BACKGROUND: Diabetes foot is one of the most serious complications of diabetes and an important cause of death and disability, traditional treatment has poor efficacy and there is an urgent need to develop a practical treatment method. AIM: To investigate whether Huangma Ding or autologous platelet-rich gel (APG) treatment would benefit diabetic lower extremity arterial disease (LEAD) patients with foot ulcers. METHODS: A total of 155 diabetic LEAD patients with foot ulcers were enrolled and divided into three groups: Group A (62 patients; basal treatment), Group B (38 patients; basal treatment and APG), and Group C (55 patients; basal treatment and Huangma Ding). All patients underwent routine follow-up visits for six months. After follow-up, we calculated the changes in all variables from baseline and determined the differences between groups and the relationships between parameters. RESULTS: The infection status of the three groups before treatment was the same. Procalcitonin (PCT) improved after APG and Huangma Ding treatment more than after traditional treatment and was significantly greater in Group C than in Group B. Logistic regression analysis revealed that PCT was positively correlated with total amputation, primary amputation, and minor amputation rates. The ankle-brachial pressure and the transcutaneous oxygen pressure in Groups B and C were greater than those in Group A. The major amputation rate, minor amputation rate, and total amputation times in Groups B and C were lower than those in Group A. CONCLUSION: Our research indicated that diabetic foot ulcers (DFUs) lead to major amputation, minor amputation, and total amputation through local infection and poor microcirculation and macrocirculation. Huangma Ding and APG were effective attreating DFUs. The clinical efficacy of Huangma Ding was better than that of autologous platelet gel, which may be related to the better control of local infection by Huangma Ding. This finding suggested that in patients with DFUs combined with coinfection, controlling infection is as important as improving circulation.
Bicyclo[1.1.0]butane-containing compounds feature a unique chemical reactivity, trigger "strain-release" reaction cascades, and provide novel scaffolds with considerable utility in the drug discovery field. We report the synthesis of new bicyclo[1.1.0]butane-linked heterocycles by a nucleophilic addition of bicyclo[1.1.0]butyl anions to 8-isocyanatoquinoline, or, alternatively, iminium cations derived from quinolines and pyridines. The resulting bicyclo[1.1.0]butanes are converted with high regioselectivity to unprecedented bridged heterocycles in a rhodium(I)-catalyzed annulative rearrangement. The addition/rearrangement process tolerates a surprisingly large range of functional groups. Subsequent chemo- and stereoselective synthetic transformations of urea, alkene, cyclopropane, and aniline moieties of the 1-methylene-5-azacyclopropa[cd]indene scaffolds provide several additional new heterocyclic building blocks. X-ray structure-validated quantum mechanical DFT calculations of the reaction pathway indicate the intermediacy of rhodium carbenoid and metallocyclobutane species.
Epileptic seizures are unpredictable events caused by abnormal discharges of a patient's brain cells. Extensive research has been conducted to develop seizure prediction algorithms based on long-term continuous electroencephalogram (EEG) signals. This paper describes a patient-specific seizure prediction method that can serve as a basis for the design of lightweight, wearable and effective seizure-prediction devices. We aim to achieve two objectives using this method. The first aim is to extract robust feature representations from multichannel EEG signals, and the second aim is to reduce the number of channels used for prediction by selecting an optimal set of channels from multichannel EEG signals while ensuring good prediction performance. We design a seizure-prediction algorithm based on a vision transformer (ViT) model. The algorithm selects channels that play a key role in seizure prediction from 22 channels of EEG signals. First, we perform a time-frequency analysis of processed time-series signals to obtain EEG spectrograms. We then segment the spectrograms of multiple channels into many non-overlapping patches of the same size, which are input into the channel selection layer of the proposed model, named Sel-JPM-ViT, enabling it to select channels. Application of the Sel-JPM-ViT model to the Boston Children's Hospital-Massachusetts Institute of Technology scalp EEG dataset yields results using only three to six channels of EEG signals that are slightly better that the results obtained using 22 channels of EEG signals. Overall, the Sel-JPM-ViT model exhibits an average classification accuracy of 93.65%, an average sensitivity of 94.70% and an average specificity of 92.78%.
The volatile oils are the effective components of Agastache rugosa, which are stored in the glandular scale. The leaves of pulegone-type A. rugosa were used as materials to observe the leaf morphology of A. rugosa at different growth stages, and the components of volatile oils in gland scales were detected by GC-MS. At the same time, qRT-PCR was used to determine the relative expression of key enzyme genes in the biosynthesis pathway of monoterpenes in volatile oils. The results showed that the density of A. rugosa glandular scale decreased first and then tended to be stable. With the growth of leaves, the relative content of pulegone decreased from 79.26% to 3.94%(89.97%-41.44%), while that of isomenthone increased from 2.43% to 77.87%(0.74%-51.01%), and the changes of other components were relatively insignificant. The correlation analysis between the relative content of monoterpenes and the relative expression levels of their key enzyme genes showed that there was a significant correlation between the relative content of menthone and isomenthone and the relative expression levels of pulegone reductase(PR)(r>0.6, P<0.01). To sum up, this study revealed the accumulation rules of the main components of the contents of the glandular scale of A. rugosa and the expression rules of the key enzyme genes for biosynthesis, which provided a scientific basis and data support for determining the appropriate harvesting period and quality control of the medicinal herbs. This study also initially revealed the biosynthesis mechanism of the monoterpenes mainly composed of pulegone and isomenthone in A. rugosa, laying a foundation for further research on the molecular mechanism of synthesis and accumulation of monoterpenes in A. rugosa.
Agastache , Cyclohexane Monoterpenes , Oils, Volatile , Oils, Volatile/analysis , Agastache/metabolism , Monoterpenes/metabolism
The complication of diabetes, which is known as diabetic foot ulcer (DFU), is a significant concern due to its association with high rates of disability and mortality. It not only severely affects patients' quality of life, but also imposes a substantial burden on the healthcare system. In spite of efforts made in clinical practice, treating DFU remains a challenging task. While mesenchymal stem cell (MSC) therapy has been extensively studied in treating DFU, the current efficacy of DFU healing using this method is still inadequate. However, in recent years, several MSCs-based drug delivery systems have emerged, which have shown to increase the efficacy of MSC therapy, especially in treating DFU. This review summarized the application of diverse MSCs-based drug delivery systems in treating DFU and suggested potential prospects for the future research.
Terpenoids are important secondary metabolites of plants that possess both pharmacological activity and economic value. Terpene synthases(TPSs) are key enzymes in the synthesis process of terpenoids. In order to investigate the TPS gene family members and their potential functions in Schizonepeta tenuifolia, this study conducted a systematic analysis of the TPS gene family of S. tenuifolia based on the whole genome data of S. tenuifolia using bioinformatics methods. The results revealed 57 StTPS members identified from the genome database of S. tenuifolia. The StTPS family members encoded 285-819 amino acids, with protein molecular weights ranging from 32.75 to 94.11 kDa, all of which were hydrophilic proteins. The StTPS family members were mainly distributed in the cytoplasm and chloroplasts, exhibiting a random and uneven physical localization pattern. Phylogenetic analysis showed that the StTPS genes family were divided into six subgroups, mainly belonging to the TPS-a and TPS-b subfamilies. Promoter analysis predicted that the TPS gene family members could respond to various stressors such as light, abscisic acid, and methyl jasmonate(MeJA). Transcriptome data analysis revealed that most of the TPS genes were expressed in the roots of S. tenuifolia, and qRT-PCR analysis was conducted on genes with high expression in leaves and low expression in roots. Through the analysis of the TPS gene family of S. tenuifolia, this study identified StTPS5, StTPS18, StTPS32, and StTPS45 as potential genes involved in sesquiterpene synthesis of S. tenuifolia. StTPS45 was cloned for the construction of an prokaryotic expression vector, providing a reference for further investigation of the function and role of the TPS gene family in sesquiterpene synthesis.
Lamiaceae , Sesquiterpenes , Phylogeny , Terpenes/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Lamiaceae/genetics
Introduction: When an intraocular lens (IOL) injector is inserted through a pre-cut corneal incision (e.g., an empirical size of 2.2 mm) during small incision cataract surgery, uncontrollable tearing to the corneal tissue may occur, which is highly associated with the incision shape, size, and location. The goal of this numerical study was to investigate the optimal incision scheme amongst three typical shapes, i.e., straight, frown, and chevron incisions using mechanical modeling and finite element analysis. Methods: Assuming that the damage is caused by the tissue fracture at the incision tips and is governed by the classical energy release rate (ERR) theory which compares the current ERR value subject to IOL injection and the material's intrinsic parameter, critical ERR G c. Results: It was found that for chevron incisions, the incision shape with an angle of 170° was superior which induced minimal ERR value, while for frown incisions, the shape with a central angle of 6° was optimal. Both chevron and frown incisions could allow a larger size of injector to inject through than a straight pre-cut. In particular, the frown incision performed the best due to its lowest corresponding ERR and easy operation. Discussion: It was also observed that regions where the embedded fibrils are more dispersed and exhibit high isotropy were more favorable. If necessary, the chevron incision was recommended to be more aligned with the direction exhibiting a larger modulus, for example, along the circumferential direction near the limbus. This study provides useful knowledge in operation design and a deep insight into mechanical damage to corneal wounds in small incision cataract surgery.
The exponential growth of stationary energy storage systems (ESSs) and electric vehicles (EVs) necessitates a more profound understanding of the degradation behavior of lithium-ion batteries (LIBs), with specific emphasis on their lifetime. Accurately forecasting the lifetime of batteries under various working stresses aids in optimizing their operating conditions, prolonging their longevity, and ultimately minimizing the overall cost of the battery life cycle. Accelerated aging, as an efficient and economical method, can output sufficient cycling information in short time, which enables a rapid prediction of the lifetime of LIBs under various working stresses. Nevertheless, the prerequisite for accelerated aging-based battery lifetime prediction is the consistency of aging mechanisms. This review, by comprehensively summarizing the aging mechanisms of various components within LIBs and the battery degradation mechanisms under stress-accelerated conditions, provides a reference for evaluating the consistency of battery aging mechanisms. Furthermore, this paper introduces accelerated aging-based lifetime prediction models and offers constructive suggestions for future research on accelerated lifetime prediction of LIBs.
Ring-opening of bicyclo[1.1.0]butanes (BCBs) is emerging as a powerful strategy for 1,3-difunctionalized cyclobutane synthesis. However, reported radical strain-release reactions are typically plagued with diastereoselectivity issues. Herein, an atom-economic protocol for the highly chemo- and diastereoselective polar strain-release ring-opening of BCBs with hydroxyarenes catalyzed by a π-acid catalyst AgBF4 has been developed. The use of readily available starting materials, low catalyst loading, high selectivity (up to >98 : 2 d.r.), a broad substrate scope, ease of scale-up, and versatile functionalizations of the cyclobutane products make this approach very attractive for the synthesis of 1,1,3-trisubstituted cyclobutanes. Moreover, control experiments and theoretical calculations were performed to illustrate the reaction mechanism and selectivity.
Cholesterol plays essential roles in biological processes, including cell membrane stability and myelin formation. Cholesterol can be metabolized to oxysterols by enzymatic or nonenzymatic ways. Nonenzymatic cholesterol metabolites, also called cholesterol-autoxidation metabolites, are formed dependent on the oxidation of reactive oxygen species (ROS) such as OH⢠or reactive nitrogen species, such as ONOO- . Cholesterol-autoxidation metabolites are abundantly produced in diseases such as inflammatory bowel disease and atherosclerosis, which are associated with oxidative stress. Recent studies have shown that cholesterol-autoxidation metabolites can further regulate the immune system. Here, we review the literature and summarize how cholesterol-autoxidation metabolites, such as 25-hydroxycholesterol (25-OHC), 7α/ß-OHC, and 7-ketocholesterol, deal with the occurrence and development of infectious diseases through pattern recognition receptors, inflammasomes, ROS production, nuclear receptors, G-protein-coupled receptor 183, and lipid availability. In addition, we include the research regarding the roles of these metabolites in COVID-19 infection and discuss our viewpoints on the future research directions.
COVID-19 , Communicable Diseases , Humans , Reactive Oxygen Species , Hydroxycholesterols/metabolism , Oxidative Stress , Oxidation-Reduction
Epizootic hemorrhagic disease (EHD) is an infectious viral disease caused by epizootic hemorrhagic disease virus (EHDV) and EHDV frequently circulates in wild and domestic ruminants. Sporadic outbreaks of EHD have caused thousands of deaths and stillbirths on cattle farms. However, not much is known about the circulating status of EHDV in Guangdong, southern China. To estimate the seroprevalence of EHDV in Guangdong province, 2886 cattle serum samples were collected from 2013 to 2017 and tested for antibodies against EHDV using a competitive ELISA. The overall seroprevalence of EHDV reached 57.87% and was highest in autumn (75.34%). A subset of positive samples were serotyped by a serum neutralization test, showing that EHDV serotypes 1 and 5-8 were circulating in Guangdong. In addition, EHDV prevalence always peaked in autumn, while eastern Guangdong had the highest EHDV seropositivity over the five-year period, displaying apparent temporal-spatial distribution of EHDV prevalence. A binary logistic model analysis indicated a significant association between cattle with BTV infections and seroprevalence of EHDV (OR = 1.70, p < 0.001). The co-infection of different serotypes of EHDV and BTV raises a high risk of potential genomic reassortment and is likely to pose a significant threat to cattle, thus urging more surveillance to monitor their circulating dynamics in China.
Bluetongue virus , Cattle Diseases , Hemorrhagic Disease Virus, Epizootic , Reoviridae Infections , Animals , Cattle , Reoviridae Infections/epidemiology , Reoviridae Infections/veterinary , Hemorrhagic Disease Virus, Epizootic/genetics , Seroepidemiologic Studies , Farms , Antibodies, Viral
As a photonic-based microwave signal generation method, the optoelectronic oscillator (OEO) has the potential of meeting the increasing demand of practical applications for high frequency, broadband tunability and ultra-low phase noise. However, conventional OEO systems implemented with discrete optoelectronic devices have a bulky size and low reliability, which extremely limits their practical applications. In this paper, a hybrid-integrated wideband tunable OEO with low phase noise is proposed and experimentally demonstrated. The proposed hybrid integrated OEO achieves a high integration level by first integrating a laser chip with a silicon photonic chip, and then connecting the silicon photonic chip with electronic chips through wire-bonding to microstrip lines. A compact fiber ring and an yttrium iron garnet filter are also adopted for high-Q factor and frequency tuning, respectively. The integrated OEO exhibits a low phase noise of -128.04 dBc/Hz @ 10 kHz for an oscillation frequency of 10â GHz. A wideband tuning range from 3â GHz to 18â GHz is also obtained, covering the entire C, X, and Ku bands. Our work demonstrates an effective way to achieve compact high-performance OEO based on hybrid integration, and has great potential in a wide range of applications such as modern radar, wireless communication, and electronic warfare systems.
Epilepsy is a recurrent chronic brain disease that affects nearly 75 million people around the world. Therefore, the ability to reliably predict epileptic seizures would be instrumental for implementing interventions to reduce brain injury and improve patients' quality of life. In addition to classical machine learning algorithms and feature engineering methods, the use of electroencephalography (EEG) to predict seizures has gradually become a mainstream trend. Here, we propose a patient-specific method to predict epileptic seizures based on EEG data acquired using spatial depth features of a three-dimensional-two-dimensional hybrid convolutional neural network (3D-2D HyCNN) model. This method facilitates the acquisition of abundant and reliable deep features from multi-channel EEG signals. We first developed a reliable data preprocessing method to reconstruct time-series EEG signals into 3D feature images. Then, the 3D-2D HyCNN model was used to extract correlation features between multiple channels of EEG signals, which are automatically exploited by the network to improve seizure prediction. The method achieved accuracy of 98.43% and 93.11%, sensitivity of 98.58% and 90.98%, and specificity of 96.86% and 92.39% on the CHB-MIT Scalp EEG dataset and the American Epilepsy Society Epilepsy Prediction Challenge dataset, respectively. The results revealed that the new algorithm is reliable. Graphical Abstract A new patient-specific epilepsy prediction approach.
Epilepsy , Quality of Life , Humans , Seizures/diagnosis , Epilepsy/diagnosis , Neural Networks, Computer , Algorithms , Electroencephalography/methods
Due to the rise of 5G, IoT, AI, and high-performance computing applications, datacenter traffic has grown at a compound annual growth rate of nearly 30%. Furthermore, nearly three-fourths of the datacenter traffic resides within datacenters. The conventional pluggable optics increases at a much slower rate than that of datacenter traffic. The gap between application requirements and the capability of conventional pluggable optics keeps increasing, a trend that is unsustainable. Co-packaged optics (CPO) is a disruptive approach to increasing the interconnecting bandwidth density and energy efficiency by dramatically shortening the electrical link length through advanced packaging and co-optimization of electronics and photonics. CPO is widely regarded as a promising solution for future datacenter interconnections, and silicon platform is the most promising platform for large-scale integration. Leading international companies (e.g., Intel, Broadcom and IBM) have heavily investigated in CPO technology, an inter-disciplinary research field that involves photonic devices, integrated circuits design, packaging, photonic device modeling, electronic-photonic co-simulation, applications, and standardization. This review aims to provide the readers a comprehensive overview of the state-of-the-art progress of CPO in silicon platform, identify the key challenges, and point out the potential solutions, hoping to encourage collaboration between different research fields to accelerate the development of CPO technology.
Small mammals can transmit and serve as a reservoir for Orientia tsutsugamushi (Ot) in nature by carrying infected mites. In Yunnan, one of China's main foci of scrub typhus, etiological evidence and genetic diversity for Ot is limited. A total of 2538 small mammals were captured seasonally from 2015 to 2016 in the three counties of Yunnan, and the spleen or liver tissue was examined for Ot based on 56 kDa nPCR. The overall prevalence of Ot was 1.77%, ranging from 0.26 to 9.09% across different species. The Gilliam strain was found in 35.6% (16/45) of the wild small mammals, followed by the Karp 11.1% (5/45) and TA763 (1/45) strains, the last of which was discovered in western Yunnan for the first time. In Lianghe, Ot infection rates in wild small mammals were higher than in the other two counties. The infection rates of Eothenomys miletus with Ot were highest in the three dominant species. Ot infection rates in wild small mammals were higher in Lianghe (1200-1400 m) and Yulong (2800-3000 m). These findings could provide research clues for further confirmation of scrub typhus foci in western Yunnan or other similar natural environments.
Because of the continued emergence of SARS-CoV-2 variants, there has been considerable interest in how to display multivalent antigens efficiently. Bacterial outer membrane vesicles (OMVs) can serve as an attractive vaccine delivery system because of their self-adjuvant properties and the ability to be decorated with antigens. Here we set up a bivalent antigen display platform based on engineered OMVs using mCherry and GFP and demonstrated that two different antigens of SARS-CoV-2 could be presented simultaneously in the lumen and on the surface of OMVs. Comparing immunogenicity, ClyA-NG06 fusion and the receptor-binding domain (RBD) of the spike protein in the OMV lumen elicited a stronger humoral response in mice than OMVs presenting either the ClyA-NG06 fusion or RBD alone. Taken together, we provided an efficient approach to display SARS-CoV-2 antigens in the lumen and on the surface of the same OMV and highlighted the potential of OMVs as general multi-antigen carriers.
Terpenoids are important secondary metabolites of plants that possess both pharmacological activity and economic value. Terpene synthases(TPSs) are key enzymes in the synthesis process of terpenoids. In order to investigate the TPS gene family members and their potential functions in Schizonepeta tenuifolia, this study conducted a systematic analysis of the TPS gene family of S. tenuifolia based on the whole genome data of S. tenuifolia using bioinformatics methods. The results revealed 57 StTPS members identified from the genome database of S. tenuifolia. The StTPS family members encoded 285-819 amino acids, with protein molecular weights ranging from 32.75 to 94.11 kDa, all of which were hydrophilic proteins. The StTPS family members were mainly distributed in the cytoplasm and chloroplasts, exhibiting a random and uneven physical localization pattern. Phylogenetic analysis showed that the StTPS genes family were divided into six subgroups, mainly belonging to the TPS-a and TPS-b subfamilies. Promoter analysis predicted that the TPS gene family members could respond to various stressors such as light, abscisic acid, and methyl jasmonate(MeJA). Transcriptome data analysis revealed that most of the TPS genes were expressed in the roots of S. tenuifolia, and qRT-PCR analysis was conducted on genes with high expression in leaves and low expression in roots. Through the analysis of the TPS gene family of S. tenuifolia, this study identified StTPS5, StTPS18, StTPS32, and StTPS45 as potential genes involved in sesquiterpene synthesis of S. tenuifolia. StTPS45 was cloned for the construction of an prokaryotic expression vector, providing a reference for further investigation of the function and role of the TPS gene family in sesquiterpene synthesis.
Phylogeny , Terpenes/metabolism , Plant Proteins/metabolism , Lamiaceae/genetics , Sesquiterpenes
