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Abstract The rapid advancement of artificial intelligence and robot technology has spurred the proposal and innovation of a coal gangue sorting robot system (CGSRS) paradigm. The time-varying raw coal flow (TVRCF) with multi-scene and full working conditions affects the gangue queue. Configuring the CGSRS scheme correctly is combative. The field environment puts forward higher requirements for the time complexity of the CGSRS multi-task allocation strategy. Therefore, this paper proposes a scheme evaluation method of the CGSRS with time-varying multi-scenario based on deep learning. Firstly, the gangue queue data set of multi-scene and full-condition TVRCF was obtained according to the belt speed, the maximum coal flow, and the uncorrelated nonlinear changes of coal flow and gangue content. The CGSRS scheme is established based on robot number and rule combination, and the multi-task allocation strategy is adjusted to generate the labels of the gangue queue. Then, the RGB sample set is established based on the labels of the gangue queue. The CGSRS scheme evaluation model is trained based on DenseNet. Finally, the CGSRS scheme evaluation method was designed to realize the prediction of a random gangue queue. In this paper, the CGSRS scheme evaluation model, the stability of the solution, and the comparison of methods are carried out. Experimental results show that the solution of the CGSRS scheme evaluation model is accurate and stable. The time complexity is significantly reduced and very stable. The CGSRS scheme evaluation method is applied to the CGSRS multi-task allocation problem, and the stability of the solution is not affected by the data. It is significantly better than the multi-task allocation strategy. The proposed method is the first attempt to apply deep learning to a multi-task allocation problem in CGSRS.

Abstract Adipose stem cell-derived exosomes (ADSC-EXO) have been demonstrated to promote osteogenic differentiation of bone marrow stem cells (BMSCs) and facilitate bone regeneration. The present study aims to investigate the effect of ADSC-EXO-loaded nano-hydroxyapatite/chitosan/poly-lactide-co-glycolide (nHA/CS/PLGA) scaffolds on maxillofacial bone regeneration using tissue engineering. ADSC-EXO was isolated and co-cultured with BMSCs, and the osteogenic differentiation of BMSCs was assessed through the detection of mineralized nodule formation, alkaline phosphatase (ALP) activity, and mRNA expression of COL1A1 and runt-related transcription factor 2 (RUNX2). The nHA/CS/PLGA scaffolds were fabricated and loaded with ADSC-EXO and BMSCs, and these tissue engineering complexes were applied to the maxillofacial bone defect region of rabbits to elucidate their bone regeneration effect. The osteogenic differentiation of BMSCs was markedly enhanced when they were co-cultured with ADSC-EXO. This was evidenced by an increase in the formation of mineralized nodule formation, ALP activity, and mRNA expression of COL1A1 and runt-related transcription factor 2 (RUNX2). In vivo experiments demonstrated that the application of ADSC-EXO and BMSCs loaded nHA/CS/PLGA scaffolds effectively repaired maxillofacial bone defects in rabbits. ADSC-EXO has been demonstrated to promote the osteogenic differentiation of BMSCs. The ADSC-EXO and BMSCs loaded nHA/CS/PLGA scaffolds have been shown to facilitate the regeneration of maxillofacial bone defects. This may serve as a potential therapeutic strategy for large-scale bone defects.

To improve the application of wheat flour and the quality of noodles, in this study, 0.25%, 0.50%, 0.75%, 1.00% (w/w) grape seed proanthocyanins (GSP) were added to wheat flour. Rheology, moisture distribution and texture quality of the dough, as well as the cooking, digestive and sensory properties of the noodles were determined. The microstructure of the noodles added GSP was observed by scanning electron microscopy (SEM) to analyze the effect of GSP on the structure of wheat gluten proteins. As the results shown, with the addition of GSP rising (0~0.75%, w/w), the modulus of elasticity (G'), viscosity (G") (G'>G"), hardness, springiness and adhesiveness of the dough increased, The maximum tensile resistance and stretching distance increased by 7.22 g and 11.16 mm, respectively. It demonstrated that the rheology and texture quality were improved. The lateral relaxation time T2 shifted to the lower and the free water content declined, which exhibited the water-holding capability was enhanced. The cooking resistance of the noodles was improved, and the hydrolysis rate and glycemic index (GI) were obviously decreased which reduced from 68.45 with no additional GSP to 61.73 (1.00% addition). At the addition of GSP of 0.75%, the highest disulfide bond content and the lowest free thiol group content occurred, moreover, the score of sensory quality was the highest. The noodles exhibited the soft, chewy, and smooth mouthfeel. In conclusion, GSP could enhance the edible quality of the product by improving the structure of the gluten protein network and lowering the glycemic index (GI) value of noodles, which illustrated GSP could be used as a potential natural flour improver.

Abstract Background Shen-Bai-Jie-Du decoction (SBJDD), a traditional Chinese herb formula developed based on evidence-based medicine, is efficacy to reduce the recurrence and carcinogenesis of colorectal adenoma. However, the mechanism of SBJDD to treat colorectal adenoma remains unclear. The present study aims to investigate the efficacy and mechanism of SBJDD on colorectal adenoma carcinogenesis from the aspects of regulating gut microbiota and short-chain fatty acids (SCFAs). Methods Twenty-one patients diagnosed with colorectal adenoma were recruited in the study and required to take SBJDD for four consecutive weeks. Analysis of gut microbiota was conducted using 16S rRNA gene amplicon sequencing, while levels of SCFAs in fecal and serum samples were determined through HPLC–MS/MS. Additionally, twenty-four Apcmin/+ mice were randomly assigned to normal diet (ND), high-fat diet (HFD), and SBJDD groups. The pharmacological effects and mechanism of SBJDD on colorectal adenoma carcinogenesis were assessed using RT-qPCR, HE staining, IHC staining, Western blot, IF staining, and Flow cytometry assays. Results Our clinical study has shown that SBJDD can regulate the gut microbiota composition and enhance SCFAs production in patients with colorectal adenoma. SBJDD alleviated colorectal adenoma formation and carcinogenesis, as well as protected the integrity of the intestinal barrier in the Apcmin/+ mice model compared to the HFD group. Additionally, SBJDD was found to regulate gut microbiota capable of producing SCFAs. G protein-coupled receptors GPR43, GPR41, and GPR109a were effectively activated in the SBJDD group, while HDAC1 and HDAC3 were inhibited. Furthermore, decreased expression levels of interleukin 1 beta (IL-1β) and interleukin 6 (IL-6), along with elevated expression level of interleukin 10 (IL-10), were observed in the colorectal tissue of the SBJDD group. Finally, SBJDD exhibited the ability to reduce the proportion of M1-type macrophages while increasing the proportion of M2-type macrophages. Conclusions Our study objectively demonstrated the pharmacological effects of SBJDD in inhibiting the progression of colorectal adenoma and investigated its mechanisms in terms of regulating gut microbiota, increasing SCFAs, and reducing colorectal inflammation.

Abstract Background Pantoea agglomerans (P. agglomerans) is a gram-negative bacterium that is commonly isolated from plant surfaces, seeds, and the environment. As an opportunistic pathogen, it can cause blood, urinary and soft tissue infections in immunocompromised patients. In central nervous system, P. agglomerans infection has been report in children and immune-compromised patients, however, infection by such bacterium in nontraumatized immune competent adults has not been reported. Here, we report a case of P. agglomerans cerebrospinal meningitis accompanied by positive anti-myeloperoxidase (MPO) antibody in a 49-year-old female who has a history of black fungus planting. Case presentation The patient manifested with repeated fever, headache, generalized muscle pain, and neurological defects. Cerebrospinal fluid (CSF) tests revealed a moderately elevated number of polymorphonuclear leukocytes (50–193 × 106/L), low glucose levels (0.54–2.44 mmo1/L), and extremely high protein content (2.42–25.42 g/L). Blood tests showed positive anti-myeloperoxidase antibodies lasting for 1.5 year before turning negative. Spine MRI showed thickening and enhancement of the whole spinal meninges. CSF metagenomic next-generation sequencing (mNGS) revealed 75,189 specific DNA reads of P. agglomerans. The patient underwent spinal laminectomy due to meningeal adhesions. Pathological results revealed fibrous tissue proliferation, inflammatory infiltration with focal necrosis and calcification in the dura mater. The patient was successfully treated with sufficient antibiotics at 1-year follow-up. Conclusions People should be alert to CNS infections caused by P. agglomerans which presented with relatively mild clinical symptoms at onset, especially for those who contucts relevant agricultural and forestry work. The CSF characterization of P. agglomerans meningitis is elevated multiple nuclei white blood cells, significantly reduced glucose content, and markedly increased protein level which may be related to the secondary spinal membrane adhesions.

Abstract Hydrogel-based delivery systems have now emerged as a pivotal platform for addressing chronic tissue defects, leveraging their innate capacity to suppress pathogenic infections and facilitate expedited tissue regeneration. In this work, an injectable hydrogel dressing, termed AgNPs-dermal matrix hydrogel (Ag@ADMH), has been designed to expedite the healing process of wounds afflicted with methicillin-resistant Staphylococcus aureus (MRSA), featuring sustained antibacterial efficacy. The synthesis of the hydrogel dressing entailed a self-assembly process of collagen fibers within an acellular dermal matrix to construct a three-dimensional scaffold, encapsulated with plant polyphenol-functionalized silver nanoparticles (AgNPs). The Ag@ADMH demonstrated exceptional biocompatibility, and enables a sustained release of AgNPs, ensuring prolonged antimicrobial activity. Moreover, the in vitro RT-qPCR analysis revealed that compared with ADMH, Ag@ADMH diminish the expression of iNOS while augmenting CD206 expression, thereby mitigating the inflammatory response and fostering wound healing. Especially, the Ag@ADMH facilitated a reduction in M1 macrophage polarization, as evidenced by a significant decrement in the M1 polarization trend and an enhanced M2/M1 ratio in dermal matrix hydrogels laden with AgNPs, corroborated by confocal microscopy and flow cytometry analyses of macrophage phenotypes. The in vivo assessments indicated that Ag@ADMH minimized fibrous capsule formation. In a full-thickness skin defect model of MRSA infection, the formulation significantly attenuated the inflammatory response by reducing MPO and CD68 expression levels, concurrently promoting collagen synthesis and CD34 expression, pivotal for vasculogenesis, thereby accelerating the resolution of MRSA-infected wounds. These attributes underscore the injectable extracellular matrix hydrogel as a formidable strategy for the remediation and regeneration of infected wounds. Graphical Abstract

Abstract Rapid and sensitive nucleic acid detection is vital in disease diagnosis and therapeutic assessment. Herein, we propose a co-freezing localized CRISPR-Cas12a (CL-Cas12a) strategy for sensitive nucleic acid detection. The CL-Cas12a was obtained through a 15-minute co-freezing process, allowing the Cas12a/crRNA complex and hairpin reporter confined on the AuNPs surface with high load efficiency, for rapid sensing of nucleic acid with superior performance to other localized Cas12a strategies. This CL-Cas12a based platform could quantitatively detect targets down to 98 aM in 30 min with excellent specificity. Furthermore, the CL-Cas12a successful applied to detect human papillomavirus infection and human lung cancer-associated single-nucleotide mutations. We also achieved powerful signal amplification for imaging Survivin mRNA in living cells. These findings highlight the potential of CL-Cas12a as an effective tool for nucleic acid diagnostics and disease monitoring. Graphical abstract

Abstract Traditionally, Eriocheir sinensis elicits wide distribution, easy accessibility, and unique taste, but the low comprehensive utilization restricts its application. The present study aimed to extract and identify peptides from the defective E. sinensis and analyze the umami mechanism of crab peptides. Virtual hydrolysis showed that protein hydrolysate prepared by the dual enzyme combination (papain and alkaline protease) had high hydrolysis degrees and umami fragments, which was consistent with the actual hydrolysis results. The three strong‐flavoring crab peptides (AADESERM, SDEERMDAL, and EERAESGES) were screened by umami prediction and amino acid sequence analysis, and the umami profiles with thresholds ranged 0.0625–0.250 mg/mL determined by sensory evaluation and electronic tongue. The AADESERM had the highest umami enhancement effect. Besides, molecular docking and molecular dynamics simulation revealed that all the three crab peptides bound stably to the active cavity of T1R1. Asp147, His71, Ala302, Cys106, and Lys379 were the crucial binding sites for umami presentation. This study was accurately identifying umami crab peptides from defective E. sinensis based on pre‐virtual hydrolysis. It will reduce the wastage of crab resources and further provide support for the high‐value utilization.

Objective Coastal wetlands, a unique type of wetland with complex hydrologic and biogeochemical cycles, have ignificant carbon sequestration potential. Research on soil organic carbon (SOC) is critical for understanding carbon cycle, climatic regulation, and ecosystem health. Methods This study focused on four typical vegetation types grown in the coastal wetlands of Lianyungang, namely, Mudflats, Seepweed, Spartina alterniflora and Reeds. We analyzed the distribution characteristics of soil organic carbon content across different plant communities, and utilized statistical methods such as pearson correlation analysis, redundancy analysis (RDA), and structural equation modeling (SEM) to explore the regulatory effects of plant community characteristics and soil physicochemical properties on soil organic carbon. Particular attention was given to the relationships between environmental factors of coastal wetlands and soil organic carbon content. Results Horizontally, the soil organic carbon content of the different plant communities decreased in the following order: Reeds ((7.79±4.72) g/kg)>Spartina alterniflora ((7.42±3.14) g/kg)>Seepweed ((4.95±3.40) g/kg)>Mudflats ((3.66±1.90) g/kg). Vertically, the soil organic carbon content decreased with increasing depth within 0-50 cm. Additionally, significant correlations were found between SOC content and soil physicochemical properties, as well as plant community characteristics. The results of the redundancy analysis indicate that soil organic carbon content is negatively correlated with BD (bulk density) in different wetland types but is positively correlated with SWC (soil water content), height, diameter, coverage, AGB (above ground biomass) and BGB (below ground biomass). The structural equation model showed that the soil water content was the most important factor affecting soil organic carbon content in coastal wetlands. Conclusion These findings can not only promote a better understanding of coastal wetlands from their ecosystem structure and function but also provide relevant data support for policy making on global climate change.

Abstract Background N 6-methyladenosine (m6A) modification of messenger RNA (mRNA) is crucial for liquid-liquid phase separation in mammals. Increasing evidence indicates that liquid-liquid phase separation in proteins and RNAs affects diabetic cardiomyopathy. However, the molecular mechanism by which m6A-mediated phase separation regulates diabetic cardiac fibrosis remains elusive. Methods Leptin receptor-deficient mice (db/db), cardiac fibroblast-specific Notch1 conditional knockout (POSTN-Cre × Notch1flox/flox) mice, and Cre mice were used to induce diabetic cardiac fibrosis. Adeno-associated virus 9 carrying cardiac fibroblast-specific periostin (Postn) promoter-driven small hairpin RNA targeting Alkbh5, Ythdf2, or Notch1, and the phase separation inhibitor 1,6-hexanediol were administered to investigate their roles in diabetic cardiac fibrosis. Histological and biochemical analyses were performed to determine how Alkbh5 and Ythdf2 regulate Notch1 expression in diabetic cardiac fibrosis. NOTCH1 was reconstituted in ALKBH5- and YTHDF2-deficient cardiac fibroblasts and mouse hearts to study its effects on mitochondrial fission and diabetic cardiac fibrosis. Heart tissue samples from patients with diabetic cardiomyopathy were used to validate our findings. Results In mice with diabetic cardiac fibrosis, decreased Notch1 expression was accompanied by high m6A mRNA levels and mitochondrial fission. Fibroblast-specific deletion of Notch1 enhanced mitochondrial fission and cardiac fibroblast proliferation and induced diabetic cardiac fibrosis in mice. Notch1 downregulation was associated with Alkbh5-mediated m6A demethylation in the 3’UTR of Notch1 mRNA and elevated m6A mRNA levels. These elevated m6A levels in Notch1 mRNA markedly enhanced YTHDF2 phase separation, increased the recognition of m6A residues in Notch1 mRNA by YTHDF2, and induced Notch1 degradation. Conversely, epitranscriptomic downregulation rescues Notch1 expression, resulting in the opposite effects. Human heart tissues from patients with diabetic cardiomyopathy were used to validate the findings in mice with diabetic cardiac fibrosis. Conclusions We identified a novel epitranscriptomic mechanism by which m6A-mediated phase separation suppresses Notch1 expression, thereby promoting mitochondrial fission in diabetic cardiac fibrosis. Our findings provide new insights for the development of novel treatment approaches for patients with diabetic cardiac fibrosis.

Abstract This study aims to uncover the molecular mechanisms underlying pediatric kidney stone formation induced by renal calcium deposition by utilizing high-throughput sequencing data to reveal the regulation of PINK1 by MyoD1. We performed transcriptome sequencing on peripheral blood samples from healthy children and children with kidney stones to obtain differentially expressed genes (DEGs). Genes related to mitochondrial oxidative stress were obtained from the Genecards website and intersected with DEGs to obtain candidate target genes. Additionally, we conducted protein-protein interaction (PPI) analysis using the STRING database to identify core genes involved in pediatric kidney stone disease (KSD) and predicted their transcription factors using the hTFtarget database. We assessed the impact of MyoD1 on the activity of the PINK1 promoter using dual-luciferase reporter assays and investigated the enrichment of MyoD1 on the PINK1 promoter through chromatin immunoprecipitation (ChIP) experiments. To validate our hypothesis, we selected HK-2 cells and established an in vitro kidney stone model induced by calcium oxalate monohydrate (COM). We evaluated the expression levels of various genes, cell viability, volume of adherent crystals in each group, as well as mitochondrial oxidative stress in cells by measuring mitochondrial membrane potential (Δψm), superoxide dismutase (SOD) activity, reactive oxygen species (ROS), and malondialdehyde (MDA) content. Mitochondrial autophagy was assessed using mtDNA fluorescence staining and Western blot analysis of PINK1-related proteins. Apoptosis-related proteins were evaluated using Western blot analysis, and cell apoptosis was measured using flow cytometry. Furthermore, we developed a rat model of KSD and assessed the expression levels of various genes, as well as the pathologic changes in rat renal tissues using H&E and von Kossa staining, transmission electron microscopy (TEM), and the expression of creatinine, blood urea nitrogen, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) to evaluate the mitochondrial oxidative stress in vivo (through measurement of Δψm, SOD activity, ROS, and MDA content). Mitochondrial autophagy was evaluated by Western blot analysis of PINK1-associated proteins. Apoptosis-related proteins were detected using Western blot analysis, and cellular apoptosis was examined using cell flow cytometry and TUNEL staining. Bioinformatics analysis revealed that the PINK1 gene is upregulated and vital in pediatric kidney stone patients. Our in vitro and in vivo experiments demonstrated that silencing PINK1 could inhibit kidney stone formation by suppressing mitochondrial oxidative stress both in vitro and in vivo. We identified MyoD1 as an upstream transcription factor of PINK1 that contributes to the occurrence of pediatric kidney stones through the activation of PINK1. Our in vivo and in vitro experiments collectively confirmed that silencing MyoD1 could inhibit mitochondrial oxidative stress, mitochondrial autophagy, and cellular apoptosis in a rat model of kidney stones by downregulating PINK1 expression, consequently suppressing the formation of kidney stones. In this study, we discovered that MyoD1 may promote kidney stone formation and development in pediatric patients by transcriptionally activating PINK1 to induce mitochondrial oxidative stress.

Abstract Epigenetic alterations, such as those in chromatin structure and DNA methylation, have been extensively studied in a number of tumor types. But oral cancer, particularly oral adenocarcinoma, has received far less attention. Here, we combined laser-capture microdissection and muti-omics mini-bulk sequencing to systematically characterize the epigenetic landscape of oral cancer, including chromatin architecture, DNA methylation, H3K27me3 modification, and gene expression. In carcinogenesis, tumor cells exhibit reorganized chromatin spatial structures, including compromised compartment structures and altered gene-gene interaction networks. Notably, some structural alterations are observed in phenotypically non-malignant paracancerous but not in normal cells. We developed transformer models to identify the cancer propensity of individual genome loci, thereby determining the carcinogenic status of each sample. Insights into cancer epigenetic landscapes provide evidence that chromatin reorganization is an important hallmark of oral cancer progression, which is also linked with genomic alterations and DNA methylation reprogramming. In particular, regions of frequent copy number alternations in cancer cells are associated with strong spatial insulation in both cancer and normal samples. Aberrant methylation reprogramming in oral squamous cell carcinomas is closely related to chromatin structure and H3K27me3 signals, which are further influenced by intrinsic sequence properties. Our findings indicate that structural changes are both significant and conserved in two distinct types of oral cancer, closely linked to transcriptomic alterations and cancer development. Notably, the structural changes remain markedly evident in oral adenocarcinoma despite the considerably lower incidence of genomic copy number alterations and lesser extent of methylation alterations compared to squamous cell carcinoma. We expect that the comprehensive analysis of epigenetic reprogramming of different types and subtypes of primary oral tumors can provide additional guidance to the design of novel detection and therapy for oral cancer.

Interactive architecture designs enable spatial forms to respond to human activities by integrating technology, programming, and spatial experience. Most interactive programs respond to established actions in a uniform manner and do not take into account the individual emotional state of the user. However, the emotional states of children and adolescents with emotional/behavioral disorders play a crucial role in their interactions, and uniform spatial responses cannot be adapted to different people. This study developed an interactive architectural system for children with emotional/behavioral disorders based on individual emotion recognition and corresponding spatial transformation. The method proposed in this study enables individuals in certain emotional categories, such as extroverted, introverted, aggressive, and defensive states, to receive matching spatial responses. Using this individuality-oriented interactive system, we built a practical pavilion in a primary school in Tianjin. This study demonstrates how combining individual emotions and spatial variations opens up new design possibilities for interactive architecture.

ABSTRACTNitrogen mainly exists as nitrate in aqueous environments. In karst areas, nitrate pollution caused by anthropogenic activities severely endangers aqueous systems. In order to identify nitrate sources, nitrate in the cave water of Mahuang Cave was comprehensively analysed using hydrochemistry, δ15N-δ18O isotopes and stable isotope analysis in R. The results indicate that the nitrate content in the cave water presented insignificant seasonal variations but significant spatial variations. Compared with the variation of δ15N-NO3−, the seasonal variation of δ18O-NO3− was positive (2.68‰) in the dry season and negative (−0.52‰) in the wet season. The variation of NO3− and Cl− and the isotopes of NO3− (δ15N, δ18O) suggest multiple sources of NO3− in the water. The average contribution of different nitrate sources in the karst cave water was assessed by the SIAR model: chemical fertilisers (46.29%) > soil nitrogen (30.57%) > manure & sewage (14.14%) > atmospheric precipitation (9.14%) in the dry season and chemical fertilisers (61.86%) > soil nitrogen (20.29%) > manure & sewage (12.43%) > atmospheric precipitation(5.57%) in the wet season. The contribution in dry and wet seasons was dominated by chemical fertilisers and soil nitrogen.

Abstract High myopia (HM) is a leading cause of blindness worldwide with currently no effective interventions available. A major hurdle lies in its often isolated perception as a purely ocular morbidity, disregarding potential systemic implications. Recent evidence suggests the existence of a gut-eye axis; however, the role of gut microbiota in the pathogenesis of HM remains largely unexplored. Herein, we provide a potential crosstalk among HM’s gut dysbiosis, microbial metabolites, and scleral remodeling. Utilizing 16S rRNA gene sequencing, we observed an altered gut microbiota profile in HM patients with a significant reduction in probiotic abundance compared with healthy controls. Subsequent targeted metabolic profiling revealed a notable decrease in plasma levels of the gut microbiota-derived metabolite indole-3-acetic acid (3-IAA) among HM patients, which is closely associated with the reduced probiotics, both negatively correlated with HM severity. Genetic analyses determined that gut microbiota are causally associated with myopia risk. Importantly, when mice subjected to HM modeling receive fecal microbiota transplantation from healthy donors, there is an increase in 3-IAA plasma levels and simultaneous retardation of HM progression along with better maintenance of collagen type I alpha 1 (COL1A1) expression in the sclera. Furthermore, 3-IAA gavage achieves similar effects. Mechanistic investigations confirm the transcriptional activation of COL1A1 by 3-IAA via promoting the enrichment of SP1 to its promoter. Together, our findings provide novel insights into the gut microbiota-eye axis in the pathogenesis of HM and propose new strategies for HM intervention by remodeling the gut microbiota and indole supplementation.

Abstract Purpose To assess the interactive relationship between blood pressure status and diabetic mellitus (DM) with ganglion cell complex (GCC) thickness in elderly individuals in rural China. Methods Participants aged 50 years and older in a rural area of Daxing District, Beijing, were recruited in this study from October 2018 to November 2018. All subjects underwent a comprehensive systemic and ocular examination. Blood pressure status was graded as normotension, controlled hypertension and uncontrolled hypertension according to blood pressure measurements and the use of any medication for hypertension treatment. GCC parameters were measured by spectral-domain optical coherence tomography (SD-OCT). Generalized linear models (GLM) adjusted for related potential confounders were used to assess the interaction between DM and blood pressure status. Results Among 1415 screened subjects (2830 eyes), a total of 1117 eyes were enrolled in the final analysis. GLM analysis showed a significant interactive relationship between DM with uncontrolled hypertension status (β = 3.868, p = 0.011). GCC thickness would decrease 0.255 μm per year as the age increased (β=-0.255, p

Background: In past studies, non-medical factors in the social-healthcare-patient triad associated with the prevalence of COVID-19 have led to delays in the presentation of patients with acute appendicitis and an increase in complications. However, as research progresses, there is increasing evidence of a clinical association between COVID-19 and the development of acute appendicitis. Methods: The effect of COVID-19 prevalence and associated factors on acute appendicitis in the control (2016–2019) and exposed (2020−2023) groups was derived from a retrospective study of 3070 patients with acute appendicitis from 2016 to 2023. Results: After the implementation of the restrictions, the rate of acute appendicitis visits in the exposed group compared to the control group dropped sharply in the initial period (P = 0.047) and recovered gradually with the relaxation of the restrictions. Similar changes occurred in the number of acute complicated appendicitis visits. In addition, after the lifting of restrictions and the COVID-19 outbreak, the proportion of acute complicated appendicitis in the exposed group increased significantly (P

Abstract Globally, breast cancer continues to be the leading cause of cancer-related incidence and mortality among females. Research has shown that sleep patterns significantly influence tumor onset and progression. In this research, the association was examined through the application of a two-sample Mendelian randomization (MR) approach. For the analysis of seven sleep patterns, genetic tools were sourced from both the UK Biobank and 23andMe, including morning/evening person (chronotype) n = 177,604, morning person (chronotype) n = 248,094, daytime dozing/sleepiness n = 193,472, getting up in the morning n = 193,717, and sleeplessness n = 193,987; sleep duration n = 192,810; and nap during the day n = 166,853. The Breast Cancer Association Consortium (BCAC) supplied genome-wide association studies (GWAS) data, including 133,384 breast cancer cases and 113,789 controls, alongside subtype-specific data with 106,278 cases and 91,477 controls. We discovered that chronotype encompasses both morning and evening types contributes to the risk of overall breast cancer. While daytime dozing and morning person (chronotype) are linked to a lower risk of breast cancer in general, In subtype-specific analyses, morning person (chronotype) was negatively associated with luminal B, HER2-negative-like, and daytime dozing was negatively correlated with luminal A-like, luminal B-like, and HER2-enriched-like. The study corroborates that chronotype is a danger element for breast cancer, aligning with previous observational findings. The association between being a morning person (chronotype) or having daytime dozing and a decreased risk of breast cancer underscores the significance of sleep patterns in formulating strategies for cancer prevention.

Abstract The human endometrial decidualization is a transformative event in the pregnant uterus that involves the differentiation of stromal cells into decidual cells. While crucial to the establishment of a successful pregnancy, the metabolic characteristics of decidual cells in vivo remain largely unexplored. Here, we integrated the single-cell RNA sequencing (scRNA-seq) datasets on the endometrium of the menstrual cycle and the maternal-fetal interface in the first trimester to comprehensively decrypt the metabolic characteristics of stromal fibroblast cells. Our results revealed that the differentiation of stromal cells into decidual cells is accompanied by increased amino acid and sphingolipid metabolism. Furthermore, metabolic heterogeneity exists in decidual cells with differentiation maturity disparities. Decidual cells with high metabolism exhibit higher cellular activity and show a strong propensity for signaling. In addition, significant metabolic reprogramming in amino acids and lipids also occurs during the transition from non-pregnancy to pregnancy in the uteri of pigs, cattle, and mice. Our analysis provides comprehensive insights into the dynamic landscape of stromal fibroblast cell metabolism, contributing to our understanding of the metabolism at the molecular dynamics underlying the decidualization process in the human endometrium.

Abstract The Span-based model can effectively capture the complex entity structure in the text, thus becoming the mainstream model for nested named entity recognition (Nested NER) tasks. However, traditional Span-based models decode each entity span independently. They do not consider the semantic connections between spans or the entities’ positional information, which limits their performance. To address these issues, we propose a Bi-Directional Context-Aware Network (Bi-DCAN) for the Nested NER. Specifically, we first design a new span-level semantic relation model. Then, the Bi-DCAN is implemented to capture this semantic relationship. Furthermore, we incorporate Rotary Position Embedding into the bi-affine mechanism to capture the relative positional information between the head and tail tokens, enabling the model to more accurately determine the position of each entity. Experimental results show that compared to the latest model Diffusion-NER, our model reduces 20M parameters and increases the F1 scores by 0.24 and 0.09 on the ACE2005 and GENIA datasets respectively, which proves that our model has an excellent ability to recognise nested entities.

Highlights Elephant trunk-inspired anisotropic wrinkling structures were formed on a sandwich-like conductive film through a controlled shrinking method. The wrinkled conductive network could withstand up to 200% tensile strain and exhibits a strain-enhanced electromagnetic interference shielding effectiveness when stretching parallel to the electric field polarization direction.

Abstract Background The treatment for bilateral synchronous multiple primary lung cancers (MPLC) remains challenging. Simultaneous bilateral video-assisted thoracic surgery (VATS) may be an optimal treatment with curative intent, but its safety and feasibility are controversial. Methods One hundred and fifty-eight patients who underwent simultaneous bilateral VATS (simultaneous group) and 79 who underwent two-staged bilateral VATS (two-staged group) were included in this study. Their medical records were retrospectively reviewed and analyzed. Results The majority of patients were female and non-smokers. The most common surgical plan was lobectomy and contralateral wedge resection in both groups. There was no significant difference in the postoperative complication rate between the simultaneous groups and two-staged group (13.3% vs. 11.4%, p = 0.73). Patients who underwent simultaneous bilateral resection had shorter hospital stays, shorter anesthesia time and less chest drainage compared with those who underwent two-staged resection. Advanced TNM stage, complicated surgical plan and aggressive lymph node resection were risk factors for postoperative complications in simultaneous bilateral VATS. Patients in two groups had similar overall survival and disease free survival (p = 0.2). Conclusions Simultaneous bilateral VATS for bilateral lung nodule resection is as safe and feasible as two-staged bilateral VATS. Patients who underwent simultaneous bilateral resection had similar or even better outcomes compared to that of the two-staged group. Simultaneous bilateral VATS is potentially an optimal treatment option for patients with erarly cTNM stage and good physical condition.

Abstract Background Culex tritaeniorhynchus is widely distributed in China, from Hainan Island in the south to Heilongjiang in the north, covering tropical, subtropical, and temperate climate zones. Culex tritaeniorhynchus carries 19 types of arboviruses. It is the main vector of the Japanese encephalitis virus (JEV), posing a serious threat to human health. Understanding the effects of environmental factors on Culex tritaeniorhynchus can provide important insights into its population structure or isolation patterns, which is currently unclear. Results In total, 138 COI haplotypes were detected in the 552 amplified sequences, and the haplotype diversity (Hd) value increased from temperate (0.534) to tropical (0.979) regions. The haplotype phylogeny analysis revealed that the haplotypes were divided into two high-support evolutionary branches. Temperate populations were predominantly distributed in evolutionary branch II, showing some genetic isolation from tropical/subtropical populations and less gene flow between groups. The neutral test results of HNQH (Qionghai) and HNHK(Haikou) populations were negative (P

Abstract Background Norepinephrine and phenylephrine are commonly used vasoactive drugs to treat hypotension during the perioperative period. The increased release of endogenous norepinephrine elicits prothrombotic changes, while parturients are generally in a hypercoagulable state. Therefore, this trial aims to investigate whether there is a disparity between equivalent doses of prophylactic norepinephrine infusion and phenylephrine infusion on prothrombotic response in patients undergoing cesarean section under spinal anesthesia. Methods Sixty-six eligible parturients will be recruited for this trial and randomly assigned to the norepinephrine or phenylephrine group. The “study drug” will be administered at a rate of 15 ml/h starting from the intrathecal injection. The primary outcome are plasma coagulation factor VIII activity (FVIII: C), fibrinogen, and D-dimer levels. The secondary outcomes include hemodynamic variables and umbilical artery blood pH value. Discussion Our study is the first trial comparing the effect of norepinephrine and phenylephrine on prothrombotic response in patients undergoing cesarean section under spinal anesthesia. Positive or negative results will all help us better understand the impact of vasoactive drugs on patients. If there are any differences, this trial will provide new evidence for maternal choice of vasoactive medications in the perioperative period. Trial registration Chinese Clinical Trial Registry ChiCTR2300077164. Registered on 1 November 2023. https://www.chictr.org.cn/ .

Abstract The proposed method for joint entity and relation extraction integrates the tasks of entity extraction and relation classification by sharing the encoding layer. However, the method faces challenges due to incongruities in the contextual information captured by these subtasks, resulting in potential feature conflicts and adverse effects on model performance. To address this, we introduced a novel joint entity and relation extraction method that incorporates multi-module feature information enhancement (MFIE) ( https://github.com/liyao345496280/Relation-extraction ). We employ a relation awareness enhancement module for the entity extraction task, which directs the model’s focus towards extracting entities closely related to potential relations using a potential relation extraction module and an attention mechanism. For the relation extraction task, we implement an entity information enhancement module that uses entity extraction results to augment the original feature information through a gating mechanism, thereby enhancing relation classification performance. Experiments on the NYT and WebNLG datasets demonstrate that our method performs well. Compared to the state-of-the-art method, the F1 score on the NYT dataset improved by 0.7%.

Cascaded H-bridge inverter (CHBI) with supercapacitors (SCs) and dc-dc stage shows significant promise for medium to high voltage energy storage applications. This paper investigates the voltage balance of capacitors within the CHBI, including both the dc-link capacitors and SCs. Balance control over the dc-link capacitor voltages is realized by the dc-dc stage in each submodule (SM), while a hybrid modulation strategy (HMS) is implemented in the H-bridge to balance the SC voltages among the SMs. Meanwhile, the dc-link voltage fluctuations are analyzed under the HMS. A virtual voltage variable is introduced to coordinate the balancing of dc-link capacitor voltages and SC voltages. Compared to the balancing method that solely considers the SC voltages, the presented method reduces the dc-link voltage fluctuations without affecting the voltage balance of SCS. Finally, both simulation and experimental results verify the effectiveness of the presented method.

Abstract Background This study aims to construct a model predicting the probability of RF in AECOPD patients upon hospital admission. Methods This study retrospectively extracted data from MIMIC-IV database, ultimately including 3776 AECOPD patients. The patients were randomly divided into a training set (n = 2643) and a validation set (n = 1133) in a 7:3 ratio. First, LASSO regression analysis was used to optimize variable selection by running a tenfold k-cyclic coordinate descent. Subsequently, a multifactorial Cox regression analysis was employed to establish a predictive model. Thirdly, the model was validated using ROC curves, Harrell’s C-index, calibration plots, DCA, and K-M curve. Result Eight predictive indicators were selected, including blood urea nitrogen, prothrombin time, white blood cell count, heart rate, the presence of comorbid interstitial lung disease, heart failure, and the use of antibiotics and bronchodilators. The model constructed with these 8 predictors demonstrated good predictive capabilities, with ROC curve areas under the curve (AUC) of 0.858 (0.836–0.881), 0.773 (0.746–0.799), 0.736 (0.701–0.771) within 3, 7, and 14 days in the training set, respectively and the C-index was 0.743 (0.723–0.763). Additionally, calibration plots indicated strong consistency between predicted and observed values. DCA analysis demonstrated favorable clinical utility. The K-M curve indicated the model’s good reliability, revealed a significantly higher RF occurrence probability in the high-risk group than that in the low-risk group (P

Abstract It is of great practical significance to explore the relationship between urbanization and CO2 emissions for the low-carbon development of cities. However, the multiscale assessment of spatial relationship between population, land and economic urbanization and CO2 emissions is lacked. In this study, we first adopted the spatial statistical methods to evaluate the spatial pattern of China’s CO2 emissions in 2019. Then, we spatially quantified China’s urbanization of land, population and economy based on statistical data. Finally, we used the geo-weighted regression model to explore the spatial relationship between urbanization and CO2 emissions at the national-economic zone-province scale. The results displayed that there is obvious spatial heterogeneity in the relationship between China’s urbanization and CO2 emissions. The significant positive correlation between urbanization and CO2 emissions were mainly located in the northeastern, eastern and southwestern regions, consistent with the characteristics of the Heihe–Tengchong Line. The uneven development of land, population and economic urbanization would lead to more CO2 emissions. We suggest that China should attend the balanced development of urban land, population and economy, and avoid the additional carbon emissions caused by incongruence, to further the development of low-carbon cities.

Abstract Temporal information in event streams plays a critical role in event‐based video frame interpolation as it provides temporal context cues complementary to images. Most previous event‐based methods first transform the unstructured event data to structured data formats through voxelisation, and then employ advanced CNNs to extract temporal information. However, voxelisation inevitably leads to information loss, and processing the sparse voxels introduces severe computation redundancy. To address these limitations, this study proposes a point‐image fusion network (PIFNet). In our PIFNet, rich temporal information from the events can be directly extracted at the point level. Then, a fusion module is designed to fuse complementary cues from both points and images for frame interpolation. Extensive experiments on both synthetic and real datasets demonstrate that our PIFNet achieves state‐of‐the‐art performance with high efficiency.

As a dual-function protein, prosaposin (PSAP) is a lysosome-associated protein that participates in a variety of cellular processes. In the lysosome, PSAP is processed to activate enzymes that degrade lipids. In addition, PSAP proteins located extracellularly are involved in cancer progression, such as proliferation and tumor death suppression signaling. Moreover, under different situations, PSAP exhibits distinct metastasis potentials in tumors. However, comprehensive insight into PSAP in cancer progression has been lacking. Here, we provide a framework of the role of PSAP in cancer and its clinical application in cancer patients, providing a novel perspective on the clinical translation of PSAP.

During shoulder arthroscopic surgery in the lateral decubitus position, effective and stable continuous traction is a basic requirement for the smooth progression of the surgery. Herein, we describe a safe, reliable, and cost-effective lateral decubitus traction assembly.

BackgroundAbdominal surgery is a common surgical procedure that is frequently associated with substantial postoperative pain. However, rescue analgesia using opioids is associated with several adverse effects. The transversus abdominis plane block (TAPB) has been demonstrated to be effective as part of multimodal analgesia. This study aims to evaluate the effects of rescue analgesia using the TAPB following abdominal surgery.MethodsNinety patients undergoing abdominal surgery and reporting a numeric rating scale (NRS) score of cough pain ≥4 on the first postoperative day were randomized to receive either sufentanil or TAPB for rescue analgesia. Pain scores and arterial oxygen pressure (PaO2) were evaluated before and after the administration of rescue analgesia. Sleep quality and gastrointestinal function were assessed postoperatively. The primary outcome was the degree of pain relief on coughing 30 min after the administration of rescue analgesia.ResultsPatients of both groups reported a significantly reduced NRS score on coughing 30 min after receiving rescue analgesia (Ppaired

Abstract Flexible electronic devices extended abilities of humans to perceive their environment conveniently and comfortably. Among them, flexible magnetic field sensors are crucial to detect changes in the external magnetic field. State‐of‐the‐art flexible magnetoelectronics do not exhibit low detection limit and large working range simultaneously, which limits their application potential. Herein, a flexible magnetic field sensor possessing a low detection limit of 22 nT and wide sensing range from 22 nT up to 400 mT is reported. With the detection range of seven orders of magnitude in magnetic field sensor constitutes at least one order of magnitude improvement over current flexible magnetic field sensor technologies. The sensor is designed as a cantilever beam structure accommodating a flexible permanent magnetic composite and an amorphous magnetic wire enabling sensitivity to low magnetic fields. To detect high fields, the anisotropy of the giant magnetoimpedance effect of amorphous magnetic wires to the magnetic field direction is explored. Benefiting from mechanical flexibility of sensor and its broad detection range, its application potential for smart wearables targeting geomagnetic navigation, touchless interactivity, rehabilitation appliances, and safety interfaces providing warnings of exposure to high magnetic fields are explored.

Electronic examination serves as an efficient method for assessing learning outcomes, yet the integration of computers into exam processes introduces potential for unreliability. In this article, we propose a formal model for electronic examinations using timed automata, providing a structured approach to understanding and managing the complexities. The electronic examination process is modeled by defining four UPPAAL templates, i.e., candidate, administrator, invigilator, and examiner. Crucial properties specific to electronic examination are encoded as specifications in UPPAAL. Verification against these properties demonstrates the validity and reliability of this model. The modelable and verifiable electronic examination designed with UPPAAL suggests great potential for deeper exploration in trustworthy digital education.

Over the past 30 years, the survival rate for osteosarcoma (OS) has remained stagnant, indicating persistent challenges in diagnosis and treatment. Photodynamic therapy (PDT) has emerged as a novel and promising treatment modality for OS. Despite apoptosis being the primary mechanism attributed to PDT, it fails to overcome issues such as low efficacy and resistance. Ferroptosis, a Fe2+-dependent cell death process, has the potential to enhance PDT's efficacy by increasing reactive oxygen species (ROS) through the Fenton reaction. In this study, we investigated the anti-tumor mechanism of PDT and introduced an innovative therapeutic strategy that synergistically induces apoptosis and ferroptosis. Furthermore, we have identified HERC1 as a pivotal protein involved in the ubiquitination and degradation of NCOA4, while also uncovering a potential regulatory factor involving NRF2. Ultimately, by targeting the HERC1-NCOA4 axis during PDT, we successfully achieved full activation of ferroptosis, which significantly enhanced the anti-tumor efficacy of PDT. In conclusion, these findings provide new theoretical evidence for further characterizing mechanism of PDT and offer new molecular targets for the treatment of OS.

We have theoretically and experimentally demonstrated the feasibility of achieving ultra-low dark current in CpBnn type detectors based on a double-barrier InAs/GaSb/AlSb type-II superlattice. By employing a structure that separates the absorption region and depletion region, the diffusion, recombination, tunneling, and surface dark currents of the photodetector (PD) have been suppressed. Experimental validation has shown that a detector with a diameter of 500 µm at a bias voltage of −0.5 V exhibits a dark current density of 2.5 × 10−6 A/cm2 at the operating temperature of 300 K. The development of PD with low dark current has paved the way for applications with high demands for low noise in the fields of gravitational wave detection and astronomical observation.

Background In recent years, with the advancement of technological innovation and the widespread application of semiconductor materials, wearable technology has emerged as a significant branch in healthcare, demonstrating considerable potential for further development. This analysis aims to explore the global scientific trends on wearable technology applications in healthcare. Methods Scientific publications on wearable technology applications in healthcare from 1 January 2003 to 31 December 2022 were retrieved from the Web of Science Core Collection. A total of 19,426 publications were included in the bibliometric analysis. VOSviewer and CiteSpace were used to conduct bibliometric and visualized analysis. Key metrics such as country, institution, author co-authorships, cited references, journal citations, and keyword co-occurrences were selected for analytical emphasis. Results The United States of America and China emerged as the top two contributing countries, with significantly higher publication compared to other countries/regions. Chinese Acad Sci and Sensors are the institution and journal with the largest number of publications, respectively. Najafi, Bijan is the most active author. Research hotspots of wearable technology were divided into four clusters based on the co-occurrence analysis of keywords: (1) Wearable Technology for Detecting and Monitoring Human Physiological Parameters; (2) Wearable Technology for Human Chronic Disease Detection and Management; (3) Wearable Technology Exercise Health and Sports Rehabilitation Therapy under Intervention; and (4) The Technical Realization of Accuracy Enhancement in Wearable Technology. Conclusions The number of annual publications on wearable technology applications in healthcare has increased over the past 20 years. This analysis identified the status, trends, hot topics, and frontiers of wearable technology applications in healthcare. These findings will help researchers quickly identify emerging themes and offer new insights into the future development of wearable technology in healthcare.

Objective To compare the 24-hour intraocular pressure (IOP) fluctuation slope curve between newly diagnosed patients with ocular hypertension (OHT) and primary open-angle glaucoma (POAG).Methods and analysis Newly diagnosed and untreated OHT and POAG patients who underwent 24-hour IOP monitoring were consecutively enrolled in the study. IOP measurements were taken every 2 hours from 8:00 to 6:00 hours the following day using an iCare PRO tonometer. Patients maintained their daily routines, with IOP measured in a seated position during the day and supine at night. The 24-hour IOP fluctuation indices, including peak, trough and overall fluctuation, were calculated. Differences in the 24-hour IOP fluctuation slope curves over time between groups were analysed using a generalised additive mixed model.Results 46 patients with OHT and 41 with POAG were included. From 2:00 to 10:00 hours, mean IOP increased by 0.69 mm Hg every 2 hours in the POAG group (p

Background: Our previous research have identified Interleukin (IL)-7 and IL-15 as prognostic biomarkers for elderly septic patients, however, little is known about the link between the serum levels of IL-7, IL-15, and lactate as well as their potential roles in the regulation of inflammation in elderly septic patients. Objectives: This study aimed at investigating the link between the serum levels of IL-7, IL-15, and lactate as well as with other factors in elderly septic patients. Design: This is a retrospective study including 129 elderly patients with sepsis who were divided into the survival group (N = 34) and the nonsurvival group (N = 95) and further subgrouped based on the Acute Physiology and Chronic Health Evaluation II (APACHE II) scores. Methods: The baseline data and clinical parameters were recorded within 24 h upon admission. Serum levels of the cytokines were quantified by the Luminex assay. Spearman correlation analysis were performed. Results: Serum levels of IL-6, IL-7, IL-15, and tumor necrosis factor-α (TNF-α) were significantly higher in the nonsurvival group ( P

Objectives: To investigate prognostic factors in patients with head and neck Mucoepidermoid Carcinoma (MEC), especially the impact of treatment modalities on survival. Methods: Patients with primary head and neck MEC between 2000 and 2015 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Prognostic factors related to Overall Survival (OS) and Cancer-Specific Survival (CSS), as well as the impact of treatments, were evaluated by multivariable Cox regression analysis. Results: We identified 2692 patients diagnosed with head and neck MEC, of whom 1397 (51.89%) had a parotid gland primary, 569 (22.14%) died, and 341 (12.67%) died of MEC. Older age (≥53 years), males, unmarried, lower income, tumor site in other head and neck areas, higher tumor grade, larger tumor size, and higher stage were related to poorer OS and CSS. Patients who did not undergo surgery (HR = 3.20, 95% CI 2.45‒4.18) had worse OS, while no significant difference was detected between partial and total organ excision on patients’ OS (p = 0.729). For combination therapy, patients who received radiotherapy only (HR = 3.21, 95% CI 2.27–4.53) or no surgery and no radiotherapy (HR = 2.59, 95% CI 1.83–3.67) were correlated with worse OS (vs. surgery only), but no significant difference was detected between surgery only and surgery combined with radiotherapy on patients’ OS (p = 0.218). For CSS, the corresponding results were consistent with OS. Conclusion: Surgical resection only may be a better survival option for head and neck MEC.

Leaves of Melaleuca alternifolia are abundant in essential oils comprising terpenoids and volatile organic compounds, which play an important role in plant abiotic stress response. However, the molecular mechanisms underlying terpenoid biosynthesis in M. alternifolia remain poorly understood. To fill this knowledge gap, we profiled terpenoid content and composition across four distinct growth phases using gas chromatography-mass spectrometry (GC/MS). We also performed an integrated analysis of gene expression in leaf tissues through full-length transcriptome sequencing combined with high throughput RNA sequencing. We identified 46,313 transcripts, 99 % (45,848 transcripts) of which were annotated using existing databases. Our study also revealed 2,792 transcription factors (TFs) and 1,812 alternative splicing (AS) events. Through weighted gene co-expression network analysis (WGCNA), we clustered these identified genes into 11 co-expressed modules. Notably, two modules—designated as blue and brown—were significantly correlated with essential oil content. Homologous annotation with the Arabidopsis database revealed that genes within the blue module are largely involved in the 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway, suggesting its pivotal role in essential oil synthesis in M. alternifolia. Furthermore, elevated expression levels of VAMP72 and DGK1 in the brown module indicate their potential function as negative regulators of essential oil synthesis. Our findings unveil key differentially expressed genes (DEGs) and pathways that can be targeted to enhance essential oil production in M. alternifolia. The identified TFs may serve as potential candidates for genetic modification through genome editing technologies. This research provides valuable insights into the processes involved in essential oil biosynthesis and highlights key genes for functional characterization in M. alternifolia.

Abstract Bridged chiral biaryls are axially chiral compounds with a medium-sized ring connecting the two arenes. Compared with plentiful methods for the enantioselective synthesis of biaryl compounds, synthetic approaches for this subclass of bridged atropisomers are limited. Here we show an atroposelective synthesis of 1,3-diaxial bridged eight-membered terphenyl atropisomers through an Co/SPDO (spirocyclic pyrrolidine oxazoline)-catalyzed aerobic oxidative coupling/desymmetrization reaction of prochiral phenols. This catalytic desymmetric process is enabled by combination of an earth-abundant Co(OAc)2 and a unique SPDO ligand in the presence of DABCO (1,4-diaza[2.2.2]bicyclooctane). An array of diaxial bridged terphenyls embedded in an azocane can be accessed in high yields (up to 99%) with excellent enantio- (>99% ee) and diastereoselectivities (>20:1 dr).

Abstract Introduction Listeriosis is a severe food-borne disease caused by Listeria monocytogenes infection. The data of listeriosis in Xi’an population are limited. The aim of this study is to evaluate the clinical features and fatality risk factors for listeriosis in three tertiary-care hospitals in Xi’an, China Methods The characteristics of demographic data, underlying diseases, clinical manifestations, laboratory indicators, cranial imaging examination, antibiotics therapeutic schemes, and clinical outcomes were collected between 2011 and 2023. Logistic regression analysis was performed. Results Seventy-one etiologically confirmed listeriosis patients were enrolled, including 12 neonatal and 59 non-neonatal cases. The majority of neonatal listeriosis presented as preterm (50%) and fetal distress (75%). The main clinical manifestations of non-neonatal listeriosis included fever (88%), headache (32%), disorder of consciousness (25%), vomiting (17%), abdominal pain (12%), and convulsions (8%). The fatality rate in neonatal cases was higher than in non-neonatal listeriosis (42 vs. 17%). Although no deaths were reported in maternal listeriosis, only two of 23 patients had an uneventful obstetrical outcome. Five maternal listeriosis delivered culture-positive neonates, three of whom decreased within 1 week post-gestation due to severe complications. Twenty-eight cases were neurolisteriosis and 43 cases were bacteremia. Neurolisteriosis had a higher fatality rate compared with bacteremia listeriosis (36 vs. 12%). The main neuroradiological images were cerebral edema/hydrocephalus, intracranial infection, and cerebral hernia. Listeria monocytogenes showed extremely low resistance to ampicillin (two isolates) and penicillin (one isolate). The fatality risk factors were the involvement of the central nervous system, hyperbilirubinemia, and hyponatremia for all enrolled subjects. Hyperuricemia contributed to the elevation of fatality risk in non-neonatal listeriosis. Conclusions When the patients suffered with symptoms of fever and central nervous system infection, they should be alert to the possibility of listeriosis. Early administration of ampicillin- or penicillin-based therapy might be beneficial for recovery of listeriosis.

This study delved into the potential application of Platanus acerifolia leaf extract (PALE) as an environmentally benign corrosion inhibitor. Evaluation of corrosion inhibition was conducted using electrochemical methods, field emission scanning electron microscopy equipped with energy dispersive spectrometer. The results reveal that PALE offers efficient protection for Q235 steel across the temperature range of 298 K–318 K, achieving a maximum corrosion inhibition efficiency of approximately 93%. Furthermore, Density functional theory (DFT) calculations and molecular dynamics (MD) simulations were performed to elucidate the spontaneous and stable adsorption of PALE molecules onto the surface of Q235 steel. This adsorption impedes the diffusion of corrosive substances towards the steel surface, thereby endowing Q235 steel with robust corrosion resistance.

Abstract A direct strategy to achieve specific treatments and reduce side effects is through cell type‐specific drug delivery. Exosomes (Exos) can be modified with folic acid (FA) to prepare drug delivery systems targeting tumor cells that highly express FA receptors. This study aimed to produce an exo drug delivery system with FA decoration and temozolomide (TMZ) loading to improve the sustained TMZ release and targeting. We used DSPE‐PEG2000‐FA to modify exos derived from astrocyte U‐87 to prepare FA‐modified exos (Astro‐exo‐FA). TMZ was encapsulated into Astro‐exo‐FA or Astro‐exo through electroporation to produce TMZ@Astro‐exo and TMZ@Astro‐exo‐FA. In vitro drug release was examined using the dialysis bag method. Through cell experiments in vitro and mouse glioma models in vivo, the effect of TMZ@Astro‐exo‐FA on U‐87 cells was determined. Exo properties were not affected by FA modification and TMZ loading. The drug release rate of TMZ@Astro‐exo‐FA was slower. TMZ@Astro‐exo‐FA uptake by U‐87 cells was higher compared to TMZ@Astro‐exo, indicating that TMZ@Astro‐exo‐FA has a stronger targeting toward U‐87 cells. TMZ@Astro‐exo‐FA remarkably reduced U‐87 cell proliferation, migration, and invasion compared with TMZ@Astro‐exo and free TMZ. Treatment with TMZ@Astro‐exo‐FA reduced the side effects of TMZ (minimal change in body weight), prolonged survival, and inhibited tumor growth in mouse glioma models, and its efficacy was stronger than that of TMZ@Astro‐exo and free TMZ. TMZ@Astro‐exo‐FA could enhance the effect of TMZ against glioma, providing novel ideas for drug targeting delivery and exploring exos as drug carriers against glioma.

Abstract Capsaicin derivatives with thiourea structure (CDTS) is highly noteworthy owing to its higher analgesic potency in rodent models and higher agonism in vitro. However, the direct synthesis of CDTS remains t one or more shortcomings. In this study, we present reported a green, facile, and practical synthetic method of capsaicin derivatives with thiourea structure is developed by using an automated synthetic system, leading to a series of capsaicin derivatives with various electronic properties and functionalities in good to excellent yields.

Anthocyanins play crucial roles in pollen protection and pollinator attraction in flowering plants. However, the mechanisms underlying flower color determination and whether floral anthocyanin regulators participate in other processes remain largely unresolved in soybeans (Glycine max). In this study, we investigated the genetic components and mechanisms governing anthocyanin biosynthesis in soybean flowers. Molecular and genetic studies have characterized two antagonistic regulators, the positive activator GmMYBA3 and the negative repressor GmMYBR1, that modulate the gene expression of anthocyanin biosynthesis in soybean flowers. Further findings revealed a regulatory interplay between GmMYBA3 and GmMYBR1 bridged by GmTT8a, highlighting the complexity of anthocyanin regulation in different soybean organs. Exploration of additional soybean cultivars demonstrated the universality of GmMYBA3 and GmMYBR1 in regulating floral anthocyanin biosynthesis- related genes, with GmF3′5′H identified as a crucial determinant of white flower color. This study provides a molecular mechanism underlying soybean flower color determination, paving the way for the molecular modification of soybean flowers to probably enhance their resistance to abiotic stresses and attractiveness to pollinators.

Abstract Leukemias and their bone marrow microenvironments undergo dynamic changes over the course of disease. However, little is known about the circulation kinetics of leukemia cells, nor the impact of specific factors on the clearance of circulating leukemia cells (CLCs) from the blood. To gain a basic understanding of CLC dynamics over the course of disease progression and therapeutic response, we apply a blood exchange method to mouse models of acute leukemia. We find that CLCs circulate in the blood for 1–2 orders of magnitude longer than solid tumor circulating tumor cells. We further observe that: (i) leukemia presence in the marrow can limit the clearance of CLCs in a model of acute lymphocytic leukemia (ALL), and (ii) CLCs in a model of relapsed acute myeloid leukemia (AML) can clear faster than their untreated counterparts. Our approach can also directly quantify the impact of microenvironmental factors on CLC clearance properties. For example, data from two leukemia models suggest that E-selectin, a vascular adhesion molecule, alters CLC clearance. Our research highlights that clearance rates of CLCs can vary in response to tumor and treatment status and provides a strategy for identifying basic processes and factors that govern the kinetics of circulating cells.

Abstract Background Human adipose stromal cells-derived extracellular vesicles (haMSC-EVs) have been shown to alleviate inflammation in acute lung injury (ALI) animal models. However, there are few systemic studies on clinical-grade haMSC-EVs. Our study aimed to investigate the manufacturing, quality control (QC) and preclinical safety of clinical-grade haMSC-EVs. Methods haMSC-EVs were isolated from the conditioned medium of human adipose MSCs incubated in 2D containers. Purification was performed by PEG precipitation and differential centrifugation. Characterizations were conducted by nanoparticle tracking analysis, transmission electron microscopy (TEM), Western blotting, nanoflow cytometry analysis, and the TNF-α inhibition ratio of macrophage [after stimulated by lipopolysaccharide (LPS)]. RNA-seq and proteomic analysis with liquid chromatography tandem mass spectrometry (LC–MS/MS) were used to inspect the lot-to-lot consistency of the EV products. Repeated toxicity was evaluated in rats after administration using trace liquid endotracheal nebulizers for 28 days, and respiratory toxicity was evaluated 24 h after the first administration. In vivo therapeutic effects were assessed in an LPS-induced ALI/ acute respiratory distress syndrome (ARDS) rat model. Results The quality criteria have been standardized. In a stability study, haMSC-EVs were found to remain stable after 6 months of storage at − 80°C, 3 months at − 20 °C, and 6 h at room temperature. The microRNA profile and proteome of haMSC-EVs demonstrated suitable lot-to-lot consistency, further suggesting the stability of the production processes. Intratracheally administered 1.5 × 108 particles/rat/day for four weeks elicited no significant toxicity in rats. In LPS-induced ALI/ARDS model rats, intratracheally administered haMSC-EVs alleviated lung injury, possibly by reducing the serum level of inflammatory factors. Conclusion haMSC-EVs, as an off-shelf drug, have suitable stability and lot-to-lot consistency. Intratracheally administered haMSC-EVs demonstrated excellent safety at the tested dosages in systematic preclinical toxicity studies. Intratracheally administered haMSC-EVs improved the lung function and exerted anti-inflammatory effects on LPS-induced ALI/ARDS model rats.

Objectives Osteoporotic vertebral fractures (OVFs) are a critical public health concern requiring urgent attention, and severe OVFs impose substantial health and economic burdens on patients and society. Analysis of the risk factors for severe OVF is imperative to actively prevent the occurrence of this degenerative disorder. This study aimed to investigate the risk factors associated with the severity of OVF, with a specific focus on changes in the paraspinal muscles. Methods A total of 281 patients with a first‐time single‐level acute OVF between January 2016 and January 2023 were enrolled in the study. Clinical and radiological data were collected and analyzed. The cross‐sectional area (CSA) and degree of fatty infiltration (FI) of the paraspinal muscles, including the multifidus muscles (MFMs), erector spinae muscles (ESMs), and psoas major muscles (PSMs), were measured by magnetic resonance imaging (MRI) of the L4/5 intervertebral discs. According to the classification system of osteoporotic fractures (OF classification) and recommended treatment plan, OVFs were divided into a low‐grade OF group and a high‐grade OF group. Univariate and multivariate logistic regression analyse s were performed to identify risk factors associated with the severity of OVF. Results Ninety‐eight patients were included in the low‐grade OF group, and 183 patients were included in the high‐grade OF group. Univariate analysis revealed a significantly higher incidence of a high degree of FI of MFMs (OR = 1.71, p = 0.002) and ESMs (OR = 1.56, p = 0.021) in the high‐grade OF group. Further multivariate logistic regression analysis demonstrated that a high degree of FI of the MFMs (OR = 1.71, p = 0.002) is an independent risk factor for the severity of OVF. Conclusion A high degree of FI of the MFMs was identified as an independent risk factor for the severity of OVF. Decreasing the degree of FI in the MFMs might lower the incidence of the severity of OVF, potentially reducing the necessity for surgical intervention in OVF patients.