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Abstract Objective Thromboangiitis obliterans (TAO) is one of the most common types of peripheral arterial disease (PAD). This study aimed to explore the characteristics of the top 100 most cited articles in the TAO. Methods A bibliometric analysis based on the Web of Science (WOS) database was performed. Literature was retrieved and ranked by the citations. Listed below are the top 100 citations, including original articles, reviews, full-length proceeding papers, and case reports that were included for analysis. The type of literature, research areas, and languages were recorded. The trends of citations including the total citations, an analysis of publication and citation numbers were conducted each year. We analyzed citations from highly cited countries, authors, institutions, and journals. Research hotspots were gathered by a visualized analysis of author keywords. Results Most of the highly cited literature was original articles. A rising trend was observed in the number of citations per year. The peaks in the number of highly cited articles appeared in the year 1998 and 2006. The majority of the articles focused on the cardiovascular system and surgery. Journal of Vascular Surgery published most of the highly cited articles. The USA and Japan contributed nearly half the number of highly cited articles. Mayo Clinic and Nagoya University were highly cited institutions. Shionoya S and Olin JW were both the author with the largest number of citations and the most highly cited author in the reference. Articles that were highly cited most often addressed the following topics: “vasculitis”, “autoimmune disease”, and “critical limb ischemia”. Keywords that were mostly used in recent years were “stem cell therapy”, “progenitor therapy”, and “immunoadsorption”. The detection of bursts of author keywords showed the following: “permeability”, “differentiation”, and “critical limb ischemia” are recent keywords that have burst. Conclusions In this study, the highly cited contributors in the field of TAO research were identified. Most cited articles in the top 100 focused on the cardiovascular system and surgery. Treatment and pathophysiology including stem cell therapy, progenitor therapy, genetics, autoimmunity, and inflammation are the hotspots of TAO.

Abstract The beginning of human settlement in the Hami Basin, located in the eastern part of Xinjiang, has been a focal question for the academic community in China. In particular, the thesis that the immigrating population from the Hexi Corridor since the late Neolithic founded the Tianshanbeilu culture has riveted the attention of scholars. Pottery wares, abundantly discovered at the synonymous cemetery of this culture, have played a key role in extrapolating population migration and cultural interaction. This paper aims to test the thesis by characterizing the chemical composition, painting pigment, and carburizing technique of 70 pottery samples from the cemetery with various scientific methods. It shows that the chemical compositions of the coarse pottery in the three colors of red, yellow, and gray, painted and unpainted alike, are remarkably different from those of fine pottery in black and red, indicating that the raw materials for the coarse and fine pottery samples are possibly procured from different sources; the pigments of the red slip and black paint are derived from hematite, black manganese ore, and carbon black; carburizing and polishing techniques are further applied to the gray coarse pottery; In combination with the compositional data of pottery samples from the Yaer cemetery also in the Hami Basin and the Xichengyi settlement in the Hexi Corridor, this paper finds that some pottery wares of the Tianshanbeilu culture were exchanged within the Hami Basin, but each site had its own production facility. No direct exchange of pottery wares with Xichengyi is attested; the similar style of pottery wares between the two sites may have resulted from population migration and technological exchange.

Understanding how human leukocyte antigen (HLA) polymorphism affects both the susceptibility and severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection will help to identify individuals at higher risk to better manage and prioritize vaccination at the clinical level and explain the differences in epidemic trends in different regions at the epidemiological level. This study compared the frequencies of HLA class I alleles (HLA-A, B) in 214 coronavirus disease 2019 (COVID-19) patients with different disease severity and 35 healthy controls and analyzed the correlations between specific HLA alleles and disease severity and T cell memory. The results showed no significant difference in HLA allele frequencies between COVID-19 patients and healthy controls (P > 0.05). The allele HLA-B*13:02 was significantly correlated with the disease severity of COVID-19 patients (P = 0.006). After adjustment for age and disease severity, the T cell responses of COVID-19 convalescents with the allele HLA-B*40:01 may be lower at six months (P = 0.044) and 12 months (P = 0.069). Moreover, these results may be due to their rare peptide anchors by analyzing the binding peptide motifs of these HLA alleles. The study may be valuable for investigating the potential association of specific HLA alleles with SARS-CoV-2 infection.

Abstract Background Clinical nurses are susceptible to compassion fatigue when exposed to various types of traumatic events in patients for extended periods of time. However, the developmental process, staging, and psychological responses distinct to each stage of compassion fatigue in nurses are not fully clarified. This study aimed to explore the processes of compassion fatigue and the psychological experiences specific to each phase of compassion fatigue among clinical nurses. Methods Charmaz’s Constructivist Grounded Theory methodology was used in this qualitative research. Semi-structured interviews were conducted with 13 clinical nurses with varying degrees of compassion fatigue from December 2020 to January 2021. Interview data were analyzed using grounded theory processes. Results The data were categorized into five separate categories and 22 sub-categories. This study found that the process of compassion fatigue is dynamic and cumulative, which was classified into five phases: compassion experience period, compassion decrement period, compassion discomfort period, compassion distress period, and compassion fatigue period. Conclusion Clinical nurses who experience compassion fatigue may go through five stages that are stage-specific and predictable. The findings can shed light on local and global applications to better understand the problem of nurses’ compassion fatigue. The interventions for addressing compassion fatigue in clinical nurses should be stage-specific, targeted, and individualized.

Abstract Background German chamomile (Matricaria chamomilla L.) is an important medicinal plant, and the essential oils in the flowers have various biological activities. Genetic transformation systems are important for plant quality improvement and molecular research. To the best of our knowledge, a genetic transformation system has not yet been reported for German chamomile. Results In this study, we developed Agrobacterium-mediated transformation protocols for German chamomile callus tissues. This involved optimizing key parameters, such as hygromycin and cefotaxime concentrations, bacterial density, and infection and co-culture durations. We also performed gas chromatography–mass spectrometry analysis to identify volatile compounds in non-transgenic and transgenic callus and hairy root tissues. Furthermore, to compare and verify the callus transformation system of German chamomile, we transferred McFPS to the hairy roots of German chamomile. The results showed that the optimal conditions for Agrobacterium-mediated callus tissue transformation were as follows: explant, petiole; cefotaxime concentration, 300 mg/L; hygromycin concentration, 10 mg/L; and bacterial solution concentration, OD600 = 0.6; callus transformation efficiency was the highest when the co-culture time was 3 days. Conclusions Establishment of a high-efficiency callus transformation system will lay the foundation for gene function identification in German chamomile.

Abstract Titanium dioxide (TiO2)-based photodynamic antibacterial (PDA) agents present a novel approach for addressing drug-resistant bacterial infections and the associated tissue damage. However, the suboptimal dispersibility, negative charge, and weak photocatalytic activity under visible light of TiO2 hinder its practical applications. This study aimed to address these limitations by developing a highly hydrophilic and dispersed Zn-TiO2/reduced graphene oxide (rGO) (HTGZ) nano-system with exceptional visible light catalytic activity and tissue repair ability. HTGZ produced an antibacterial ratio over 98% within a short time, likely due to the enhanced production of reactive oxygen species under visible light. After being co-cultured for 4 days, L929 cells and BMSCs maintained over 90% activity, indicating that HTGZ had no significant cytotoxicity. Furthermore, the transcriptomic and metabolic analyses revealed that the antibacterial mechanism mainly came from the destruction of cell membranes and the disruption of various metabolic processes, such as purine metabolism and fatty acid biosynthesis. Critically, results of in vivo experiments had authenticated that HTGZ significantly promoted infected tissue regeneration by slaughtering bacteria and release Zn2+. After 14 days, the wound area was only one-third that of the control group. Overall, the enhanced antibacterial efficacy and wound-healing potential position HTGZ as a promising nano-antibacterial medication for the clinical treatment of infectious bacterial diseases.

Abstract Background Compared with a lower neutrophil to lymphocyte ratio(NLR), a higher one denotes severe asthma exacerbation in hospitalized asthmatic children. In addition, NLR is significantly higher in pediatric patients with community-acquired pneumonia (CAP) than those without. Nevertheless, its role in pediatric patients with concomitant asthmatic exacerbation and CAP remains unknown. Methods In this retrospective study including 1032 pediatric patients aged 5 to 14 years old, the diagnostic and prognostic value of NLR in children with concomitant asthmatic exacerbation and non-severe CAP were investigated. Results The sensitivity and specificity of NLR for a diagnosis of CAP in patients with asthmatic exacerbation were 56.9% and 90.1%, respectively. The cutoff value of NLR for a diagnosis of CAP in patients with asthmatic exacerbation was 4.15 (P

The body of a high-speed train is a composite structure composed of different materials and structures. This makes the design of a noise-reduction scheme for a car body very complex. Therefore, it is important to clarify the key factors influencing sound insulation in the composite structure of a car body. This study uses machine learning to evaluate the key factors influencing the sound insulation performance of the composite floor of a high-speed train. First, a comprehensive feature database is constructed using sound insulation test results from a large number of samples obtained from laboratory acoustic measurements. Subsequently, a machine learning model for predicting the sound insulation of a composite floor is developed based on the random forest method. The model is used to analyze the sound insulation contributions of different materials and structures to the composite floor. Finally, the key factors influencing the sound insulation performance of composite floors are identified. The results indicate that, when all material characteristics are considered, the sound insulation and surface density of the aluminum profiles and the sound insulation of the interior panels are the three most important factors affecting the sound insulation of the composite floor. Their contributions are 8.5%, 7.3%, and 6.9%, respectively. If only the influence of the core material is considered, the sound insulation contribution of layer 1 exceeds 15% in most frequency bands, particularly at 250 and 500 Hz. The damping slurry contributed to 20% of the total sound insulation above 1000 Hz. The results of this study can provide a reference for the acoustic design of composite structures.

Abstract Background Kirsten rat sarcoma (KRAS) and mutant KRASG12D have been implicated in human cancers, but it remains unclear whether their activation requires ubiquitination. This study aimed to investigate whether and how F-box and leucine-rich repeat 6 (FBXL6) regulates KRAS and KRASG12D activity in hepatocellular carcinoma (HCC). Methods We constructed transgenic mouse strains LC (LSL-Fbxl6 KI/+ ;Alb-Cre, n = 13), KC (LSL-Kras G12D/+ ;Alb-Cre, n = 10) and KLC (LSL-Kras G12D/+ ;LSL-Fbxl6 KI/+ ;Alb-Cre, n = 12) mice, and then monitored HCC for 320 d. Multiomics approaches and pharmacological inhibitors were used to determine oncogenic signaling in the context of elevated FBXL6 and KRAS activation. Co‑immunoprecipitation (Co-IP), Western blotting, ubiquitination assay and RAS activity detection assay were employed to investigate the underlying molecular mechanism by which FBXL6 activates KRAS. The pathological relevance of the FBXL6/KRAS/extracellular signal-regulated kinase (ERK)/mammalian target of rapamycin (mTOR)/proteins of relevant evolutionary and lymphoid interest domain 2 (PRELID2) axis was evaluated in 129 paired samples from HCC patients. Results FBXL6 is highly expressed in HCC as well as other human cancers (P

The establishment of the comprehensive geological disaster prevention and control system in Yunnan province stands as China’s most extensive and grand-scale endeavor in safeguarding the prevention and control of geological disasters in China. Its implementation has led to a significant reduction in the occurrence of geological disasters, resulting in a substantial decrease in both casualties and missing persons affected by such disasters. This accomplishment has yielded remarkable outcomes in disaster prevention and mitigation. Based on the results of 12 series monographic studies, this paper provides an overview of the implementation of the system and its disaster prevention and mitigation effects. It summarizes the main scientific and technological achievements, with a particular focus on the causes and patterns of plateau geological disasters, understanding of special rock and soil disaster control mechanisms, susceptibility zoning evaluation, comprehensive remote sensing identification of geological hazards, progress in automated monitoring and early warning, and the development of geological environment information standard system. These achievements can provide valuable insights for the comprehensive geological disaster prevention and control in Yunnan Province.

Many geminiviruses, including members of the genus Begomovirus, produce a protein known as C4 or AC4. Whereas C4/AC4 typically consists of more than 80 amino acid residues, a few are much shorter. The significance of these shorter C4/AC4 proteins in viral infection and why the virus maintains their abbreviated length is not yet understood. The AC4 of the begomovirus Tomato leaf curl Hsinchu virus contains only 65 amino acids, but it extends to 96 amino acids when the natural termination codon is replaced with a normal codon. We discovered that both interrupting and extending AC4 were harmful to tomato leaf curl Hsinchu virus (ToLCHsV). The extended AC4 (EAC4) also showed a reduced ability to promote the infection of the heterologous virus Potato virus X than the wild-type AC4. When the wild-type AC4 was fused with yellow fluorescent protein (AC4-YFP), it was predominantly found in chloroplasts, whereas EAC4-YFP was mainly localized to the cell periphery. These results suggest that ToLCHsV's AC4 protein is important for viral infection, and the virus may benefit from the abbreviated length, because it may lead to chloroplast localization. [Graphic: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Peptostreptococcus anaerobius is an anaerobic bacterium, which has been found selectively en-riched in the fecal and mucosal microbiota of colorectal cancer (CRC) patients. Emerging evidence suggest P. anaerobius may contribute to the development of CRC in human. In this study, we designed a multi-epitope chimeric vaccine against P. anaerobius PCWBR2, a recently identified adhesin that interacts directly with colon cell lines by binding α2/β1 integrin frequently overexpressed in human CRC tumors and cell lines. Immunoinformatics tools predicted six cytotoxic T lymphocyte epitopes, five helper T lymphocyte epitopes, and six linear B lymphocyte epitopes. The predicted epitopes were joined with AAY or GPGPG linkers and a previously reported TLR4 agonist was added to the vaccine construct's N terminal as an adjuvant using EAAAK linkers and the order of epitopes was optimized. Further in silico analysis revealed that the vaccine construct possesses satisfactory antigenicity, allergenicity, solubility, physicochemical properties, adjuvant-TLR4 molecular docking, and immune profile characteristics. Our study provided a promising design for vaccines against P. anaerobius.

Abstract Objectives Rheumatoid arthritis (RA) is a chronic autoimmune disease with complex causes and recurrent attacks that can easily develop into chronic arthritis and eventually lead to joint deformity. Our study aims to elucidate potential mechanism among control, new-onset RA (NORA) and chronic RA (CRA) with multi-omics analysis. Methods A total of 113 RA patients and 75 controls were included in our study. Plasma and stool samples were obtained for 16S rRNA sequencing, internally transcribed spacer (ITS) sequencing and metabolomics analysis. And PBMCs were obtained for RNA sequencing. We used three models, logistic regression, least absolute shrinkage and selection operator (LASSO), and random forest, respectively, to distinguish NORA from CRA, and finally we validated model performance using an external cohort of 26 subjects. Results Our results demonstrated intestinal flora disturbance in RA development, with significantly increased abundance of Escherichia-Shigella and Proteobacteria in NORA. We also found that the diversity was significantly reduced in CRA compared to NORA through fungi analysis. Moreover, we identified 29 differential metabolites between NORA and CRA. Pathway enrichment analysis revealed significant dysregulation of glycerophospholipid metabolism and phenylalanine metabolism pathways in RA patients. Next, we identified 40 differentially expressed genes between NORA and CRA, which acetylcholinesterase (ACHE) was the core gene and significantly enriched in glycerophospholipid metabolism pathway. Correlation analysis showed a strong negatively correlation between glycerophosphocholine and inflammatory characteristics. Additionally, we applied three approaches to develop disease classifier models that were based on plasma metabolites and gut microbiota, which effectively distinguished between new-onset and chronic RA patients in both discovery cohort and external validation cohort. Conclusions These findings revealed that glycerophospholipid metabolism plays a crucial role in the development and progression of RA, providing new ideas for early clinical diagnosis and optimizing treatment strategies.

Abstract In China, several problems were common in the telemedicine systems, such as the poor network stability and difficult interconnection. A new telemedicine system jointly driven by multinetwork integration and remote control has been designed to address these problems. A multilink aggregation algorithm and an overlay network for telemedicine system (ONTMS) were developed to improve network stability, and a non‐intervention remote control method was designed for Internet of Things (IoT) devices/systems. The authors monitored the network parameters, and distributed the questionnaire to participants, for evaluating the telemedicine system and services. Under a detection bandwidth of 8 Mbps, the aggregation parameters of Unicom 4G, Telecom 4G, and China Mobile 4G were optimal, with an uplink bandwidth, delay, and packet loss ratio (PLR) of 7.93 Mbps, 58.80 ms, and 0.06%, respectively. These parameters were significantly superior to those of China Mobile 4G, the best single network (p < 0.001). Through the ONTMS, the mean round‐trip transporting delay from Beijing to Sanya was 76 ms, and the PLR was 0 at vast majority of time. A total of 1988 participants, including 1920 patients and 68 doctors, completed the questionnaires. More than 97% of participants felt that the audio and video transmission and remote control were fluent and convenient. 96% of patients rated the telemedicine services with scores of 4 or 5. This system has shown robust network property and excellent interaction ability, and satisfied the needs of patients and doctors.

Abstract We previously described a nucleolar protein RSL1D1 but distributed throughout the nucleus in HCT116 colorectal cancer (CRC) cells to facilitate G1/S transition by inhibiting p53 signaling. Here, we found another nucleolar protein, programmed cell death 11 (PDCD11), also with an “Extra-nucleolar” localization in CRC cells but to regulate G2/M checkpoint. This protein directly interacts with p53 and HDM2 in the nucleoplasm, thereby recruiting p53 to HDM2 for ubiquitination and degradation. The ensuing downregulation of p53 increases the CDK1 level to help the cells pass G2/M checkpoint. Upon DNA damage stress, PDCD11 gains the power to upregulate CDK1 independently of p53. Beyond these, PDCD11 also upregulates CDC25C in a p53-independent manner to dephosphorylate CDK1 to facilitate G2/M transition. Downregulation of PDCD11 greatly reduced cancer cell growth in vitro and in vivo, additionally sensitized cells to DNA damage signals, highlighting that PDCD11 is a crucial driving factor of CRC and a potential target for cancer treatment.

The bacterial ATP-competitive GyrB/ParE subunits of type II topoisomerase are important anti-bacterial targets to treat super drug-resistant bacterial infections. Herein we discovered novel pyrrolamide-type GyrB/ParE inhibitors based on the structural modifications of the candidate AZD5099 that was withdrawn from the clinical trials due to safety liabilities such as mitochondrial toxicity. The hydroxyisopropyl pyridazine compound 28 had a significant inhibitory effect on Gyrase (GyrB, IC50 = 49 nmol/L) and a modest inhibitory effect on Topo IV (ParE, IC50 = 1.513 μmol/L) of Staphylococcus aureus. It also had significant antibacterial activities on susceptible and resistant Gram-positive bacteria with a minimum inhibitory concentration (MIC) of less than 0.03 μg/mL, which showed a time-dependent bactericidal effect and low frequencies of spontaneous resistance against S. aureus. Compound 28 had better protective effects than the positive control drugs such as DS-2969 (5) and AZD5099 (6) in mouse models of sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. It also showed better bactericidal activities than clinically used vancomycin in the mouse thigh MRSA infection models. Moreover, compound 28 has much lower mitochondrial toxicity than AZD5099 (6) as well as excellent therapeutic indexes and pharmacokinetic properties. At present, compound 28 has been evaluated as a pre-clinical drug candidate for the treatment of drug-resistant Gram-positive bacterial infection. On the other hand, compound 28 also has good inhibitory activities against stubborn Gram-negative bacteria such as Escherichia coli (MIC = 1 μg/mL), which is comparable with the most potent pyrrolamide-type GyrB/ParE inhibitors reported recently. In addition, the structure–activity relationships of the compounds were also studied.

Green macroalgae bloom (GMB), with the dominant species of Ulva prolifera, has regularly occurred since 2007 along the China coast. Although disaster prevention and control achieved favorable results in 2020, the satellite-observed GMB annual maximum coverage (AMC) rebounded sharply in 2021 to an unprecedented level. The reasons for this rebound and the significant interannual variability over past 15 years are still open questions. Here, by using long-term time-series (2007–2022) optical and Synthetic Aperture Radar satellite observations (1000+ scenes), meteorological data and water quality statistics, the mechanism analysis was performed by exploring effects from natural factors and human activities. Two key determinants for AMC are successfully identified from numerous potential factors which are the macroalgae distribution in a key area (the Subei Shoal) during a critical period (from April to May 20) and the nutrient availability. Furthermore, by using these two parameters, a novel model for AMC prediction (R2 = 0.87, p

AbstractExploring the genetic basis of adaptive divergence at fine spatial scales can broaden our basic understanding of evolution and how organisms may adapt to changing environments in the future. Cave-associated microhabitats provide a unique opportunity to gain insight into microgeographic adaptation. We studied the genetic architecture of microhabitat-related divergence in flower phenology and leaf traits between two sister species of Primulina, P. depressa and P. danxiaensis, which live in sympatry but occupy contrasting microhabitats. We identified 40 significant quantitative trait loci (QTLs) associated with the interspecific differences in these microhabitat adaptation traits. Flowering time was controlled by one major-effect and six minor-effect QTLs, while leaf traits were influenced by 9–12 QTLs of small to moderate effect. The genetic architecture of the flowering time and the specific leaf area was genetically independent of other traits. Our results suggest that microhabitat adaptation in sympatric populations of Primulina differs according to different traits, with leaf traits diverging with the accumulation of many small changes and flowering phenology being driven by major effect variance.

Purpose: In breast cancer (BC) patients with clinical axillary lymph node metastasis (cN+) undergoing neoadjuvant therapy (NAT), precise axillary lymph node (ALN) assessment dictates therapeutic strategy. There is a critical demand for a precise method to assess the axillary lymph node (ALN) status in these patients. Materials and methods: A retrospective analysis was conducted on 160 BC patients undergoing NAT at Fujian Medical University Union Hospital. We analyzed baseline and two-cycle reassessment dynamic contrast-enhanced MRI (DCE-MRI) images, extracting 3668 radiomic and 4096 deep learning features, and computing 1834 delta-radiomic and 2048 delta-deep learning features. Light Gradient Boosting Machine (LightGBM), Support Vector Machine (SVM), RandomForest, and Multilayer Perceptron (MLP) algorithms were employed to develop risk models and were evaluated using 10-fold cross-validation. Results: Of the patients, 61 (38.13 %) achieved ypN0 status post-NAT. Univariate and multivariable logistic regression analyses revealed molecular subtypes and Ki67 as pivotal predictors of achieving ypN0 post-NAT. The SVM-based “Data Amalgamation” model that integrates radiomic, deep learning features, and clinical data, exhibited an outstanding AUC of 0.986 (95 % CI: 0.954–1.000), surpassing other models. Conclusion: Our study illuminates the challenges and opportunities inherent in breast cancer management post-NAT. By introducing a sophisticated, SVM-based “Data Amalgamation” model, we propose a way towards accurate, dynamic ALN assessments, offering potential for personalized therapeutic strategies in BC.

This paper systematically investigates the changes in material properties during electrohydrodynamic (EHD) drying, the discharge characteristics of the EHD system as well as the active ingredients, textural properties (hardness, adhesiveness, etc.) and moisture distribution of yam under EHD, air drying and hot air drying were investigated. The results showed that the active particles and the ionized wind generated during the discharge process of the electrohydrodynamic drying device had a significant effect on the drying. Compared to thermal drying, 21 kV drying resulted in the most complete cellular structure, the best internal bound water content as well as textural properties of yam. It played a positive role in the retention of internal nutrients in yam, and the total phenol and allantoin contents were increased by 25.74% and 81.99%, respectively. These results elucidate the advantages of electrohydrodynamic drying in yam drying and provide a reference for the application of EHD in drying.

The classical nonlinear fatigue cumulative damage model Manson-Halford is widely used in fatigue life analysis and prediction, but this model lacks consideration for the effects of load interaction. At present, some studies have proposed new correction models to overcome the shortcomings of classical models. However, the problem with these models is that the parameters are difficult to determine, resulting in a cumbersome application process or the correction process is based only on a single parameter. Insufficient correction leads to large fluctuations in life prediction errors. To overcome the above problems, this article proposes a new correction method and establishes a new improved model. Unlike existing models, the newly improved model is based solely on S-N curve parameters and does not require additional material parameters. It fully considers the relationship between adjacent loads and the difference in fatigue life under different stress states, and dynamically modifies the classical model based on larger influence weights. By conducting multi-level fatigue tests on 300M steel, a new improved model was used to accurately predict its remaining fatigue life. Compared with the classical model, the prediction error was reduced by 11.75 %. Utilized fatigue test data from various other materials to predict the fatigue life of the improved model under different levels of stress loading. The results indicate that in the vast majority of cases, the improved model has the highest prediction accuracy among all compared models, with a minimum relative prediction error of only 3.79 % and small fluctuations in prediction error. Compared with the classical model, the maximum reduction in relative prediction error after model improvement reached 28.73 %, indicating the effectiveness and accuracy of the new improved model.

Soil-derived CO2 flux (SCF) plays a key role in mitigating global warming, and the accurate prediction of SCF is the basis for the accurate prediction of climate change. To explore the changes in SCF, discover soil respiration patterns, and accurately predict soil respiration CO2 flux, we used a self-developed soil respiration monitoring device to collect soil CO2 flux data, and proposed a Dish-ECA-Adain-Autoformer (DEAF) combination model with adaptive feature aggregation and bias correction of the Autoformer improvement network to accurately predict the changes in soil respiration. To explore the potential feature patterns in the CO2 flux time series data, the trend and seasonal features of the data were enhanced using inverse contrast based on Fourier continuous transform. The irregular features of the local segments in the unit time were eliminated by adaptive aggregation convolution, and the residual linkage was applied to obtain the potential paradigm of the sequence changes. In the self-constructed CO2 flux dataset, MSE and MAE of the proposed model reached 0.296 and 0.328, respectively, with an average improvement of 34.4% compared to the unimproved model. In the experiments on the public time series dataset, the average improvement was approximately 20.2%, indicating that the model can effectively mine the time series information of the data and the correlation information of the feature dimensions to improve the prediction performance and verify the accuracy and universality of the proposed model. Additionally, the short-, medium-, and long-term prediction results showed that the DEAF model fitted the soil CO2 flux data well, providing a reference basis for the accurate prediction of soil CO2 flux.

Background: Ocular neovascular diseases, which contribute significantly to vision loss, lack effective preventive treatments. Recent studies have highlighted the significant involvement of immune cells in neovascular retinopathy. Myeloid-derived suppressor cells (MDSCs) promote the development of neovascularization, but it is unknown whether they participate in pathological neovascularization and whether they are expected to be a therapeutic target. Method: We investigated the role of MDSCs in promoting pathological angiogenesis using an oxygen-induced retinopathy (OIR) model, employing flow cytometry, immunofluorescence, and smart-seq analysis. Then, we evaluated the proportion of MDSCs in patient blood samples using flow cytometry. Additionally, we assessed the effect of MDSC depletion using an anti-Gr-1 monoclonal antibody on retinal vasculopathy and alterations in retinal microglia. Results: In the OIR model, an elevated ratio of MDSCs was observed in both blood and retinal tissue during phase II (Neovascularization). The depletion of MDSCs resulted in reduced retinal neovascularization and vaso-obliteration, along with a decrease in microglia within the neovascularization area. Furthermore, analysis of gene transcripts associated with MDSCs indicated activation of vascular endothelial growth factor (VEGF) regulation and inflammation. Importantly, infants with ROP exhibited a higher proportion of MDSCs in their blood samples. Conclusion: Our results suggested that excessive MDSCs represent an unrecognized feature of ocular neovascular diseases and be responsible for the retinal vascular inflammation and angiogenesis, providing opportunities for new therapeutic approaches to ocular neovascular disease.

Ferroptosis, driven by an imbalance in redox homeostasis, has recently been identified to regulate macrophage function and inflammatory responses. SENP3 is a redox-sensitive de-SUMOylation protease that plays an important role in macrophage function. However, doubt remains on whether SENP3 and SUMOylation regulate macrophage ferroptosis. For the first time, the results of our study suggest that SENP3 sensitizes macrophages to RSL3-induced ferroptosis. We showed that SENP3 promotes the ferroptosis of M2 macrophages to decrease M2 macrophage proportion in vivo. Mechanistically, we identified the ferroptosis repressor FSP1 as a substrate for SUMOylation and confirmed that SUMOylation takes place mainly at its K162 site. We found that SENP3 sensitizes macrophages to ferroptosis by interacting with and de-SUMOylating FSP1 at the K162 site. In summary, our study describes a novel type of posttranslational modification for FSP1 and advances our knowledge of the biological functions of SENP3 and SUMOylation in macrophage ferroptosis.

Background This study aimed to provide a comprehensive assessment of burden estimates and the secular trend of vision loss due to retinopathy of prematurity (ROP) among people younger than 20 years, at the global, regional and national levels.Methods Data were obtained from the Global Burden of Disease Study 2019 database. The average annual percentage change (AAPC) was calculated to quantify the temporal trends in the measures of vision loss.Results In 2019, the global age-standardised rates (ASRs) of prevalence per 100 000 population was 86.4 for vision loss, specifically, 35 for moderate vision loss, 19.9 for severe vision loss, 31.6 for blindness due to ROP among people younger than 20 years. Moreover, the ASR of years lived with disability per 100 000 was 10.6 for vision loss, specifically, 1.1 for moderate vision loss, 3.6 for severe vision loss, 5.9 for blindness, respectively. From 1990 to 2019, the ASR of prevalence of blindness and vision loss due to ROP significantly increased, while its burden slightly decreased. Males showed higher ASR of prevalence than females in 2019, whereas females have larger increasing trend than males from 1990 to 2019. The global highest ASR of disease burden was observed in South Asia and Southern sub-Saharan Africa, as well as low sociodemographic index (SDI) regions in 2019.Conclusions Globally, although the burden decreased, the prevalence of childhood and adulthood vision loss due to ROP continues to increase. Reasonable resource allocation and advanced intervention are recommended to prevent and control the vision loss due to ROP.

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic subverted people’s lives and potentially affected the management and prognosis of pre-existing dermatoses. The study aims to identify factors influencing the outcomes of dermatoses during a rapid and widespread Omicron outbreak in China following the adjustment of the COVID-19 policy.Materials and methodsThis retrospective observational study involved outpatients visiting the dermatology department at a tertiary referral hospital in Beijing, China between December 2022 and February 2023. Demographics, COVID-19 characteristics, treatment modalities, and dermatosis outcomes were subjected to statistical analysis.ResultsThe odds ratio (OR) for vitiligo aggravation during COVID-19 was 0.497 [95% confidence interval (CI): 0.254–0.973, p = 0.038] compared to total patients with various dermatoses. Psoriasis patients with a maximum body temperature (Tmax) over 38.6°C during COVID-19 were 2.833 times more likely to experience dermatosis aggravation (OR: 2.833 [1.029–7.803], p = 0.041). Moreover, autoimmune bullous disease (AIBD) patients receiving biologics treatment exhibited a reduced likelihood of aggravation during the COVID-19 outbreak (OR: 0 [0–0.531], p = 0.011).ConclusionVitiligo exhibits lower aggravation rates during COVID-19 than other dermatoses. A higher body temperature during COVID-19 infection can increase the risk of psoriasis aggravation. Biologics treatment reduces the risk of AIBD aggravation during the COVID-19 outbreak.

Abstract Global sea wave monitoring is of utmost importance for tasks such as analysis of ocean climate change, offshore fisheries, and early warning of marine disasters. Significant wave height (SWH) is one of the most vital and widely used metrics for measuring sea waves in marine research. Hence, obtaining high precision and extensive coverage measurements of SWH is of great significance for comprehensive sea wave studies. A data set is constructed by combining wave spectrometer and scatterometer data from China‐French Ocean Satellite, synthetic aperture radar (SAR) wave mode data from Sentinel‐1, and altimeter data from Jason‐3 and HY‐2B through space‐time matching method. The multi‐sources integrated data set is used to complete the reconstruction of the wide swath SWH. A model based on stacked autoencoder and deep neural network (SAE‐DNN) is developed. The SWH reconstructed by the model is evaluated with the training‐independent test set. The results demonstrate that the accuracy of the SAE‐DNN model is significantly improved by incorporating SAR joint quasi‐synchronous observations and the root mean square error can reach 0.217 m, which is comparable to the SWH measured by altimeter and highlights the effectiveness and reliability of the model in accurately reconstructing SWH. We further examine and analysis the distance variations between SWH reconstruction sites and Surface Wave Investigation and Monitoring observations, the influence of different SAR features, and the influence of sea state, highlighting the benefits of incorporating SAR data into SAE‐DNN model.

BackgroundAs one of the most prevalent primary lung tumors, non-small cell lung cancer (NSCLC) has garnered considerable research interest due to its high metastasis rates and poor prognosis outcomes. Across different cancer types, metabolic processes are required for tumors progression and growth, thus interfering with such processes in NSCLC may therapeutically viable for limiting/halting disease progression. Therefore, comprehending how metabolic processes contribute to growth and survival mechanisms in cancers, including NSCLC, may elucidate key functions underpinning tumor cell metabolism. However, no bibliometric analyses have been published in this field, therefore we address this knowledge gap here.MethodsBetween 2013 and 2023 (December 28th), articles related to the NSCLC and metabolism (NSCLC-Met) field were retrieved from the Web of Science Core Collection (WoSCC). To fully dissect NSCLC-Met research directions and articles, we used the Bibliometrix package in R, VOSviewer and CiteSpace software to visually represent global trends and hotspots.ResultsBetween 2013 and 2023, 2,246 NSCLC-Met articles were retrieved, with a continuous upward trend and rapid development observed year on year. Cancers published the most articles, with Cancer Research recording the highest average citation numbers. Zhang Li from China was the most prolific author, but the highest number of authors came from the USA. China, USA, and Italy were the top three countries with the highest number of published articles, with close cooperation identified between countries. Recent hotspots and research directions were reflected by “lung adenocarcinoma”, “immunotherapy”, “nivolumab”, “checkpoint inhibitors”, “blockade”, and “pembrolizumab”, while “gut microbiome”, “egfr” and “dose painting” were important topics for researchers.ConclusionFrom our analyses, scientists can now explore new hotspots and research directions in the NSCLC-Met field. Further in-depth research in this field will undoubtedly provide more new insights on disease diagnostics, treatment, and prognostics.

Abstract According to the latest evidence, the microbial metabolite Urolithin A (UA), known for its role in promoting cellular health, modulates CD8+ T cell‐mediated antitumor activity. However, the direct target protein of UA and its underlying mechanism remains unclear. Here, this research identifies ERK1/2 as the specific target crucial for UA‐mediated CD8+ T cell activation. Even at low doses, UA markedly enhances the persistence and effector functions of primary CD8+ cytotoxic T lymphocytes (CTLs) and human chimeric antigen receptor (CAR) T cells both in vitro and in vivo. Mechanistically, UA interacts directly with ERK1/2 kinases, enhancing their activation and subsequently facilitating T cell activation by engaging ULK1. The UA‐ERK1/2‐ULK1 axis promotes autophagic flux in CD8+ CTLs, enhancing cellular metabolism and maintaining reactive oxygen species (ROS) levels, as evidenced by increased oxygen consumption and extracellular acidification rates. UA‐treated CD8+ CTLs also display elevated ATP levels and enhanced spare respiratory capacity. Overall, UA activates ERK1/2, inducing autophagy and metabolic adaptation, showcasing its potential in tumor immunotherapy and interventions for diseases involving ERKs.

Protaetia brevitarsis larvae (PBL) are soil insects important for the soil organic carbon cycle, and PBL frass not only contains a large amount of humic acid but also affects the diversity, novelty, and potential functions of actinomycetes. Here, we characterized and assessed the actinomycete. The operational taxonomic unit (OTU) data showed that 90% of the actinomycetes cannot be annotated to species, and pure culture and genome analysis showed that 35% of the strains had the potential to be new species, indicating the novelty of PBL frass actinomycetes. Additionally, genome annotation showed that many gene clusters related to antifungal, antibacterial and insecticidal compound synthesis were identified, and confrontation culture confirmed the antifungal activities of the actinomycetes against soil-borne plant pathogenic fungi. The incubation experiment results showed that all isolates were able to thrive on media composed of straw powder and alkaline lignin. These results indicated that PBL hindgut-enriched actinomycetes could survive in soil by using the residual lignocellulose organic matter from plant residues, and the antibiotics produced not only give them a competitive advantage among soil microflora but also have a certain inhibitory effect on plant diseases and pests. This study suggests that the application of PBL frass can not only supplement soil humic acid but also potentially affect the soil microbiota of cultivated land, which is beneficial for the healthy growth of crops.

The Agulhas Return Current (ARC) transports warm tropical and subtropical waters eastward into the southern Indian Ocean. It plays a crucial role in the oceanographic connections between the Indian, Atlantic, and Southern oceans. Modern oceanographic observations show that the latitudinal position of the ARC varies interannually. However, its historical positional variations remain poorly understood. Calcareous nannofossils can be a good indicator of ancient current migration, although their record in the Southwest Indian Ocean is poorly studied. This research aims to understand the characteristics and downcore variation of the calcareous nannofossil assemblages and trace the record of the ancient ARC. To achieve these goals, this study analyzed pelagic sediments of multicore 34IV-SWIR-S021MC03, 34IV-SWIR-S032MC04, and 34IV-SWIR-S040MC05 from the Southwest Indian Ocean. A total of 13 nannofossil species have been identified. The assemblages belong to the subtropical convergence zone regime. They are characterized by warm and cold water species, dominated by Emiliania huxleyi, Calcidiscus leptoporus, Gephyrocapsa muellerae, and Florisphaera profunda. According to the AMS14C age model and phytoplankton ecological signatures, this study establishes a calcareous nannofossil indicator to trace the migration of the ancient ARC during the last 40 kyr. The result shows three periods of migration: 40–22 kyr, the ancient ARC was in the far north and was moving southward; 22–14 kyr, a transitional period, the ancient ARC was moving northward; 14–3 kyr, the ARC was moving southward. This further suggests that the migration of the ancient ARC is more complex than the two recognized phases, and there were essential turning points around the last glacial maximum period. It also acknowledges that the ancient ARC is sensitive to interglacial periods and can be influenced simultaneously by the Southern Hemisphere monsoon and westerly winds.

Summary: Depressive symptoms usually precede the cognitive decline in Alzheimer disease (AD) and worsen the clinical outcome. However, the neural circuitry mediating early emotional dysfunction, especially depressive symptoms in AD, remains elusive. Anterior cingulate cortex (ACC) is closely related to depression and vulnerable in AD. By quantitative whole-brain mapping and electrophysiological recording, we found that the decreased axonal calcium activity in neurons of ACC and the glutamatergic projection from ACC to the ventral hippocampal CA1 (vCA1) is significantly impaired in 3-month-old 5×FAD mice, which exhibit depressive-like phenotype before cognition defects in early stage. The activation of ACC-vCA1 circuit by chemogenetic manipulation efficiently ameliorated the early depressive-like behaviors in 5×FAD mice. We further identified the upregulated neuregulin-1 (Nrg1) in ACC impaired the excitatory synaptic transmission from the ACC to vCA1 in AD. Our work reveals the role of ACC-vCA1 circuit in regulating AD associated depression symptom in a mouse model of AD.

Spintronic devices have become a crucial technology for overcoming the power consumption bottleneck in integrated circuits, due to their low power consumption, high-speed processing capability. Two-dimensional materials offer potential for performance enhancement and device miniaturization in spintronics because of their unique electronic and spin properties. Specifically, two-dimensional transition metal dichalcogenides (2D TMDs) are favored in the field of spintronics for their strong spin–orbit coupling effects, enabling effective control over the electron spin state. However, the preparation techniques for 2D TMDs are still in the exploratory stage. In this work, we explore novel preparation method combining magnetron sputtering and molecular beam epitaxy, leading to wafer-scale high-quality monocrystalline PtTe2 thin films. Further, Spin-Orbit Torque (SOT) efficiency is investigated in PtTe2-based heterostructures, which reveals a significant spin Hall angle of over 0.094. Our work provides a new way to fabricate the wafer-scale PtTe2 thin films and confirms a large SOT efficiency, which indicates the great promise for spintronic applications.

Background Although cardiovascular mortality continued declining from 2000 to 2019, the rate of this decrease decelerated. We aimed to assess the trends and disparities in risk factor control and treatment among US adults with atherosclerotic cardiovascular disease to find potential causes of the deceleration. Methods and Results A total of 55 ,021 participants, aged ≥20 years, from the 1999 to 2018 National Health and Nutrition Examination Survey were included, of which 5717 were with atherosclerotic cardiovascular disease. Risk factor control was defined as hemoglobin A1c

BackgroundAdrenocortical carcinoma (ACC) is an aggressive endocrine malignancy with limited therapeutic options. Treating advanced ACC with mitotane, the cornerstone therapy, remains challenging, thus underscoring the significance to predict mitotane response prior to treatment and seek other effective therapeutic strategies.ObjectiveWe aimed to determine the efficacy of mitotane via an in vitro assay using patient-derived ACC cells (PDCs), identify molecular biomarkers associated with mitotane response and preliminarily explore potential agents for ACC.MethodsIn vitro mitotane sensitivity testing was performed in 17 PDCs and high-throughput screening against 40 compounds was conducted in 8 PDCs. Genetic features were evaluated in 9 samples using exomic and transcriptomic sequencing.ResultsPDCs exhibited variable sensitivity to mitotane treatment. The median cell viability inhibition rate was 48.4% (IQR: 39.3-59.3%) and -1.2% (IQR: -26.4-22.1%) in responders (n=8) and non-responders (n=9), respectively. Median IC50 and AUC were remarkably lower in responders (IC50: 53.4 µM vs 74.7 µM, P

The dynamics of excited‐state charge transfer (CT) in second near‐infrared (NIR‐II) fluorophore proceeds with conformational change that govern fluorescence. Unveiling the relationship between CT dynamics and conformational change in excited state is of great fundamental significance in optimizing NIR‐II fluorescence but remains less explored. This study unveils the pivotal role of large conformational change in promoting the evolution of emissive CT state into nonemissive CT state in NIR‐II fluorophore (CA‐BBT). Spectroscopic and computational results reveal that large conformational rotation/twisting leads to a pronounced increase in the CT character in excited state. This heightened CT character in CA‐BBT enables a rapid evolution of emissive CT state into a nonemissive CT state within 1.4 ps, as observed by ultrafast spectroscopy. Subsequently, this nonemissive state dominates nonradiative decay, resulting in very low NIR‐II fluorescence. Preventing such detrimental evolution by constraining the conformational dynamics of CA‐BBT results in a 10‐fold enhancement of NIR‐II fluorescence, enabling high‐resolution dynamic visualization of vasculature within osteosarcoma. This study offers a profound understanding of the relationship between CT dynamics and conformational changes in NIR‐II fluorescence, presenting innovative perspectives to develop bright NIR‐II fluorophores.

Summary: Despite the promising outcomes of immune checkpoint inhibitors (ICIs), resistance to ICI presents a new challenge. Therefore, selecting patients for specific ICI applications is crucial for maximizing therapeutic efficacy. Herein, we curated 69 human esophageal squamous cell cancer (ESCC) patients’ tumor microenvironment (TME) single-cell transcriptomic datasets to subtype ESCC. Integrative analyses of the cellular network and transcriptional signatures of T cells and myeloid cells define distinct ESCC subtypes characterized by T cell exhaustion, and interleukin (IL) and interferon (IFN) signaling. Furthermore, this approach classifies ESCC patients into ICI responders and non-responders, as validated by whole tumor transcriptomes and liquid biopsy-based single-cell transcriptomes of anti-PD-1 ICI responders and non-responders. Our study stratifies ESCC patients based on TME transcriptional network, providing novel insights into tumor niche remodeling and potentially predicting ICI responses in ESCC patients.

Introduction: Different land use patterns affect access to ecosystem services as well as differences in farmers’ well-being. Methods: The Loess Plateau, which has a fragile ecological environment, was chosen as the study region. On the one hand, information on the importance and accessibility of ESs, as well as the subjective and objective well-being of farmers, was obtained through semistructured interviews and questionnaires. On the other hand, regional differences for the impact of ESs on the well-being of farmers were explored based on a structural equation model.Results: The results indicated that the impact of ESs on farmers’ well-being was crucial for all three village types, but the extent of the impact varied, and the key ESs varied across villages. For hilly villages and gully villages, crops and firewood were the two common ES types that were important. However, water conservation was the key ES type for farmers in hilly villages, and pest control was the key ES type for farmers in gully villages. Fruits, water conservation and recreation were the key ES types in the river villages.Discussion: A focus on the regional differences for the impacts of ESs on farmers’ well-being is meaningful for policy practice. We can contribute to farmers’ well-being by optimising land use allocation and land ecological control to improve their ES access in different regions, which is effective in differentiating and enhancing the sustainability of different regions.

Ginsenoside Rg1 (Rg1), a monomer saponin component, is one of the components with the highest content in total saponins of Panaxnotoginseng. It had various pharmacological effects. The bioavailability of oral tablets is only 1–20 %, and it is eliminated quickly in the blood. The development of new dosage forms and new routes of administration of ginsenoside Rg1 with sustained release and high bioavailability has become a significant problem to be solved. The Rg1 liposomes study used a thin film dispersion ultrasound method for its preparation. This study focused the pharmacokinetic parameters of ginsenoside Rg1 liposomes in rats through the lung perfusion method. Ginsenoside Rg1 liposomes were round and uniform in shape, the particle size was 2–3 μm, and the encapsulation efficiency of ginsenoside Rg1 liposome was 51.2 %. Results showed that, after pulmonary administration of ginsenoside Rg1, the time of ginsenoside Rg1 detected by Rg1 liposomes was longer than that of Rg1 solution, the relative bioavailability of ginsenoside Rg1 liposome lung administration AUC liposome/AUC solution = 122.67 %. These results provided the scientific theoretical and experimental basis for further development of new dosage forms and new routes of administration of ginsenoside Rg1.

ABSTRACT: The processing and analysis of massive high-dimensional datasets are important issues in precision livestock farming (PLF). This study explored the use of multivariate analysis tools to analyze environmental data from multiple sensors located throughout a broiler house. An experiment was conducted to collect a comprehensive set of environmental data including particulate matter (TSP, PM10, and PM2.5), ammonia, carbon dioxide, air temperature, relative humidity, and in-cage and aisle wind speeds from 60 locations in a typical commercial broiler house. The dataset was divided into 3 growth phases (wk 1–3, 4–6, and 7–9). Spearman's correlation analysis and principal component analysis (PCA) were used to investigate the latent associations between environmental variables resulting in the identification of variables that played important roles in indoor air quality. Three cluster analysis methods; k-means, k-medoids, and fuzzy c-means cluster analysis (FCM), were used to group the measured parameters based on their environmental impact in the broiler house. In general, the Spearman and PCA results showed that the in-cage wind speed, aisle wind speed, and relative humidity played critical roles in indoor air quality distribution during broiler rearing. All 3 clustering methods were found to be suitable for grouping data, with FCM outperforming the other 2. Using data clustering, the broiler house spaces were divided into 3, 2, and 2 subspaces (clusters) for wk 1 to 3, 4 to 6, and 7 to 9, respectively. The subspace in the center of the house had a poorer air quality than other subspaces.

Bone defects and non-union are prevalent in clinical orthopedy, and the outcomes of current treatments are often suboptimal. Bone tissue engineering offers a promising approach to treating these conditions effectively. Bone morphogenetic protein 9 (BMP9) can commit mesenchymal stem cells to osteogenic lineage, and a knowledge of the underlying mechanisms may help advance the field of bone tissue engineering. Leucine-rich repeats containing G protein-coupled receptor 4 (LGR4), a member of G protein-coupled receptors, is essential for modulating bone development. This study is aimed at investigating the impact of LGR4 on BMP9-induced osteogenesis in mesenchymal stem cells as well as the underlying mechanisms. Bone marrow stromal cells from BMP9-knockout mice exhibited diminished LGR4 expression, and exogenous LGR4 clearly restored the impaired osteogenic potency of the bone marrow stromal cells. Furthermore, LGR4 expression was increased by BMP9 in C3H10T1/2 cells. LGR4 augmented the benefits of BMP9-induced osteogenic markers and bone formation, whereas LGR4 inhibition restricted these effects. Meanwhile, the BMP9-induced lipogenic markers were increased by LGR4 inhibition. The protein levels of Raptor and p-Stat3 were elevated by BMP9. Raptor knockdown or p-Stat3 suppression attenuated the osteoblastic markers and LGR4 expression brought on by BMP9. LGR4 significantly reversed the blocking effect of Raptor knockdown or p-Stat3 suppression on the BMP9-induced osteoblastic markers. Raptor interacts with p-Stat3, and p-Stat3 activates the LGR4 promoter activity. In conclusion, LGR4 boosts BMP9 osteoblastic potency in mesenchymal stem cells, and BMP9 may up-regulate LGR4 via the mTORC1/Stat3 signal activation.

Abstract Acoustic communication plays important roles in the survival and reproduction of anurans. The perception and discrimination of conspecific sound signals of anurans were always affected by masking background noise. Previous studies suggested that some frogs evolved the high‐frequency hearing to minimize the low‐frequency noise. However, the molecular mechanisms underlying the high‐frequency hearing in anurans have not been well explored. Here, we cloned and obtained the coding regions of a high‐frequency hearing‐related gene (KCNQ4) from 11 representative anuran species and compared them with orthologous sequences from other four anurans. The sequence characteristics and evolutionary analyses suggested the highly conservation of the KCNQ4 gene in anurans, which supported their functional importance. Branch‐specific analysis showed that KCNQ4 genes were under different evolutionary forces in anurans and most anuran lineages showed a generally strong purifying selection. Intriguingly, one significantly positively selected site was identified in the anuran KCNQ4 gene based on FEL model. Positive selection was also found along the common ancestor of Ranidae and Rhacophoridae as well as the ancestral O. tianmuii based on the branch‐site analysis, and the positively selected sites identified were involved in or near the N‐terminal ion transport and the potassium ion channel functional domain of the KCNQ4 genes. The present study revealed valuable information regarding the KCNQ4 genes in anurans and provided some new insights for the underpinnings of the high‐frequency hearing in frogs.

Abstract The development of magnetocaloric materials with a significantly enhanced volumetric cooling capability is highly desirable for the application of adiabatic demagnetization refrigerators in confined spatial environments. Here, the thermodynamic characteristics of a magnetically frustrated spin‐7/2 Gd9.33[SiO4]6O2 is presented, which exhibits strongly correlated spin disorder below ≈1.5 K. A quantitative model is proposed to describe the magnetization results by incorporating nearest‐neighbor Heisenberg antiferromagnetic and dipolar interactions. Remarkably, the recorded magnetocaloric responses are unprecedentedly large and applicable below 1.0 K. It is proposed that the S = 7/2 spin liquids serve as versatile platforms for investigating high‐performance magnetocaloric materials in the sub‐kelvin regime, particularly those exhibiting a superior cooling power per unit volume.

Abstract Inadequate β‐cell mass and insulin secretion are essential for the development of type 2 diabetes (T2D). TNF‐α‐induced protein 8‐like 1 (Tipe1) plays a crucial role in multiple diseases, however, a specific role in T2D pathogenesis remains largely unexplored. Herein, Tipe1 as a key regulator in T2D, contributing to the maintenance of β cell homeostasis is identified. The results show that the β‐cell‐specific knockout of Tipe1 (termed Ins2‐Tipe1BKO) aggravated diabetic phenotypes in db/db mice or in mice with high‐fat diet‐induced diabetes. Notably, Tipe1 improves β cell mass and function, a process that depends on Gαs, the α subunit of the G‐stimulating protein. Mechanistically, Tipe1 inhibited the K48‐linked ubiquitination degradation of Gαs by recruiting the deubiquitinase USP5. Consequently, Gαs or cAMP agonists almost completely restored the dysfunction of β cells observed in Ins2‐Tipe1BKO mice. The findings characterize Tipe1 as a regulator of β cell function through the Gαs/cAMP pathway, suggesting that Tipe1 may emerge as a novel target for T2D intervention.

Lodging is a crucial factor that limits wheat yield and quality in wheat breeding. Therefore, accurate and timely determination of winter wheat lodging grading is of great practical importance for agricultural insurance companies to assess agricultural losses and good seed selection. However, using artificial fields to investigate the inclination angle and lodging area of winter wheat lodging in actual production is time-consuming, laborious, subjective, and unreliable in measuring results. This study addresses these issues by designing a classification-semantic segmentation multitasking neural network model MLP_U-Net, which can accurately estimate the inclination angle and lodging area of winter wheat lodging. This model can also comprehensively, qualitatively, and quantitatively evaluate the grading of winter wheat lodging. The model is based on U-Net architecture and improves the shift MLP module structure to achieve network refinement and segmentation for complex tasks. The model utilizes a common encoder to enhance its robustness, improve classification accuracy, and strengthen the segmentation network, considering the correlation between lodging degree and lodging area parameters. This study used 82 winter wheat varieties sourced from the regional experiment of national winter wheat in the Huang-Huai-Hai southern area of the water land group at the Henan Modern Agriculture Research and Development Base. The base is located in Xinxiang City, Henan Province. Winter wheat lodging images were collected using the unmanned aerial vehicle (UAV) remote sensing platform. Based on these images, winter wheat lodging datasets were created using different time sequences and different UAV flight heights. These datasets aid in segmenting and classifying winter wheat lodging degrees and areas. The results show that MLP_U-Net has demonstrated superior detection performance in a small sample dataset. The accuracies of winter wheat lodging degree and lodging area grading were 96.1% and 92.2%, respectively, when the UAV flight height was 30 m. For a UAV flight height of 50 m, the accuracies of winter wheat lodging degree and lodging area grading were 84.1% and 84.7%, respectively. These findings indicate that MLP_U-Net is highly robust and efficient in accurately completing the winter wheat lodging-grading task. This valuable insight provides technical references for UAV remote sensing of winter wheat disaster severity and the assessment of losses.

Abstract Objective The purpose of this retrospective study was to describe the clinicopathological characteristics of primary adenoid cystic carcinoma (ACC) of the palate and to identify the factors affecting prognosis. Methods The medical records of 85 patients with primary ACC of the palate treated with surgery, with or without adjuvant radiotherapy/chemotherapy, from 2009 to 2019 were reviewed. The relationship of different clinical parameters with locoregional recurrence (LR), distant metastasis (DM), and overall survival (OS) were analyzed. Results Median follow‐up time was 44.6 months. LR and DM rates were 24.7% and 25.9%, respectively, and the 5‐year OS and disease‐free survival (DFS) rates were 85.9% and 55.1%, respectively. Multivariate analysis showed that positive margins were independently associated with the risk of LR (p

Honeysuckle, valued for its wide-ranging uses in medicine, cuisine, and aesthetics, faces a significant challenge in cultivation due to powdery mildew, primarily caused by the Erysiphe lonicerae pathogen. The interaction between honeysuckle and E. lonicerae, especially concerning disease progression, remains insufficiently understood. Our study, conducted in three different locations, found that honeysuckle naturally infected with E. lonicerae showed notable decreases in total flavonoid content, with reductions of 34.7%, 53.5%, and 53.8% observed in each respective site. Controlled experiments supported these findings, indicating that artificial inoculation with E. lonicerae led to a 20.9% reduction in flavonoid levels over 21 days, worsening to a 54.8% decrease by day 42. Additionally, there was a significant drop in the plant’s total antioxidant capacity, reaching an 81.7% reduction 56 days after inoculation. Metabolomic analysis also revealed substantial reductions in essential medicinal components such as chlorogenic acid, luteolin, quercetin, isoquercetin, and rutin. Investigating gene expression revealed a marked decrease in the relative expression of the LjPAL1 gene, starting as early as day 7 post-inoculation and falling to a minimal level (fold change = 0.29) by day 35. This trend was mirrored by a consistent reduction in phenylalanine ammonia-lyase activity in honeysuckle through the entire process, which decreased by 72.3% by day 56. Further analysis showed significant and sustained repression of downstream genes LjFNHO1 and LjFNGT1, closely linked to LjPAL1. We identified the mechanism by which E. lonicerae inhibits this pathway and suggest that E. lonicerae may strategically weaken the honeysuckle’s disease resistance by targeting key biosynthetic pathways, thereby facilitating further pathogen invasion. Based on our findings, we recommend two primary strategies: first, monitoring medicinal constituent levels in honeysuckle from E. lonicerae-affected areas to ensure its therapeutic effectiveness; and second, emphasizing early prevention and control measures against honeysuckle powdery mildew due to the persistent decline in crucial active compounds.

Abstract Background In recent years,the lack of specific markers for the diagnosis of colorectal cancer has led to an upward trend in both morbidity and mortality from this condition. There is an urgent need to identify molecular biomarkers that contribute to early cancer detection. This study aimed to identify specific exosomal microRNAs that hold potential as diagnostic biomarkers for CRC. Methods We screened for differentially expressed miRNAs using the CRC exosome dataset GSE39833. To validate the results in the public database, we collected serum from 168 CRC patients and 168 healthy volunteers. The expression levels of exosomal miR‐1470 in healthy volunteers and CRC patients were analyzed using qRT‐PCR. To evaluate the diagnostic potential of the selected miR‐1470 in distinguishing CRC patients from healthy controls, we analyzed its receiver operating characteristic curve. To explore the biological functions of miR‐1470 in CRC cell lines, we detected the miR‐1470's ability to regulate the growth and metastasis of CRC cells by CCK8, transwell and other assays after transfection of miR‐1470 in SW480, HCT‐116 cells. Results Exosomal miR‐1470 exhibited significant up‐regulation in CRC patients compared to healthy volunteers. The ROC curve analysis revealed an area under the curve (AUC) of 0.74 (95% confidence interval: 0.6876–0.7920) for exosomal miR‐1470, indicating its potential as a diagnostic biomarker. Furthermore, the expression level of miR‐1470 in CRC patients showed correlations with age, metastasis, and HDL content. We overexpressed miR‐1470 in CRC cell lines. CCK8 proliferation assay showed that miR‐1470 promoted the proliferation ability of SW480 and HCT‐116 cells. Transwell assay showed that miR‐1470 promoted the migration and invasion ability of SW480 and HCT‐116 cells. Conclusion This suggested that non‐invasive diagnosis of CRC is possible by detecting the level of miR‐1470 in exosomes, which has important implications for early detection and treatment of this disease.