng soils than in the control soil, while fungal diversity decreased in aged ginseng soil and increased in young ginseng soil (1- and 2-year-old). Ascomycota and Basidiomycota showed a consistent increasing/decreasing trend in cultivated ginseng soils of all ages compared to the control. In addition, ginseng cultivation resulted in a substantial decrease in the complexity of soil bacterial networks but a slight decrease in the complexity of fungal networks. The results from the linear discriminant size effect (LEfSe) analysis showed that beneficial microorganisms were biomarkers of the young ginseng soil, including Nitrosospira, Cephalotrichum and Humicola, while harmful microorganisms were biomarkers of aged ginseng, such as Plectosphaerella, Cladosporium and Alternaria. PICRUSt2 analysis revealed that the increase in the incidence of ginseng disease with continuous cultivation time may be related to the decreases in amino acid synthesis and physiological metabolism and the increase in fungal saprophytes. Soil pH was the most common and best predictor of bacterial and fungal community structure, followed by TOC and ammonium nitrogen (NH4+-N) contents. Meanwhile, the decreased of soil pH, TOC and AK may be the driving factors for the growth of ginseng soil pathogens. Overall, this study revealed the changing ginseng rhizosphere soil microbial community at different continuous cultivation times, provided a theoretical basis for ginseng cultivation, and promoted the development of medicinal plants such as ginseng.

By 2060, nearly 100 million people in the USA will be over the age of 65 years. One-third of these older adults will have root caries, and nearly 80% will have dental erosion. These conditions can cause pain and loss of tooth structure that interfere with eating, speaking, sleeping, and quality of life. Current treatments for root caries and dental erosion have produced unreliable results. For example, the glass-ionomer-cement or composite-resin restorations used to treat these lesions have annual failure rates of 44% and 17%, respectively. These limitations and the pressing need to treat these conditions in the aging population are driving a focus on microinvasive strategies, such as sealants and varnishes. Sealants can inhibit caries on coronal surfaces, but they are ineffective for root caries. For healthy, functionally independent elders, chlorhexidine varnish applied every 3 months inhibits root caries, but this bitter-tasting varnish stains the teeth. Fluoride gel inhibits root caries, but requires prescriptions and daily use, which may not be feasible for some older patients. Silver diamine fluoride can both arrest and inhibit root caries but stains the treated tooth surface black. The limitations of current approaches and high prevalence of root caries and dental erosion in the aging population create an urgent need for microinvasive therapies that can: (a) remineralize damaged dentin; (b) inhibit bacterial activity; and (c) provide durable protection for the root surface. Since cavitated and non-cavitated root lesions are difficult to distinguish, optimal approaches will treat both. This review will explore the multi-factorial elements that contribute to root surface lesions and discuss a multi-pronged strategy to both repair and protect root surfaces. The strategy integrates engineered peptides, novel polymer chemistry, multi-scale structure/property characterization and predictive modeling to develop a durable, microinvasive treatment for root surface lesions.

BackgroundAlthough the gut microbiota may be involved in obesity onset and progression, the exact association of the gut microbiota in metabolically healthy obesity (MHO) remains largely unknown.MethodsAn integrated paired-sample metagenomic analysis was conducted to investigate the gut microbial network and biomarkers of microbial species from the MHO and healthy non-obese subjects in the GMrepo database. Further explorations were performed in the MHO mice model using a multiomics analysis to detect changes in the composition and function of the intestinal microbiome and associated metabolites.ResultsIn the human study, 314 matched metagenomic data were qualified for the final analysis. We identified seven significantly changed species possibly involved in MHO pathogenesis (MHO-enriched: Bacteroides vulgatus, Megamonas sp; MHO-depleted: Butyrivibrio crossotus, Faecalibacterium prausnitzii, Bacteroides cellulosilyticus; Eubacterium siraeum; Bacteroides massiliensis). In the murine study, we found 79 significantly-changed species which may have possible associations with the MHO phenotype. The depletion of Bacteroides cellulosilyticus was commonly recognized in the human and murine MHO phenotype. Consistent with the metagenomic data, liquid chromatography-mass spectrometry (LC/MS) revealed significantly changed gut metabolites, which may promote MHO pathogenesis by altering the amino acids and lipid metabolic pathways. In the microbe-metabolites interaction analysis, we identified certain fatty acids (Dodecanedioic acid, Arachidic Acid, Mevalonic acid, etc.) that were significantly correlated with the MHO-enriched or depleted species.ConclusionThis study provides insights into identifying specific microbes and metabolites that may involve in the development of obesity without metabolic disorders. Future modalities for MHO intervention may be further validated by targeting these bacteria and metabolites.

Meningococcal meningitis caused by Neisseria meningitidis is a reportable infectious disease in China, due to the high incidence of meningitis in the era before the availability of vaccines. The disease incidence was markedly reduced after meningococcal vaccination was introduced in the 1980s. Currently, there are polysaccharide, conjugate, and combined vaccine formulations against meningococcal meningitis in the Chinese market, almost all of which are produced by domestic manufacturers. It is necessary to further enhance national meningococcal surveillance to improve the level of prevention and control of meningococcus. However, the immune efficacy and persistence of immunity of vaccines should be monitored. More importantly, additional investments should be made to develop serogroup B meningococcal vaccines.

Two-stage ensemble-based forecasting methods have been studied extensively in the wind power forecasting field. However, deep learning-based wind power forecasting studies have not investigated two aspects. In the first stage, different learning structures considering multiple inputs and multiple outputs have not been discussed. In the second stage, the model extrapolation issue has not been investigated. Therefore, we develop four deep neural networks for the first stage to learn data features considering the input-and-output structure. We then explore the model extrapolation issue in the second stage using different modeling methods. Considering the overfitting issue, we propose a new moving window-based algorithm using a validation set in the first stage to update the training data in both stages with two different moving window processes. Experiments were conducted at three wind farms, and the results demonstrate that the model with single-input–multiple-output structure obtains better forecasting accuracy compared to existing models. In addition, the ridge regression method results in a better ensemble model that can further improve forecasting accuracy compared to existing machine learning methods. Finally, the proposed two-stage forecasting algorithm can generate more accurate and stable results than existing algorithms.

BackgroundThe neutrophil-to-lymphocyte ratio (NLR) is a biomarker reflecting the balance between inflammation (as indicated by the neutrophil count) and adaptive immunity (as indicated by the lymphocyte count). We aimed to estimate ability of NLR at admission and at day 1 for predicting stroke outcome after two reperfusion therapies: intravenous thrombolysis (IVT) and mechanical thrombectomy (MT).MethodsA retrospective analysis was performed on patients who received recombinant human tissue plasminogen activator (IVT) and/or underwent MT for acute ischemic stroke (AIS) at the First Affiliated Hospital of Wenzhou Medical University (Wenzhou, China) from January 2018 to December 2020. Blood samples were taken on admission to hospital and on day 1 after stroke onset. Binary logistic regression models were applied to investigate potential associations between NLR at admission or day 1 and the following outcomes: symptomatic intracerebral hemorrhage (sICH), dependence, and mortality at 90 days. The ability of NLR to predict AIS outcome was analyzed using receiver operating characteristic (ROC) curves.ResultsData for 927 patients (576 IVT and 351 MT) were reviewed. High admission NLR was associated with dependence in IVT treatment [adjusted odds ratio (OR) 1.21, 95% confidence interval (CI) 1.14–1.23] and 90-day mortality in MT patients (OR 1.09, 95% CI 1.04–1.13). In IVT patients, high NLR at day 1 predicted dependence (OR 1.09, 95% CI 1.02–1.11), sICH (OR = 1.07, 95% CI 1.01–1.12), and 90-day mortality (OR 1.06, 95% CI 1.01–1.15). In MT patients, high NLR at day 1 also predicted dependence (OR 1.08, 95% CI 1.02–1.11) and sICH (OR 1.03, 95% CI 1.01–1.09). ROC analysis confirmed that NLR at day 1 could predict dependence (cut-off 4.2; sensitivity 68.7%; specificity 79.6%), sICH (cut-off 5.1; sensitivity 57.9%, specificity 73.5%), and death (cut-off 5.4; sensitivity 78.8%; specificity 76.4%) in IVT patients. Z values of area under the curves were compared between admissioin and day 1 NLR in IVT patients and showed day 1 NLR can better predict dependence (Z = 2.8, p = 0.004) and 90-day death (Z = 2.8, p = 0.005).ConclusionsNLR is a readily available biomarker that can predict AIS outcome after reperfusion treatment and day 1 NLR is even better than admission NLR.

Dioscorea cirrhosa is a plant that is used as a dye as well as in medicine. Many metabolites with pharmacological activity exist in the tubers of D. cirrhosa. However, little is known about the mechanism regulating biosynthesis in these metabolites. In this study, transcriptome and metabolome profiling were performed in four color tubers. A total of 531 metabolites, including 62 flavonoids, were identified. Epicatechin and proanthocyanin B2 were the key metabolites that exhibited high content levels in the four tubers. These metabolites were divided into nine classes with distinct change patterns. A total of 22,865 differentially expressed genes (DEGs) were identified by transcriptome analysis. Among these DEGs, we identified 67 candidate genes related to the flavonoid biosynthesis pathway and three genes that played pivotal roles in proanthocyanin (PA) synthesis. A weighted gene co-expression network analysis (WGCNA) revealed that the two modules, “MEblue” and “MEblack,” were two key gene sets strongly associated with phenylpropanoid and flavonoid biosynthesis. We also found that the plant hormone signal transduction biological process exhibited activity in the late stage of tuber color formation. Additionally, we identified 37 hub transcript factors related to flavonoid biosynthesis, of which 24 were found to be highly associated with flavonoid pathway genes. In addition to the MYB-bHLH-WD40 (MBW) genes, we found that the plant hormone gene families exhibited high expression levels. This study provides a reference for understanding the synthesis of D. cirrhosa tuber metabolites at the molecular level and provides a foundation for the further development of D. cirrhosa related plant pigments as well as its further use in the pharmaceutical industry.

BackgroundThe lung immune prognostic index (LIPI), composed of serum lactate dehydrogenase (LDH) and the derived neutrophil to lymphocyte ratio (dNLR), is a novel prognostic factor of lung cancer. The prognostic effect of the LIPI has never been verified in osteosarcoma.MethodsWe retrospectively reviewed the osteosarcoma patients with metachronous metastasis from January 2016 to January 2021 in West China Hospital. We collected and analyzed the clinical data and constructed the LIPI for osteosarcoma. The correlation between the LIPI and metastasis was analyzed according to the Kaplan–Meier method and Cox regression analysis with hazard ratios (HRs) and 95% confidence intervals (CIs). Univariate analysis and multivariate analysis were conducted to clarify the independent risk factors of metastasis. The nomogram model was established by R software, version 4.1.0.ResultsThe area under the curve (AUC) and best cutoff value were 0.535 and 91, 0.519, and 5.02, 0.594 and 2.77, 0.569 and 227.14, 0.59 and 158, and 0.607 and 2.05 for ALP, LMR, NLR, PLR, LDH, and dNLR, respectively. The LIPI was composed of LDH and dNLR and showed a larger AUC than other hematological factors in the time-dependent operator curve (t-ROC). In total, 184 patients, 42 (22.8%), 96 (52.2%), and 46 (25.0%) patients had LIPIs of good, moderate, and poor, respectively (P

Arrhythmias are clinically prevalent with a high mortality rate. They impose a huge economic burden, thereby substantially affecting the quality of life. Sodium-glucose co-transporter 2 inhibitor (SGLT2i) is a new type of hypoglycemic drug, which can regulate blood glucose level safely and effectively. Additionally, it reduces the occurrence and progression of heart failure and cardiovascular events significantly. Recently, studies have found that SGLT2i can alleviate the occurrence and progression of cardiac arrhythmias; however, the exact mechanism remains unclear. In this review, we aimed to discuss and summarize new literature on different modes in which SGLT2i ameliorates the occurrence and development of cardiac arrhythmias.

Metformin is a first-line drug for the clinical treatment of type 2 diabetes; however, it always leads to gastrointestinal tolerance, low bioavailability, short half-life, etc. Liposome acts as an excellent delivery system that could reduce drug side effects and promote bioavailability. Hyodeoxycholic acid, a cholesterol-like structure, can regulate glucose homeostasis and reduce the blood glucose levels. As an anti-diabetic active ingredient, hyodeoxycholic acid modifies liposomes to make it overcome the disadvantages of metformin as well as enhance the hypoglycemic effect. By adapting the thin-film dispersion method, three types of liposomes with different proportions of hyodeoxycholic acid and metformin were prepared (HDCA:ME-(0.5:1)-Lips, HDCA:ME-(1:1)-Lips, and HDCA:ME-(2:1)-Lips). Further, the liposomes were characterized, and the anti-type 2 diabetes activity of liposomes was evaluated. The results from this study indicated that three types of liposomes exhibited different characteristics—Excessive hyodeoxycholic acid decreased encapsulation efficiency and drug loading. In the in vivo experiments, liposomes could reduce the fasting blood glucose levels, improve glucose tolerance, regulate oxidative stress markers and protect liver tissue in type 2 diabetic mice. These results indicated that HDCA:ME-(1:1)-Lips was the most effective among the three types of liposomes prepared and showed better effects than metformin. Hyodeoxycholic acid can enhance the hypoglycemic effect of metformin and play a suitable role as an excipient in the liposome.

Abstract Background Aberrant DNA methylation is significantly associated with breast cancer. Methods In this study, we aimed to determine novel methylation biomarkers using a bioinformatics analysis approach that could have clinical value for breast cancer diagnosis and prognosis. Firstly, differentially methylated DNA patterns were detected in breast cancer samples by comparing publicly available datasets (GSE72245 and GSE88883). Methylation levels in 7 selected methylation biomarkers were also estimated using the online tool UALCAN. Next, we evaluated the diagnostic value of these selected biomarkers in two independent cohorts, as well as in two mixed cohorts, through ROC curve analysis. Finally, prognostic value of the selected methylation biomarkers was evaluated breast cancer by the Kaplan-Meier plot analysis. Results In this study, a total of 23 significant differentially methylated sites, corresponding to 9 different genes, were identified in breast cancer datasets. Among the 9 identified genes, ADCY4, CPXM1, DNM3, GNG4, MAST1, mir129-2, PRDM14, and ZNF177 were hypermethylated. Importantly, individual value of each selected methylation gene was greater than 0.9, whereas predictive value for all genes combined was 0.9998. We also found the AUC for the combined signature of 7 genes (ADCY4, CPXM1, DNM3, GNG4, MAST1, PRDM14, ZNF177) was 0.9998 [95% CI 0.9994–1], and the AUC for the combined signature of 3 genes (MAST1, PRDM14, and ZNF177) was 0.9991 [95% CI 0.9976–1]. Results from additional validation analyses showed that MAST1, PRDM14, and ZNF177 had high sensitivity, specificity, and accuracy for breast cancer diagnosis. Lastly, patient survival analysis revealed that high expression of ADCY4, CPXM1, DNM3, PRDM14, PRKCB, and ZNF177 were significantly associated with better overall survival. Conclusions Methylation pattern of MAST1, PRDM14, and ZNF177 may represent new diagnostic biomarkers for breast cancer, while methylation of ADCY4, CPXM1, DNM3, PRDM14, PRKCB, and ZNF177 may hold prognostic potential for breast cancer.

In this paper, a two-timescale radio access network (RAN) slicing and computing task offloading problem is investigated for a cloud-enabled autonomous vehicular network (C-AVN). We aim at jointly maximizing the communication and computing resource utilization with diverse quality-of-service (QoS) guarantee for autonomous driving tasks. Specifically, to capture the small-timescale network dynamics, a computing task scheduling problem is formulated as a stochastic optimization program, for maximizing the long-term network-wide computation load balancing with minimum task offloading variations. Due to the large problem size and unavailable network state transition probabilities, we employ cooperative multi-agent deep Q-learning (MA-DQL) with fingerprint to solve the problem by learning the set of stationary task offloading policies with stabilized convergence. Given the task offloading decisions, we further study a RAN slicing problem in a large timescale, which is formulated as a convex optimization program. We focus on optimizing the radio resource slicing ratios among base stations, to maximize the aggregate network utility with statistical QoS provisioning for autonomous driving tasks. Based on the impact of radio resource slicing on computation load balancing, we propose a two-timescale hierarchical optimization framework to maximize both communication and computing resource utilization. Extensive simulation results are provided to demonstrate the effectiveness of the proposed framework in comparison with state-of-the-art schemes.

BackgroundTo determine the non-inferiority of the seven common serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F) in the 13-valent pneumococcal conjugate vaccine (PCV13) with each serotype conjugated to a tetanus toxoid carrier protein and adsorbed on aluminum phosphate and the superiority of its six additional serotypes (1, 3, 5, 6A, 7F, and 19A) to the serotypes in the PCV7.MethodsParticipants were evenly randomized in a 1:1 ratio into either the PCV13 or PCV7 groups, to receive three doses of the vaccine at the age of 3, 4, and 5 months, respectively, and a booster dose between 12 and 15 months of age. Serotype-specific antibodies were measured using a standardized enzyme-linked immunosorbent assay (ELISA) and opsonophagocytic activity (OPA) microcolony assay method.ResultsA total of 1,040 healthy infants were enrolled. All the seven common serotypes in the PCV13 were non-inferior to those in the PCV7 in terms of the serotype-specific IgG production induced; however, non-inferiority was not shown for serotype 6B after the infant series. The proportion of subjects who reached OPA antibody titers ≥ 1:8 in the PCV13 group was 89.25% or higher. Local reactions and systemic events were mild or moderate in severity and similar between the two groups. No new safety signals were observed.ConclusionThe newly developed PCV13 was immunogenic for all serotypes and had a comparable safety profile to the marketed PCV7.

Arginase is a key hydrolase in the urea cycle that hydrolyses L-arginine to urea and L-ornithine. Increasing number of studies in recent years demonstrate that two mammalian arginase isoforms, arginase 1 (ARG1) and arginase 2 (ARG2), were aberrantly upregulated in various types of cancers, and played crucial roles in the regulation of tumor growth and metastasis through various mechanisms such as regulating L-arginine metabolism, influencing tumor immune microenvironment, etc. Thus, arginase receives increasing focus as an attractive target for cancer therapy. In this review, we provide a comprehensive overview of the physiological and biological roles of arginase in a variety of cancers, and shed light on the underlying mechanisms of arginase mediating cancer cells growth and development, as well as summarize the recent clinical research advances of targeting arginase for cancer therapy.

Rice growth requires a large amount of water, and planting rice will increase the contradiction between supply and demand of water resources. Paddy field fallowing is important for the sustainable development of an agricultural region, but it remains a great challenge to accurately and quickly monitor the extent and area of fallowed paddy fields. Paddy fields have unique physical features associated with paddy rice during the flooding and transplanting phases. By comparing the differences in phenology before and after paddy field fallowing, we proposed a phenology-based fallowed paddy field mapping algorithm. We used the Google Earth Engine (GEE) cloud computing platform and Landsat 8 images to extract the fallowed paddy field area on Sanjiang Plain of China in 2018. The results indicated that the Landsat8, GEE, and phenology-based fallowed paddy field mapping algorithm can effectively support the mapping of fallowed paddy fields on Sanjiang Plain of China. Based on remote sensing monitoring, the total fallowed paddy field area of Sanjiang Plain is 91 543 ha. The resultant fallowed paddy field map is of high accuracy, with a producer (user) accuracy of 83% (81%), based on validation using ground-truth samples. The Landsat-based map also exhibits high consistency with the agricultural statistical data. We estimated that paddy field fallowing reduced irrigation water by 384–521 million cubic meters on Sanjiang Plain in 2018. The research results can support subsidization grants for fallowed paddy fields, the evaluation of fallowed paddy field effects and improvement in subsequent fallowed paddy field policy in the future.

Leptospira interrogans serogroup Canicola is one of the most important pathogens causing leptospirosis and is used as a vaccine strain of the current Chinese human leptospirosis vaccine. To characterize leptospiral pathogens, L. interrogans serogroup Canicola vaccine strain 611 and circulating isolate LJ178 from different hosts at different periods were sequenced using a combined strategy of Illumina X10 and PacBio technologies, and a comprehensive comparative analysis with other published Leptospira strains was conducted in this study. High levels of genomic similarities were observed between vaccine strain 611 and circulating isolate LJ178; both had two circular chromosomes and two circular extrachromosomal replicons. Compared with the strain 611 genome, 132 single nucleotide polymorphisms and 92 indels were found in strain LJ178. The larger lipopolysaccharide biosynthesis locus of serogroup Canicola was identified in both genomes. The phylogenetic analysis based on whole-genome sequences revealed that serogroup Canicola was not restricted to a specific host or geographic location, suggesting adaptive evolution associated with the ecologic diversity. In summary, our findings provide insights into a better molecular understanding of the component strains of human leptospirosis vaccine in China. Furthermore, these data detail the genetic composition and evolutionary relatedness of Leptospira strains that pose a health risk to humans.

A genome-wide association study (GWAS) reported PLCL2 on chromosome 3p24. 3 (rs4618210:A>G) as a novel susceptibility locus for myocardial infarction in the Japanese population. As the most common pathological process, atherosclerosis leads to metabolic syndrome (MetS)-related ischaemic stroke (IS) and myocardial infarction. Hypothesizing that polymorphisms of the PLCL2 gene might be associated with the onset and prognosis of IS in MetS patients, we performed the following study in a Chinese Han population. A total of 709 cases (patients with MetS plus IS) and 711 controls (patients with MetS) were enrolled. A fine-mapping strategy was adopted to identify tagged single nucleotide polymorphisms (SNPs) of the PLCL2 gene, and improved multiplex ligation detection reaction (iMLDR) technology was used to genotype the selected SNPs. Logistic regression was used to analyse the values of the selected SNPs for the risk of IS between the cases and controls, adjusting for sex, age, hypertension, dyslipidaemia, hyperglycaemia, smoking and drinking. To compare the mean age of IS onset among different risk score groups, a genetic risk score was constructed for each case. The cumulative risk of IS events in the case group was presented using a cumulative incidence curve. All cases were followed up for 3 months, and functional outcomes were recorded prospectively. Two SNPs (rs4685423 and rs4618210) were significantly related to the risk of IS in MetS patients. For rs4685423, patients who were AA homozygotes were less likely to suffer from IS than C-allele carriers (OR 0.718; 95% CI 0.567–0.909; multivariate-adjusted, P = 0.006). For rs4618210, A-allele carriers were less likely to develop IS than patients who were GG homozygotes (OR 0.679; 95% CI 0.548–0.841; multivariate-adjusted, P < 0.001). As the genetic risk score increased, the mean age at IS onset decreased (log-rank P = 0.010). There was no statistically significant difference in the distribution of the 90-day modified Rankin Scale (mRS) outcomes across the rs4685423 (P = 0.319) or rs4618210 polymorphisms (P = 0.148). Our findings suggested that genetic polymorphisms of PLCL2 might be associated with the onset of MetS-related IS. Further studies are warranted to validate our findings in other ethnic populations.