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Abstract Background The prevalence of stroke disability associated with high BMI has significantly increased over the past three decades. However, it remains uncertain whether high body-mass index (BMI) exerts a similar impact on the disease burden of different stroke subtypes. The aim of this study is to assess the long-term trends of stroke and subtypes mortality attributable to high BMI in China between 1990 and 2019. Methods Data on stroke and subtypes mortality attributable to high BMI in China was extracted in the Global Burden of Disease (GBD) 2019. The trends of age-standardized mortality rate (ASMR) were calculated using the linear regression and age-period-cohort framework. Results The changing trend of ASMR on stroke attributable to high BMI in China differed among subtypes, with an estimated annual percentage change (EAPC) and 95%CI of 2.04 (1.86 to 2.21) for ischemic stroke (IS), 0.36 (-0.03 to 0.75) for intracerebral hemorrhage (ICH), and − 4.62 (-5.44 to -3.78) for subarachnoid hemorrhage (SAH). Net and local drift analyses revealed a gradual increase in the proportion of older people with IS and a gradual increase in the proportion of younger people with hemorrhagic strokes. The cohort and period rate ratios varied by subtype, showing an increasing trend for IS and ICH but a decreasing trend for SAH. The stroke mortality attributable to high BMI increased significantly with age for IS and ICH, peaking between ages 50–70 for SAH. Notably, males had higher ASMR related to stroke but exhibited slighter declines or higher growth compared to females in China. Moreover, the population affected by fatal strokes tended to be older among females but more evenly distributed across a wider age range encompassing both younger and older individuals. Conclusion The research findings indicate a rising trend in the ASMR of stroke and subtypes attributable to high BMI in China from 1990 to 2019, with different patterns of change for different subtypes, genders and ages. Consequently, it is imperative for public health authorities in China to formulate guidelines for specific stroke subtypes, genders and ages to prevent the burden of stroke attributable to high BMI.

Abstract Background 2-Phenylethanol (2-PE) is one of the most widely used spices. Recently, 2-PE has also been considered a potential aviation fuel booster. However, the lack of scientific understanding of the 2-PE biosynthetic pathway and the cellular response to 2-PE cytotoxicity are the most important obstacles to the efficient biosynthesis of 2-PE. Results Here, metabolic engineering and tolerance engineering strategies were used to improve the production of 2-PE in Komagataella phaffii. First, the endogenous genes encoding the amino acid permease GAP1, aminotransferase AAT2, phenylpyruvate decarboxylase KDC2, and aldehyde dehydrogenase ALD4 involved in the Ehrlich pathway and the 2-PE stress response gene NIT1 in K. phaffii were screened and characterized via comparative transcriptome analysis. Subsequently, metabolic engineering was employed to gradually reconstruct the 2-PE biosynthetic pathway, and the engineered strain S43 was obtained, which produced 2.98 g/L 2-PE in shake flask. Furthermore, transcriptional profiling analyses were utilized to screen for novel potential tolerance elements. Our results demonstrated that cells with knockout of the PDR12 and C4R2I5 genes exhibited a significant increase in 2-PE tolerance. To confirm the practical applications of these results, deletion of the PDR12 and C4R2I5 genes in the hyper 2-PE producing strain S43 dramatically increased the production of 2-PE by 18.12%, and the production was 3.54 g/L. Conclusion This is the highest production of 2-PE produced by K. phaffii via l-phenylalanine conversion. These identified K. phaffii endogenous elements are highly conserved in other yeast species, suggesting that manipulation of these homologues might be a useful strategy for improving aromatic alcohol production. These results also enrich the understanding of aromatic compound biosynthetic pathways and 2-PE tolerance, and provide new elements and strategies for the synthesis of aromatic compounds by microbial cell factories.

Abstract Diabetic nephropathy (DN) is a critical inflammatory condition linked to diabetes, affecting millions worldwide. This study employs Mendelian randomization (MR) to explore the causal relationship between immune cell signatures and DN, analyzing over 731 immune signatures and incorporating data from 1400 metabolites to investigate potential mediators. Despite no statistically significant influence of DN on immunophenotypes after FDR correction, some phenotypes with unadjusted low P-values warranted mention, including CD34 on Hematopoietic Stem Cell (Myeloid cell Panel), CD45 on CD33− HLA DR− (Myeloid cell Panel). Furthermore, three immunophenotypes were identified to have a significant impact on DN risk: CD16−CD56 on HLA DR+ NK (TBNK Panel), CD45 on HLA DR+ T cell (TBNK Panel), and CD33dim HLA DR+ CD11b+ AC (Myeloid cell Panel). Our findings underscore the critical role of immune cells in DN, highlighting potential mediators and offering new insights into its underlying mechanisms.

Abstract The vector forces at the human-mattress interface are not only crucial for understanding the distribution of vertical and shear forces exerted on the human body during sleep but also serves as a significant input for biomechanical models of sleeping positions, whose accuracy determines the credibility of predicting musculoskeletal system loads. In this study, we introduce a novel method for calculating the interface vector forces. By recording indentations after supine and lateral positions using a vacuum mattress and 3D scanner, we utilize image registration techniques to align body pressure distribution with the mattress deformation scanning images, thereby calculating the vector force values for each unit area (36.25 mm × 36.25 mm). This method was validated through five participants attendance from two perspectives, revealing that (1) the mean summation of the vertical force components is 98.67% ± 7.21% body weight, exhibiting good consistency, and mean ratio of horizontal component force to body weight is 2.18% ± 1.77%. (2) the predicted muscle activity using the vector forces as input to the sleep position model aligns with the measured muscle activity (%MVC), with correlation coefficient over 0.7. The proposed method contributes to the vector force distribution understanding and the analysis of musculoskeletal loads during sleep, providing valuable insights for mattress design and evaluation.

Abstract Background Postoperative delirium (POD) is a common complication that is characterized by acute onset of impaired cognitive function and is associated with an increased mortality, a prolonged duration of hospital stay, and additional healthcare expenditures. The incidence of POD in elderly patients undergoing laparoscopic radical colectomy ranges from 8 to 54%. Xenon has been shown to provide neuroprotection in various neural injury models, but the clinical researches assessing the preventive effect of xenon inhalation on the occurrence of POD obtained controversial findings. This study aims to investigate the effects of a short xenon inhalation on the occurrence of POD in elderly patients undergoing laparoscopic radical colectomy. Methods/design This is a prospective, randomized, controlled trial and 132 patients aged 65–80 years and scheduled for laparoscopic radical colectomy will be enrolled. The participants will be randomly assigned to either the control group or the xenon group (n = 66 in each group). The primary outcome will be the incidence of POD in the first 5 days after surgery. Secondary outcomes will include the subtype, severity, and duration of POD, postoperative pain score, Pittsburgh Sleep Quality Index (PQSI), perioperative non-delirium complications, and economic parameters. Additionally, the study will investigate the activation of microglial cells, expression of inflammatory factors in colon tissues, plasma inflammatory factors, and neurochemical markers. Discussion Elderly patients undergoing laparoscopic radical colectomy are at a high risk of POD, with delayed postoperative recovery and increased healthcare costs. The primary objective of this study is to determine the preventive effect of a short xenon inhalation on the occurrence of POD in these patients. Trial registration Chinese Clinical Trial Registry ChiCTR2300076666. Registered on October 16, 2023, http://www.chictr.org.cn .

Abstract Diabetic kidney disease, known as a glomerular disease, arises from a metabolic disorder impairing renal cell function. Mitochondria, crucial organelles, play a key role in substance metabolism via oxidative phosphorylation to generate ATP. Cells undergo metabolic reprogramming as a compensatory mechanism to fulfill energy needs for survival and growth, attracting scholarly attention in recent years. Studies indicate that mitochondrial metabolic reprogramming significantly influences the pathophysiological progression of DKD. Alterations in kidney metabolism lead to abnormal expression of signaling molecules and activation of pathways, inducing oxidative stress-related cellular damage, inflammatory responses, apoptosis, and autophagy irregularities, culminating in renal fibrosis and insufficiency. This review delves into the impact of mitochondrial metabolic reprogramming on DKD pathogenesis, emphasizing the regulation of metabolic regulators and downstream signaling pathways. Therapeutic interventions targeting renal metabolic reprogramming can potentially delay DKD progression. The findings underscore the importance of focusing on metabolic reprogramming to develop safer and more effective therapeutic approaches.

Abstract Background and aim Traditional Chinese medicine (TCM) is widely used by patients with amyotrophic lateral sclerosis (ALS). However, their reasons and experience in using TCM have received insufficient attention. Therefore, we conducted a mixed method study to gain insights into this issue. Materials and methods This study was conducted on the basis of the China Amyotrophic Lateral Sclerosis Registry of Patients with Traditional Chinese Medicine (CARE-TCM). Data were collected from Dongzhimen Hospital through a mixed method approach, including a questionnaire and a semi-structured interview. Patients with ALS who were using TCM when they were initially registered with CARE-TCM and who had been followed-up for over six months were recruited. The questionnaires’ outcomes were statistically outlined, and the interview transcripts were thematically analysed to identify themes and sub-themes. Results Fifty-two and sixteen patients were included in the questionnaire and semi-structured interview groups, respectively. Patients used TCM with the hope of regulating their body holistically to improve nonmotor symptoms and quality of life (QOL). Those who recognised TCM as ineffective tended to discontinue it after a three-month trial period. Although quality was a major concern, herbal medicine (HM) was the most frequently used modality among all participants (n = 52), with the majority (n = 44, 84.6%) continuing to use it. Patients emphasised in-person consultations as a crucial part of TCM treatment. However, the disability caused by disease often made this interaction unattainable. Conclusion Nonmotor symptoms and QOL hold substantial importance for patients with ALS using TCM. HM is a more suitable modality than other TCM treatment modalities, but patients are facing challenges in seeking HM treatment. It is necessary to promote the implementation of hierarchical diagnosis and treatment, thus making TCM more accessible. Trial registration ClinicalTrials.gov identifier: NCT04885374 (registered on May 13, 2021).

Abstract To estimate the rate of death, and disability-adjusted life years (DALYs) and project the disease burden of ischemic stroke due to relevant risk factors in young adults age 20–49 years by sex in China. Data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 were used. The age-standardized mortality (ASMR), age-standardized DALYs rate (ASDR), and estimated annual percentage changes (EAPC) were calculated to evaluate the temporal trends from 1990 to 2019. We also used the NORDPRED model to predict ASMR for ischemic stroke due to related risk factors in Chinese young adults over the next 10 years. From 1990 to 2019, the general age-standardized mortality [from 2.39 (1.97 to 2.99) in 1990 to 1.8 (1.41 to 2.18) in 2019, EAPC = − 1.23] and DALYs rates (from 171.7 (140.34 to 212.36) in 1990 to 144.4 (114.29 to 177.37) in 2019, EAPC = − 0.86) decreased for ischemic stroke in young adults in China. ASMR and ASDR decreased for all level 1 risk factors (including behavioral, environmental/occupational, and metabolic) from 1990 to 2019, with the slightest decrease for metabolic risks [ASMR from 1.86 (1.39 to 2.41) in 1990 to 1.53 (1.15 to 1.92) in 2019, ASDR from 133.68 (99.96 to 173.89) in 1990 to 123.54 (92.96 to 156.98) in 2019] and the largest decrease for environmental/occupational risks [ASMR from 1.57 (1.26 to 1.98) in 1990 to 1.03 (0.78 to 1.29) in 2019, ASDR from 110.91 (88.44 to 138.34) in 1990 to 80.03 (61.87 to 100.33) in 2019]. In general, high body-mass index, high red meat intake, and ambient particulate matter pollution contributed to the large increase in ASMR and ASDR between 1990 and 2019. Significant reductions in ASMR and ASDR were observed in low vegetables intake, household air pollution from solid fuels, lead exposure, and low fiber intake. In addition, there were sex differences in the ranking of ASMR attributable to risks in ischemic stroke. The disease burden of ischemic stroke attributable to relevant risk factors in young adults in China is greater and has a faster growth trend or a slower decline trend in males than in females (except for secondhand smoke). The apparent increasing trend of ASMR attributable to high fasting plasma glucose, high systolic blood pressure, high body-mass index, and high red meat intake was observed in males but not in females. The projected analysis showed an increasing trend in ASMR between 1990 and 2030 for all specific metabolic risks for males, but a decreasing trend for females. ASMR attributable to ambient particulate matter pollution showed an increasing trend from 1990 to 2030 for both males and females. The burden of ischemic stroke in young adults in China showed a downward trend from 1990 to 2019. Specific risk factors associated with the burden of ischemic stroke varied between the sexes. Corresponding measures need to be developed in China to reduce the disease burden of ischemic stroke among young adults.

Abstract Background Solute carrier family 34 member 2 (SLC34A2) has been implicated in the development of various malignancies. However, the clinical significance and underlying molecular mechanisms of SLC34A2 in esophageal squamous cell carcinoma (ESCC) remain elusive. Methods Western blotting, quantitative real‐time PCR and immunohistochemistry were utilized to evaluate the expression levels of SLC34A2 mRNA/protein in ESCC cell lines or tissues. Kaplan–Meier curves were employed for survival analysis. CCK‐8, colony formation, EdU and xenograft tumor model assays were conducted to determine the impact of SLC34A2 on ESCC cell proliferation. Cell cycle was examined using flow cytometry. RNA‐sequencing and enrichment analysis were carried out to explore the potential signaling pathways. The autophagic flux was evaluated by western blotting, mRFP‐GFP‐LC3 reporter system and transmission electron microscopy. Immunoprecipitation and mass spectrometry were utilized for identification of potential SLC34A2‐interacting proteins. Cycloheximide (CHX) chase and ubiquitination assays were conducted to test the protein stability. Results The expression of SLC34A2 was significantly upregulated in ESCC and correlated with unfavorable clinicopathologic characteristics particularly the Ki‐67 labeling index and poor prognosis of ESCC patients. Overexpression of SLC34A2 promoted ESCC cell proliferation, while silencing SLC34A2 had the opposite effect. Moreover, SLC34A2 induced autophagy to promote ESCC cell proliferation, whereas inhibition of autophagy suppressed the proliferation of ESCC cells. Further studies showed that SLC34A2 interacted with an autophagy‐related protein STX17 to promote autophagy and proliferation of ESCC cells by inhibiting the ubiquitination and degradation of STX17. Conclusions These findings indicate that SLC34A2 may serve as a prognostic biomarker for ESCC.

Abstract Antimicrobial resistance remains a significant global threat, driving up mortality rates worldwide. Ribosomally synthesized and post-translationally modified peptides have emerged as a promising source of novel peptide antibiotics due to their diverse chemical structures. Here, we report the discovery of new aminovinyl-(methyl)cysteine (Avi(Me)Cys)-containing peptide antibiotics through a synergistic approach combining biosynthetic rule-based omics mining and heterologous expression. We first bioinformatically identify 1172 RiPP biosynthetic gene clusters (BGCs) responsible for Avi(Me)Cys-containing peptides formation from a vast pool of over 50,000 bacterial genomes. Subsequently, we successfully establish the connection between three identified BGCs and the biosynthesis of five peptide antibiotics via biosynthetic rule-guided metabolic analysis. Notably, we discover a class V lanthipeptide, massatide A, which displays excellent activity against gram-positive pathogens, including drug-resistant clinical isolates like linezolid-resistant S. aureus and methicillin-resistant S. aureus, with a minimum inhibitory concentration of 0.25 μg/mL. The remarkable performance of massatide A in an animal infection model, coupled with a relatively low risk of resistance and favorable safety profile, positions it as a promising candidate for antibiotic development. Our study highlights the potential of Avi(Me)Cys-containing peptides in expanding the arsenal of antibiotics against multi-drug-resistant bacteria, offering promising drug leads in the ongoing battle against infectious diseases.

With the overconsumption of fossil carbon resources, resulting in a large amount of CO2 and other greenhouse gas emissions, caused by global climate change has become one of the major challenges facing all mankind. At the same time, the development and utilization of coal resources will produce a large amount of coal-based solid wastes containing calcium and magnesium, such as fly ash, desulfurization gypsum and other solid wastes. How to realize efficient CO2 capture and sequestration is a very challenging issue nowadays, as well as the large-scale comprehensive utilization of fly ash, coal gasification slag, and other large-scale heavy polluting industrial solid wastes is still in need of a breakthrough. Under the goal of “double carbon”, CO2 mineralization from coal-based solid waste is a potential strategy to effectively address global warming, and mineral carbonation of coal-based solid wastes containing calcium and magnesium has great prospects for carbon dioxide capture and sequestration (CCS) as well as for the resource-based disposal of solid waste. However, the industrial application bottleneck of CO2 mineralization in coal-based solid waste is still unable to break through. This paper reviews the current development of CO2 mineralization from fly ash (FA), desulfurization gypsum (FGDG), and coal gasification slag (CGS), with the aim of exploring the reasons for their technical limitations. Firstly, this paper briefly elaborates on the pathways for CO2 mineralization of coal based solid waste, revealing the reaction process and principles of CO2 mineralization of coal based solid waste. Secondly, the mineralization potential and process of typical coal-based solid waste were summarized and compared to clarify the mechanism of the regulation of the process parameters on the product properties during CO2 mineralization process. Finally, the performance of CO2 mineralization products from coal-based solid waste was summarized, and the feasibility of the mineralization process and its environmental impact were elucidated using a Life Cycle Assessment (LCA). This paper will provide optimization suggestions on the process technology of coal-based solid waste CO2 mineralization to promote the strategic goal of low-carbon transformation in the coal industry.

Abstract Background Microbial secondary metabolites play a crucial role in the intricate interactions within the natural environment. Among these metabolites, ribosomally synthesized and post-translationally modified peptides (RiPPs) are becoming a promising source of therapeutic agents due to their structural diversity and functional versatility. However, their biosynthetic capacity and ecological functions remain largely underexplored. Results Here, we aim to explore the biosynthetic profile of RiPPs and their potential roles in the interactions between microbes and viruses in the ocean, which encompasses a vast diversity of unique biomes that are rich in interactions and remains chemically underexplored. We first developed TrRiPP to identify RiPPs from ocean metagenomes, a deep learning method that detects RiPP precursors in a hallmark gene-independent manner to overcome the limitations of classic methods in processing highly fragmented metagenomic data. Applying this method to metagenomes from the global ocean microbiome, we uncover a diverse array of previously uncharacterized putative RiPP families with great novelty and diversity. Through correlation analysis based on metatranscriptomic data, we observed a high prevalence of antiphage defense-related and phage-related protein families that were co-expressed with RiPP families. Based on this putative association between RiPPs and phage infection, we constructed an Ocean Virus Database (OVD) and established a RiPP-involving host-phage interaction network through host prediction and co-expression analysis, revealing complex connectivities linking RiPP-encoding prokaryotes, RiPP families, viral protein families, and phages. These findings highlight the potential of RiPP families involved in prokaryote-phage interactions and coevolution, providing insights into their ecological functions in the ocean microbiome. Conclusions This study provides a systematic investigation of the biosynthetic potential of RiPPs from the ocean microbiome at a global scale, shedding light on the essential insights into the ecological functions of RiPPs in prokaryote-phage interactions through the integration of deep learning approaches, metatranscriptomic data, and host-phage connectivity. This study serves as a valuable example of exploring the ecological functions of bacterial secondary metabolites, particularly their associations with unexplored microbial interactions. Video Abstract

AIM: To investigate systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) levels in patients with type 2 diabetes at different stages of diabetic retinopathy (DR). METHODS: This retrospective study included 141 patients with type 2 diabetes mellitus (DM): 45 without diabetic retinopathy (NDR), 47 with non-proliferative diabetic retinopathy (NPDR), and 49 with proliferative diabetic retinopathy (PDR). Complete blood counts were obtained, and NLR, PLR, and SII were calculated. The study analysed the ability of inflammatory markers to predict DR using receiver operating characteristic (ROC) curves. The relationships between DR stages and SII, PLR, and NLP were assessed using multivariate logistic regression. RESULTS: The average NLR, PLR, and SII were higher in the PDR group than in the NPDR group (P=0.011, 0.043, 0.009, respectively); higher in the NPDR group than in the NDR group (P

In recent years, China's real estate prices have continued to rise, preventing the bursting of the house price bubble, and the various risks it triggers has become an important issue that governments at all levels have to face. In this paper, the backward sup ADF (BSADF) method was used to dynamically portray the evolution of real estate price bubbles in 31 large and medium-sized cities in China over a period of 11 years, from 2013 to 2021, and the dynamic relationship between the degree of financial support for real estate (hereinafter referred to as financial support) and house price bubbles in cities was investigated by employing a panel vector autoregressive (PVAR) model with panel data. The results showed that: Multiple cyclical bubbles significantly existed in the real estate markets of the cities during the study period, and in general, house price bubbles appeared earlier in the more economically developed regions than in the less economically developed regions and have spread to the less economically developed regions. Financial support contributed to house price bubbles, supporting the theory of excessive financial support. Furthermore, the results of the sub-sample showed that financial support contributed most strongly to house price bubbles in cities in the northern region.

Since the catalytic activity of most nanozymes is still far lower than the corresponding natural enzymes, there is urgent need to discover novel highly efficient enzyme-like materials. In this work, Co3V2O8 with hollow hexagonal prismatic pencil structures were prepared as novel artificial enzyme mimics. They were then decorated by photo-depositing Ag nanoparticles (Ag NPs) on the surface to further improve its catalytic activities. The Ag NPs decorated Co3V2O8 (ACVPs) showed both excellent oxidase- and peroxidase-like catalytic activities. They can oxidize the colorless 3,3’,5,5’-tetramethylbenzidine rapidly to induce a blue change. The enhanced enzyme mimetic activities can be attributed to the surface plasma resonance (SPR) effect of Ag NPs as well as the synergistic catalytic effect between Ag NPs and Co3V2O8, accelerating electron transfer and promoting the catalytic process. ACVPs were applied in constructing a colorimetric sensor, validating the occurrence of the Fenton reaction, and disinfection, presenting favorable catalytic performance. The enzyme-like catalytic mechanism was studied, indicating the chief role of ⋅O2- radicals in the catalytic process. This work not only discovers a novel functional material with double enzyme mimetic activity but also provides a new insight into exploiting artificial enzyme mimics with highly efficient catalytic ability.

Abstract Background An idiopathic macular hole (IMH) is a full-thickness anatomic defect extending from the internal limiting membrane to the photoreceptor layer of the macula without any known cause. Recently, clinical laboratory markers of systemic inflammatory status derived from complete blood counts have been evaluated in ocular diseases. This study aimed to explore whether they could predict the development and progression of IMHs. Methods A retrospective review of 36 patients with IMH and 36 sex-and-age-matched patients with cataracts was conducted. We collected complete blood counts of all participating individuals and calculated systemic immunoinflammatory indicators. The maximum base diameter of the IMH (BD), minimum diameter of the IMH (MIN), height of the IMH (H), area of the intraretinal cyst (IRC), and curve lengths of the detached photoreceptor arms were measured on optical coherence tomography (OCT) images. We used these values to calculate the macular hole index (MHI), tractional hole index (THI), diameter hole index (DHI), hole form factor (HFF), and macular hole closure index (MHCI). We performed a receiver operating characteristic (ROC) curve analysis of 30 patients with IMH who were followed up 1 month after surgery. Results Lymphocyte counts were significantly higher in the IMH group. No other significant differences were observed between the IMH and control groups. Lymphocyte counts in the IMH group were significantly negatively correlated with MIN and BD and were significantly positively correlated with MHI, THI, and MHCI. However, lymphocyte counts were not significantly correlated with H, IRC, DHI, and HFF. In the ROC analysis, BD, MIN, MHI, THI, and MHCI were significant predictors of anatomical outcomes. According to the cut-off points of the ROC analysis, lymphocyte counts were compared between the above-cut-off and below-cut-off groups. Lymphocyte counts were significantly higher in the MIN ≤ 499.61 μm, MHI ≥ 0.47, THI ≥ 1.2, and MHCI ≥ 0.81 groups. There were no significant differences between the above-cut-off and below-cut-off BD groups. Conclusions Although inflammation may not be an initiating factor, it may be involved in IMH formation. Lymphocytes may play a relatively important role in tissue repair during the developmental and postoperative recovery phases of IMH.

Background: Our study aimed to assess the radiation sensitivity of BT20, a human breast tumor cell line, using the laser-trapping technique and compare it with N2a and 4T1 cells. Additionally, we investigated the impact of the antitumor compound 2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD) on radiation sensitivity. Methods and Materials: We employed laser trapping to calculate both the threshold ionization energy (TIE) and threshold radiation dose (TRD) for BT20, N2a, and 4T1 cells. We assessed the effect of DMDD on BT20 cells’ radiosensitivity and conducted comparisons across these cell lines. Results: Our findings reveal that DMDD significantly enhances the radiosensitivity of BT20 breast carcinoma cells. Moreover, we observed distinct trends in TIE and TRD across the three cell lines, with differences attributed to variations in cell size and composition. When multiple cell ionizations were considered, a notable reduction in TRD was observed, implicating factors such as the chain effect of ionizing radiation and the influence of DMDD. The study found that TIE increased with the number of cells in the trap while TRD consistently decreased across all three cell lines, suggesting comparable radiation sensitivity, and oligostilbene treatment further reduced TRD, presenting the potential for enhancing therapeutic ratios in cancer treatment. Conclusion: The antitumor compound DMDD enhances the radiosensitivity of BT20 breast carcinoma cells, highlighting its potential in cancer treatment. Furthermore, our study underscores the impact of cell size and multiple-cell ionizations on TRD. Leveraging laser trapping techniques, biocompatible nanoparticles, and advanced optical tweezers opens promising avenues for personalized and effective cancer therapy approaches.

Abstract Studies suggest that mangiferin (MAF) has good therapeutic effects on chronic bronchitis and hepatitis. Also, it is one of the antiviral ingredients in Anemarrhena asphodeloides Bunge. However, its effect on the LPS‐induced inflammation and intestinal flora during sepsis remains unclear yet. In the present study, LPS‐stimulated inflammation RAW264.7 cells and LPS‐induced sepsis mice were used to evaluate the efficacy of MAF in vitro and in vivo. 16S rDNA sequencing was performed to analyze the characteristics of intestinal flora of the sepsis mice. It has been demonstrated that MAF (12.5 and 25 μg/mL) significantly inhibited protein expressions of TLR4, MyD88, NF‐κB, and TNF‐α in the LPS‐treated cells and reduced the supernatant TNF‐α and IL‐6 levels. In vivo, MAF (20 mg/kg) markedly protected the sepsis mice and reduced the serum TNF‐α and IL‐6 levels. Also, MAF significantly downregulated the protein expressions of TLR4, NF‐κB, and MyD88 in the livers. Importantly, MAF significantly attenuated the pathological injuries of the livers and small intestines. Further, MAF significantly increased proportion of Bacteroidota and decreased the proportions of Firmicutes, Desulfobacterota, Actinobacteriota, and Proteobacteria at phylum level, and it markedly reduced the proportions of Escherichia‐Shigella, Pseudoalteromonas, Staphylococcus at genus level. Moreover, MAF affects some metabolism‐related pathways such as citrate cycle (TCA cycle), lipoic acid metabolism, oxidative phosphorylation, bacterial chemotaxis, fatty acid biosynthesis, and peptidoglycan biosynthesis of the intestinal flora. Thus, it can be concluded that MAF as a treatment reduces the inflammatory responses in vitro and in vivo by inhibiting the TLR4/ MyD88/NF‐κB pathway, and corrects intestinal flora imbalance during sepsis to some degree.

Biological soil crusts (biocrusts) constitute a crucial biological component of the soil surface in arid and semi-arid ecosystems. Understanding the variations in soil microbial community assembly across biocrust successional stages is essential for a deeper comprehension of microbial biodiversity and desert ecosystem functioning. However, knowledge about the mechanisms of microbial community assembly and the factors influencing its development remains limited. In this study, we utilized amplicons sequencing to assess the compositions of bacterial and fungal communities in bare sand and three types of biocrusts (light cyanobacterial biocrusts, dark cyanobacterial biocrusts, and moss crusts). Subsequently, we analyzed the ecological processes shaping microbial community composition and structure, along with the influencing factors. Our results revealed a significant increase in bacterial diversity and no significant changes in fungal diversity during biocrust development. The relative abundances of the copiotrophic bacteria (e.g., Actinobacteria, Acidobacteria, and Bacteroidetes) showed significant increases, while oligotrophic bacteria (e.g., Proteobacteria and Firmicutes) decreased over time. Moreover, the relative abundances of Ascomycota, which exhibit strong resistance to adverse environmental conditions, significantly decreased, whereas Basidiomycota, known for their ability to degrade lignin, significantly increased throughout biocrust development. Additionally, stochastic processes (dispersal limitation and drift) predominantly drove the assemblies of both bacterial and fungal communities. However, the relative importance of deterministic processes (homogeneous selection) in bacterial assembly increased during biocrust development. Structural equation modeling indicated that bacterial community assembly was primarily related to soil water content, whereas fungal community assembly was primarily related to total organic carbon. These findings provide a scientific foundation for investigating the formation and development of biocrusts, and further insights into the conservation and sustainable management of biocrust resources under future climate change scenarios.

Purpose Research on bone metastasis in esophageal cancer (EC) is relatively limited. Once bone metastasis occurs in patients, their prognosis is poor, and it severely affects their quality of life. Currently, there is a lack of convenient tumor markers for early identification of bone metastasis in EC. Our research aims to explore whether neutrophil-lymphocyte ratio (NLR) can predict bone metastasis in patients with EC. Methods Retrospective analysis of clinical indicators was performed on 604 patients with EC. They were divided into groups based on whether or not there was bone metastasis, and the patients’ coagulation-related tests, blood routine, tumor markers and other indicators were collected. The receiver operating characteristic curve (ROC) were used to determine the predictive ability of parameters such as NLR for bone metastasis in EC, and univariate and multivariate logistic regression analyses were conducted to determine the impact of each indicator on bone metastasis. Using binary logistic regression to obtain the predictive probability of NLR combined with tumor markers. Results ROC curves analysis suggested that the area under the curve (AUC) of the NLR was 0.681, with a sensitivity of 79.2% and a specificity of 52.6%, which can be used as a predictive factor for bone metastasis in EC. Multivariate logistic regression analysis showed that high NLR (odds ratio [OR]: 2.608, 95% confidence interval [CI]: 1.395-4.874, P = 0.003) can function as an independent risk factor for bone metastasis in patients with EC. Additionally, high PT, high APTT, high FDP, high CEA, high CA724, low hemoglobin, and low platelet levels can also predict bone metastasis in EC. When NLR was combined with tumor markers, the area under the curve was 0.760 (95% CI: 0.713-0.807, P

BackgroundAlthough the risk of prostate cancer (PCa) varies across different ages and genetic risks, it’s unclear about the effects of genetic-specific and age-specific prostate-specific antigen (PSA) screening for PCa.MethodsWeighed and unweighted polygenic risk scores (PRS) were constructed to classify the participants from the PLCO trial into low- or high-PRS groups. The age-specific and PRS-specific cut-off values of PSA for PCa screening were determined with time-dependent receiver-operating-characteristic curves and area-under-curves (tdAUCs). Improved screening strategies integrating PRS-specific and age-specific cut-off values of PSA were compared to traditional PSA screening on accuracy, detection rates of high-grade PCa (Gleason score ≥7), and false positive rate.ResultsWeighted PRS with 80 SNPs significantly associated with PCa was determined as the optimal PRS, with an AUC of 0.631. After stratifying by PRS, the tdAUCs of PSA with a 10-year risk of PCa were 0.818 and 0.816 for low- and high-PRS groups, whereas the cut-off values were 1.42 and 1.62 ng/mL, respectively. After further stratifying by age, the age-specific cut-off values of PSA were relatively lower for low PRS (1.42, 1.65, 1.60, and 2.24 ng/mL for aged

The newly built Compact Laser Plasma Accelerator–Therapy facility at Peking University will deliver 60 J/1 Hz laser pulses with 30 fs duration. Driven by this petawatt laser facility, proton beams with energy up to 200 MeV are expected to be generated for tumor therapy. During high-repetition operation, both prompt radiation and residual radiation may cause safety problems. Therefore, human radiological safety assessment before commissioning is essential. In this paper, we simulate both prompt and residual radiation using the Geant4 and FLUKA Monte Carlo codes with reasonable proton and as-produced electron beam parameters. We find that the prompt radiation can be shielded well by the concrete wall of the experimental hall, but the risk from residual radiation is nonnegligible and necessitates adequate radiation cooling. On the basis of the simulation results, we discuss the constraints imposed by radiation safety considerations on the annual working time, and we propose radiation cooling strategies for different shooting modes.

Abstract Microvesicles (MVs) containing proteins, nucleic acid or organelles are shed from the plasma membrane. Although the mechanisms of MV budding are well elucidated, the connection between endosomal trafficking and MV formation remains poorly understood. In this report, RAB22A is revealed to be crucial for EGFR‐containing MVs formation by the RAB GTPase family screening. RAB22A recruits TBC1D2B, a GTPase‐activating protein (GAP) of RAB7A, to inactivate RAB7A, thus preventing EGFR from being transported to late endosomes and lysosomes. RAB22A also engages SH3BP5L, a guanine‐nucleotide exchange factor (GEF) of RAB11A, to activate RAB11A on early endosomes. Consequently, EGFR is recycled to the cell surface and packaged into MVs. Furthermore, EGFR can phosphorylate RAB22A at Tyr136, which in turn promotes EGFR‐containing MVs formation. Our findings illustrate that RAB22A acts as a sorter on early endosomes to sort EGFR to recycling endosomes for MV shedding by both activating RAB11A and inactivating RAB7A.

Background and objectivesFatigue has been associated with adverse effects on recovery from ischemic stroke based on previous observational research. The purpose of our study was to explore the potential causal association of fatigue with poor functional outcome after ischemic stroke by employing Mendelian randomization (MR).MethodsA set of instrumental variables, comprising 36 single-nucleotide polymorphisms (SNPs) that are only related to fatigue, were derived from a genome-wide association study (GWAS) that included 449,019 general individuals. The functional outcomes after ischemic stroke were derived from a GWAS (Genetics of Ischemic Stroke Functional Outcome Network) involving 6,021 survivors. Two-sample MR methods were used to assess the causal effect, including inverse variance weighted, MR-Egger, weighted median, simple mode, and weighted mode. In bidirectional MR analysis, the reverse causal association was analyzed using the Wald ratio method. The mediation effects of lipid metabolites were analyzed using two-step MR analysis.ResultsGenetic liability to fatigue was causally associated with the poor functional outcome (modified Rankin Scale ≥3 at 3 months) after ischemic stroke (OR = 4.20, 95%CI [1.11–15.99], p 0.05). The results of the two-step MR showed that cholesteryl esters to total lipids ratio in large very low-density lipoprotein (VLDL) (ME = −0.13, p

Grammar error correction systems are pivotal in the field of natural language processing (NLP), with a primary focus on identifying and correcting the grammatical integrity of written text. This is crucial for both language learning and formal communication. Recently, neural machine translation (NMT) has emerged as a promising approach in high demand. However, this approach faces significant challenges, particularly the scarcity of training data and the complexity of grammar error correction (GEC), especially for low-resource languages such as Indonesian. To address these challenges, we propose InSpelPoS, a confusion method that combines two synthetic data generation methods: the Inverted Spellchecker and Patterns+POS. Furthermore, we introduce an adapted seq2seq framework equipped with a dynamic decoding method and state-of-the-art Transformer-based neural language models to enhance the accuracy and efficiency of GEC. The dynamic decoding method is capable of navigating the complexities of GEC and correcting a wide range of errors, including contextual and grammatical errors. The proposed model leverages the contextual information of words and sentences to generate a corrected output. To assess the effectiveness of our proposed framework, we conducted experiments using synthetic data and compared its performance with existing GEC systems. The results demonstrate a significant improvement in the accuracy of Indonesian GEC compared to existing methods.

Abstract Buildings increase the urban surface roughness and reduce near‐surface wind speeds in the urban canopy due to the drag effect. Urban heat storage and other effects cause urban warming as well, which decreases the urban boundary layer stability and enhances the turbulence exchange between upper and lower layer. As upper momentum is transported downward, the wind speed of urban canopy increases. Quantitative descriptions of these mechanisms are still lacking currently. This paper presents high‐resolution numerical simulation results of a mega city, Shanghai, China from 2016 to 2020 using the building effect parameterization in WRF (WRF‐BEP) with urban morphological parameters. The dynamic and thermal effects of building morphology on urban canopy wind speed were separated and their quantitative expression functions were given. The results indicate that the influence of building morphology on urban canopy wind speed is mainly dynamic resulting in a wind speed attenuation of approximately 50% and nearly constant. The thermal effect of building morphology on urban canopy wind speed increases with the urban heat island intensity, and the thermal effect could increase urban canopy wind speed by about 30% under the condition of strong urban heat island. The relative contributions of the dynamic and thermal effects of building morphology to urban canopy wind speed change with the wind speed. As wind speed increases, the contribution of the thermal effect of building morphology to urban canopy wind speed gradually decreases. This paper provides a quantitative relationship between the urban canopy wind speed variation and urban morphology, as well as urban heat island intensity.

BackgroundA common sense is that lower serum cholesterol levels are better. However, a growing number of researches have questioned this especially for the oldest old. The current study was to assess the association between total cholesterol and all-cause mortality in a group of people aged 85 years old and over.MethodsWe selected 903 Chinese old participants who aged ≥85 years from the Chinese Longitudinal Healthy Longevity Survey(CLHLS) at baseline in 2012. The participants were followed up until death or until December 31, 2014. The outcome was all-cause mortality. The univariate and multivariate Cox regression analyses were used to estimate risk levels of all-cause mortality. We stratified the participants into three groups (

This study aimed to determine the association between sleep quality and mental health in COVID-19 carriers in China and evaluate the moderating effects of perceived social support. 1283 asymptomatic COVID-19 carriers were enrolled from March 2022 to April 2022 among Ruijin Jiahe Fangcang shelter hospital in Shanghai, China. They were assessed using the Pittsburgh Sleep Quality Index (PSQI), the General Health Questionnaire (GHQ), and the Perceived Social Support Scale (PSSS) respectively. Participants had an average age of 39.64 years and 59.6 % of whom were male. In total, 34.3 % of participants presented with poor sleep quality; 41.1 % showed bad mental health. Sleep quality was positively related to mental health (r = 0.321, P

Coalbed methane well sand (pulverized coal) problem restricts the production life of coalbed methane well, resulting in high maintenance costs, reduce productivity, and because of the large contact area between thin interbed coal seam and surrounding rock, the problem of sand production (pulverized coal) is prominent. In the Surat Basin of Australia, the coal seam cementation is loose and the coal/mud/sandstone interlayer is complex. In the statistical wells, 100% of the production wells have different degrees of sand production problems, and 33.5% of which have serious sand production, frequent workover operations, and high production costs. Based on the systematic analysis of the reservoir characteristics, sand production characteristics and production rules in Surat Basin, the comprehensive sand discharge prevention technology of “expansion packer + blind tube” and “screw pump + slurry rotor + automatic shunt valve + drilling through casing shoes” is adopted according to the research on the particle settlement law, combined with the prediction of sand production level and the optimization of sand control technology. The problem of sand production in coal measure strata in Surat Basin has been solved in stages. The field application results show that the average continuous production time of a single well increases from 275 days to nearly 400 days, and the workover frequency is reduced by nearly 50%.

ObjectiveA finite-time disturbance observer-based optimal backstepping control (FDO-OBC) method is proposed for the issue of unknown disturbances and formation changes in the formation trajectory tracking of unmanned surface vehicles (USVs).MethodsFirst, the USV formation control framework is established on the basis of the virtual structure method, and the kinematics and dynamics formation controllers are designed. Second, a finite-time disturbance observer is introduced to estimate and compensate for unknown environmental disturbances in real time. Further, a dynamic trajectory optimization strategy based on optimal backstepping control is proposed for the trajectory tracking issue of formation change, and the information of the disturbance observer is used to calculate the optimal control input and achieve the dynamic optimization of USV formation trajectory tracking. Finally, Lyapunov stability theory is used to demonstrate the stability of the designed formation control method.ResultsThe simulation results indicate that the proposed control strategy can effectively improve the accuracy and robustness of the USV formation system.ConclusionThe FDO-OBC method provides a new technical means for the design of USV formation control systems under unknown environmental disturbances.

Abstract We aimed to investigate the characteristics of intestinal metabolomics and non-invasive biomarkers for early diagnosis of late-onset sepsis (LOS) by analyzing gut metabolites in preterm infants with LOS. We collected stool samples from septic and healthy preterm infants for analysis by liquid chromatography–mass spectrometry. 123 different metabolites were identified and 13 pathways were mainly involved. Glycine, serine, and threonine metabolism; glyoxylate and dicarboxylic acid metabolism; glutathione metabolism; primary bile acid biosynthesis; steroid synthesis; pentose and glucuronic acid interconversion may be involved in the pathogenesis of LOS in preterm infants. The significant changes of N-Methyldopamine, cellulose, glycine, gamma-Glutamyltryptophan, N-Ribosylnicotinamide and 1alpha, 25-dihydroxycholecalciferol showed specific diagnostic values and as non-invasive biomarkers for LOS.

Abstract Background Laryngeal cancer (LC) is a malignant tumor with high incidence and mortality. We aim to explore key genes as novel biomarkers to find potential target of LC in clinic diagnosis and treatment. Methods We retrieved GSE143224 and GSE84957 datasets from the Gene Expression Omnibus database to screen the differentially expressed genes (DEGs). Hub genes were identified from protein-protein interaction networks and further determined using receiver operating characteristic curves and principal component analysis. The expression of hub gene was verified by quantitative real time polymerase chain reaction. The transfection efficiency of BCL2 interacting protein like (BNIPL) was measured by western blot. Proliferation, migration, and invasion abilities were detected by Cell Counting Kit-8, wound-healing, and transwell assays, respectively. Results Total 96 overlapping DEGs were screened out from GSE143224 and GSE84957 datasets. Six hub genes (BNIPL, KRT4, IGFBP3, MMP10, MMP3, and TGFBI) were identified from PPI network. BNIPL was selected as the target gene. The receiver operating characteristic curves of BNIPL suggested that the false positive rate was 18.5% and the true positive rate was 81.5%, showing high predictive values for LC. The expression level of BNIPL was downregulated in TU212 and TU686 cells. Additionally, overexpression of BNIPL suppressed the proliferation, migration, and invasion of TU212 and TU686 cells. Conclusion BNIPL is a novel gene signature involved in LC progression, which exerts an inhibitory effect on LC development. These findings provide a novel insight into the pathogenesis of LC.

In order to investigate the asphalt mixture enhancement due to the granular anti-rutting additives, the multiple stress creep recovery (MSCR) test and wheel tracking test were performed to examine the effects of three anti-rutting additives on the high-temperature performance of binders and mixtures, respectively. Further, the interaction mechanism between anti-rutting additives and asphalt binder was revealed via a fluorescence microscopy (FM) test. The results indicate that the incorporation of anti-rutting additives causes a substantial increase in elasticity behavior for binders, along with a massive enhancement of dynamic stability for mixtures. Further, the enhancement of performance is not conclusively determined by the compatibility between the additive and asphalt. Instead, unmelted viscous-flow additives contribute to the enhancement of mixtures by interlocking, filling voids, cementing and wrapping the aggregate, which are essential mechanisms of mixture modification. This study contributes to selecting appropriate additives in engineering and enhancing anti-rutting additives based on their modification mechanism.

The overall water resources in ecologically fragile mining areas in our country are scarce, but in some areas, mine water inflow is exceptionally large. The identification of abnormal mine water sources in ecologically fragile mining areas is of great significance for the protection of the ecological environment in the mining areas. This study takes the Yushuwan coal mine with a water inflow exceeding 1000 m3/h as the research background. Based on the analysis of the characteristics of mine water inflow, 30 water samples were collected from the main aquifers and mine water inflow points in the study area, and high-throughput microbial sequencing of water samples was conducted. The sequencing results were analyzed using Alpha diversity analysis, Beta diversity analysis, and differential analysis of microbial composition to systematically study the characteristics of microbial communities in mine water bodies and analyze the sources of mine water filling. The research results indicate that the high-throughput test results have passed the Coverage index test, verifying its feasibility for identifying mine water filling. However, water samples that have close contact with human activities show a greater abundance of microorganisms, which need to be effectively avoided in sampling. The abundance and diversity of microorganisms in the shallow loose aquifer of Yushuwan Coal Mine are relatively high, with the highest abundance being found in genera such as Novosphingobium, Fusobacterium, and Sulfuricum. The microbial richness of the bedrock aquifer represented by the Zhiluo Formation is relatively low, but the microbial diversity is high, with the highest microbial abundance being found in genera such as Comamonas, Vermiphilaceae, and Paeniglutamicacter. The most dominant phylum among all water samples is Proteobacteria, accounting for 35.5% to 89.7%. Alpha diversity, PCoA, and NSDM analysis revealed that the water inflow in the Yushu Bay mine is mainly composed of loose layers and Zhiluo Formation. However, Beta diversity analysis found that with the release of static reserves in the Zhiluo Formation, the water source for filling the loose layer of Lishi loess further increases. Comprehensive analysis shows that the Yushuwan coal mine currently adopts a water filling mode of rapid release of bedrock aquifer and continuous release of Lishi Formation aquifer. The statistical analysis results of mine water inflow confirm this conclusion. The statistical analysis results of mine water inflow confirm this conclusion. This study provides a new method for identifying water filling in aquifers with similar chemical compositions.

The filtered-x normalized least mean square (FxNLMS) algorithm is widely used in active noise control (ANC) systems. However, for cyclostationary input signals, the noise reduction performance of the FxNLMS algorithm is affected by the periodic power of cyclostationary inputs, which leads to a larger steady-state mean square deviation (MSD) than the filtered-x least mean squares (FxLMS) algorithm. In this paper, a new adaptive combination algorithm of FxNLMS and FxLMS is proposed to suppress cyclostationary input noise with fast convergence and low steady-state MSD. The mixing parameter for combining the two algorithms is obtained by minimizing the energy of the posterior error and updated using the time-average method. The mathematical analysis including the mean square convergence and computational complexity are performed. The simulation results show that the proposed combined-FxNLMS-FxLMS algorithm can efficiently combine the respective advantages of FxNLMS and FxLMS algorithms and improve the noise reduction performance of the ANC system.

In response to the limited capability of extracting semantic information in knowledge graph completion methods, we propose a model that combines spatial transformation and attention mechanisms (STAM) for knowledge graph embedding. Firstly, spatial transformation is applied to reorganize entity embeddings and relation embeddings, enabling increased interaction between entities and relations while preserving shallow information. Next, a two-dimensional convolutional neural network is utilized to extract complex latent information among entity relations. Simultaneously, a multi-scale channel attention mechanism is constructed to enhance the capture of local detailed features and global semantic features. Finally, the surface-level shallow information and latent information are fused to obtain feature embeddings with richer semantic expression. The link prediction results on the public datasets WN18RR, FB15K237 and Kinship demonstrate that STAM achieved improvements of 8.8%, 10.5% and 6.9% in the mean reciprocal rank (MRR) evaluation metric compared to ConvE, for the respective datasets. Furthermore, in the link prediction experiments on the hydraulic engineering dataset, STAM achieves better experimental results in terms of MRR, Hits@1, Hits@3 and Hits@10 evaluation metrics, demonstrating the effectiveness of the model in the task of hydraulic engineering knowledge graph completion.

Abstract Background This study aimed to explore the effects of breast milk feeding volume on the early behavioral neurodevelopment of extremely preterm infants (gestational age

The unmanned aerial vehicle (UAV) based remote sensing has drawn increased attention in precision agriculture. Lightweight optical and thermal sensors have been used widely on UAVs for a range of applications, and have been proposed by some as the best approach to map soil moisture at farm scales. However, passive microwave remote sensing has been widely acknowledged as the most accurate soil moisture mapping technology, and adopted by the soil moisture and ocean salinity and soil moisture active and passive satellite missions. Accordingly, it is postulated that this will also be the best technique for UAV-based near-surface soil moisture remote sensing, overcoming the spatial resolution limitation from low earth orbit altitude. Being so far limited by sensor availability, only a small number of studies have illustrated the potential of UAV-based near-surface soil moisture mapping using L-band microwave radiometers, and there has been no direct comparison with the thermal-optical alternative. To guide the design of future UAV-based soil moisture mapping systems, airborne optical, thermal infrared, and passive microwave observations collected from a scientific aircraft at low altitude over a center-pivot irrigation farm in Tasmania, Australia were used in this study to simulate UAV-based observations, and the performances of the thermal-optical and microwave techniques when compared at 75 m scale. The L-band microwave emission showed a superior sensitivity to near-surface soil moisture, and a higher and more consistent soil moisture retrieval accuracy than thermal-optical, with a root-mean-squared error of 0.05–0.06 m3/m3 and 0.05–0.09 m3/m3, respectively.

Abstract Norepinephrine (NA), a stress hormone, can accelerate hair graying by binding to β2 adrenergic receptors (β2AR) on melanocyte stem cells (McSCs). From this, NA-β2AR axis could be a potential target for preventing the stress effect. However, identifying selective blockers for β2AR has been a key challenge. Therefore, in this study, advanced computer-aided drug design (CADD) techniques were harnessed to screen natural molecules, leading to the discovery of rhynchophylline as a promising compound. Rhynchophylline exhibited strong and stable binding within the active site of β2AR, as verified by molecular docking and dynamic simulation assays. When administered to cells, rhynchophylline effectively inhibited NA-β2AR signaling. This intervention resulted in a significant reduction of hair graying in a stress-induced mouse model, from 28.5% to 8.2%. To gain a deeper understanding of the underlying mechanisms, transcriptome sequencing was employed, which revealed that NA might disrupt melanogenesis by affecting intracellular calcium balance and promoting cell apoptosis. Importantly, rhynchophylline acted as a potent inhibitor of these downstream pathways. In conclusion, the study demonstrated that rhynchophylline has the potential to mitigate the negative impact of NA on melanogenesis by targeting β2AR, thus offering a promising solution for preventing stress-induced hair graying. Graphical Abstract

Mellow and thick taste (MTT) is considered to be a typical taste characteristic of high-quality Pu-erh ripe tea. However, the role of polysaccharide conjugates remains unclear. In this study, the infusion of different grades of Pu-erh ripe tea was isolated to fractions by sensory-guided ultrafiltration technology and the key taste substances of MTT in Pu-erh ripe tea were identified and confirmed in the sensory reconstruction experiment. Further separation, purification and structural identification of the polysaccharide conjugates were carried out. Involving in aggregation morphology, the ultrafiltration fraction exhibited obvious MTT than other fractions. The main MTT compound (PRTPS-5), mainly composed of the rhamnose, galactose, arabinose and mannose, had a molecular weight of 22.93 kDa. The main chain of PRTPS-5 comprised α-L-Araf-(1→, →2,4)-α-L-Rhap-(1→, →2)-α-L-Rhap-(1→, α-D-Galp-(1→, →4)-α-D-GalpA-6-OMe-(1→, →4)-α-D-Manp-(1→, →3,6)-β-D-Galp-(1 → and →5)-α-L-Araf-(1 → and contained multiple pectic characteristic peaks. This result had scientific guiding significance for the quality enhancement of Pu-erh ripe tea.

Hydrothermal reactions can convert lignin into carbon dots, and the process often uses acids as additives, but the mechanism of action is not clear. In this study, lignin-based carbon dots were successfully prepared by HNO3-assisted one-pot hydrothermal method. The mechanism of the influence of the acidic environment on the structure and optical properties of lignin-based carbon dots was also investigated by changing the addition amount of HNO3. It was found that the particle size distribution of carbon dots collected was 1-5 nm, and they could emit bright blue fluorescence under violet light irradiation with the highest fluorescence quantum yield of 10.17%. HNO3 acts on the branched chains and ether bonds of alkali lignin, prompting the depolymerization of lignin and re-cross-linking and condensation to form lignin-based carbon dots. With the increase of HNO3 addition, the carbon core of lignin-based carbon dots gradually transformed from amorphous structure to complete graphene-like structure, and the emission wavelength of lignin-based carbon dots shifted from 517 nm to 499 nm, and the fluorescence quantum yield was increased from 2.61% to 10.17% by the effect of integrated N doping, which is of great significance for the analysis of the conformational relationship of lignin-based carbon dots, and for the guidance of the high-efficiency synthesis of lignin-based carbon dots.

IntroductionThis study used Bacillus amyloliquefaciens DGL1 isolated from the arid sandy land of the Qinghai–Tibetan Plateau as the research strain and investigated the effects of DGL1 on the biomass, physiology, and metabolites of Medicago sativa under different intensities of drought stress to provide a high-quality bacterial source and a theoretical basis for the research and development of biological fertilizer suitable for arid areas.MethodsThe exopolysaccharides (EPS), 1-Aminocyclopropane-1-carboxylate deaminase (ACC), and phosphorus solubilizing capacity of DGL1 were determined. The effects of a DGL1 suspension on alfalfa biomass, physiological indexes, degree of peroxidation of cell membranes, and activity of antioxidant enzymes were determined after irrigating roots under drought stress. The effects on soil physicochemical properties were also evaluated, and metabolomics analysis was performed to explore the effect of DGL1 on the metabolites of alfalfa under drought stress.ResultsStrain DGL1 produced extracellular polysaccharide EPS and ACC deaminase and was capable of phosphorus solubilization. Treatment with DGL1 increased the biomass of alfalfa under different degrees of drought stress, significantly increased the activities of alfalfa antioxidant enzymes Super Oxide Dismutase (SOD), Peroxidase (POD), and catalase (CAT), reduced the content of MDA and H2O2, and increased the content of quick-acting phosphorus, quick-acting potassium, ammonium nitrogen, and nitrate nitrogen in the soil, thus improving soil fertility. Through metabolomics analysis, DGL1 was shown to affect amino acid metabolic pathways, such as arginine, leucine, glutamate, and tyrosine, as well as the levels of energy-providing polysaccharides and lipids, in alfalfa under 15% PEG-6000 drought stress, enhancing alfalfa’s capacity to resist drought stress.DiscussionStrain DGL1 enhances the drought suitability of alfalfa and has the potential for dryland development as a biological agent.

Twenty-four-hour movement behaviors have significant implications for physical and mental health throughout one’s lifespan. Consistent with movement behaviors, several countries have formulated and published 24-h movement guidelines. This review summarized the studies related to 24-h movement guidelines among children and adolescents from six databases (MEDLINE, EMBASE, PubMed, Web of Science, CINAHL, and SPORTDiscus). In a total of 61 studies that discussed compliance with 24-h movement guidelines, the overall adherence rate was very low (7.6%), with boys exceeding girls, children surpassing adolescents, and regional differences. A total of 39 studies examined the associations between 24-h movement guidelines and health indicators. Findings indicated that meeting all three guidelines was favorably associated with adiposity, cardiometabolic health, mental and social health, physical fitness, health-related quality of life, academic achievement, cognitive development, perceived health, dietary patterns, and myopia. Future research should utilize longitudinal and experimental designs to enhance our understanding of the associations between 24-h movement guidelines and health indicators, thereby aiding the formulation and refinement of such guidelines.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, CRD42023481230.

To research the emotional interaction between customers and service staff, single-modal stimuli are being used to activate subjects’ emotions while multimodal emotion stimuli with better efficiency are often neglected. This study aims to construct a multimodal emotion stimuli database (CCSIAS) with video records of real work status of 29 service staff and audio clips of interactions between customers and service staff by setting up wide-angle cameras and searching in company’s Ocean Engine for 15 consecutive days. First, we developed a tool to assess the emotional statuses of customers and service staff in Study 1. Second, 40 Masters and PhD students were invited to assess the audio and video data to evaluate the emotional states of customers and service staff in Study 2, using the tools developed in Study 1. Third, 118 participants were recruited to test the results from Study 2 to ensure the stability of the derived data. The results showed that 139 sets of stable emotional audio & video data were constructed (26 sets were high, 59 sets were medium and 54 sets were low). The amount of emotional information is important for the effective activation of participants’ emotional states, and the degree of emotional activation of video data is significantly higher than that of the audio data. Overall, it was shown that the study of emotional interaction phenomena requires a multimodal dataset. The CCSIAS (https://osf.io/muc86/) can extend the depth and breadth of emotional interaction research and can be applied to different emotional states between customers and service staff activation in the fields of organizational behavior and psychology.

Abstract Acoustic echo cancellation (AEC) methods aim to suppress the acoustic coupling for hands‐free speech communication. Traditional AEC works by identifying the acoustic impulse response using adaptive algorithms. With recent research advances, deep learning has become an attractive choice for AEC. This paper introduces a two‐stage bidirectional long short term memory (TS‐BLSTM) framework, incorporating multi‐head self‐attention mechanisms after each BLSTM block. This is aimed at better capturing contextual information and further enhancing ability of the model to handle complex acoustic scenarios. The BLSTM blocks are utilized to aggregate magnitude spectrum information, modelling both time and frequency dependencies. Additionally, dilation convolution is introduced to broaden the range of information in each convolution output. The magnitude decoder estimates a mask for the input, resulting in the generation of an estimated magnitude spectrum for near‐end speech. Experimental results indicate that the proposed method achieves promising outcomes.

IntroductionBacillus amyloliquefaciens DGL1, isolated from the arid sandy areas in Dagler, Qinghai Province, China, promotes the growth of Avena sativa variety “Qing Yan 1”.MethodsTo elucidate the transcriptomic changes in the oat root system following interaction with DGL1 and to reveal the molecular mechanism by which DGL1 promotes oat growth, treatment and control groups of oat roots at 2, 4, 8, and 12 h after inoculation with a suspension of strain DGL1 were analyzed using Illumina high-throughput transcriptome sequencing technology. The differentially expressed genes were determined through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, and the metabolic pathways and key genes were analyzed.ResultsThe results showed that 7874, 13,392, 13,169, and 19,026 differentially expressed genes were significantly enriched in the glycolysis/gluconeogenesis pathway, amino acid metabolism, nitrogen metabolism, plant hormone signal transduction, and other related metabolic pathways in the oat roots at 2, 4, 8, and 12 h after inoculation with a DGL1 suspension. The GO and KEGG enrichment analyses revealed that the genes encoding plasma membrane ATPase, phosphoglycerate kinase gene PGK, ammonium transporter protein gene AMT, cellulose synthase gene CSLF6, and growth hormone response family gene IAA18 were significantly upregulated.DiscussionIt is hypothesized that the pro-growth mechanism of strain DGL1 in oats is the result of the coordination of multiple pathways through the promotion of oat energy metabolism, phytohormone signaling, secondary metabolite synthesis, and amino acid metabolism.

Abstract Background Pseudomyxoma peritonei (PMP) is a rare clinical malignant syndrome, and its rarity causes a lack of pathology research. This study aims to quantitatively analyze HE‐stained pathological images (PIs), and develop a new predictive model integrating digital pathological parameters with clinical information. Methods Ninety‐two PMP patients with complete clinic‐pathological information, were included. QuPath was used for PIs quantitative feature analysis at tissue‐, cell‐, and nucleus‐level. The correlations between overall survival (OS) and general clinicopathological characteristics, and PIs features were analyzed. A nomogram was established based on independent prognostic factors and evaluated. Results Among the 92 PMP patients, there were 34 (37.0%) females and 58 (63.0%) males, with a median age of 57 (range: 31–76). A total of 449 HE stained images were obtained for QuPath analysis, which extracted 40 pathological parameters at three levels. Kaplan–Meier survival analysis revealed eight clinicopathological characteristics and 20 PIs features significantly associated with OS (p

Abstract Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by the unresolved synovial inflammation for tissues‐destructive consequence, which remains one of significant causes of disability and labor loss, affecting about 0.2–1% global population. Although treatments with disease‐modifying antirheumatic drugs (DMARDs) are effective to control inflammation and decrease bone destruction, the overall remission rates of RA still stay at a low level. Therefore, uncovering the pathogenesis of RA and expediting clinical transformation are imminently in need. Here, we summarize the immunological basis, inflammatory pathways, genetic and epigenetic alterations, and metabolic disorders in RA, with highlights on the abnormality of immune cells atlas, epigenetics, and immunometabolism. Besides an overview of first‐line medications including conventional DMARDs, biologics, and small molecule agents, we discuss in depth promising targeted therapies under clinical or preclinical trials, especially epigenetic and metabolic regulators. Additionally, prospects on precision medicine based on synovial biopsy or RNA‐sequencing and cell therapies of mesenchymal stem cells or chimeric antigen receptor T‐cell are also looked forward. The advancements of pathogenesis and innovations of therapies in RA accelerates the progress of RA treatments.