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Three carbazole‐substituted anthracene 2CbzAn, 26CbzAn, and 246CbzAn have been developed. The introduction of these carbazole substituents could generate more triplet states with energy levels close to 2× E(T1) that could successfully facilitate the triplet‐triplet annihilation upconversion (TTA‐UC) process to achieve high upconversion quantum yield (UCQY). This observation aligns with the Adachi theory about TTA‐UC mechanisms. In organic light‐emitting diode (OLED) device investigation, in a non‐doped state show an external quantum efficiency (EQEmax) of 5.82% with exceptional pure‐blue emission (CIEy of 0.101), and the DPaNIF doped DMPPP/26CbzAn bilayer structure reaches an impressive EQEmax of 11.12%.

Sepsis is a dysregulated immune response to infection that comes with multiple organ dysfunction and high mortality. The management of sepsis relies heavily on early recognition and diagnosis, but current diagnostic methods have limitations in timeliness, sensitivity, and discriminability. This study aims to discover novel biomarkers for sepsis diagnosis. Four datasets from different regions were analyzed using weighted gene co-expression network analysis (WGCNA), and genes with high Gene Significance values across these datasets were overlapped. Finally, two genes, CD177 and ANXA3, were identified. ANXA3 was validated as a potential sepsis biomarker by checking multiple datasets and Receiver Operating Characteristic (ROC) Curve Analysis. Of note, ANXA3 could distinguish not only between adult and child sepsis patients and healthy controls, but also between septic shock and cardiogenic shock. Moreover, a murine sepsis model was established and the results showed that the transcription of ANXA3 in peripheral blood of septic mice was significantly higher than that of healthy controls, while Escherichia coli infection alone did not significantly increase the transcription level of this gene. Subsequent studies of sepsis in mice revealed that the predictive effect of Anxa3 on sepsis could be observed as early as 6 h post-modeling. Interestingly, ANXA3 expression was predominantly up-regulated in myeloid cells, up-regulated in spleen, down-regulated in lung, and not detected in liver after sepsis modeling. Taken together, this study provides a way for the discovery of biomarkers and finds that ANXA3 may be a novel diagnostic biomarker for sepsis.

BackgroundAn innovative way to quantify obesity that appropriately captures levels of visceral and body fat is the Body Roundness Index (BRI). The purpose of this study is to look at the relationship between BRI and osteoporosis (OP) in adult Americans.MethodsThis study utilized data from the National Health and Nutrition Examination Survey (NHANES) collected between 2007 and 2018. NHANES is a research program designed to assess the health and nutritional status of adults and children in the United States. It conducts surveys focusing on various populations and health-related topics. Logistic regression analysis was employed to investigate the relationship between BRI and OP, adjusting for various covariates. BRI was categorized into four levels to further explore the association trends between different BRI levels and OP, enhancing the robustness of the results. Using restricted cubic spline (RCS) analysis, the dose–response relationship between BRI and OP was illustrated. Subgroup analyses were also carried out to evaluate the consistency and robustness of the findings.ResultsThis study included 8,899 participants aged 50 years and older, among whom 763 had OP. BRI and the prevalence of OP were inversely correlated in the fully adjusted model (OR = 0.79, 95% CI: 0.69–0.86). The prevalence of OP considerably reduced with higher BRI levels when BRI was converted from a continuous to a categorical variable in comparison to the lowest BRI quartile. RCS analysis revealed an L-shaped negative correlation between BRI and OP prevalence, with a threshold effect analysis identifying a breakpoint at BRI = 5.29. Each unit increase in BRI to the left of this breakpoint was linked to a 36% decrease in the probability of OP (OR = 0.64, 95% CI: 0.57–0.72). Based on stratified factor subgroup analyses, it was shown that the negative correlation between BRI and OP persisted.ConclusionIn a large, representative sample of American adults, this study identified a significant negative correlation between BRI and the prevalence of OP. Specifically, as BRI increases, the prevalence of osteoporosis decreases. Maintaining an appropriate and healthy BRI level may play a critical role in the prevention of osteoporosis. Therefore, regular monitoring of BRI and the adoption of appropriate health measures are essential for reducing the risk of osteoporosis.

Hypobaric hypoxia causes altitude sickness and significantly affects human health. As of now, focusing on rats different proteomic and metabolic changes exposed to different hypoxic times at extreme altitude is blank. Our study integrated in vivo experiments with tandem mass tag (TMT)- and gas chromatography time-of-flight (GC-TOF)-based proteomic and metabolomic assessments, respectively. Male Sprague-Dawley rats were exposed to long-term constant hypoxia for 40 days or short-term constant hypoxia for three days, and their responses were compared with those of a normal control group. Post-hypoxia, serum marker assays related to lipid metabolism revealed significant increases in the levels of low-density lipoprotein (LDL), triglycerides (TG), and total cholesterol (TC) in the liver. In contrast, high-density lipoprotein (HDL) levels were upregulated in the long-term constant hypoxia cohorts and were significantly reduced in the short-term constant hypoxia cohorts. Furthermore, metabolic pathway analysis indicated that glycerolipid and glycerophospholipid metabolisms were the most significantly affected pathways in long-term hypoxia group. Subsequently, RT-qPCR analyses were performed to corroborate the key regulatory elements, including macrophage galactose-type lectin (MGL) and Fatty Acid Desaturase 2 (FADS2). The results of this study provide new information for understanding the effects of different hypobaric hypoxia exposure protocols on protein expression and metabolism in low-altitude animals.

In natural language processing (NLP), a Question Answering System (QAS) refers to a system or model that is designed to understand and respond to user queries in natural language. As we navigate through the recent advancements in QAS, it can be observed that there is a paradigm shift of the methods used from traditional machine learning and deep learning approaches towards transformer-based language models. While significant progress has been made, the utilization of these models for historical QAS and the development of QAS for Malay language remain largely unexplored. This research aims to bridge the gaps, focusing on developing a Multilingual QAS for history of Malaysia by utilizing a transformer-based language model. The system development process encompasses various stages, including data collection, knowledge representation, data loading and pre-processing, document indexing and storing, and the establishment of a querying pipeline with the retriever and reader. A dataset with a collection of 100 articles, including web blogs related to the history of Malaysia, has been constructed, serving as the knowledge base for the proposed QAS. A significant aspect of this research is the use of the translated dataset in English instead of the raw dataset in Malay. This decision was made to leverage the effectiveness of well-established retriever and reader models that were trained on English data. Moreover, an evaluation dataset comprising 100 question-answer pairs has been created to evaluate the performance of the models. A comparative analysis of six different transformer-based language models, namely DeBERTaV3, BERT, ALBERT, ELECTRA, MiniLM, and RoBERTa, has been conducted, where the effectiveness of the models was examined through a series of experiments to determine the best reader model for the proposed QAS. The experimental results reveal that the proposed QAS achieved the best performance when employing RoBERTa as the reader model. Finally, the proposed QAS was deployed on Discord and equipped with multilingual support through the incorporation of language detection and translation modules, enabling it to handle queries in both Malay and English. Doi: 10.28991/ESJ-2024-08-02-019 Full Text: PDF

AIM: To investigate the protective effects, antioxidant potential, and anti-inflammatory mechanisms of eicosane on glutamate-induced cell damage and on N-methyl-D-aspartate (NMDA)-induced retinal ganglion cell (RGC) injury in a mouse model of glaucoma. METHODS: The protective effects of eicosane on the rat R28 retinal precursor cell line were assessed using cell counting kit-8 assays and Hoechst-propidium iodide staining. Intracellular reactive oxygen species (ROS) production was measured using the fluorescent probe 2'-7'-dichlorofluorescin diacetate and flow cytometry. The protective role of eicosane on NMDA-induced RGC injury in a mouse glaucoma model was determined by immunostaining of frozen sections of retina. The effects of eicosane on the metabolome of the retina in mice with NMDA-induced RGC damage were evaluated by liquid chromatography-mass spectroscopy (LC-MS) and untargeted metabolomics analyses. RESULTS: Eicosane treatment significantly attenuated glutamate-induced damage to R28 cells in vitro. Eicosane also protected RGCs against NMDA-induced injury in a mouse glaucoma model. Untargeted metabolomics analyses showed that eicosane increased multiple metabolites, including L-arginine and L-carnitine, in the retina. CONCLUSION: Eicosane has protective effects, antioxidant potential, and anti-inflammatory properties in an in vitro model of glutamate-induced cell damage and in an in vivo model of NMDA-induced RGC injury in mouse glaucoma through modulation of L-arginine and/or L-carnitine metabolism.

Abstract EEG/MEG source imaging (ESI) aims to find the underlying brain sources to explain the observed EEG or MEG measurement. Multiple classical approaches have been proposed to solve the ESI problem based on different neurophysiological assumptions. To support clinical decision-making, it is important to estimate not only the exact location of the source signal but also the extended source activation regions. Existing methods may render over-diffuse or sparse solutions, which limit the source extent estimation accuracy. In this work, we leverage the graph structures defined in the 3D mesh of the brain and the spatial graph Fourier transform (GFT) to decompose the spatial graph structure into sub-spaces of low-, medium-, and high-frequency basis. We propose to use the low-frequency basis of spatial graph filters to approximate the extended areas of brain activation and embed the GFT into the classical ESI methods. We validated the classical source localization methods with the corresponding improved version using GFT in both synthetic data and real data. We found the proposed method can effectively reconstruct focal source patterns and significantly improve the performance compared to the classical algorithms.

AIM: To assess effectivity and safety of trifocal intraocular lenses (IOLs) and capsular tension rings in treating cataract patients with axial high myopia. METHODS: A prospective nonrandomized controlled clinical trial was conducted. Totally 98 eyes (74 patients) who underwent femtosecond laser-assisted cataract surgery (FLACS) with trifocal IOLs were enrolled in the study and followed up for 2y after surgery: 46 eyes (33 patients) with capsular tension ring implantation in the long axial lengths (AL) group (260.05). The dysfunctional lens index and total modulation transfer function (MTF) average height were similar between the two groups. The postoperative internal coma aberrations in the axial high myopia eyes were significantly higher than that in the normal AL group (P

Abstract Real-world data on effectiveness and safety of a single non-vitamin K antagonist oral anticoagulant in the Chinese population with atrial fibrillation (AF) are limited. This study reports characteristics of patients treated with edoxaban and factors associated with dosing patterns from routine care in China. ETNA-AF-China (NCT04747496) is a multicentre, prospective, observational study enrolling edoxaban-treated patients from four economic regions with a targeted 2-year follow-up. Of the 4930 patients with AF (mean age: 70.2 ± 9.5 years; male, 57.1%), the mean creatinine clearance (CrCl), CHA2DS2-VASc, and HAS-BLED scores were 71.2 mL/min, 2.9, and 1.6. Overall, 6.4% of patients were perceived as frail by investigators. Available label dose reduction criteria (N = 4232) revealed that 3278 (77.5%) patients received recommended doses and 954 (22.5%) non-recommended doses. Northeast (53.0%) and West (43.1%) regions had the highest prescriptions of 60 mg and 30 mg recommended doses, respectively. Non-recommended 30 mg doses were more frequently prescribed in patients with antiplatelet use and history of heart failure than recommended 60 mg. Multivariate analysis identified advanced age as the strongest associated factor with non-recommended doses. Frailty had the strongest association with 30 mg except for age, and history of TIA was the most relevant factor associated with 60 mg. In conclusion, patients in the ETNA-AF-China study were predominantly aged 65 years and older, had mild-to-moderate renal impairment and good label adherence. Advanced age was associated with non-recommended doses, with frailty most common for non-recommended 30 mg and a history of TIA for the non-recommended 60 mg dose.

Summary: Intervertebral disc is a highly rhythmical tissue. As a key factor linking biorhythm and inflammatory response, the shielding effect of NR1D1 in the process of intervertebral disc degeneration remains unclear. Here, we first confirmed that NR1D1 in the nucleus pulposus tissue presents periodic rhythmic changes and decreases in expression with intervertebral disc degeneration. Second, when NR1D1 was activated by SR9009 in vitro, NLRP3 inflammasome assembly and IL-1β production were inhibited, while ECM synthesis was increased. Finally, the vivo experiments further confirmed that the activation of NR1D1 can delay the process of disc degeneration to a certain extent. Mechanistically, we demonstrate that NR1D1 can bind to IL-1β and NLRP3 promoters, and that the NR1D1/NLRP3/IL-1β pathway is involved in this process. Our results demonstrate that the activation of NR1D1 can effectively reduce IL-1β secretion, alleviate LPS-induced NPMSC pyroptosis, and protect ECM degeneration.

The operation of the integrated energy system is one of the hot spots in the current energy research field. With the reform of the energy field mechanism, the integrated energy system with multi-micro-energy grids poses great challenges to the operation of the power grid. Aimed at the economic and operational problems caused by the integration of multi-micro-energy grid integrated energy systems into the upper distribution network, a multi-temporal and spatial scale optimization operation strategy for integrated energy of micro-energy grid considering demand response is proposed. Moreover, a multi-dimensional energy supply and demand balance model from the perspective of energy is constructed. Furthermore, a multi-time-space scale operation model with upper, middle, and lower layers of collaborative optimization is established. The upper layer adopts day-ahead scheduling, the middle layer adopts intraday scheduling, and the lower layer adopts real-time scheduling with replaceable, transferable, and curtailable loads for demand response optimization. Calculation examples show that this strategy can realize the co-ordination and complementation of multi-dimensional energy sources, realize the coordinated operation of multiple energy sources at different time and space scales, and improve the economy of system operation.

Abstract Background The mechanism of microbiota assembly is one of the main problems in microbiome research, which is also the primary theoretical basis for precise manipulation of microbial communities. Bacterial quorum sensing (QS), as the most common means for bacteria to exchange information and interactions, is characterized by universality, specificity, and regulatory power, which therefore may influence the assembly processes of human microbiota. However, the regulating role of QS in microbiota assembly is rarely reported. In this study, we developed an optimized in vitro oral biofilm microbiota assembling (OBMA) model to simulate the time-series assembly of oral biofilm microbiota (OBM), by which to excavate the QS network and its regulating power in the process. Results By using the optimized OBMA model, we were able to restore the assembly process of OBM and generate time-series OBM metagenomes of each day. We discovered a total of 2291 QS protein homologues related to 21 QS pathways. Most of these pathways were newly reported and sequentially enriched during OBM assembling. These QS pathways formed a comprehensive longitudinal QS network that included successively enriched QS hubs, such as Streptococcus, Veillonella-Megasphaera group, and Prevotella-Fusobacteria group, for information delivery. Bidirectional cross-talk among the QS hubs was found to play critical role in the directional turnover of microbiota structure, which in turn, influenced the assembly process. Subsequent QS-interfering experiments accurately predicted and experimentally verified the directional shaping power of the longitudinal QS network in the assembly process. As a result, the QS-interfered OBM exhibited delayed and fragile maturity with prolonged membership of Streptococcus and impeded membership of Prevotella and Fusobacterium. Conclusion Our results revealed an unprecedented longitudinal QS network during OBM assembly and experimentally verified its power in predicting and manipulating the assembling process. Our work provides a new perspective to uncover underlying mechanism in natural complex microbiota assembling and a theoretical basis for ultimately precisely manipulating human microbiota through intervention in the QS network. Video Abstract

Abstract Early spring cold spells can lead to leaf chlorosis during the rice seedling greening process. However, the physiological and molecular mechanisms underlying the rice greening process under low-temperature conditions remain unknown. In this study, comparative transcriptome and morphophysiological analyses were performed to investigate the mechanisms mediating the responses of the Koshihikari (Kos) and Kasalath (Kas) rice cultivars to chilling stress. According to their growth-related traits, electrolyte leakage, and chlorophyll fluorescence parameters, Kos was more tolerant to low-temperature stress than Kas. Moreover, chloroplast morphology was more normal (e.g., oval) in Kos than in Kas at 17 °C. The comparative transcriptome analysis revealed 610 up-regulated differentially expressed genes that were common to all four comparisons. Furthermore, carotenoid biosynthesis was identified as a critical pathway for the Kos response to chilling stress. The genes in the carotenoid biosynthesis pathway were expressed at higher levels in Kos than in Kas at 17 °C, which was in accordance with the higher leaf carotenoid content in Kos than in Kas. The lycopene β-cyclase and lycopene ε-cyclase activities increased more in Kos than in Kas. Additionally, the increases in the violaxanthin de-epoxidase and carotenoid hydroxylase activities in Kos seedlings resulted in the accumulation of zeaxanthin and lutein and mitigated the effects of chilling stress on chloroplasts. These findings have clarified the molecular mechanisms underlying the chilling tolerance of rice seedlings during the greening process.

Lipids are necessary nutrients for fish and play an important role in growth and metabolism. This study analyzed the effects of dietary lipid levels on growth performance, flesh quality, antioxidant status, and lipid metabolism of juvenile rice flower carp (Cyprinus carpio). The results showed that the weight gain rate and specific growth rate increased initially and then decreased with increasing dietary lipid levels, which 5.82 % dietary lipid level had the best growth in rice flower carp. Dietary lipid levels also affect the nutrition and quality of fish flesh. With the increase of dietary lipid levels, the hardness, adhesiveness, springiness, gumminess and chewiness of muscle showed a trend of increase and then decrease. Moreover, there are similar changes in the activity of antioxidant enzymes in the muscle, and the content of ROS and MDA was significantly higher than other levels at 11.80 % dietary lipid level. The expression of Nrf2 mRNA and some downstream antioxidant enzyme genes was the contrary. Furthermore, the content of TG, TC, and LDL-C in serum and liver increased with increasing dietary lipid levels. Meanwhile, it was observed that the lipid accumulation increased in the liver. The mRNA expression of ATGL and CPT1 genes associated with lipid metabolism in liver increased firstly and then decreased, the expression of FASN, PPARγ, and SREBP1 gradually increased, and reached its maximum at 11.8 % dietary lipid level. The above results showed that the growth performance of juvenile rice flower carp was optimal when the dietary lipid level of 5.82 %, and the nutrition and quality of fish flesh also has good effects. However, the dietary lipid level of 11.80 % inhibited the weight gain and induced oxidative stress and lipid metabolism disorders of rice flower carp, which can affect their flesh quality and health.

Infrared lasers have an extensive range of applications in sensing, detection, communication, medicine, and other fields. The principle of directly pumping solid-state lasers is simple, and it can easily achieve high-power and high-efficiency laser output, which is one of the important means to obtain infrared lasers. Incorporating rare earth ions into the substrate as the gain medium for directly pumping solid-state lasers can alter their optical performance and further enhance the performance of the laser. Lasers based on rare earth ion doping have a small volume, high conversion efficiency, good beam quality, wide tuning range, and multiple operating modes. Therefore, the proportion of rare earth ions doped as the gain medium for activating ions is currently very large. In this review, Ho3+, Tm3+, and Er3+ are selected as the representative rare earth ions, and their optical properties, such as luminous power and fluorescence lifetime, when doped in different substrates, such as crystals, ceramics, and fibers, are introduced, respectively, to illustrate their feasibility as infrared laser gain media. In addition, we show the different optical properties when doped with two ions, three ions, and four ions, demonstrating their great potential as infrared laser gain media.

Seedling mode plays a crucial role in the rice production process, as it significantly affects the growth and development of seedlings. Among the various seedling modes, the seedling tray overlapping for seed emergence mode (STOSE mode) has been demonstrated to be effective in enhancing seedling quality. However, the impact of this mode on the germination and growth of seeds with varying plumpness remains uncertain. To investigate the effect of the STOSE mode on seedling emergence characteristics, growth uniformity, and nutrient uptake of seeds with varying plumpness levels, we conducted a study using super early rice Zhongzao 39 (ZZ39) as the test material. The seeds were categorized into three groups: plumped, mixed, and unplumped. The results indicated that the STOSE mode significantly improved the seedling rate for all types of seeds in comparison to the seedling tray nonoverlapping for seed emergence mode (TSR mode). Notably, the unplumped seeds exhibited the most pronounced enhancement effect. The soluble sugar content of the seeds increased significantly after 2 days of sowing under the STOSE mode, whereas the starch content exhibited a significant decrease. Furthermore, the STOSE mode outperformed the TSR mode in several aspects including seedling growth uniformity, aboveground dry matter mass, root traits, and nutrient uptake. Overall, the STOSE mode not only promoted the germination and growth of plumped and mixed seeds but also had a more pronounced impact on unplumped seeds.

Abstract Depression is highly prevalent and easily relapses. Psychological interventions are effective for the prevention of depression relapse. This systematic review and network meta-analysis aimed to compare the efficacy at the same follow-up time points of psychological interventions in depression. We searched PubMed, Embase, and PsycINFO via OVID, and the Cochrane Library published up to December 12, 2021, and PubMed up to July 1, 2022. The primary outcome was depression relapse, considering the same time points that were extracted on survival curves or relapse curves. The study protocol was registered with PROSPERO, CRD42022343327. A total of 2,871 patients were included from 25 RCTs. Mindfulness-based cognitive therapy (MBCT) was significantly better than placebo at the 3 months, the 6 months, and the 9 months at follow-up. Cognitive behavioral therapy (CBT) was significantly better than treatment as usual at the 3 months, the 9 months, the 12 months, and the 15 months at follow-up. CBT was significantly better than placebo at the 21 months and the 24 months at follow-up. Behavioral activation therapy was significantly better than placebo at the 21 months and the 24 months at follow-up. Interpersonal psychotherapy was significantly better than placebo at the 24-month follow-up. All psychological interventions included in the study were significantly better than supportive counseling most of the time. The results were robust in various sensitivity and subgroup analyses. In conclusion, MBCT had a continuous effect in preventing relapse of depression. CBT had the longest but not continuous effect in preventing relapse of depression. The effects of behavioral activation therapy and interpersonal therapy for the prevention of depression appeared late. All psychological interventions included in the study were more effective than supportive counseling. More evidence is needed from large comparative trials that provide long-term follow-up data.

Abstract Background To provide real‐world outcomes for the combination of etoposide and platinum as a first‐line treatment for advanced thymic neuroendocrine neoplasms (TNENs). Methods Retrospective analysis was performed on patients with advanced TNENs confirmed by pathology who received etoposide combined with platinum as a first‐line chemotherapy in our institution between 2010 and 2022. Results A total of 16 patients were included in this study. Twelve patients (75%) received etoposide combined with cisplatin, and four patients (25%) received etoposide combined with carboplatin. Efficacy was evaluated in all patients, with an objective response rate of 31.3%. One patient achieved a complete response, four achieved a partial response, and in eight patients the disease remained stable; the disease control rate was 81.3%. The median progression‐free survival (PFS) was 7.2 months with a 95% confidence interval (CI) of 2.1–12.3 months. The median overall survival (OS) was 50.4 months with a 95% CI of 32.1–68.8 months. No significant difference in efficacy was observed between the treatment groups with regards to PFS (p = 0.095) and OS (p = 0.061). Treatment‐related adverse events were observed in all 12 patients when evaluated for toxicity, manifesting as hematologic toxicity. Grade 3–4 bone marrow suppression occurred in six patients (50%). No treatment‐related deaths were recorded. Conclusion This retrospective analysis, conducted in a real‐life setting, suggests that the combination of etoposide and platinum has a promising anti‐tumor activity in advanced TNENs, with a clinically significant overall response rate.

Optimizing the breeding techniques and increasing the hatching rate of Andrias davidianus offspring necessitates a thorough understanding of its parental care behaviors. However, A. davidianus’ nocturnal and cave-dwelling tendencies pose significant challenges for direct observation. To address this problem, this study constructed a dataset for the parental care behavior of A. davidianus, applied the target detection method to this behavior for the first time, and proposed a detection model for A. davidianus’ parental care behavior based on the YOLOv8s algorithm. Firstly, a multi-scale feature fusion convolution (MSConv) is proposed and combined with a C2f module, which significantly enhances the feature extraction capability of the model. Secondly, the large separable kernel attention is introduced into the spatial pyramid pooling fast (SPPF) layer to effectively reduce the interference factors in the complex environment. Thirdly, to address the problem of low quality of captured images, Wise-IoU (WIoU) is used to replace CIoU in the original YOLOv8 to optimize the loss function and improve the model’s robustness. The experimental results show that the model achieves 85.7% in the mAP50-95, surpassing the YOLOv8s model by 2.1%. Compared with other mainstream models, the overall performance of our model is much better and can effectively detect the parental care behavior of A. davidianus. Our research method not only offers a reference for the behavior recognition of A. davidianus and other amphibians but also provides a new strategy for the smart breeding of A. davidianus.

The current situation of the energy crisis requires various industries around the world to seek technological upgrades to achieve energy conservation. The renovation of power grid lines, transformers, and substations significantly affects the comprehensive benefits of power transmission/distribution systems, and the optimization of specific parameters of these elements plays a critical role in their operational performance. In order to determine the effects of these parameters and realize their accurate optimization, herein, we establish a method combining an analytic hierarchy process and an entropy weight method to calculate the weightings of the indexes, and then evaluate the comprehensive benefits through a cloud model. Based on the evaluation system above, a case study was utilized to analyze the power transmission/distribution system of a designated area in Wuhan City, and the results showed that the comprehensive benefits increased by around 5.4% compared to 2022, and could be upgraded to level IV in the cloud model with the technical transformation. This exhibits the effectiveness and the application feasibility of this evaluation system.

2,2′,4,4′-tetra-bromodiphenytol ether (BDE-47) is one of the ubiquitous organic pollutants in mangrove sediments. To reveal the toxic effects of BDE-47 on mangrove plants, the mangrove species Kandelia obovate was used to investigate the photosynthetic capacity effects and the molecular mechanisms involved after BDE-47 exposure at environment-related levels (50, 500, and 5000 ng g−1 dw). After a 60-day exposure, the photosynthetic capacity was inhibited in K. obovata seedlings, and a decrease in the stomatal density and damage in the chloroplast ultrastructure in the leaves were found. Transcriptome sequencing showed that, following exposure to BDE-47, gene expression in photosynthesis-related pathways was predominantly suppressed in the leaves. The bioinformatics analysis indicated that BDE-47 exerts toxicity by inhibiting photosystem I activity and chlorophyll a/b-binding protein-related genes in the leaves of K. obovata. Thus, this study provides preliminary theoretical evidence for the toxic mechanism effect of BDE-47 on photosynthesis in mangrove species.

The estimated ultimate recovery (EUR) of a single well must be predicted to achieve scale-effective shale gas extraction. Accurately forecasting EUR is difficult due to the impact of various geological, engineering, and production factors. Based on data from 200 wells in the Weiyuan block, this paper used Pearson correlation and mutual information to eliminate the factors with a high correlation among the 31 EUR influencing factors. The RF-RFE algorithm was then used to identify the six most important factors controlling the EUR of shale gas wells. XGBoost, RF, SVM, and MLR models were built and trained with the six dominating factors screened as features and EUR as labels. In this process, the model parameters were optimized, and finally the prediction accuracies of the models were compared. The results showed that the thickness of a high-quality reservoir was the dominating factor in geology; the high-quality reservoir length drilled, the fracturing fluid volume, the proppant volume, and the fluid volume per length were the dominating factors in engineering; and the 360−day flowback rate was the dominating factor in production. Compared to the SVM and MLR models, the XG Boost and the RF models based on integration better predicted EUR. The XGBoost model had a correlation coefficient of 0.9 between predicted and observed values, and its standard deviation was closest to the observed values’ standard deviation, making it the best model for EUR prediction among the four types of models. Identifying the dominating factors of shale gas single-well EUR can provide significant guidance for development practice, and using the optimized XGBoost model to forecast the shale gas single-well EUR provides a novel idea for predicting shale gas well production.

The rapid spread of the coronavirus disease (COVID-19) pandemic in over 200 countries poses a substantial threat to human health. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, can be discharged with feces into the drainage system. However, a comprehensive understanding of the occurrence, presence, and potential transmission of SARS-CoV-2 in sewers, especially in community sewers, is still lacking. This study investigated the virus occurrence by viral nucleic acid testing in vent stacks, septic tanks, and the main sewer outlets of community where confirmed patients had lived during the early days of the epidemic in Wuhan, China. The results indicated that the risk of long-term emission of SARS-CoV-2 to the environment via vent stacks of buildings was low after confirmed patients were hospitalized. SARS-CoV-2 were mainly detected in the liquid phase, as opposed to being detected in aerosols, and its RNA in the sewage of septic tanks could be detected for only four days after confirmed patients were hospitalized. The surveillance of SARS-CoV-2 in sewage could be a sensitive indicator for the possible presence of asymptomatic patients in the community, though the viral concentration could be diluted more than ten times, depending on the sampling site, as indicated by the Escherichia coli test. The comprehensive investigation of the community sewage drainage system is helpful to understand the occurrence characteristics of SARS-CoV-2 in sewage after excretion with feces and the feasibility of sewage surveillance for COVID-19 pandemic monitoring.

Abstract Purpose To evaluate the application of swept-source optical coherence tomography (SS-OCT) and pentacam scheimpflug tomography in posterior capsule opacification (PCO) severity assessment. Methods The posterior capsule image region segmentation and adaptive threshold algorithm are used to process the SS-OCT scanned image to obtain the posterior capsule thickness (PCT). Scheimpflug tomography reconstructed and analysized by image J software can obtain the average gray value and evaluate the effectiveness with the two methods. Result One hundred sixty-two IOL eyes of 101 patients were divided into two groups, laser group (65 eyes) with the mean PCT was 8.0 ± 2.7 pixel unit and the mean gray value of the eyes was 66 ± 33 pixel unit. However, these figures in the control group (97 eyes) were 5.0 ± 0.9 and 11 ± 17. The sensitivity, specificity and area under curve(AUC) of SS-OCT PCT were 85%, 74% and 0.942,the sensitivity, specificity and AUC of Pentacam gray value were 91%, 76% and 0.947, respectively. After using the multivariable model of generalized estimation equation to corrected the dependence of subjects' eyes, it was found that SS-OCT PCT, Pentacam gray value, low vision quality of life questionnaire (LVQ questionnaire) for distance vision, and mobility and lighting dimension were significantly correlated with the PCO score (P = 0.012, P = 0.001, P = 0.005, respectively). Conclusion The region segmentation and adaptive threshold algorithm of posterior capsule image will accurately quantify the posterior capsule. Computer aided quantifications of posterior capsule are of great significance in the early surgical decision-making of PCO. The average occurrence time of most PCO was around 34 months, and the severity of PCO worsened with increasing postoperative time.

Abstract Background The influence of genetic factors on the pharmacokinetics and clinical outcomes of rivaroxaban in patients with non-valvular atrial fibrillation (NVAF) is poorly understood. This study aimed to explore the effects of CYP3A4/5, ABCB1, and ABCG2 gene polymorphisms on the trough concentrations and the bleeding risk of rivaroxaban in NVAF patients. Patients and methods This study is a prospective multicenter study. The patient's blood samples were collected to detect the steady-state trough concentrations of rivaroxaban and gene polymorphisms. We visited the patients regularly at month 1, 3, 6, and 12 to record bleeding events and medications. Results A total of 95 patients were enrolled in this study, and 9 gene loci were detected. For the dose-adjusted trough concentration ratio (Ctrough/D) of rivaroxaban, the homozygous mutant type was significantly lower than wild type at ABCB1 rs4148738 locus (TT vs. CC, P = 0.033), and the mutant type was significantly lower than the wild type at ABCB1 rs4728709 locus (AA + GA vs. GG, P = 0.008). ABCB1 (rs1045642, rs1128503), CYP3A4 (rs2242480, rs4646437), CYP3A5 (rs776746), and ABCG2 (rs2231137, rs2231142) gene polymorphisms had no significant effect on the Ctrough/D of rivaroxaban. For the bleeding events, we found that there were no significant differences among genotypes of all gene loci. Conclusion This study found for the first time that ABCB1 rs4148738 and rs4728709 gene polymorphisms had a significant impact on the Ctrough/D of rivaroxaban in NVAF patients. CYP3A4/5, ABCB1, and ABCG2 gene polymorphisms were not associated with the bleeding risk of rivaroxaban.

Objective Exosomes in the central nervous system (CNS) have become an attractive area of research with great value. However, few bibliometric analysis has been conducted. The study aimed to visualize the scientific trends and research hotspots of exosomes in the CNS by bibliometric analysis. Methods All potential articles and reviews on exosomes in the CNS published in English from 2001 to 2021 were extracted from the Web of Science Core Collection. The visualization knowledge maps of critical indicators, including countries/regions, institutions, authors, journals, references, and keywords, were generated by CiteSpace and VOSviewer software. Besides, each domain's quantitative and qualitative analysis was also considered. Results A total of 2,629 papers were included. The number of exosomes-related publications and citations regarding CNS increased yearly. These publications came from 2,813 institutions in 77 countries/regions, led by the United States and China. Harvard University was the most influential institution, while the National Institutes of Health was the most critical funding source. We identified 14,468 authors, among which Kapogiannis D had the most significant number of articles and the highest H-index, while Théry C was the most frequently co-cited. The cluster analysis of keywords generated 13 clusters. In summary, the topic of biogenesis, biomarker, and drug delivery will serve as hotspots in future research. Conclusion Exosomes-related CNS research has gained considerable attention in the past 20 years. The sources and biological functions of exosomes and their promising role in diagnosing and treating CNS diseases are considered hotspots in this field. The clinical translation of the results from exosomes-related CNS research will be of great importance in the future.

Abstract KATP channels are metabolic sensors for intracellular ATP/ADP ratios, play essential roles in many physiological processes, and are implicated in a spectrum of pathological conditions. SUR2A-containing KATP channels differ from other subtypes in their sensitivity to Mg-ADP activation. However, the underlying structural mechanism remains poorly understood. Here we present a series of cryo-EM structures of SUR2A in the presence of different combinations of Mg-nucleotides and the allosteric inhibitor repaglinide. These structures uncover regulatory helix (R helix) on the NBD1-TMD2 linker, which wedges between NBD1 and NBD2. R helix stabilizes SUR2A in the NBD-separated conformation to inhibit channel activation. The competitive binding of Mg-ADP with Mg-ATP to NBD2 mobilizes the R helix to relieve such inhibition, allowing channel activation. The structures of SUR2B in similar conditions suggest that the C-terminal 42 residues of SUR2B enhance the structural dynamics of NBD2 and facilitate the dissociation of the R helix and the binding of Mg-ADP to NBD2, promoting NBD dimerization and subsequent channel activation.

Abstract Background We aimed to determine the clinical. outcomes of various immune checkpoint inhibitor (ICI) combinations for the treatment of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations. The results predicted the treatment efficacy of these combinations. Methods From July 15, 2016 to March 22, 2022, 85 NSCLC patients with EGFR mutations, enrolled at the Zhejiang Cancer Hospital, received ICI combinations after resistance to prior EGFR-tyrosine kinase inhibitors (EGFR-TKIs). These patients were diagnosed with EGFR mutations using an amplification refractory mutation system PCR (ARMS-PCR) and next-generation sequencing (NGS). Survival times were analyzed using the Kaplan–Meier method and log-rank test. Results Patients who received ICIs combined with anti-angiogenic therapy had longer progression-free survival (PFS) and overall survival (OS) than patients who received ICIs combined with chemotherapy. There was no significant difference in survival time between patients who received ICIs combined with chemotherapy and anti-angiogenic therapy and patients who received ICIs combined with anti-angiogenic therapy or ICIs combined with chemotherapy, which was due to the limitation sample size of patients who received ICIs combined with chemotherapy and anti-angiogenic therapy. Patients with L858R mutations had a longer PFS and OS than patients with exon 19 deletions. T790M negative patients benefited more from ICI combinations, compared with T790M positive patients. In addition, there was no significant difference in PFS and OS between patients with TP53 co-mutations and patients without a TP53 co-mutation. We also found that patients with prior first-generation EGFR-TKI resistance had longer PFS and OS than prior third-generation EGFR-TKI resistance patients. There was no new adverse event in this study. Conclusions EGFR-mutated patients who received ICIs combined with anti-angiogenic therapy had longer PFS and OS than patients with ICIs combined with chemotherapy. Patients with L858R or without T790M mutation benefited more from ICI combinations. Besides, patients with prior first-generation EGFR-TKI resistance could benefit more from ICIs combinations than prior third-generation EGFR-TKI resistance patients.

Eosinophilic pneumonia (EP) is a rare but noteworthy adverse effect linked to dupilumab, an interleukin-4 (IL-4) and IL-13 inhibitor used in the managing atopic diseases. The underlying mechanisms, potential predisposing factors, clinical characteristics, and optimal management strategies for dupilumab-induced EP remain unclear. We report a 71-year-old patient who developed acute EP after the first 600-mg dose of dupilumab. Eosinophils (EOSs) were also transiently increased (up to 1,600 cells/μl). After the acute EP was effectively treated with glucocorticoids, dupilumab treatment was continued. Rash, itching, and immunoglobulin E levels continued to decrease in the patient, and no further pulmonary adverse events occurred. We combined this case with a literature review of nine articles and analyzed data from 93 cases reported in the FDA Adverse Event Reporting System (FAERS) database of patients developing EP after dupilumab use. Our findings imply that dupilumab may induce EP, particularly in individuals over 45 years old, those with a history of respiratory diseases, and those who have previously used inhaled or systemic steroids. Vigilance is required, especially when there is a persistent elevation in peripheral blood EOSs during treatment. Although steroid treatment can effectively manage EP, more data are needed to determine the safety of resuming dupilumab treatment after controlling pneumonia.

Objective: To explore the mechanism of ursolic acid (UA) against acute B lymphoblastic leukaemia (B-ALL) based on network pharmacological analysis, molecular docking and experimental verification. Methods: The core targets, functional processes, and biological pathways of UA in B-ALL were predicted by network pharmacology and molecular docking. The efficacy and mechanism of UA against B-ALL were verified through in vitro experiments such as cell viability assays, CCK-8 assays, LDH assays, AO/EB staining, flow cytometry, and Western blot assays. Results: Network pharmacology analysis of the core targets indicated that the effects of UA on B-ALL were related to programmed cell death (apoptosis and pyroptosis). Molecular docking results showed that FOS, CASP8, MAPK8, IL-1β and JUN were the key targets of UA against B-ALL. The MTS assay showed that UA decreased the viability of Reh cells in a concentration- and time-dependent manner. Cellular and Western blot experiments found that UA induced Reh cell apoptosis and pyroptosis by upregulating the JNK signalling pathway. Conclusions: Our findings demonstrated that UA could induce Reh cell apoptosis and pyroptosis by activating the JNK signalling pathway to exert anti-B-ALL effects. This indicates that UA may become a potential drug for the effective treatment of B-ALL.

Background: Adrenal insufficiency (AI) caused by immune checkpoint inhibitors (ICIs) is an extremely rare immune-related adverse event (irAE). The detailed clinical characteristics and outcomes of patients with ICI-induced AI are unavailable. This study aimed to explore the clinical characteristics and efficacy of treatment in patients with ICI-induced AI. Methods: We retrospectively collected information on patients diagnosed with AI caused by ICIs at LiShui Municipal Central Hospital and Zhejiang Cancer Hospital, including baseline characteristics, laboratory results, symptoms, treatment outcomes of AI, and hormone use. Survival outcomes were calculated using the Kaplan–Meier method and stratified according to the different situations. Results: From December 2020 to February 2023, among 1014 patients treated with ICI therapy, a total of twenty patients were diagnosed with ICI-induced AI. Most of the patients were men (80%, n = 16), with a performance status (PS) of 0 − 1 (95%, n = 19). The median (range) age was 65.9 (49−80) years and 14 patients (70%) were treated with ICIs as first-line therapy. The majority of the patients (70%, n = 14) experienced grade 3 − 4 AI. All patients received corticosteroid replacement therapy, and only 7 patients recovered. The median time to the diagnosis of AI after starting ICI therapy was 5.2 (3.0 − 7.5) months. The objective response rate was 70% and median progression-free survival in these patients was 16.0 months (95% confidence interval: 11.7 − 20.3 months). Conclusions: ICI-induced AI is a rare irAE, and close monitoring of cortisol levels is important. Patients diagnosed with AI after receiving immunotherapy seem to have a favorable outcome.

Abstract Background Immunotherapy has exhibited efficacy in thymic carcinoma patients; however, there are insufficient data to confirm this efficacy in thymoma. The toxicity of immunotherapy also remains to be determined. Methods The efficacy and safety of immunotherapy were analyzed in 11 thymoma patients who received PD‐1 inhibitors according to a range of relevant indexes including the objective response rate (ORR), disease control rate (DCR), progression‐free survival (PFS), overall survival (OS), and immunotherapy‐related adverse events. Results The PFS and OS rates for all patients were 12.8 and 56.5 months, respectively. No difference in efficacy was detected between monotherapy and combination therapy (PFS: 12.8 vs 2.2 months, P = 0.787; OS: 73.8 vs 56.5 months, P = 0.367). The ORRs and DCRs for all patients were 27.3% and 90.9%, respectively. The incidence of adverse events was 45.5% among the 11 thymoma patients, including immune‐related myocarditis (36.4%), immune‐related liver damage (18.2%), and myasthenia gravis (18.2%). In the whole cohort of patients, the rate of adverse events of grade 3 or higher was 36.4%. The rates of adverse events of grade 3 or 4 in B3‐type and non‐B3‐type thymoma patients were 0% and 62.5%, respectively. Conclusions Immunotherapy elicited a response in thymoma patients; however, more attention should be paid to the immune‐related adverse events.

Fundus vascular diseases, including neovascular age-related macular degeneration(nAMD)and diabetic retinopathy(DR), are the leading causes of visual impairment worldwide. With the accelerated aging and increased incidence of diabetes, the prevalence of these two fundus diseases will continue to rise. Currently, intraocular injection of anti-vascular endothelial growth factor(anti-VEGF)remains the first-line treatment for fundus vascular diseases, but disadvantages exist, such as frequent intraocular injections, high cost and poor compliance, thus more durable and effective therapeutic strategies need to be explored. The successful application of gene therapy in inherited retinal diseases(IRDs)provides a new idea for the treatment of fundus vascular diseases. With the ongoing of several clinical trials, gene therapy for fundus vascular diseases is expected to be employed in the clinical setting. But there still remain some concerns, including the optimal therapeutic targets selection, administration route and safety issues. This review focuses on the application and prospect of gene augmentation and gene editing-mediated anti-VEGF therapy for the treatment of nAMD and DR.

Endogenous microRNAs (miRNA) in tumors are currently under exhaustive investigation as potential therapeutic agents for cancer treatment. Nevertheless, RNase degradation, inefficient and untargeted delivery, limited biological effect, and currently unclear side effects remain unsettled issues that frustrate clinical application. To address this, a versatile targeted delivery system for multiple therapeutic and diagnostic agents should be adapted for miRNA. In this study, we developed membrane-coated PLGA-b-PEG DC-chol nanoparticles (m-PPDCNPs) co-encapsulating doxorubicin (Dox) and miRNA-190-Cy7. Such a system showed low biotoxicity, high loading efficiency, and superior targeting ability. Systematic delivery of m-PPDCNPs in mouse models showed exceptionally specific tumor accumulation. Sustained release of miR-190 inhibited tumor angiogenesis, tumor growth, and migration by regulating a large group of angiogenic effectors. Moreover, m-PPDCNPs also enhanced the sensitivity of Dox by suppressing TGF-β signal in colorectal cancer cell lines and mouse models. Together, our results demonstrate a stimulating and promising m-PPDCNPs nanoplatform for colorectal cancer theranostics.