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Abstract Liver fibrosis is a chronic liver disease with progressive wound healing reaction caused by liver injury. Currently, there is no FDA approved drugs for liver fibrosis. Human adipose mesenchymal stem cells (hADSCs) have shown remarkable therapeutic effects in liver diseases. However, few studies have evaluated the therapeutic role of hADSCs in liver fibrosis, and the detailed mechanism of action is unknown. Here, we investigated the in vitro and in vivo anti-fibrosis efficacy of hADSCs and identified important metabolic changes and detailed mechanisms through transcriptomic and metabolomic analyses. We found that hADSCs could inhibit the proliferation of activated hepatic stellate cells (HSCs), promote their apoptosis, and effectively inhibit the expression of pro-fibrotic protein. It can significantly reduce collagen deposition and liver injury, improve liver function and alleviate liver inflammation in cirrhotic mouse models. In addition, transcriptome analysis revealed that the key mechanism of hADSCs against liver fibrosis is the regulation of AGE-RAGE signaling pathway. Metabolic analysis showed that hADSCs influenced changes of metabolites in lipid metabolism. Therefore, our study shows that hADSCs could reduce the activation of hepatic stellate cells and inhibit the progression of liver fibrosis, which has important potential in the treatment of liver fibrosis as well as other refractory chronic liver diseases.

The prospect of employing chemoimmunotherapy targeted towards the endoplasmic reticulum (ER) presents an opportunity to amplify the synergistic effects of chemotherapy and immunotherapy. In this study, we initially validated celastrol (CEL) as an inducer of immunogenic cell death (ICD) by promoting ER stress and autophagy in colorectal cancer (CRC) cells. Subsequently, an ER-targeted strategy was posited, involving the codelivery of CEL with PD-L1 small interfering RNAs (siRNA) using KDEL peptide-modified exosomes derived from milk (KME), to enhance chemoimmunotherapy outcomes. Our findings demonstrate the efficient transportation of KME to the ER via the Golgi-to-ER pathway. Compared to their non-targeting counterparts, KME exhibited a significant augmentation of the CEL-induced ICD effect. Additionally, it facilitated the release of danger signaling molecules (DAMPs), thereby stimulating the antigen-presenting function of dendritic cells and promoting the infiltration of T cells into the tumor. Concurrently, the ER-targeted delivery of PD-L1 siRNA resulted in the downregulation of both intracellular and membrane PD-L1 protein expression, consequently fostering the proliferation and activity of CD8+ T cells. Ultimately, the ER-targeted formulation exhibited enhanced anti-tumor efficacy and provoked anti-tumor immune responses against orthotopic colorectal tumors in vivo. Collectively, a robust ER-targeted delivery strategy provides an encouraging approach for achieving potent cancer chemoimmunotherapy.

Abstract Notoginseng saponin R1; ginsenosides Rg1, Re, Rb1, and Rd; the sum of the five saponins; and underground-part fresh weight (UPFW) of single plants were used as quality evaluation indices for Panax notoginseng (Burk.) F. H. Chen (P. notoginseng). Comprehensive evaluation of P. notoginseng samples from 30 production areas was performed using that MaxEnt model. Spatial pattern changes in suitable P. notoginseng habitats were predicted for current and future periods (2050s, 2070s, and 2090s) using SSP126 and SSP585 models. The results revealed that temperature, precipitation, and solar radiation were important environmental variables. Suitable habitats were located mainly in Yunnan, Guizhou, and Sichuan Provinces. The distribution core of P. notoginseng is predicted to shift southeast in the future. The saponin content decreased from the southeast to the northwest of Yunnan Province, which was contrary to the UPFW trend. This study provides the necessary information for the protection and sustainable utilization of P. notoginseng resources, and a theoretical reference for its application in the quality evaluation of Chinese medicinal products.

Numerous analytical models have been developed to predict ground deformations induced by tunneling, which is a critical issue in tunnel engineering. However, the accuracy of these predictions is often limited by errors and uncertainties resulting from model selection and parameter fittings, given the paucity of monitoring data in field settings. This paper proposes a novel approach to estimate tunnelling-induced ground deformations by applying Bayesian model averaging to several representative prediction models. By accounting for both model and parameter uncertainties, this approach enables more realistic predictions of ground deformations than individual models. Specifically, our results indicate that the Gonzalez-Sagaseta model outperforms other models in predicting ground surface settlements, while the Loganathan-Poulos model is most suitable for predicting subsurface vertical and horizontal deformations. Importantly, our analysis reveals that when monitoring data are sparse, model uncertainties may contribute up to 78.7% of the total uncertainties. Thus, obtaining sufficient data for parameter fitting is crucial for accurate predictions. The proposed method in this study offers a more realistic and efficient prediction of tunnelling-induced ground deformations.

Abstract Background A promoter is a specific sequence in DNA that has transcriptional regulatory functions, playing a role in initiating gene expression. Identifying promoters and their strengths can provide valuable information related to human diseases. In recent years, computational methods have gained prominence as an effective means for identifying promoter, offering a more efficient alternative to labor-intensive biological approaches. Results In this study, a two-stage integrated predictor called “msBERT-Promoter” is proposed for identifying promoters and predicting their strengths. The model incorporates multi-scale sequence information through a tokenization strategy and fine-tunes the DNABERT model. Soft voting is then used to fuse the multi-scale information, effectively addressing the issue of insufficient DNA sequence information extraction in traditional models. To the best of our knowledge, this is the first time an integrated approach has been used in the DNABERT model for promoter identification and strength prediction. Our model achieves accuracy rates of 96.2% for promoter identification and 79.8% for promoter strength prediction, significantly outperforming existing methods. Furthermore, through attention mechanism analysis, we demonstrate that our model can effectively combine local and global sequence information, enhancing its interpretability. Conclusions msBERT-Promoter provides an effective tool that successfully captures sequence-related attributes of DNA promoters and can accurately identify promoters and predict their strengths. This work paves a new path for the application of artificial intelligence in traditional biology.

Abstract Background Vibrio parahaemolyticus is the predominant etiological agent of seafood-associated foodborne illnesses on a global scale. It is essential to elucidate the mechanisms by which this pathogen disseminates. Given the existing research predominantly concentrates on localized outbreaks, there is a pressing necessity for a comprehensive investigation to capture strains of V. parahaemolyticus cross borders. Results This study examined the frequency and genetic attributes of imported V. parahaemolyticus strains among travelers entering Shanghai Port, China, between 2017 and 2019.Through the collection of 21 strains from diverse countries and regions, Southeast Asia was pinpointed as a significant source for the emergence of V. parahaemolyticus. Phylogenetic analysis revealed clear delineation between strains originating from human and environmental sources, emphasizing that underlying genome data of foodborne pathogens is essential for environmental monitoring, food safety and early diagnosis of diseases. Furthermore, our study identified the presence of virulence genes (tdh and tlh) and approximately 120 antibiotic resistance-related genes in the majority of isolates, highlighting their crucial involvement in the pathogenesis of V. parahaemolyticus. Conclusions This research enhanced our comprehension of the worldwide transmission of V. parahaemolyticus and its antimicrobial resistance patterns. The findings have important implications for public health interventions and antimicrobial stewardship strategies, underscoring the necessity for epidemiological surveillance of pathogen at international travel hubs.

In this work, different transformed β matrix was obtained in Ti–5Al–7.5 V alloy. The alloy with equiaxed αp phase and transformed β matrix containing α′ martensite and β phase exhibits good combination of strength and plasticity, as well as a high work hardening rate. A concurrent operation of stress-induced α″ martensitic transformation, deformation twinning and dislocation slips was observed governing the deformation process of this alloy. The alloy with equiaxed αp phase and transformed β matrix containing secondary αs plates and retained β phase shows a high strength and plasticity but low work hardening rate, which is caused by dislocation slips.HighlightsThe quenched Ti–5Al–7.5 V alloy exhibits a high work hardening rate, approximately 5500 MPa.The dependence of work hardening rate of Ti–5Al–7.5 V alloy on transformed β matrix is revealed.Concurrent operations of stress-induced α″ martensitic transformation, deformation twinning and dislocation slips govern deformation of the studied alloy.

Spatial transcriptome technology can parse transcriptomic data at the spatial level to detect high-throughput gene expression and preserve information regarding the spatial structure of tissues. Identifying spatial domains, that is identifying regions with similarities in gene expression and histology, is the most basic and critical aspect of spatial transcriptome data analysis. Most current methods identify spatial domains only through a single view, which may obscure certain important information and thus fail to make full use of the information embedded in spatial transcriptome data. Therefore, we propose an unsupervised clustering framework based on multiview graph convolutional networks (MVST) to achieve accurate spatial domain recognition by the learning graph embedding features of neighborhood graphs constructed from gene expression information, spatial location information, and histopathological image information through multiview graph convolutional networks. By exploring spatial transcriptomes from multiple views, MVST enables data from all parts of the spatial transcriptome to be comprehensively and fully utilized to obtain more accurate spatial expression patterns. We verified the effectiveness of MVST on real spatial transcriptome datasets, the robustness of MVST on some simulated datasets, and the reasonableness of the framework structure of MVST in ablation experiments, and from the experimental results, it is clear that MVST can achieve a more accurate spatial domain identification compared with the current more advanced methods. In conclusion, MVST is a powerful tool for spatial transcriptome research with improved spatial domain recognition.

Objective To examine the effects of fish oil supplements on the clinical course of cardiovascular disease, from a healthy state to atrial fibrillation, major adverse cardiovascular events, and subsequently death.Design Prospective cohort study.Setting UK Biobank study, 1 January 2006 to 31 December 2010, with follow-up to 31 March 2021 (median follow-up 11.9 years).Participants 415 737 participants, aged 40-69 years, enrolled in the UK Biobank study.Main outcome measures Incident cases of atrial fibrillation, major adverse cardiovascular events, and death, identified by linkage to hospital inpatient records and death registries. Role of fish oil supplements in different progressive stages of cardiovascular diseases, from healthy status (primary stage), to atrial fibrillation (secondary stage), major adverse cardiovascular events (tertiary stage), and death (end stage).Results Among 415 737 participants free of cardiovascular diseases, 18 367 patients with incident atrial fibrillation, 22 636 with major adverse cardiovascular events, and 22 140 deaths during follow-up were identified. Regular use of fish oil supplements had different roles in the transitions from healthy status to atrial fibrillation, to major adverse cardiovascular events, and then to death. For people without cardiovascular disease, hazard ratios were 1.13 (95% confidence interval 1.10 to 1.17) for the transition from healthy status to atrial fibrillation and 1.05 (1.00 to 1.11) from healthy status to stroke. For participants with a diagnosis of a known cardiovascular disease, regular use of fish oil supplements was beneficial for transitions from atrial fibrillation to major adverse cardiovascular events (hazard ratio 0.92, 0.87 to 0.98), atrial fibrillation to myocardial infarction (0.85, 0.76 to 0.96), and heart failure to death (0.91, 0.84 to 0.99).Conclusions Regular use of fish oil supplements might be a risk factor for atrial fibrillation and stroke among the general population but could be beneficial for progression of cardiovascular disease from atrial fibrillation to major adverse cardiovascular events, and from atrial fibrillation to death. Further studies are needed to determine the precise mechanisms for the development and prognosis of cardiovascular disease events with regular use of fish oil supplements.

Although particular attention has been paid to responses of hydrocarbon storage and percolation capacity to the devitrification concerning lacustrine tuffaceous shale reservoirs in recent years, there is still a lack of systematical and comparative investigation on differential patterns and potential triggering mechanisms concerning development of the pore-microfracture systems and characteristics of surface wettability between the fresh-water and saline lacustrine settings, which is of considerable importance in fully understanding of genesis and spatial distribution of dessert reservoir intervals of tuffaceous shale reservoirs, and to provide further conceptual basis for deciphering shale-oil movability of saline lacustrine fine-grained mixed sedimentary sequences. In this study, tuffaceous shales from both the Upper Triassic Yanchang Formation in the Ordos Basin and Middle Permian Jingjingzigou Formation in the Junggar Basin are targeted to unravel the differential behavior of tuff devitrification and potential impacts on reservoir wettability and pore connectivity concerning fresh-water and saline lacustrine settings, and we present new results here from integrated analyses and combined interpretation of FE-SEM, Image Pro Plus (IPP) software image processing, contact angle and spontaneous imbibition experiments. In view of comparative analysis from representative samples, the tuffaceous shales from saline lacustrine environments are characterized by well-developed intergranular-intercrystalline and dissolution pores, and inorganic microfractures, generally yield a higher plane porosity of representative pore-fracture spaces and spontaneous imbibition slopes, a relatively lower average of n-decane contact angles and corresponding wettability parameters. The saline lacustrine tuffaceous shales are thus suspected to have undergone more intense devitrification resulting in a higher amount of devitrification and associated dissolution pores, and a relatively better connectivity between isolated micropore systems with adjacent microfractures. This would significantly facilitate the interface wettability reversal and occurrence of movable hydrocarbon fluid in microscopic reservoir spaces. Finally, a comprehensive and conceptual model is established illustrating the effects of differential devitrification on reservoir-forming patterns concerning tuffaceous shales developed in the fresh-water and saline lacustrine settings, respectively. These findings are of great theoretical and practical significance to enrich theory of high-quality reservoir formation and shale-oil accumulation in saline lacustrine tuffaceous shale reservoirs, and lay the foundation for guiding efficient exploration of continental fine-grained mixed sedimentary sequences.

Abstract Background For chronic hepatitis B virus (HBV) infection patients, increasing evidence has demonstrated the effectiveness of expanding the indications and applicable population for antiviral therapy. However, the expanded indication of antiviral therapy for hepatocellular carcinoma (HCC) remains to be further explored. Methods 196 HBV-related HCC patients who received radical hepatectomy and nucleos(t)ide analogues (NAs) therapy at Sichuan Provincial People’s Hospital were enrolled in this study. HCC recurrence, overall survival (OS), early virological (VR) and biochemical responses (BR) of patients were compared between different NAs therapy and the use of anti-programmed cell death protein 1 (PD-1) therapy. Results NAs therapy at different timing of surgery was a strong independent risk factor for postoperative recurrence and overall mortality of HBV-related HCC patients. Furthermore, in HCC patients who received postoperative anti-PD-1 therapy, patients with HBV DNA

Achieving efficient low-voltage actuation of microelectromechanical system (MEMS) resonators in high-temperature environments poses a difficult topic due to the thermal interference and the risk of high-temperature failure. In this work, the single-crystal diamond (SCD) resonators fabricated through the ion implantation-assisted lift-off (IAL) technique exhibit a SCD-on-SCD cantilever structure. We propose an electrical actuation system based on the electrostatic effect specifically designed for SCD MEMS resonators with a low radio-frequency amplitude of ∼ 100 mV. The SCD resonators demonstrate stable and efficient actuation across a wide temperature range, from room temperature to 500 °C. Importantly, the actuation voltage exhibits little impact on the resonance frequency and the Q factor of the resonator. The SCD resonator showcases exceptional thermal stability in resonance frequency, with a low temperature coefficient of frequency (TCF) below −12 ppm/°C up to 500 °C. The developed actuation scheme holds tremendous potential as a robust platform for realizing SCD MEMS devices, particularly in applications requiring high integration at high temperatures.

Biosensing is vital for many areas like disease diagnosis, infectious disease prevention, and point-of-care monitoring. Microfluidics has been evidenced to be a powerful tool for biosensing via integrating biological detection processes into a palm-size chip. Based on the chip structure, microfluidics has two subdivision types: open microfluidics and closed microfluidics, whose operation methods would be diverse. In this review, we summarize fundamentals, liquid control methods, and applications of open and closed microfluidics separately, point out the bottlenecks, and propose potential directions of microfluidics-based biosensing.

The monitoring of open-pit mining and reclamation activities is an important part of ecological protection across various countries. Among the many methods of monitoring open-pit mining areas, satellite remote sensing is the most widely used and effective. However, few works have been conducted to map open-pit mines over a larger geographical scale, or have considered complex land cover types, or a wide variety of mine properties. This work proposes a framework for mapping open-pit mines for areas over complex land cover and mining properties, including preprocessing, classification, and postprocessing steps. First, the pixels that did not contain mines were masked, second the mines were divided into two categories according to their spectral characteristics, then the selected samples and classified to obtain the classification results of mines, and third mis-classified pixels were removed. This work used Landsat images and Google Earth Engine to map the open-pit mines over Shanxi in 5-year steps from 2000 to 2020. The average producer and user accuracy of the results was found to be 79.4% and 83.2% respectively. The experimental results showed that open-pit mining areas in Shanxi first increased and subsequently decreased over the past twenty years. Additionally, the new preprocessing, classification, and postprocessing workflow was found to be effective, especially in environments with more vegetative cover.

Abstract Spectral emissivity is an essential and sensitive parameter to characterize the radiative capacity of the solid surface in scientific and engineering applications, which would be non-negligibly affected by surface morphology. However, there is a lack of assessment of the effect of roughness on emissivity and a straightforward method for estimating the emissivity of rough surfaces. This paper established an estimating method based on constructing random rough surfaces to predict rough surface (Geometric region) emissivity for metal solids. Based on this method, the emissivity of ideal gray and non-gray body surfaces was calculated and analyzed. The calculated and measured spectral emissivities of GH3044, K465, DD6, and TC4 alloys with different roughness were compared. The results show that the emissivity increases with the roughness degree, and the enhancement effect weakens with the increase of roughness or emissivity due to the existing limit (emissivity ε = 1.0). At the same time, the roughness would not change the overall spectral distribution characteristics but may attenuate the local features of the spectral emissivity. The estimated results are in good agreement with the experimental data for the above alloys’ rough surfaces. This study provides a new reliable approach to obtaining the spectral emissivity of rough surfaces. This approach is especially beneficial for measuring objects in extreme environments where emissivity is difficult to obtain. Meanwhile, this study promotes an understanding of surface morphology’s effect mechanism on emissivity.

Foodborne diseases are major public health problems globally. Metagenomics has emerged as a widely used tool for pathogen screening. In this study, we conducted an updated Tn5 transposase-assisted RNA/DNA hybrid co-tagmentation (TRACE) library construction approach. To address the detection of prevalent known foodborne viruses and the discovery of unknown pathogens, we employed both specific primers and oligo-T primers during reverse transcription. The method was validated using clinical samples confirmed by RT-qPCR and compared with standard RNA-seq library construction methods. The mapping-based approach enabled the retrieval of nearly complete genomes (>95%) for the majority of virus genome segments (86 out of 88, 97.73%), with a mean coverage depth of 21,494.53× (ranging from 77.94× to 55,688.58×). Co-infection phenomena involving prevalent genotypes of Norovirus with Astrovirus and Human betaherpesvirus 6B were observed in two samples. The updated TRACE-seq exhibited superior performance in viral reads percentages compared to standard RNA-seq library preparation methods. This updated method has expanded its target pathogens beyond solely Norovirus to include other prevalent foodborne viruses. The feasibility and potential effectiveness of this approach were then evaluated as an alternative method for surveilling foodborne viruses, thus paving the way for further exploration into whole-genome sequencing of viruses.

This paper has investigated the growth of α grain during lamellar decomposition of Ti‐48Al‐7Nb‐2.5V‐1Cr alloy. In the (α + γ) phase region, the α grains have started to grow by consuming the adjacent α grains, accompanied by decomposition of γ lamellae (γL). Since the growth rate of α grains is faster than the decomposition of γL, the growth of the α grains is hindered by the γL, while the hindering effect decreases with the γL decomposition. Once the hindrance of the γL is gone, the α grains will continue to grow and the grain size can even reach the millimetre level. The α grain growth does not show a specific pattern. The growing α grain may also be consumed by the adjacent α grains, resulting in irregular grain morphology.

Vibrio parahaemolyticus is a significant cause of foodborne illness, and its incidence worldwide is on the rise. It is thus imperative to develop a straightforward and efficient method for typing strains of this pathogen. In this study, we conducted a pangenome analysis of 75 complete genomes of V. parahaemolyticus and identified the core gene mtlA with the highest degree of variation, which distinguished 44 strains and outperformed traditional seven-gene-based MLST when combined with aer, another core gene with high degree of variation. The mtlA gene had higher resolution to type strains with a close relationship compared to the traditional MLST genes in the phylogenetic tree built by core genomes. Strong positive selection was also detected in the gene mtlA (ω > 1), representing adaptive and evolution in response to the environment. Therefore, the panel of gene mtlA and aer may serve as a tool for the typing of V. parahaemolyticus, potentially contributing to the prevention and control of this foodborne disease.

Introduction: Although previous studies investigated the potential adverse effects of endocrine-disrupting chemicals (EDCs) on biological age acceleration and aging-related diseases, the mixed effect of multiple types of EDCs on biological age acceleration, including its potential underlying mechanism, remains unclear. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) were used to analyze biological age measures, including Klemera-Doubal method biological age (KDM-BA), phenotypic age, and homeostatic dysregulation (HD). Weight quantile sum (WQS) regression was performed to screen biological age-related EDCs (BA-EDCs) and assess the mixed effect of BA-EDCs on biological age acceleration and aging-related disease. Targets of BA-EDCs were obtained from three databases, while heart aging-related genes were obtained from the Aging Anno database. Protein–protein interaction (PPI) network and MCODE algorithm were applied to identify potential interactions between BA-EDC targets and heart aging-related genes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to identify related pathways. Results: This cross-sectional study included 1,439 participants. A decile increase in BA-EDCs co-exposure was associated with 0.31 years and 0.17 years of KDM-BA and phenotypic age acceleration, respectively. The mixed effect of BA-EDCs was associated with an increased prevalence of atherosclerotic cardiovascular disease (ASCVD). Vitamins C and E demonstrated a significant interaction effect on the association between BA-EDCs and KDM-BA acceleration. PPI network and functional enrichment analysis indicated that the AGE-RAGE signaling pathway in diabetic complications was significantly enriched. Conclusion: Our results showed that the co-exposure effect of BA-EDCs was associated with biological age acceleration and ASCVD, with the AGE-RAGE signaling pathway being the underlying mechanism. Vitamins C and E may also be an actionable target for preventing EDC-induced biological aging.

2,2′,7,7′-Tetrakis(N,N-di-p-methoxyphenyl)-amine-9,9′-spirobifluorene (Spiro-OMeTAD) represents the state-of-the-art hole-transporting material (HTM) in n-i-p perovskite solar cells (PSCs). However, its susceptibility to stability issues has been a long-standing concern. In this study, we embark on a comprehensive exploration of the untapped potential within the family of spiro-type HTMs using an innovative anisotropic regulation strategy. Diverging from conventional approaches that can only modify spirobifluorene with single functional group, this approach allows us to independently tailor the two orthogonal components of the spiro-skeleton at the molecular level. The newly designed HTM, SF-MPA-MCz, features enhanced thermal stability, precise energy level alignment, superior film morphology, and optimized interfacial properties when compared to Spiro-OMeTAD, which contribute to a remarkable power conversion efficiency (PCE) of 24.53% for PSCs employing SF-MPA-MCz with substantially improved thermal stability and operational stability. Note that the optimal concentration for SF-MPA-MCz solution is only 30 mg/ml, significantly lower than Spiro-OMeTAD (>70 mg/ml), which could remarkably reduce the cost especially for large-area processing in future commercialization. This work presents a promising avenue for the versatile design of multifunctional HTMs, offering a blueprint for achieving efficient and stable PSCs.

Copper-doped Zinc Tellurium (ZnTe:Cu) films were deposited on borosilicate glass using magnetron co-sputtering technique. The influence of the substrate temperature on the structural, morphological, optical and electrical properties of ZnTe:Cu films was investigated by X-ray diffraction (XRD), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), UV–Vis spectrophotometer and Hall effect measurement system. The results indicate that substrate temperature significantly affects the properties of the ZnTe:Cu films. When the substrate temperature increases from room temperature to 600 °C, the (111)-preferred orientation of ZnTe:Cu films is gradually replaced by the (220)-preferred orientation. At high substrate temperatures (≥500 °C), the CuxTe phase appears in the ZnTe:Cu films, resulting in higher carrier concentration (>1019 cm−3) and lower resistivity (

Objective: We examined the relationships between infants’ growth trajectories and prenatal exposure to air pollution, which is still under-investigated. Methods: A birth cohort study was constructed using medical records of pregnant women and infants born between 2015 and 2019 in Foshan, China. Using satellite-based spatial-temporal models, prenatal exposure to air pollutants including particulate matter with an aerodynamic dimension of < 2.5 µm (PM2.5), sulfur dioxide (SO2), nitrogen dioxide (NO2), and ozone (O3) was assessed at each woman's residence. Latent class growth modeling was used to identify trajectories of physical (body length and weight) growth and neurodevelopment, which were repeatedly measured within 1 year after birth. Logistic regression models were used to investigate the associations between prenatal exposure to air pollution and the risks of growth disorders, adjusting for an array of potential confounders. Results: We identified two growth trajectories for body length [normal: 3829 (93%); retardation: 288 (7%)], three for weight [normal: 2475 (59.6%); retardation: 390 (9.4%); overgrowth: 1287 (31%)], and two for neurodevelopment [normal: 956 (66.1%); retardation: 491 (33.9%)]. For exposure over whole pregnancy, SO2 was associated with an increased risk of body length retardation (OR for per 1 µg/m3 increment: 1.09, 95%CI: 1.01–1.17); PM2.5 (OR: 1.05, 95%CI: 1.03–1.07), SO2 (OR: 1.15, 95%CI: 1.08–1.22), and NO2 (OR: 1.05, 95%CI: 1.03–1.07) were positively associated with neurodevelopmental retardation. Such associations appeared stronger for exposures over the first and second trimesters. No significant associations were detected for weight growth. Conclusions: Maternal exposure to air pollution during pregnancy was associated with higher risks of impairments in both physical growth, particularly body length, and neurodevelopment.

Abstract Background Abstracting cerebrovascular disease (CeVD) from inpatient electronic medical records (EMRs) through natural language processing (NLP) is pivotal for automated disease surveillance and improving patient outcomes. Existing methods rely on coders’ abstraction, which has time delays and under-coding issues. This study sought to develop an NLP-based method to detect CeVD using EMR clinical notes. Methods CeVD status was confirmed through a chart review on randomly selected hospitalized patients who were 18 years or older and discharged from 3 hospitals in Calgary, Alberta, Canada, between January 1 and June 30, 2015. These patients’ chart data were linked to administrative discharge abstract database (DAD) and Sunrise™ Clinical Manager (SCM) EMR database records by Personal Health Number (a unique lifetime identifier) and admission date. We trained multiple natural language processing (NLP) predictive models by combining two clinical concept extraction methods and two supervised machine learning (ML) methods: random forest and XGBoost. Using chart review as the reference standard, we compared the model performances with those of the commonly applied International Classification of Diseases (ICD-10-CA) codes, on the metrics of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Result Of the study sample (n = 3036), the prevalence of CeVD was 11.8% (n = 360); the median patient age was 63; and females accounted for 50.3% (n = 1528) based on chart data. Among 49 extracted clinical documents from the EMR, four document types were identified as the most influential text sources for identifying CeVD disease (“nursing transfer report,” “discharge summary,” “nursing notes,” and “inpatient consultation.”). The best performing NLP model was XGBoost, combining the Unified Medical Language System concepts extracted by cTAKES (e.g., top-ranked concepts, “Cerebrovascular accident” and “Transient ischemic attack”), and the term frequency-inverse document frequency vectorizer. Compared with ICD codes, the model achieved higher validity overall, such as sensitivity (25.0% vs 70.0%), specificity (99.3% vs 99.1%), PPV (82.6 vs. 87.8%), and NPV (90.8% vs 97.1%). Conclusion The NLP algorithm developed in this study performed better than the ICD code algorithm in detecting CeVD. The NLP models could result in an automated EMR tool for identifying CeVD cases and be applied for future studies such as surveillance, and longitudinal studies.

Abstract Background Increasing body fat or decreasing muscle and bone mass were associated with worse health outcomes in the adult population. The effects of nickel exposure on body composition are not known. The aim of the current study was to investigate the relationship between urinary nickel levels and body compositions. Materials and methods Two thousand seven hundred sixty-two participants were included in the analysis from the National Health and Nutrition Examination Surveys of 2017–2018 after excluding participants who have missing data on urinary nickel and those with missing all body mass component data. We used weighted generalized linear models to explore the relationship between urinary nickel and body mass components under interpolating missing covariable values. Simultaneously, sensitivity analyses and subgroup analysis were conducted to verify stability of analysis result. Curve fitting and saturation effect analysis were used to explore the possible nonlinear relationship between urine nickel and body compositions. Results Among the 2,762 participants, the average urinary nickel level was 1.58 ug/L. The weighted generalized linear models, the sensitivity analyses and subgroup analyses found no significant linear relationship between urinary nickel and body compositions. For body weight, BMI, TLM, ALM, TRF, TOF and BMC, the urine nickel saturation effect values were 0.76, 0.74, 0.5, 0.67, 0.64, 0.48, and 0.45 ug/L, respectively. For each 1 ug/L rise in urinary nickel levels at levels below the turning point, body weight increases (β = 9.06, 95% CI = 2.75, 15.36, p = 0.01), BMI increases (β = 3.20, 95% CI = 1.36, 5.05, p =

Thermal storage tanks are the most widely used devices for thermodynamic storage. Their stratification performance is a key factor in determining their effectiveness. In this study, a structure was proposed to improve the thermal stratification of an elbow-type thermal storage tank. An experimental study was conducted on its exothermic properties for applications in hot water storage tanks. An experimental analysis was performed to investigate the exothermic properties of the proposed structure, and the results were compared with those obtained from simulations using CFD (ANSYS 19.1) software. To investigate the effect of thermal stratification on the water inlet structure, the Richardson number, hot water output rate, and MIX number of the elbow inlet structure were compared with those of the water distributor inlet structure. The results show that the MIX numbers corresponding to the inlet structures of the two types of tanks, the elbow and water distributor types, are not very different. These values were almost identical to the Richardson numbers. Under the same working conditions, the hot water output rate was 84.90% for the elbow inlet structure and 76.39% for the water distributor inlet structure. In conclusion, elbow-type water inlet structures are easy to install, and the manufacturing process is simplified.

This paper conducts an in-depth study and evaluation of pedestrian paths, with a particular focus on the anti-slip performance and walking comfort of wooden chip pedestrian walkways. Through controlled experiments, a comparative analysis was performed between wooden chip pedestrian walkways and ordinary paved brick walkways. The experimental results indicate that under dry conditions, the anti-slip performance of various road surfaces is good. However, in wet environments, the anti-slip performance of paved brick roads deteriorates significantly. In contrast, wooden chip pedestrian walkways, especially those mixed with asphalt and wood chips, exhibit excellent anti-slip properties and comfort. Additionally, the study reveals that the comfort of wooden chip pedestrian walkways is significantly better than that of paved brick walkways, and the comfort of asphalt materials is slightly better than emulsified asphalt. It is worth mentioning that fine wood chips provide less comfort than coarse wood chips. Although reducing the thickness can enhance comfort, considering the service life of the road, a thickness of 4–6 cm is most suitable. Finally, asphalt and wooden chip mixtures with coarse wood chips possess good water permeability, making them suitable for permeable drainage pavement designs, effectively reducing road surface water accumulation.

Hybrid gold-based perovskite derivatives typically exhibit low optical bandgaps and high optical absorption coefficients, rendering them promising for photovoltaic applications. In this study, we successfully synthesized six new hybrid gold-based perovskite derivatives, namely [(C6H8N2)(AuI4)(AuI2)](3AMPY), [(C6H14N2)(AuI4)(AuI2)](3AMP), [(C8H12N)(AuI4)](2PEAI), [(C4H14N2O)(AuI4)2](OBA), [(C6H18N2O2)3(AuI4)4(I3)2](DDA), and [(C10H26N2O3)(AuI4)(I3)](TOTA), through a straightforward and efficient hydrothermal method, achieving millimeter-sized single crystals. The structural analysis of the single crystals revealed variations in crystal structures arising from differences in constituent units and their spatial positioning relationships. First-principles calculations ascertained their high optical absorption coefficients in the visible light spectrum and indirect bandgap properties. Theoretical models indicated that the spectroscopic limited maximum efficiency (SLME) values of 3AMPY, 2PEAI, DDA, and TOTA approached approximately 30% in films of 0.5 μm thickness, signifying their potential candidacy as solar cell absorbers.

With the rapid development of deep learning, its powerful capabilities make it possible to perform mechanical fault diagnosis of high-voltage circuit breakers (HVCBs). Among deep learning approaches, the convolutional neural network is widely used. However, while it can extract features effectively, it also has some limitations. Specifically, it depends on a large number of training data and only takes data information into account without considering structural information. These shortcomings lead to unused information and unsatisfactory model results. To address these shortcomings, this paper proposes AKNN-DMGCN, a novel dynamic multi-attention graph convolutional network based on an adaptively constructed graph, which can achieve high accuracy and robust mechanical fault diagnosis of HVCBs. First, a novel adaptive k-nearest neighbor (AKNN) graph construction method is proposed to construct informative graphs. The AKNN method can mine the relationship between the original data samples and utilize the data and label information. Thus, it has high fault tolerance to noise signals and can construct a structure graph with rich and accurate information, which can improve the overall model performance. Then, a dynamic multi-attention graph convolutional network (DMGCN) is applied for mechanical fault diagnosis of HVCBs. DMGCN fully utilizes structural and numerical information representing HVCB signals to perform classification. DMGCN has a dynamic multi-attention mechanism with strong expressive ability, which allows it to achieve high diagnostic accuracy. The experimental results indicate that the accuracy of AKNN-DMGCN reaches 97.22% on a balanced dataset and 95.01% on an imbalanced dataset, which demonstrates that the proposed method is effective for both balanced and imbalanced samples.

High-voltage circuit breakers (HVCBs) handle the important tasks of controlling and safeguarding electricity networks. In the case of insufficient data samples, improving the accuracy of the traditional HVCB mechanical fault diagnosis method is difficult, so it poses challenges in meeting performance requirements for mechanical fault diagnosis. In this study, a HVCB fault diagnosis method is introduced. It utilizes a combination of grey wolf optimization (GWO) and multi-grained cascade forest (gcForest) algorithms to resolve these issues and improve the accuracy of HVCB mechanical fault diagnosis. To simplify the original vibration signal, the input feature quantity for the fault diagnosis method is obtained by calculating the energy entropy of the wavelet packet decomposition. The GWO algorithm is employed to optimize the parameters of the gcForest model, leading to identification of the optimum parameter configuration. Subsequently, the diagnostic effect in the case of a small sample size was analyzed through a VS1 vacuum circuit breaker example, and the accuracy reached 95.89%. In the case of unbalanced samples, further analysis and comparison with different methods confirm the feasibility and efficiency of the combination of GWO and gcForest algorithms. This study provides an effective solution for the diagnosis of mechanical faults in HVCBs.

The COVID-19 pandemic has reshaped our daily lives and the way we interact with urban green–blue spaces (UGBS), particularly in the economically challenged regions of Northwest China. Our study, utilizing surveys and social media, delves into the pandemic’s impact on UGBS engagement in this area, offering critical insights for urban planning amidst a global health crisis. We found a gender-balanced but preference-specific engagement in UGBS, with women and married couples in the Chengguan District of Lanzhou city showing affinity. Moreover, educational levels and proximity to academic institutions emerged as key factors influencing UGBS use, pointing to the importance of educational attainment in engagement diversity. Enhancing safety, creating child-friendly and leisure facilities for families, and designing vibrant spaces for socializing are vital, and placing UGBS near educational districts could also promote environmental awareness and scientific learning. Furthermore, the pandemic has reshaped public priorities, elevating the value of accessible, safe UGBS. This shift is evidenced by varied motivations for UGBS visits, with an emphasis on health, nature connectivity, and leisure. Women, older adults, and families, each with their distinct reasons, were drawn to UGBS for activities ranging from recreation to relaxation. Our findings advocate for the creation of multifunctional UGBS that cater to these varied interests, incorporating features such as air-purifying plants, scenic pathways, and zones for family activities, all underpinned by enhanced safety and accessibility. The study also highlights distinct transportation preferences among residents of Chengguan’s northern and southern parts, suggesting a tailored approach to urban infrastructure that accommodates pedestrian access and public transit use. To prevent overcrowding, adjusting facility hours and event timings based on peak visitation times is recommended. Moreover, improving walkways and public transport connectivity is essential not just for convenience but also for ensuring that these green spaces are equitable and financially accessible, fostering inclusive access to these essential urban areas. During the pandemic, social media revealed a growing search for spiritual fulfillment within UGBS, highlighting their importance in societal well-being and coping mechanisms. In response, there’s a compelling opportunity for UGBS to evolve by incorporating designated areas for spiritual relaxation, along with mental health support services. By actively monitoring social media feedback and trends, these spaces can adapt and refine their offerings, ensuring that they meet the community’s changing needs more effectively. Our study highlights the importance of tailoring UGBS to meet diverse community needs, especially during crises. It emphasizes creating multifunctional, accessible UGBS that reflect demographic trends, transportation habits, and public preferences, aiming to boost community resilience and well-being. Drawing from research conducted amidst a worldwide crisis, our study provides key recommendations for the future evolution of UGBS, urging the creation of inclusive environments that bolster the health and well-being of urban populations.

Since 2019, major breakthroughs have been made in the prospecting of the Lower Cretaceous sandstone-type uranium deposits in the northern Ordos Basin. The Lower Cretaceous sandstone layer is expected to become another important sandstone-type uranium prospecting target after the Middle Jurassic. Establishing the metallogenic model of the Lower Cretaceous provides a better guide for prospecting work. Based on previous regional geological, drilling cores, and analytical data, the authors systematically summarized the basic geological characteristics of uranium mineralization in the Lower Cretaceous in this area and preliminarily established the uranium metallogenic model of the Lower Cretaceous.The results suggest the six Lower Cretaceous rock types can be divided into three geochemical types. Uranium mineralization mainly occurs in the brown-gray sandstone, which is the transition zone from brown-red sandstone to green sandstone. The green sandstone is formed by oxidation first and then reduction.The metallogenic type is dominated by interlayer oxidation, supplemented by phreatic oxidation in the Late Cretaceous. The Lower Cretaceous "secondary oxidation" uranium metallogenic model can be divided into three stages: first oxidation mineralization stage, large-scale reduction mineralization stage, and second oxidation mineralization stage.These research results can provide a new idea for uranium exploration in new strata of Ordos Basin.

The increasing global demand for sustainable urban development has led to the widespread adoption of Green Infrastructure (GI) worldwide. However, there remains a lack of understanding regarding public support for implementing GI specifically at industrial sites. This study focuses on promoting industrial GI (IGI) and examines residents' willingness to pay (WTP) for GI installation and the nonmarket value of GI is estimated using the travel cost method (TCM). Among respondents residing in neighborhoods surrounding industrial areas, a significant proportion (90%) expressed their WTP for GI promotion. The aggregated annual WTP for IGI and Neighbourhood GI (NGI) were estimated to be approximately CNY 16.2 million and CNY 21.9 million, respectively. Moreover, the annual nonmarket value provided by IGI and NGI to human well-being was estimated to be around CNY 4.5 million and CNY 20.7 million, respectively. The study reveals that middle-aged and middle-income groups exhibit a higher propensity for WTP, with specific GI measures such as rain gardens, vegetated swales, trees, and naturalized landscaping receiving greater WTP intentions. The primary challenges identified for promoting IGI include cost, policy, and maintenance considerations. This study recommends customizing planning approaches for IGI promotion, considering diverse demographics, including constructing youth apartments near industrial areas, implementing age-friendly design features, and enhancing landscape design in elderly communities. Disseminating GI knowledge through media and partnering with local organizations for awareness enhancement is essential for encouraging higher WTP. The effectiveness of water features and pedestrian-friendly areas in improving and promoting IGI spaces is also highlighted. These findings offer valuable insights to policymakers and city planners, facilitating the identification of more effective GI designs for promoting sustainable urban environments that align with societal preferences and demands.

The mainstream polishing methods were reviewed in light of polycrystalline CVD diamond wafer with large area. The principles, equipment, and processes of the mainstream polishing methods were reviewed, and the processing characteristics of these methods were compared. The material removal rate (MRR), polishing rate (PR), and minimum surface roughness (Ra) obtained by each polishing method were summed up. The non-contact method has a relatively higher MRR than the contact method, while the contact method has a relatively smaller final roughness than the non-contact method. Two factors, K (K = ΔRa/Δm, ΔRa is the reduction of the surface roughness, Δm is the mass loss) and CI (CI = K/t, t is the total polishing time), were proposed to evaluate the influence of the polishing parameters on the polishing course in the contact polishing methods and to describe the feature of each polishing method, respectively. The variation of the K value indicated that the polishing load and the polishing plate speed did not always influence the polishing effect monotonically in every contact polishing method, and it should be optimized to obtain fine surface roughness with the tiny mass loss. The CI value showed that the non-contact polishing method possessed the feature of high roughness improvement with low mass loss in the unit polishing time. These results reveal how to move forward on the path to polishing large area polycrystalline CVD diamond wafer.

A resonator with a high Q factor is generally pursued in the single-crystal diamond (SCD) microelectromechanical system (MEMS) for high-performance sensors. In this report, we investigate the oxygen etching effect of SCD on the Q factors of the SCD resonators by using the Raman spectroscopy spatial mapping. We aim to establish the etch pit effect on the Q factors of the SCD MEMS resonators. The 2D Raman imaging technique discloses the dislocations and the local stress in the SCD MEMS resonators in microscale. It is observed that the full width half maximum (FWHM) of the Raman spectra of the SCD resonators has marked relationship with the Q factors of the SCD resonators. The etch pits resulted from the dislocations have weak influence on the Q factors of the SCD resonators.

Central nervous system (CNS) disorders present a growing and costly global health challenge, accounting for over 11% of the diseases burden in high-income countries. Despite current treatments, patients often experience persistent symptoms that significantly affect their quality of life. Dietary polysaccharides have garnered attention for their potential as interventions for CNS disorders due to their diverse mechanisms of action, including antioxidant, anti-inflammatory, and neuroprotective effects. Through an analysis of research articles published between January 5, 2013 and August 30, 2023, encompassing the intervention effects of dietary polysaccharides on Alzheimer’s disease, Parkinson’s disease, depression, anxiety disorders, autism spectrum disorder, epilepsy, and stroke, we have conducted a comprehensive review with the aim of elucidating the role and mechanisms of dietary polysaccharides in various CNS diseases, spanning neurodegenerative, psychiatric, neurodevelopmental disorders, and neurological dysfunctions. At least four categories of mechanistic bases are included in the dietary polysaccharides’ intervention against CNS disease, which involves oxidative stress reduction, neuronal production, metabolic regulation, and gut barrier integrity. Notably, the ability of dietary polysaccharides to resist oxidation and modulate gut microbiota not only helps to curb the development of these diseases at an early stage, but also holds promise for the development of novel therapeutic agents for CNS diseases. In conclusion, this comprehensive review strives to advance therapeutic strategies for CNS disorders by elucidating the potential of dietary polysaccharides and advocating interdisciplinary collaboration to propel further research in this realm.

Resumo Fundamento Muitos estudos clínicos confirmaram que a legumain está intimamente relacionada à aterosclerose. Infelizmente, chegaram-se a conclusões diferentes e ainda faltam análises e estudos sobre as características da placa aterosclerótica em pacientes com níveis plasmáticos aumentados de legumain. Objetivos Este estudo teve como objetivo investigar a correlação entre as características da legumain e da placa aterosclerótica coronariana. Métodos Um total de 81 pacientes com doença cardíaca aterosclerótica coronariana (DCAC), incluindo 43 pacientes com angina instável (AI) e 38 pacientes com angina estável (AE), foram examinados por angiografia coronária. Foi realizado ultrassom intravascular (IVUS) para avaliar as características das placas ateroscleróticas coronarianas, e os níveis plasmáticos de legumain também foram medidos. Valores de p < 0,05 foram considerados significativos. Resultados A concentração de legumain foi significativamente maior nos dois subgrupos de doença coronariana do que no grupo controle (todos p

Abstract. Background:. DOK3 (Downstream of kinase 3) is involved primarily with immune cell infiltration. Recent research reported the role of DOK3 in tumor progression, with opposite effects in lung cancer and gliomas; however, its role in prostate cancer (PCa) remains elusive. This study aimed to explore the role of DOK3 in PCa and to determine the mechanisms involved. Methods:. To investigate the functions and mechanisms of DOK3 in PCa, we performed bioinformatic and biofunctional analyses. Samples from patients with PCa were collected from West China Hospital, and 46 were selected for the final correlation analysis. A lentivirus-based short hairpin ribonucleic acid (shRNA) carrier was established for silencing DOK3. A series of experiments involving the cell counting kit-8, bromodeoxyuridine, and flow cytometry assays were performed to identify cell proliferation and apoptosis. Changes in biomarkers from the nuclear factor kappa B (NF-κB) signaling pathway were detected to verify the relationship between DOK3 and the NF-κB pathway. A subcutaneous xenograft mouse model was performed to examine phenotypes after knocking down DOK3 in vivo. Rescue experiments with DOK3 knockdown and NF-κB pathway activation were designed to verify regulating effects. Results:. DOK3 was up-regulated in PCa cell lines and tissues. In addition, a high level of DOK3 was predictive of higher pathological stages and worse prognoses. Similar results were observed with PCa patient samples. After silencing DOK3 in PCa cell lines 22RV1 and PC3, cell proliferation was significantly inhibited while apoptosis was promoted. Gene set enrichment analysis revealed that DOK3 function was enriched in the NF-κB pathway. Mechanism experiments determined that knockdown of DOK3 suppressed activation of the NF-κB pathway, increased the expressions of B-cell lymphoma-2 like 11 (BIM) and B-cell lymphoma-2 associated X (BAX), and decreased the expression of phosphorylated-P65 and X-linked inhibitor of apoptosis (XIAP). In the rescue experiments, pharmacological activation of NF-κB by tumor necrosis factor-α (TNF-α) partially recovered cell proliferation after the knockdown of DOK3. Conclusion:. Our findings suggest that overexpression of DOK3 promotes PCa progression by activating the NF-κB signaling pathway.

Abstract Background Hepatocellular carcinoma (HCC) is labeled with high mortality and tolerance to chemotherapy. Sorafenib has been the first‐line treatment option in HCC patients for past decades, while the therapeutic effect was limited in almost HCC patients. Methods In this study, we analyzed public omics data of HCC patients with different responses to Sorafenib treatment. To confirm the role of integrins A5 and B1 (ITGA5 and ITGB1) in Sorafenib resistance, we generated the Sorafenib‐resistant (Sor‐R) cell lines and cells overexpressing ITGA5 or ITGB1. Hypoxia level was measured using Hypoxy probe by flow cytometry, while vasculogenic mimicry was detected and quantified by CD31 and periodic acid schiff staining. Results Hypoxia was upregulated in non‐responsive patients, accompanied with genes involved in encoding extracellular matrix components and angiogenesis such as ITGA5 and ITGB1. Sor‐R hepatoma cell lines were constructed to measure expression and role of candidate genes. ITGA5 and ITGB1 were augmented in Sor‐R cells. Upregulation of ITGA5 or ITGB1 reduced the sensitivity to Sorafenib in HepG2 and Huh7 cells, aggravated the hypoxic condition and resulted in formation of vascular mimicry. Conclusions These findings suggested that hypoxia associated vascular mimicry account for non‐response to Sorafenib treatment in HCC patients. ITGA5 and ITGB1 may serve as effective predictors of HCC patients' outcome after Sorafenib treatment, which also provides a new target for HCC patients resistant to Sorafenib.

Background: Depression has caused enormous health burden to human worldwide. Glycemia has been found as one important risk factor of depression. However, the biological mechanism underlying this relationship remained largely unknown. Methods: This analysis was derived from a cohort of 33,151 participants in the UK Biobank who provided brain magnetic resonance imaging data from 2014 to 2020. Participants were classified into diabetic, prediabetic and non-diabetic groups, as well as groups aged ≥60 years and

Abstract Liver fibrosis is a chronic liver disease with the presence of progressive wound healing response caused by liver injury. Currently, there are no approved therapies for liver fibrosis. Exosomes derived from human adipose mesenchymal stem cells (hADMSCs-Exo) have displayed a prominent therapeutic effect on liver diseases. However, few studies have evaluated therapeutic effect of hADMSCs-Exo in liver fibrosis and cirrhosis, and its precise mechanisms of action remain unclear. Herein, we investigated anti-fibrotic efficacy of hADMSCs-Exo in vitro and in vivo, and identified important metabolic changes and the detailed mechanism through transcriptomic and metabolomic profiling. We found hADMSCs-Exo could inhibit the proliferation of activated hepatic stellate cells through aggravating apoptosis and arresting G1 phase, effectively inhibiting the expression of profibrogenic proteins and epithelial-to-mesenchymal transition (EMT) in vitro. Moreover, it could significantly block collagen deposition and EMT process, improve liver function and reduce liver inflammation in liver cirrhosis mice model. The omics analysis revealed that the key mechanism of hADMSCs-Exo anti-hepatic fibrosis was the inhibition of PI3K/AKT/mTOR signaling pathway and affecting the changes of metabolites in lipid metabolism, and mainly regulating choline metabolism. CHPT1 activated by hADMSCs-Exo facilitated formation and maintenance of vesicular membranes. Thus, our study indicates that hADMSCs-Exo can attenuate hepatic stellate cell activation and suppress the progression of liver fibrosis, which holds the significant potential of hADMSCs-Exo for use as extracellular nanovesicles-based therapeutics in the treatment of liver fibrosis and possibly other intractable chronic liver diseases. Graphical Abstract

Rare sugars are a kind of prebiotics with special chemical structure and bioactivities such as regulate intestinal flora, inhibit pathogen, resist oxidation, improve immunity, antitumor and so on. Rare sugars were widely used in the production of health food, infant formula food, dairy products as well as functional drinks. Nowadays, series progress has been made in the discovering of novel rare sugar, structural analysis, optimization of producing process, enzyme engineering, metabolic engineering and Izumoring strategy research. This paper reviews and prospects above advances, focuses on the research progress of bioactivity and biotransformation of rare sugars, and discusses their industrial application potential, existing problems and solutions, to provide a theoretical basis for the development, function mining and industrial production and utilization of rare sugars.

MEMS resonant sensing devices require both HF ( f ) and low dissipation or high quality factor ( Q ) to ensure high sensitivity and high speed. In this study, we investigate the resonance properties and energy loss in the first three resonance modes, resulting in a significant increase in f‧Q product at higher orders. The third order resonance exhibits an approximately 15-fold increase in f‧Q product, while the Q factor remains nearly constant. Consequently, we achieved an ultrahigh f‧Q product exceeding 10 ^12 Hz by higher-order resonances in single-crystal diamond cantilevers.

Electromagnetic radiation at higher harmonics of the plasma frequency ( ω ∼ n ω _pe , n > 2) has been occasionally observed in type II and type III solar radio bursts, yet the underlying mechanism remains undetermined. Here we present two-dimensional fully kinetic electromagnetic particle-in-cell simulations with high spectral resolution to investigate the beam-driven plasma emission process in weakly magnetized plasmas of typical coronal conditions. We focused on the generation mechanisms of high-harmonic emission. We found that a larger beam velocity ( u _d ) favors the generation of the higher-harmonic emission. The emissions grow later for higher harmonics and decrease in intensity by ∼2 orders of magnitude for each jump of the harmonic number. The second and third harmonic (H _2 and H _3 ) emissions get closer in intensity with larger u _d . We also show that (1) the H _3 emission is mainly generated via the coalescence of the H _2 emission with the Langmuir waves, i.e., H _2 + L → H _3 , wherein the coalescence with the forward-propagating beam-Langmuir wave leads to the forward-propagating H _3 , and coalescence with the backward-propagating Langmuir wave leads to the backward-propagating H _3 ; and (2) the H _4 emission mainly arises from the coalescence of the H _3 emission with the forward- (backward-)propagating Langmuir wave, in terms of H _3 + L → H _4 .

In the laser powder bed fusion additive manufacturing process, the quality of fabrications is intricately tied to the laser–matter interaction, specifically the formation of the melt pool. This study experimentally examined the intricacies of melt pool characteristics and surface topography across diverse laser powers and speeds via single-track laser scanning on a bare plate and powder bed for 316L stainless steel. The results reveal that the presence of a powder layer amplifies melt pool instability and worsens irregularities due to increased laser absorption and the introduction of uneven mass from the powder. To provide a comprehensive understanding of melt pool dynamics, a high-fidelity computational model encompassing fluid dynamics, heat transfer, vaporization, and solidification was developed. It was validated against the measured melt pool dimensions and morphology, effectively predicting conduction and keyholing modes with irregular surface features. Particularly, the model explained the forming mechanisms of a defective morphology, termed swell-undercut, at high power and speed conditions, detailing the roles of recoil pressure and liquid refilling. As an application, multiple-track simulations replicate the surface features on cubic samples under two distinct process conditions, showcasing the potential of the laser–matter interaction model for process optimization.

BackgroundBisphenol A (BPA), bisphenol S (BPS), and bisphenol F (BPF) are widely used in various consumer products. They are environmental contaminants with estrogenic properties that have been linked to various health outcomes. Understanding their impact on body composition is crucial for identifying potential health risks and developing preventive strategies. However, most current studies have only focused on their relationship with BMI. ObjectiveThis study aimed to investigate the association between urinary levels of BPA, BPS, and BPF and body composition, including BMI, lean mass, and fat mass, in a large population-based sample. MethodsWe conducted a cross-sectional analysis using data from the National Health and Nutrition Examination Survey 2003-2016. Body composition data were assessed using dual-energy X-ray absorptiometry, which provided precise measurements of lean mass, fat mass, and other indicators. We used multivariate linear regression models to estimate the associations, adjusting for potential confounders such as age, gender, race, socioeconomic factors, and lifestyle variables. ResultsThe results revealed significant associations between bisphenol exposure and body composition. After adjusting for covariates, BPS showed a positive association with BMI, with quartiles 3 and 4 having 0.91 (95% CI 0.34-1.48) and 1.15 (95% CI 0.55-1.74) higher BMI, respectively, compared with quartile 1 (P

Objectives: The ocean is a huge ecosystem with diverse marine life. Scientists have found a large number of natural products with unique structural features and excellent biological activity from these organisms. Marine-derived sulphur-containing alkaloids are a significant family of natural products with diverse structures and bioactivities. In this paper, the chemical and biological diversity of 972 sulfur-containing alkaloids derived from marine organisms reported from 1982 to 2022 were reviewed, and the structure–activity relationship was briefly analyzed, in order to provide reference for the discovery, synthesis, biological activity research and drug development of such compounds. Key findings: A total of 972 marine-derived sulphur-containing alkaloids have been collected. Among them, 80.36% of sulphur-containing alkaloids are from marine sponges, fungi, tunicates and bacteria. Moreover, cytotoxicity is their most significant property, About 1/3 sulphur-containing organisms are reported to be cytotoxic. Aming them, discorhabdins, curacins, tanjungides, leptosins, and latrunculins exhibit better cytotoxicity. In addition, the structure–activity relationships of the cytotoxicity of these compounds have been summarized for further investigation. Summary: In this paper, the chemical and bioactivity diversity of marine-derived sulphur-containing alkaloids were reviewed, which are a significant family of natural products with diverse structures and bioactivities. 972 sulphur-containing alkaloids were obtained from marine algae, sponges, cnidarians, tunicates, echinoderms, molluscs, bryozoans, dinoflagellates, cyanobacteria, bacteria and fungi, which possessed a wide spectrum of pharmacology including cytotoxicity, antibacterial, antifungal, antimitotic, antiviral, and other activities.