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To solve the problem of low cementitious activity of steel slag (SS), N, N-bis(2-hydroxyethyl)-2-aminoethanesulfonic acid sodium salt (BES-Na) and triethanolamine (TEA) were used in this study to improve the hydration activity of SS. However, there are no comparative studies on the effects of BES-Na and TEA on the hydration of SS-Portland cement (PC) systems. This study compared the hydration process and strength development of SS-PC systems in the presence of BES-Na and TEA, as well as the complexing ability of BES-Na and TEA. The results showed that both BES-Na and TEA improved the early compressive strength of SS-PC mortar, but TEA did not contribute to the late compressive strength, while BES-Na still improved the late compressive strength. At the same dosage, TEA accelerated aluminates hydration more than BES-Na and retarded/inhibited silicates hydration more than BES-Na. This difference in effect on hydration can be attributed to the difference in their complexing ability. TEA has a stronger complexing ability with metal ions than BES-Na, which is beneficial for accelerating aluminates hydration, but this not only prolonged the hydration induction period but also inhibited silicates hydration. BES-Na has a weaker complexing ability relative to TEA. Although BES-Na has a weaker accelerating effect on aluminates hydration, it has a lesser effect on silicates hydration and even accelerates silicates hydration at low dosage. This study also showed that BES-Na is an alternative additive to TEA, which could help expand the application of BES-Na in cementitious materials.

Abstract Objective Our study focused on the effects and molecular mechanisms of kaempferol, a major active component of Eucommia ulmoides Oliver (EUO), on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Methods Target molecules for EUO, osteoarthritis, and osteogenic differentiation were identified through network pharmacology analysis. BMSCs were isolated and treated with various concentrations of kaempferol. Optimal concentration was determined through MTT assays. Osteogenic differentiation was assessed using alkaline phosphatase (ALP) and Alizarin Red S staining, while osteogenic markers (Collagen I, RUNX2, and OPN) and CAV-1 expression were analyzed using RT-qPCR and Western blot. The effects of combined treatment with kaempferol and an overexpression vector for CAV-1 (oe-CAV-1) on osteogenic differentiation were also observed. Results Network pharmacology analysis identified kaempferol as the primary active component influencing CAV-1 targeted in subsequent experiments. It was found that 10 µM kaempferol was optimal for treating BMSCs. Post-treatment, significant increases in ALP activity and calcium deposition were observed, along with elevated expression of osteogenic markers, and decreased CAV-1. Overexpression of CAV-1 significantly reversed the promotive effects of kaempferol on BMSC osteogenic differentiation, effectively inhibiting the process. Conclusion Collectively, kaempferol promotes osteogenic differentiation in BMSCs by inhibiting CAV-1 expression.

Abstract Purpose This study explored potential categories of dyadic disease appraisal differences among patients hospitalized with chronic heart failure (CHF) in China and analyzed the main factors influencing these categories. Methods A survey was conducted using various tools and scales, including the Chinese version of the Memorial Heart Failure Symptom Appraisal Scale, Heart failure self-care index scale, Social Support Rating Scale, Zarit burden interview, and Self-rating anxiety scale. The data was collected from patients who were hospitalized with CHF in the cardiology department of one of two tertiary hospitals in Nanchong City, China. The dyadic disease appraisal categories were identified using latent profile analysis (LPA). Multiple logistic regression analysis was also employed to analyze the factors influencing the formation of potential categories of differences in dyadic disease appraisal in CHF patients. Results A total of 262 pairs of hospitalized CHF patients and their caregivers participated in this study. The dyadic disease appraisal of CHF patients was potentially categorized as the "negative difference group" (28 individuals, 10.7%) and the "positive or convergence group" (234 persons, 89.3%). The results showed that the factors influencing the categorization of dyadic disease appraisal differences included the patient's social support, disease progression, and Caregivers anxiety level, burden, gender, educational attainment, and age (p

Presently, the application of big data in the construction industry encounters numerous obstacles and involves diverse stakeholders, with the intricate network of relationships between these factors and stakeholders remaining unclear. Investigating stakeholders’ management priorities and collaborative patterns can facilitate the development of BDAC. Therefore, this study employs a two-mode social network analysis to explore stakeholders’ power and attitudes toward the factors of BDAC. Firstly, the initial list of stakeholders and factors is identified based on the literature and expert interviews, followed by a questionnaire to establish stakeholder–factor relationships and construct the network. Subsequently, the adjacency matrix, centrality, core–periphery structure, and hierarchical cluster are adopted to analyze the network. The results found that (1) technical factors need to be addressed by all stakeholders due to complexity; (2) due to the low resource similarity of factors and low power similarity of stakeholders, all stakeholders should be involved in the collaboration; and (3) government, developers, and consultants, as core stakeholders, exhibit a proactive inclination towards collaborative efforts in addressing central factors, and can coordinate with peripheral stakeholders. Consequently, this study establishes a stakeholder collaboration model centered on the government–developer–consultant trio, which provides clear responsibility allocation and strategic guidance for fostering long-term, effective collaboration in BDAC.

Abstract Background Anxiety and depression are prevalent comorbidities in patients with chronic obstructive pulmonary disease (COPD). However, existing research has yielded conflicting findings regarding the effects of social frailty on anxiety and depression. The primary aim of this study is to validate the relationship between social frailty and social support with anxiety and depression in patients with acute exacerbations of COPD (AECOPD) and to investigate whether social support could explain the variations in prior study outcomes for patients with AECOPD. Methods Of the 315 patients hospitalized with AECOPD at the respiratory intensive care unit of a large tertiary care institution in Sichuan Province of China, between August 2022 and June 2023 who were surveyed, 306 were included in the analysis after excluding missing data. We conducted a logistic regression analysis to examine the associations of social frailty and social support with anxiety and depression and performed mediation analyses to examine whether social support mediates the relationship of social frailty with anxiety and depression. Results The logistic regression analysis revealed that social frailty did not associate anxiety or depression in patients with AECOPD. The mediation analysis supported this idea and indicated that while social frailty does not directly influence anxiety or depression, it can through social support. Conclusions The findings suggest that while social frailty may not directly impact anxiety or depression in patients with AECOPD, social support plays a crucial mediating role. Enhancing social support can indirectly alleviate anxiety and depression among these patients. Enhancing social support networks should thus be prioritized by healthcare providers and family members to improve mental health outcomes in this patient population.

The unique flavor properties and rich nutrients of traditional fermented food are closely related to its complex and variable microbial structure, which also makes it difficult to control the quality of final fermented product. In order to explore the changes of microbial structure and sensory property and nutritional property in the process of food fermentation and the internal relationship between them, the data analysis process is a key step. Therefore, it is necessary to establish a fast and accurate data analysis method for quality control of fermented food. Machine learning has the advantages of high-dimensional simplification rate, large data throughput and high prediction accuracy, showing great application potential in the field of quality control of fermented food. Hence, machine learning has become one of the research hotspots. This paper reviews the application of machine learning in the quality control of fermented food. On the basis of an overview of common models of machine learning, this paper systematically summarizes the application of machine learning in the prediction of microbial structure evolution, flavor compound composition analysis and customization of personalized consumption in the process of food fermentation. The problems and developmental trends in the application of machine learning to quality control of traditional fermented food are summarized and prospected. Although the application of machine learning in fermented food is still confined by the problems such as insufficient general applicability of the model, limited quality indicators, and limited personalized consumption scenario, etc., with the iterative update of the technical model, the adaptation for multi-factors and whole process, and the application expansion in the background of personalized consumption, machine learning will show a greater value for practical application in the field of fermented food. The purpose of this study is to provide guidance for the further application of machine learning in the standardized and controllable production of traditional fermented food.

Abstract Background Triple-negative breast cancer (TNBC) represents a highly aggressive subset of breast malignancies characterized by its challenging clinical management and unfavorable prognosis. While TFAP2A, a member of the AP-2 transcription factor family, has been implicated in maintaining the basal phenotype of breast cancer, its precise regulatory role in TNBC remains undefined. Methods In vitro assessments of TNBC cell growth and migratory potential were conducted using MTS, colony formation, and EdU assays. Quantitative PCR was employed to analyze mRNA expression levels, while Western blot was utilized to evaluate protein expression and phosphorylation status of AKT and ERK. The post-transcriptional regulation of TFAP2A by miR-8072 and the transcriptional activation of SNAI1 by TFAP2A were investigated through luciferase reporter assays. A xenograft mouse model was employed to assess the in vivo growth capacity of TNBC cells. Results Selective silencing of TFAP2A significantly impeded the proliferation and migration of TNBC cells, with elevated TFAP2A expression observed in breast cancer tissues. Notably, TNBC patients exhibiting heightened TFAP2A levels experienced abbreviated overall survival. Mechanistically, TFAP2A was identified as a transcriptional activator of SNAI1, a crucial regulator of epithelial-mesenchymal transition (EMT) and cellular proliferation, thereby augmenting the oncogenic properties of TFAP2A in TNBC. Moreover, miR-8072 was unveiled as a negative regulator of TFAP2A, exerting potent inhibitory effects on TNBC cell growth and migration. Importantly, the tumor-suppressive actions mediated by the miR-8072/TFAP2A axis were intricately associated with the attenuation of AKT/ERK signaling cascades and the blockade of EMT processes. Conclusions Our findings unravel the role and underlying molecular mechanism of TFAP2A in driving tumorigenesis of TNBC. Targeting the TFAP2A/SNAI1 pathway and utilizing miR-8072 as a suppressor represent promising therapeutic strategies for treating TNBC.

Abstract Myocardial infarction, commonly known as a heart attack, is a serious condition caused by the abrupt stoppage of blood flow to a part of the heart, leading to tissue damage. A significant aspect of this condition is reperfusion injury, which occurs when blood flow is restored but exacerbates the damage. This review first addresses the role of the innate immune system, including neutrophils and macrophages, in the cascade of events leading to myocardial infarction and reperfusion injury. It then shifts focus to the critical involvement of CD4+ T helper cells in these processes. These cells, pivotal in regulating the immune response and tissue recovery, include various subpopulations such as Th1, Th2, Th9, Th17, and Th22, each playing a unique role in the pathophysiology of myocardial infarction and reperfusion injury. These subpopulations contribute to the injury process through diverse mechanisms, with cytokines such as IFN-γ and IL-4 influencing the balance between tissue repair and injury exacerbation. Understanding the interplay between the innate immune system and CD4+ T helper cells, along with their cytokines, is crucial for developing targeted therapies to mitigate myocardial infarction and reperfusion injury, ultimately improving outcomes for cardiac patients.

IntroductionThe association between inflammatory blood markers (IBMs) (monocyte-to-lymphocyte ratio [MLR], neutrophil-to-lymphocyte ratio [NLR], and platelet-to-lymphocyte ratio [PLR]) and breast cancer has been extensively studied. However, the predictive role of IBMs in the neoadjuvant response of human epidermal growth factor receptor 2 (HER2)-positive breast cancer remains unclear.MethodsThis study included 744 patients with HER2 positive breast cancer treated with neoadjuvant therapy. Baseline MLR, NLR, and PLR data were collected to investigate the association between IBMs and pathological complete response (pCR).ResultsMLR, NLR, and PLR were not associated with neoadjuvant response in the overall population before and after matching. Subgroup analysis stratified by neoadjuvant therapy suggested that these IBMs play a diverse predictive role in response to chemotherapy alone and chemotherapy plus anti-HER2 therapy. A high MLR and NLR, but not PLR, were associated with lower pCR rates in HER2-targeted therapy (MLR: OR=0.67, P=0.023; NLR: OR=0.665, P=0.02; PLR: OR=0.801, P=0.203). Among the anti-HER2 treatment population, patients with a high MLRs (pCR rate, 40.2%) could be divided into MLRhigh/NLRhigh (pCR rate, 36.3%) and MLRhigh/NLRlow (pCR rate, 48.9%) groups when the NLR was considered. The pCR rates of the MLRhigh/NLRlow and low-MLR groups were similar (pCR rate, 47.6%). A comparable stratification effect was observed in patients with high NLR.ConclusionsIBMs play a diverse predictive role in pCR in HER2-positive breast cancer stratified by neoadjuvant regimens. The combination of high MLR and high NLR enabled better identification of patients with poor responses to anti-HER2 therapy than high MLR or NLR alone.

In the era of big data, the propagation of malicious software poses a significant threat to corporate data security. To safeguard data assets from the encroachment of malware, it is essential to conduct a dynamic analysis of various information propagation behaviors within software. This paper introduces a dynamic analysis detection method for malicious behavior based on feature extraction (MBDFE), designed to effectively identify and thwart the spread of malicious software. The method is divided into three stages: First, variable-length N-gram algorithms are utilized to extract subsequences of varying lengths from the sample APl call sequences as continuous dynamic features. Second, feature selection techniques based on information gain are employed to identify suitable classification features. Lastly, recurrent neural networks (RNN) are applied for the classification training and prediction of diverse software behaviors. Experimental results and analysis demonstrate that this approach can accurately detect and promptly interrupt the information dissemination of malicious software when such behavior occurs, thereby enhancing the precision and timeliness of malware detection.

Tetracycline (TC) residues in the environment are harmful to plants and animals; earthworms play an important role in detoxicating tetracycline in the soil. However, the response of different systems of the geophagous earthworm to TC and its degradation products is still not understood well. To understand this problem, Metaphire guillelmi were exposed to the soil contaminated by 100 mg kg−1 tetracycline for 21 days. Liquid chromatography was used to detect the tetracycline concentration and its degradation products in different organs of earthworms on the 1st, 7th, and 21st day. Structural equation model (SEM) was used to determine the cumulative interaction of TC among different systems of earthworm. The results showed that the degradation ability of TC of digestive organs (98.29–99.77 %) was stronger than that of reproductive organs (87.46–98.64 %). The main metabolic pathway of TC in earthworms might be direct dehydration. Anhydrotetracycline was the main degradation product in earthworm organs and could last long in production organs. For lipid soluble pollutants, such as TC, the digestive system of earthworms might be the main pathway for absorbing pollutants from the soil. Furthermore, earthworms can expedite the degradation of organic pollutants. Meanwhile, they also need to absorb more nutrients like nitrogen and phosphorus, to counteract the impact of pollutants on their antioxidant system and reproductive organs. Our study improves our understanding of the degradation and detoxification mechanism of earthworms to TC, and provides useful information for further assessment of the soil eco-risk.

Globally, water scarcity threatens food security, especially in arid and semi-arid food-producing regions, such as the Hetao Irrigation District (HID), where the water consumption during the non-growth season (spring irrigation, autumn irrigation) accounts for more than 30 % of the total irrigation volume. Meanwhile, mapping the characteristics of spatial and temporal evolution of the area of cropland irrigated in the spring and autumn and the pattern of water consumption is crucial for strengthening the management of agricultural water use. Evaporation and infiltration of irrigation water are difficult to capture in time due to insufficient timeliness or accuracy of single remote sensing data. This study integrates seven remote sensing datasets (Landsat5, Landsat7, Landsat8, HJ-1A/B, GF-1, Sentinel-2 and MODIS) for the first time to build a high spatial-temporal resolution dataset, and combines the water index NDWI and MNDWI to extract the maximum water range formed after irrigation by manually adjusting the threshold method. In addition to the global land use/cover dataset (GLC FCS30–1985_2020), the cropland layer was superimposed to accurately identify the cropland spring irrigation and autumn irrigation range from 2000 to 2021 in the HID. In the past 20 years, spring-irrigated (SI) areas increased by 1012.60 km2 (+49.96 %), and the autumn-irrigated (AI) areas decreased by 512.63 km2 (-11.02 %). Combined with the quantity of water diversion and displacement, the characteristics of irrigation water consumption in the non-growth season were further analysed. The results showed that the water consumption of spring irrigation increased by 0.67×108 m3 (+22.26 %), and that of autumn irrigation increased by 4.34×108 m3 (+38.82 %). The decrease of autumn- irrigated area and the increase of water consumption were mainly related to the stability of autumn irrigation water, imperfect irrigation and drainage conditions and insufficient field water management. In 2020­2021, the area of non-growth “autumn irrigation - spring irrigation” repeated irrigation is about 1271.52 km2, which can be used as a key control area. This study provides a theoretical basis and direction for rational water use in non-growth seasons of irrigation districts.

Abstract Liver cancer remains one of the most prevalent malignancies worldwide with high incidence and mortality rates. Due to its subtle onset, liver cancer is commonly diagnosed at a late stage when surgical interventions are no longer feasible. This situation highlights the critical role of systemic treatments, including targeted therapies, in bettering patient outcomes. Despite numerous studies on the mechanisms underlying liver cancer, tyrosine kinase inhibitors (TKIs) are the only widely used clinical inhibitors, represented by sorafenib, whose clinical application is greatly limited by the phenomenon of drug resistance. Here we show an in-depth discussion of the signaling pathways frequently implicated in liver cancer pathogenesis and the inhibitors targeting these pathways under investigation or already in use in the management of advanced liver cancer. We elucidate the oncogenic roles of these pathways in liver cancer especially hepatocellular carcinoma (HCC), as well as the current state of research on inhibitors respectively. Given that TKIs represent the sole class of targeted therapeutics for liver cancer employed in clinical practice, we have particularly focused on TKIs and the mechanisms of the commonly encountered phenomena of its resistance during HCC treatment. This necessitates the imperative development of innovative targeted strategies and the urgency of overcoming the existing limitations. This review endeavors to shed light on the utilization of targeted therapy in advanced liver cancer, with a vision to improve the unsatisfactory prognostic outlook for those patients.

Abstract Background Malnutrition is related to impaired oral health and function that causes poor dietary intake, declining the general health of older adults. The role of dietary intake in the association between oral function and nutritional status of Chinese older adults (aged 75 and above) was examined in this cross-sectional study. Methods Through the randomized cluster sampling method, 267 older adults living in rural areas of Qingdao, Shandong (aged 81.4 ± 4.3, 75–94 years) were chosen as the primary research participants. A Mini Nutritional Assessment - Short Form was used to determine nutritional status, and Food Frequency Questionnaire and 24-hour Food Intake Recall were used to assess dietary intake. The oral function was evaluated by analyzing the teeth, oral problems, bite force, tongue pressure, lip sealing pressure, chewing function questionnaire, whole saliva flow rate, 10-Item Eating Assessment Tool, and water swallow test. Results Based on the MNA-SF score, it was divided into a well-nourished group and a malnutrition group, with the malnutrition group comprising 40.6% of participants. The participants in the malnutrition group showed a higher rate of xerostomia, lower bite force, tongue pressure, and lip sealing pressure, and higher Chewing Function Questionnaire and 10-Item Eating Assessment Tool scores. Furthermore, their plant fat, iron, cereals and potatoes, vegetables, fruits, and seafood intake were relatively low. The regression model indicated that exercise frequency, stroke, chewing and swallowing function, intake of vegetables and fruits were risk factors for nutritional status of older adults. Conclusion Malnutrition was relatively common among the Chinese older adults aged 75 and above, and it was significantly correlated with exercise frequency, stroke, chewing and swallowing function, and intake of vegetables and fruits. Therefore, nutrition management should be carried out under the understanding and guidance of the oral function and dietary intake of the older adults.

Abstract The abnormally expressed microRNAs (miRNAs) serve as crucial indicators for disease diagnosis and are strongly associated with the progression of various diseases. The quantification of miRNAs is highly significant for the clinical diagnosis and treatment of various types of cancers. This study utilizes the CRISPR/Cas13a system, which combines CRISPR RNA (crRNA) and CRISPR-associated Cas13a, to recognize the miRNA directly and specifically, thus activating the trans-cleavage activity of Cas13a. By integrating the CRISPR-Cas13a system with an exonuclease-iii (Exo-iii)-assisted chain cleavage of silver ions (Ag+)-aptamer and an Ag+ -based color reaction, a method for the detection of miRNA that is specific and sensitive is developed. This approach demonstrated exceptional sensitivity in detecting miRNA, with a low detection limit of 5.12 fM. Moreover, the suggested method was effectively utilized to precisely measure the amount of miRNA in intricate biological samples, demonstrating its practical applicability. Furthermore, due to its elevated sensitivity and simple probe design and fluorophore labeling, the suggested colorimetric technique holds great potential for use in clinical diagnostics.

Abstract Objective To evaluate effects of bone marrow sparing (BMS) radiotherapy on decreasing the incidence of acute hematologic toxicity (HT) for locoregionally advanced cervical cancer (LACC) patients treated by pelvic irradiation. Materials and methods LACC patients were recruited prospectively from May 2021 to May 2022 at a single center and were evenly randomized into the BMS group and the control group. All patients received pelvic irradiation with concurrent cisplatin (40 mg/m2 weekly), followed by brachytherapy and BM V40

Proteolysis targeting chimeras (PROTACs), as a novel therapeutic drug model, has received widespread attention from academia and the pharmaceutical industry. PROTAC technology has led researchers to focus on developing chemical biology tool properties due to the unique operating mechanism and protein dynamic regulatory properties. In recent years the rapid development of PROTAC technology has gradually made PROTACs an essential tool for target identification and validation. To further promote the application of PROTAC tools in drug discovery and basic medical science research, this review distinguished target identification and validation concepts. Furthermore, research progress in PROTAC technology was summarized.

Abstract Background The aim of this study was to investigate the clinical features of Nocardia infections, antibiotic resistance profile, choice of antibiotics and treatment outcome, among others. In addition, the study compared the clinical and microbiological characteristics of nocardiosis in bronchiectasis patients and non-bronchiectasis patients. Methods Detailed clinical data were collected from the medical records of 71 non-duplicate nocardiosis patients from 2017 to 2023 at a tertiary hospital in Zhengzhou, China. Nocardia isolates were identified to the species level using MALDI-TOF MS and 16S rRNA PCR sequencing. Clinical data were collected from medical records, and drug susceptibility was determined using the broth microdilution method. Results Of the 71 cases of nocardiosis, 70 (98.6%) were diagnosed as pulmonary infections with common underlying diseases including bronchiectasis, tuberculosis, diabetes mellitus and chronic obstructive pulmonary disease (COPD). Thirteen different strains were found in 71 isolates, the most common of which were N. farcinica (26.8%) and N. cyriacigeorgica (18.3%). All Nocardia strains were 100% susceptible to both TMP-SMX and linezolid, and different Nocardia species showed different patterns of drug susceptibility in vitro. Pulmonary nocardiosis is prone to comorbidities such as bronchiectasis, diabetes mellitus, COPD, etc., and Nocardia is also frequently accompanied by co-infection of the body with pathogens such as Mycobacterium and Aspergillus spp. Sixty-one patients underwent a detailed treatment regimen, of whom 32 (52.5%) received single or multi-drug therapy based on TMP-SMX. Bronchiectasis was associated with a higher frequency of Nocardia infections, and there were significant differences between the bronchiectasis and non-bronchiectasis groups in terms of age distribution, clinical characteristics, identification of Nocardia species, and antibiotic susceptibility (P

Alterations in the gut-microbiome-brain axis are increasingly being recognized to be involved in Alzheimer’s disease (AD) pathogenesis. However, the functional consequences of enteric dysbiosis linking gut microbiota and brain pathology in AD progression remain largely undetermined. The present work investigated the causal role of age-associated temporal decline in butyrate-producing bacteria and butyrate in the etiopathogenesis of AD. Longitudinal metagenomics, neuropathological, and memory analyses were performed in the 3×Tg-AD mouse model. Metataxonomic analyses showed a significant temporal decline in the alpha diversity marked by a decrease in butyrate-producing bacterial communities and a concurrent reduction in cecal butyrate production. Inferred metagenomics analysis identified the bacterial acetyl-CoA pathway as the main butyrate synthesis pathway impacted. Concomitantly, there was an age-associated decline in the transcriptionally permissive acetylation of histone 3 at lysines 9 and 14 (H3K9/K14-Ac) in hippocampal neurons. Importantly, these microbiome-gut-brain changes preceded AD-related neuropathology, including oxidative stress, tau hyperphosphorylation, memory deficits, and neuromuscular dysfunction, which manifest by 17–18 months. Initiation of oral administration of tributyrin, a butyrate prodrug, at 6 months of age mitigated the age-related decline in butyrate-producing bacteria, protected the H3K9/K14-Ac status, and attenuated the development of neuropathological and cognitive changes associated with AD pathogenesis. These data causally implicate age-associated decline in butyrate-producing bacteria as a key pathogenic feature of the microbiome-gut-brain axis affecting the onset and progression of AD. Importantly, the regulation of butyrate-producing bacteria and consequent butyrate synthesis could be a significant therapeutic strategy in the prevention and treatment of AD.

Abstract Novel active DNA transposons, such as Spy transposons from the PHIS superfamily, are identified through bioinformatics in this study. The native transposases cgSpy and cvSpy displayed transposition activities of approximately 85% and 35% compared to the hyperactive piggyBac transposase (hyPB). The cgSpy transposon showed unique characteristics, including a lack of overproduction inhibition and reduced efficiency for insertion sizes between 3.1 to 8.5 kb. Integration preferences of cgSpy are found in genes and regulatory regions, making it suitable for genetic manipulation. Evaluation in T‐cell engineering demonstrated that cgSpy‐mediated chimeric antigen receptor (CAR) modification is comparable to the PB system, indicating its potential utility in cell therapy. This study unveils the promising application of the active native transposase, Spy, from Colletes gigas, as a valuable tool for genetic engineering, particularly in T‐cell manipulation.

Objectives Limited evidence exists on the association of Pap test utilisation with comorbidity and functional impairment among middle-aged non-Hispanic black (NHB) women in the USA. We aimed to assess whether middle-aged NHB women with a higher burden of comorbidity and functional impairment have a lower rate of Pap test utilisation.Design Nationwide cross-sectional survey in the USA.Setting 2018 Behavioral Risk Factor Surveillance System.Participants 6359 middle-aged NHB women.Exposures and outcome The primary exposures were comorbidity and functional impairment. The outcome of interest was whether a woman reported having a Pap test in the last 3 years.Data analysis We fit unadjusted and multivariable logistic regression models to calculate ORs and 95% CI for comorbidity and functional impairment. Sensitivity analysis was restricted to women without a history of hysterectomy or cancer. We added interaction terms between exposures and age, as well as lifestyle indicators.Results Of the 6359 women, 4141 (65.1%) had comorbidity and 2429 (38.2%) had functional impairment. Middle-aged NHB women with comorbidity (≥2 vs 0, aOR=0.72, 95% CI=0.61 to 0.85, p trend0.05). However, the magnitude of these associations was stronger among women with adverse lifestyle factors (eg, comorbidity ≥2 v.s. 0, aOR=0.53, 95% CI=0.40, to 0.71; functional impairment ≥2 v.s. 0, aOR=0.35, 95% CI=0.16, to 0.72 among binge drinkers).Conclusion Comorbidity or functional impairment could be a potential barrier to Pap test utilisation among middle-aged NHB women in the USA. Our study highlights the importance of implementing targeted intervention programmes and prioritised health resource allocation to promote Pap test utilisation. Cohort studies with clear temporality and indicators reflecting disease severity will be essential for further understanding this association.

Cyanobacteria have great potential in CO2-based bio-manufacturing and synthetic biological studies. The filamentous cyanobacterium, Leptolyngbya sp. strain BL0902, is comparable to Arthrospira (Spirulina) platensis in commercial-scale cultivation while proving to be more genetically tractable. Here, we report the analyses of the whole genome sequence, gene inactivation/overexpression in the chromosome and deletion of non-essential chromosomal regions in this strain. The genetic manipulations were performed via homologous double recombination using either an antibiotic resistance marker or the CRISPR/Cpf1 editing system for positive selection. A desD-overexpressing strain produced γ-linolenic acid in an open raceway photobioreactor with the productivity of 0.36 g·m−2·d−1. Deletion mutants of predicted patX and hetR, two genes with opposite effects on cell differentiation in heterocyst-forming species, were used to demonstrate an analysis of the relationship between regulatory genes in the non-heterocystous species. Furthermore, a 50.8-kb chromosomal region was successfully deleted in BL0902 with the Cpf1 system. These results supported that BL0902 can be developed into a stable photosynthetic cell factory for synthesizing high value-added products, or used as a model strain for investigating the functions of genes that are unique to filamentous cyanobacteria, and could be systematically modified into a genome-streamlined chassis for synthetic biological purposes.

The Loess Plateau is marked by intense neotectonic activity and frequent earthquakes. Its unique physico-mechanical properties, combined with the granular overhead pore structure of loess, render it prone to seismic landslides triggered by strong earthquakes. Different types of loess seismic landslides have distinct formation mechanisms, disaster-causing characteristics, and risk assessment programs. In this study, the risk of seismic-collapsed loess landslides as one of the types of loess seismic landslides was evaluated on the Loess Plateau. A risk zoning map for seismic-collapsed loess landslides on the Loess Plateau, considering various exceedance probabilities, was compiled by assessing eight factors. These factors include peak ground acceleration, microstructure of loess, and were evaluated using both the minimum disaster-causing seismic peak ground acceleration zoning method and the analytic hierarchy process. The following conclusions were obtained: (1) Earthquakes are the primary inducing factor for seismic-collapsed loess landslides, with other factors serving as influencers, among which the microstructure of loess carries the highest weight; (2) Across various exceedance probabilities, the likelihood of seismic-collapsed loess landslides occurring at 63% of the 50-year exceedance probability is low. Moreover, as the minimum hazard-causing seismic peak ground acceleration increases, the risk of occurrence of seismic-collapsed loess landslides rises, leading to a gradual expansion of the area share in moderate and high-risk zones; (3) Hazard evaluation results align well with existing data on seismic-collapsed loess landslides and findings from field investigations. The case of seismic-collapsed loess landslides induced by the M6.2 magnitude earthquake in Jishishan County, China, is presented as an illustration. The combined use of the minimum hazard-causing seismic peak ground acceleration zoning method and the analytic hierarchy process method offers a reference for geohazard hazard assessment, with earthquakes as the primary inducing factor and other factors as influencers.

Abstract Background Right-side aortic arch concomitant with Kommerell’s diverticulum (KD) is a rare and complex ailment, and there is no consensus on the optimal strategy to deal with this congenital anomaly. We retrospectively analyzed and summary of the cases treated in our center with individual treatment methods for different situations. Methods Between September 2018 and December 2021, 10 patients experienced surgical therapy at our institution who presented with a Kommerell’s diverticulum arising from an aberrant subclavian artery from the right-side aortic arch. Four main surgical techniques were applied to those patients: 1. total arch replacement with frozen elephant trunk implantation (n = 2); 2. hybrid procedure combining open arch repair and endovascular intervention (n = 1); 3. total endovascular repair using thoracic endovascular aortic repair (TEVAR) with or without left subclavian artery (LSCA) revascularization (n = 6); 4. direct repair underwent endoaneurysmorrhaphy. Clinical characteristics and outcomes were collected. Results The mean age of these 10 patients was 56.5 years (range 29–79 years) and only 1 woman. The pathology includes aortic dissection (n = 6) and aneurysm (n = 4). The mean diverticulum size was 41.4 [24.2–56.8] mm. There were no in-hospital deaths, and the median hospital stay was 22 [15–43] days. During the follow-up period (21.4 months, 1–44 months), one died of an unknown cause and one died of esophageal fistula. Two patients underwent second-stage endovascular intervention for distal lesion. And none of the patients had endoleak during the follow-up period. Conclusions Each of the procedures we have mentioned here has its advantages and disadvantages; individualized treatment should meet the appropriate indications. A single-branched stent graft is feasible and effective in the treatment of aortic disease combined with Kommerell’s diverticulum.

Abstract Objective To use deep learning to segment the mandible and identify three-dimensional (3D) anatomical landmarks from cone-beam computed tomography (CBCT) images, the planes constructed from the mandibular midline landmarks were compared and analyzed to find the best mandibular midsagittal plane (MMSP). Methods A total of 400 participants were randomly divided into a training group (n = 360) and a validation group (n = 40). Normal individuals were used as the test group (n = 50). The PointRend deep learning mechanism segmented the mandible from CBCT images and accurately identified 27 anatomic landmarks via PoseNet. 3D coordinates of 5 central landmarks and 2 pairs of side landmarks were obtained for the test group. Every 35 combinations of 3 midline landmarks were screened using the template mapping technique. The asymmetry index (AI) was calculated for each of the 35 mirror planes. The template mapping technique plane was used as the reference plane; the top four planes with the smallest AIs were compared through distance, volume difference, and similarity index to find the plane with the fewest errors. Results The mandible was segmented automatically in 10 ± 1.5 s with a 0.98 Dice similarity coefficient. The mean landmark localization error for the 27 landmarks was 1.04 ± 0.28 mm. MMSP should use the plane made by B (supramentale), Gn (gnathion), and F (mandibular foramen). The average AI grade was 1.6 (min–max: 0.59–3.61). There was no significant difference in distance or volume (P > 0.05); however, the similarity index was significantly different (P

In modern high-density farming, seasonal change, fishing, transportation, and other conditions easily cause mechanical abrasion of fish skin. This leads to alterations in the material balance of the epidermal mucus composition of fish, preventing normal immune function. Subsequently, the risk of disease increases. In this study, grass carp (Ctenopharyngodon idella) was used as an object to investigate immune-related enzyme activities, structural characteristics, and physiological changes of its epidermal mucous cells caused by mechanical abrasion. Furthermore, we explored the changes in body surface mucus composition and microbial community diversity and structure. Our results showed that mechanical abrasion stimulation, significantly changed the activities of immune-related enzymes, such as lysozyme (LZM), alkaline phosphatase (AKP), and acid phosphatase (ACP) were within 24 h (P

BackgroundPostoperative acute kidney injury (PO-AKI) is a prevalent complication among patients with acute type A aortic dissection (aTAAD) for which unrecognized trajectories of renal function recovery, and their heterogeneity, may underpin poor success in identifying effective therapies.MethodsThis was a retrospective, single-center cohort study in a regional Great Vessel Center including patients undergoing aortic dissection surgery. Estimated glomerular filtration rate (eGFR) recovery trajectories of PO-AKI were defined through the unsupervised latent class mixture modeling (LCMM), with an assessment of patient and procedural characteristics, complications, and early-term survival. Internal validation was performed by resampling.ResultsA total of 1,295 aTAAD patients underwent surgery and 645 (49.8%) developed PO-AKI. Among the PO-AKI cohort, the LCMM identified two distinct eGFR trajectories: early recovery (ER-AKI, 51.8% of patients) and late or no recovery (LNR-AKI, 48.2% of patients). Binary logistic regression identified five critical determinants regarding poor renal recovery, including chronic kidney disease (CKD) history, renal hypoperfusion, circulation arrest time, intraoperative urine, and myoglobin. LNR-AKI was associated with increased mortality, continuous renal replacement therapies, mechanical ventilation, ICU stay, and hospital stay. The assessment of the predictive model was good, with an area under the curve (AUC) of 0.73 (95% CI: 0.69–0.76), sensitivity of 61.74%, and specificity of 75.15%. The internal validation derived a consistent average AUC of 0.73. The nomogram was constructed for clinicians' convenience.ConclusionOur study explored the PO-AKI recovery patterns among surgical aTAAD patients and identified critical determinants that help to predict individuals at risk of poor recovery of renal function.

The Uygur medicinal material Mesua ferrea L. has different plant sources in the market. The flower bud of Mammea siamensis T. Anders, which originated from Myanmar and Thailand, is actually used in the dosage room of Uygur hospitals and pharmaceutical enterprises in Xinjiang Region. On the contrary, flowers of Mesua ferrea L. are less frequently used. In this study, the taxonomic characteristics, liquid chromatography-mass spectrometry (LC/MS) and liquid chromatography (HPLC) were used to compare the similarities and differences between the two species. The results showed that the flowers of the two plants were significantly different in morphology, but the similarity of chemical components was high. At the same time, the study also found that Mesua ferrea L. and Mammea siamensis T. Anders contain a large amount of vitexin and isovitexin, which can be used for qualitative and quantitative research. This study provides a reference for the identification, development and utilization of Mesua ferrea L medicinal materials and the revision of quality standards.

(1) Background: In lung cancer, the use of small-molecule inhibitors, chemotherapy and immunotherapy has led to unprecedented survival benefits in selected patients. Considering most patients will experience a relapse within a short period of time due to single drug resistance, combination therapy is also particularly important to improve patient prognosis. Therefore, more robust biomarkers to predict responses to immunotherapy, targeted therapy, chemotherapy and rationally drug combination therapies may be helpful in clinical treatment choices. (2) Methods: We defined tumor-specific T cells (TSTs) and their features (TSTGs) by single-cell RNA sequencing. We applied LASSO regression to filter out the most survival-relevant TSTGs to form the Tumor-specific T cell score (TSTS). Immunological characteristics, enriched pathways, and mutation were evaluated in high- and low TSTS groups. (3) Results: We identified six clusters of T cells as TSTs in lung cancer, and four most robust genes from 9 feature genes expressed only on tumor-specific T cells were screened to construct a tumor-specific T cells score (TSTS). TSTS was positively correlated with immune infiltration and angiogenesis and negatively correlated with malignant cell proliferation. Moreover, potential vascular-immune crosstalk in lung cancer provides the theoretical basis for combined anti-angiogenic and immunotherapy. Noticeable, patients in high TSTS had better response to ICB and targeted therapy and patients in the low TSTS group often benefit from chemotherapy. (4) Conclusion: The proposed TSTS is a promising indicator to predict immunotherapy, targeted therapy and chemotherapy responses in lung cancer patients for helping clinical treatment choices.

Abstract Robustness and generalization are two challenging problems for learning point cloud representation. To tackle these problems, we first design a novel geometry coding model, which can effectively use an invariant eigengraph to group points with similar geometric information, even when such points are far from each other. We also introduce a large-scale point cloud dataset, PCNet184. It consists of 184 categories and 51,915 synthetic objects, which brings new challenges for point cloud classification, and provides a new benchmark to assess point cloud cross-domain generalization. Finally, we perform extensive experiments on point cloud classification, using ModelNet40, ScanObjectNN, and our PCNet184, and segmentation, using ShapeNetPart and S3DIS. Our method achieves comparable performance to state-of-the-art methods on these datasets, for both supervised and unsupervised learning. Code and our dataset are available at https://github.com/MingyeXu/PCNet184 .

Abstract Objective To compare the effectiveness of seven major interventions [Bulevirtide (BLV), Interferon (IFN), Nucleoside analogs (NAs), BLV + IFN, BLV + NAs, IFN + NAs, and Placebo] to treat chronic hepatitis D. Methods We followed PRISMA-NMA guidelines, searched databases (Cochrane Library, PubMed, EMBASE, and Web Of Science) for eligible randomized controlled trials (RCTs), and applied STATA17.0 software to execute the meta-analysis. Results We included 14 randomized controlled trials (814 patients) comparing seven different interventions. The results of the network meta-analysis showed that: ① Sustained virological response (after 24 weeks of follow-up): Four intervention groups (BLV + IFN, IFN alone, IFN + NAs, and NAs alone) were effective (relative risk (RR) = 13.30, 95% confidence interval (Cl) [1.68,105.32], RR = 12.13, 95% Cl [1.46,101.04], RR = 5.05, 95% Cl [1.68,15.19], RR = 5.03, 95% Cl [1.66,15.20]), with no statistically significant differences between the four groups. The top three in probability rankings were: BLV + NAs, BLV + IFN, and BLV alone (surface under the cumulative ranking curve (SUCRA) = 86.8%, 80.3%, and 48.4%; ② Sustained biochemical response (after 24 weeks of follow-up): BLV + IFN and IFN were superior to BLV (RR = 14.71, 95% Cl [1.14,189.07], RR = 16.67, 95% Cl [1.39,199.52]). The top three were BLV alone, BLV + NAs, and BLV + IFN (SUCRA = 86.9%,81.2%, and 64.3%). ③ Histological response: NAs were superior to BLV (RR = 2.08, 95% Cl [1.10,3.93]), whereas the difference between other treatment regimens was not statistically significant, and the top three in the probability ranking were BLV alone, BLV + NAs, and BLV + IFN (SUCRA = 75.6%, 75.6%, and 61.8%). Conclusions IFN, IFN + BLV, and IFN + NAs were effective in clearing HDV RNA and normalizing alanine aminotransferase levels; however, IFN and IFN + NAs had a high rate of viral relapse at 24 weeks post-treatment follow-up. There was no additional benefit of adding NAs to IFN therapy for chronic hepatitis D; however, the combination of IFN + BLV significantly improved short-term HDV RNA clearance, which showed strong synergistic effects. The seven regimens included in the study did not contribute significantly to liver histological improvement. Therefore, the IFN + BLV combination has the most potential as a treatment option to improve the long-term prognosis or even cure chronic hepatitis D. Trial registration This systematic evaluation and meta-analysis was registered with PROSPERO under the registration number: CRD42022314544.)

Abstract Background Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy with a poor prognosis. The underlying functions and mechanisms of circular RNA and SUMOylation in the development of ICC remain poorly understood. Methods Circular RNA hsa_circ_0001681 (termed Circ-RAPGEF5 hereafter) was identified by circular RNA sequencing from 19 pairs of ICC and adjacent tissue samples. The biological function of Circ-RAPGEF5 in tumor proliferation and metastasis was examined by a series of in vitro assays. A preclinical model was used to validate the therapeutic effect of targeting Circ-RAPGEF5. RNA pull-down and dual-luciferase reporter assays were used to access the RNA interactions. Western blot and Co-IP assays were used to detect SUMOylation levels. Results Circ-RAPGEF5, which is generated from exons 2 to 6 of the host gene RAPGEF5, was upregulated in ICC. In vitro and in vivo assays showed that Circ-RAPGEF5 promoted ICC tumor proliferation and metastasis, and inhibited apoptosis. Additionally, high Circ-RAPGEF5 expression was significantly correlated with a poor prognosis. Further investigation showed that SAE1, a potential target of Circ-RAPGEF5, was also associated with poor oncological outcomes. RNA pull-down and dual-luciferase reporter assays showed an interaction of miR-3185 with Circ-RAPGEF5 and SAE1. Co-IP and western blot assays showed that Circ-RAPGEF5 is capable of regulating SUMOylation. Conclusion Circ-RAPGEF5 promotes ICC tumor progression and SUMOylation by acting as a sponge for miR-3185 to stabilize SAE1. Targeting Circ-RAPGEF5 or SAE1 might be a novel diagnostic and therapeutic strategy in ICC.

Heavy metal ions such as cadmium, mercury, lead, and arsenic in the soil cannot be degraded naturally and are absorbed by crops, leading to accumulation in agricultural products, which poses a serious threat to human health. Therefore, establishing a rapid and efficient method for detecting heavy metal ions in agricultural products is of great significance to ensuring the health and safety. In this study, a novel optimized spectrometric method was developed for the rapid and specific colorimetric detection of cadmium ions based on N-(2-Acetamido)-iminodiacetic acid (ADA) and Victoria blue B (VBB) as the chromogenic unit. The safety evaluation of ADA showed extremely low biological toxicity in cultured cells and live animals. The standard curve is y = 0.0212x + 0.1723, R2 = 0.9978, and LOD = 0.08 μM (0.018 mg/kg). The liner concentrations detection range of cadmium is 0.1–10 μM. An inexpensive paper strip detection method was developed with a detection limit of 0.2 μM to the naked eye and a detection time of less than 1 min. The method was successfully used to assess the cadmium content of rice, soybean, milk, grape, peach, and cabbage, and the results correlated well with those determined by inductively coupled plasma–mass spectrometry (ICP-MS). Thus, our study demonstrated a novel rapid, safe, and economical method for onsite, real-time detection of cadmium ions in agricultural products.

A series of novel piperidamide-3-carboxamide derivatives were synthesized and evaluated for their inhibitory activities against cathepsin K. Among these derivatives, compound H-9 exhibited the most potent inhibition, with an IC50 value of 0.08 µM. Molecular docking studies revealed that H-9 formed several hydrogen bonds and hydrophobic interactions with key active-site residues of cathepsin K. In vitro, H-9 demonstrated anti-bone resorption effects that were comparable to those of MIV-711, a cathepsin K inhibitor currently in phase 2a clinical trials for the treatment of bone metabolic disease. Western blot analysis confirmed that H-9 effectively downregulated cathepsin K expression in RANKL-reduced RAW264.7 cells. Moreover, in vivo experiments showed that H-9 increased the bone mineral density of OVX-induced osteoporosis mice. These results suggest that H-9 is a potent anti-bone resorption agent targeting cathepsin K and warrants further investigation for its potential anti-osteoporosis values.

Objective To investigate the compatibility of human albumin and its internal packaging materials of Sinopharm Lanzhou Biopharmaceutical Co., Ltd. Methods One batch of inner packaging materials (medium borosilicate glass-molded injection bottle and halogenated butyl rubber plug for injection) was extracted with 4 extraction solvents to conduct the toxicological evaluation of potential inner packaging extracts. Through the simulated acceleration test, the trend analysis of the elements in the sample and the inner surface of the glass bottle were observed, and the routine drug inspection items during the long-term stability test process were determined. Results The detection results of the leaching elements of the internal packaging materials did not exceed the limit of 50%, and the organic matter safety threshold (margin of safety, MOS) was greater than 1.0, indicating that both the leaching elements and the organic matter had no safety risk to the user under the current exposure. The results of the simulated acceleration test show that the drug will not have the risk of peeling tablets after the long-term stability condition was placed for a period of time, and the routine inspection items of the long-term stability test drugs all meet the requirements of the pharmacopoeia. Conclusion The inner packaging material has no significant impact on the quality of drugs and has good overall compatibility, making it suitable for packaging human albumin.

Abstract Acquired resistance to chemotherapy is one of the major causes of mortality in advanced nasopharyngeal carcinoma (NPC). However, effective strategies are limited and the underlying molecular mechanisms remain elusive. In this study, through transcriptomic profiling analysis of 23 tumor tissues, we found that NOTCH3 was aberrantly highly expressed in chemoresistance NPC patients, with NOTCH3 overexpression being positively associated with poor clinical outcome. Mechanistically, using an established NPC cellular model, we demonstrated that enhancer remodeling driven aberrant hyperactivation of NOTCH3 in chemoresistance NPC. We further showed that NOTCH3 upregulates SLUG to induce chemo-resistance of NPC cells and higher expression of SLUG have poorer prognosis. Genetic or pharmacological perturbation of NOTCH3 conferred chemosensitivity of NPC in vitro and overexpression of NOTCH3 enhanced chemoresistance of NPC in vivo. Together, these data indicated that genome-wide enhancer reprogramming activates NOTCH3 to confer chemoresistance of NPC, suggesting that targeting NOTCH3 may provide a potential therapeutic strategy to effectively treat advanced chemoresistant NPC.

Long non-coding RNAs (lncRNAs) participate in acute lung injury (ALI). However, their latent biological function and molecular mechanism have not been fully understood. In the present study, the global expression profiles of lncRNAs and mRNAs between the control and lipopolysaccharide (LPS)-stimulated groups of human normal lung epithelial cells (BEAS-2B) were determined using high-throughput sequencing. Overall, a total of 433 lncRNAs and 183 mRNAs were differentially expressed. A lncRNA–mRNA co-expression network was established, and then the top 10 lncRNAs were screened using topological methods. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis results showed that the key lncRNAs targeting mRNAs were mostly enriched in the inflammatory-related biological processes. Gene set variation analysis and Pearson’s correlation coefficients confirmed the close correlation for the top 10 lncRNAs with inflammatory responses. A protein–protein interaction network analysis was conducted based on the key lncRNAs targeting mRNAs, where IL-1β, IL-6, and CXCL8 were regarded as the hub genes. A competing endogenous RNA (ceRNA) modulatory network was created with five lncRNAs, thirteen microRNAs, and twelve mRNAs. Finally, real-time quantitative reverse transcription-polymerase chain reaction was employed to verify the expression levels of several key lncRNAs in BEAS-2B cells and human serum samples.

Abstract Background Sleep problems and cognitive changes are typical in pregnant women with depressive symptoms. However, the relationship between sleep quality and executive dysfunction remains unclear. This study aims to explore the differences in sleep quality and cognitive inhibition between pregnant women with and without depressive symptoms in the third trimester of pregnancy and investigate the correlations between sleep quality, cognitive inhibition and depressive symptoms. Methods In the third trimester, 169 women without depressive symptoms and 88 women with depressive symptoms participated in the study. Edinburgh Postpartum Depression Questionnaire (EPDS) was used to assess depressive symptoms, and Pittsburgh Standard Sleep Quality Index Questionnaire (PSQI) was used to investigate sleep quality. The color-word Stroop task is used to evaluate cognitive inhibition. Results Compared with women without depressive symptoms, pregnant women with depressive symptoms showed worse sleep quality and Stroop task performances (response speed and accuracy). In addition, the speed of cognitive inhibition plays a mediating role in the relationship between sleep quality and prenatal depressive symptoms. Conclusion This research emphasizes the importance of sleep quality screening and cognitive training for depression during pregnancy and childbirth in ensuring women’s mental health during pregnancy and childbirth.

Abstract The extensive usage and production of copper may lead to toxic effects in organisms due to its accumulation in the environment. Traditional methods for copper detection are time consuming and infeasible for field usage. It is necessary to discover a real-time, rapid and economical method for detecting copper to ensure human health and environmental safety. Here we developed a colorimetric paper strip method and optimized spectrum method for rapid detection of copper ion based on the specific copper chelator bathocuproinedisulfonic acid disodium salt (BCS). Both biological assays and chemical methods verified the specificity of BCS for copper. The optimized reaction conditions were 50 mM Tris–HCl pH 7.4, 200 µM BCS, 1 mM ascorbate and less than 50 µM copper. The detection limit of the copper paper strip test was 0.5 mg/L by direct visual observation and the detection time was less than 1 min. The detection results of grape, peach, apple, spinach and cabbage by the optimized spectrum method were 0.91 μg/g, 0.87 μg/g, 0.19 μg/g, 1.37 μg/g and 0.39 μg/g, respectively. The paper strip assays showed that the copper contents of grape, peach, apple, spinach and cabbage were 0.8 mg/L, 0.9 mg/L, 0.2 mg/L, 1.3 mg/L and 0.5 mg/L, respectively. These results correlated well with those determined by inductively coupled plasma-mass spectrometry (ICP-MS). The visual detection limit of the paper strip based on Cu-BCS-AgNPs was 0.06 mg/L. Our study demonstrates the potential for on-site, rapid and cost-effective copper monitoring of foods and the environment.

Abstract Background Preimplantation genetic testing (PGT) for monogenic disorders (PGT-M) for germline mosaicism was previously highly dependent on polymerase chain reaction (PCR)-based directed mutation detection combined with linkage analysis of short tandem repeats (STRs). However, the number of STRs is usually limited. In addition, designing suitable probes and optimizing the reaction conditions for multiplex PCR are time-consuming and laborious. Here, we evaluated the effectiveness of next generation sequencing (NGS)-based haplotype linkage analysis in PGT of germline mosaicism. Methods PGT-M with NGS-based haplotype linkage analysis was performed for two families with maternal germline mosaicism for an X-linked Duchenne muscular dystrophy (DMD) mutation (del exon 45–50) or an autosomal TSC1 mutation (c.2074C > T). Trophectoderm biopsy and multiple displacement amplification (MDA) were performed for a total of nine blastocysts. NGS and Sanger sequencing were performed in genomic DNA of family members and embryonic MDA products to detect DMD deletion and TSC1 mutation, respectively. Single nucleotide polymorphism (SNP) sites closely linked to pathogenic mutations were detected with NGS and served in haplotype linkage analysis. NGS-based aneuploidy screening was performed for all embryos to reduce the risk of pregnancy loss. Results All nine blastocytes showed conclusive PGT results. Each family underwent one or two frozen-thawed embryo transfer cycles to obtain a clinical pregnancy, and the prenatal diagnosis showed that the fetus was genotypically normal and euploid for both families. Conclusions NGS-SNP could effectively realize PGT for germline mosaicism. Compared with PCR-based methods, the NGS-SNP method with increased polymorphic informative markers can achieve a greater diagnostic accuracy. Further studies are warranted to verify the effectiveness of NGS-based PGT of germline mosaicism cases in the absence of surviving offsprings.

BackgroundFollowing the COVID-19 pandemic, another large-scale respiratory epidemic has emerged in China, causing significant social impact and disruption. The article is to explore the patients’ psychological and behavioral responses to the enhancement of healthcare quality.MethodsBased on the five dimensions of the Self-Regulation Common-Sense Model, we developed an interview outline to explore the process by which patients identify disease symptoms to guide action plans and coping strategies. The researchers used a semi-structured interview format to simultaneously collect data online and offline. This study gathered data from 12 patients with mixed respiratory infections, comprising 58% females and 42% males; the average age was 30.67 years (SD 20.00), with 91.7% infected with two pathogens and 8.3% with three. The data analysis employed the KJ method, themes were inductively analyzed and categorized from semi-structured interview results, which were then organized into a coherent visual and logical pathway.Key resultsThe study identified 5 themes: (1) Autonomous Actions Prior to Seeking Medical Care; (2) Decision-Making in Seeking Hospital Care; (3) Disease Shock; (4) Public Crisis Response; (5) Information Cocoon.ConclusionThe pandemic of respiratory infectious diseases has not ceased in recent years. Following the COVID-19 pandemic, China is now facing a trend of concurrent epidemics involving multiple respiratory pathogens. This study centers on patients’ health behaviors, exploring the potential relationships among various factors that affect these behaviors. The aim is to provide references and grounds for the improvement of healthcare services when such public health events reoccur.

Objective: To investigate and analyse the quality of life (QoL) of patients with chronic kidney disease (CKD) undergoing maintenance haemodialysis (MHD), explore influencing factors and provide a basis for formulating corresponding intervention measures. Methods: A cross-sectional study was conducted on 190 patients with CKD undergoing MHD in hospital between March 2021 and March 2022. A general information questionnaire and the Kidney Disease Quality of Life Short Form were used to collect data. The QoL scores of patients with CKD undergoing MHD were calculated and compared by t-test and analysis of variance. Pearson correlation analysis was used to analyse the correlation between QoL scores and related factors. Stepwise multiple linear regression analysis was used to screen the influencing factors of QoL. Results: The total score of QoL of patients with CKD undergoing MHD was 59.32 ± 11.67, and the scores of physical component summary, mental component summary and kidney disease component summary were 50.21 ± 9.32, 48.76 ± 10.81 and 66.34 ± 12.76, respectively. The QoL scores of patients with CKD undergoing MHD were significantly different in age, education level, marital status, employment status, monthly income, dialysis frequency, dialysis duration and complications (p

BackgroundIt is well established that females are more susceptible to the toxic effects of alcohol, although the exact mechanisms are still poorly understood. Previous studies noted that alcohol reduces the expression of mitogen-activated protein kinase phosphatase 1 (MKP1), a negative regulator of mitogen-activated protein kinases (MAPK) in the liver. However, the role of hepatocyte- specific MKP1 in the pathogenesis of alcohol-associated liver disease (ALD) remains uncharacterized. This study aimed to evaluate the role of hepatocyte-specific MKP1 in the susceptibility and sexual dimorphism in alcohol-induced liver injury.MethodsC57Bl/6 mice were used in an intragastric ethanol feeding model of alcohol-associated steatohepatitis (ASH). Hepatocyte-specific Mkp1-/- knockout and (Mkp1+/+ “f/f” male and female mice were subjected to the NIAAA chronic plus binge model. Primary mouse hepatocytes were used for in vitro studies. Liver RNA sequencing was performed on an Illumina NextSeq 500. Liver injury was evaluated by plasma alanine transaminase (ALT), hepatic ER stress and inflammation markers. Statistical analysis was carried out using ANOVA and the unpaired Student’s t-test.ResultsASH was associated with the severe injury accompanied by increased endoplasmic reticulum (ER) stress and significant downregulation of Dusp1 mRNA expression. In vitro, ethanol treatment resulted in a time-dependent decrease in Dusp1 mRNA and protein expression in primary hepatocytes in both males and females; however, this effect was significantly more pronounced in hepatocytes from females. In vivo, female mice developed more liver injury in a chronic plus binge model which was accompanied by a significant decrease in liver Dusp1 mRNA expression. In comparison, liver Dusp1 was not changed in male mice, while they developed milder injury to alcohol. Mkp1 deletion in hepatocytes led to increased alcohol induced liver injury, ER stress and inflammation in both sexes.ConclusionHepatocyte Mkp1 plays a significant role in alcohol induced liver injury. Alcohol downregulates Mkp1 expression in hepatocytes in a sex dependent manner and could play a role in sexual dimorphism in increased female susceptibility to alcohol.

Summary: Lung adenocarcinoma (LUAD) is one of the leading causes of cancer-related death worldwide. Epithelial-mesenchymal transition (EMT) plays an important role in malignant tumor progression. Recently, accumulating evidence has shown that autophagy is involved in the regulation of EMT-induced migration. Therefore, the exploration of targets to inhibit EMT by targeting autophagy is important. In this study, we found that OVO-like zinc finger 2 (OVOL2) may be a key target for regulating autophagy-induced EMT. Firstly, we found that OVOL2 expression was dramatically downregulated in LUAD. Low expression of OVOL2 is an indicator of poor prognosis in LUAD. In vitro experiments have shown that downregulation of OVOL2 expression induces EMT, thereby promoting malignant biological behavior, such as proliferation, migration, and invasion of LUAD cells. Interestingly, autophagy is a key step in regulating OVOL2 and inducing EMT. Furthermore, OVOL2 regulates autophagy through the MAPK signaling pathway, ultimately inhibiting the malignant progression of LUAD.

Surface harmless storage of concentrated full tailings (CFTs) involves the technology of adding a curing agent to the tailings slurry discharged from the thickener to realize the modification of the tailings and centralized storage of the tailings on the surface to realize the harmless treatment of the tailings. High water content of tailings is still the key technical problem that restricts the harmless storage of piles at present. Regarding the above problems, we implemented the consolidation test and numerical simulation of seepage-stress coupling consolidation of CFT, clarified the consolidation characteristics and parameters of CFT under different curing ages, and conducted a comparative analysis of pore water pressure in the whole cross-section of piles with different drainage schemes based on the results of the test. In addition, we also clarified the drainage effect of interlayer drainage on reducing the excess pore water pressure of piles and compared the simulation results of the pore water pressure of piles under different permeability coefficients. The results show that as the permeability coefficient of the concentrated tailings material decreases, the pore pressure accumulation inside piles under the same drainage scheme is more serious, and the length of time for consolidation and stabilization becomes longer. Therefore, it is recommended that the excess porous water pressure be relieved by means of increased drainage facilities under a small permeability coefficient.

Hotpot provides a multilevel unique flavor experience and is preferred by consumers who value various taste preferences. In the present study, results showed that alcohols, phenols, hydrocarbons, and others were the commonly predominant volatiles in all butter hotpot samples (74.43%∼92.92%). However, there were merely 25 codetected compounds determined among a total of 318 aroma compounds because of the discrepant ingredients and processing technique of hotpot samples, which were sampled from several representative manufacturers. Therefore, for the first time, multiple GC-Q-TOF/MS and GC-Orbitrap-MS methods were performed to explore the more 44 potential aroma compounds of butter hotpot, in which alpha-terpinyl, acetate, nonanal, piperitone, and (E)-lignstilde could further cause the differences in flavor intensity of spices aroma, smell of grease, and roasted, charred, and nutty (p

Recent advancements in comprehending the properties of low-temperature plasmas (LTPs) have spurred the creation of plasma medicine. Nonetheless, there exists limited scientific evidence concerning its mechanism of impeding proliferative scarring. This study aims to investigate the role of LTPs in hypertrophic scar (HS) formation. Establishing rabbit ear scar models, two groups were individually treated with salvianolic acid B (SAB) gel and low-temperature plasmas for six weeks, while the control group was not treated. The expression levels of cytokines, including TGF-β1, p-Smad3, and MMP-2, in rabbit serum were assessed using ELISA in this study. Additionally, hematoxylin-eosin staining and Masson’s trichrome staining were conducted on proliferative scar tissue to observe the arrangement of collagen fibers and determine the density of fibroblasts. Immunohistochemical analysis was also performed to obtain the percentage of type I collagen and α-SMA positive expression area. The findings indicated that the scars in both the SAB and LTP groups were narrower than those in the model group. The scar tissues treated with LTP or SAB showed a lower level of TGF-β1 and p-Smad3. In addition, α-SMA was significantly reduced in the LTP-treated group. Furthermore, the type I collagen expression was lower in the LTP group. These results suggest that LTP could have a comparable effect to SAB in hindering the development of HSs. It could potentially enhance skin scarring by impeding collagen deposition and fibroblast proliferation in HSs via the TGF-β/Smad signaling pathway. This investigation may provide a new perspective on HS treatment.

ABSTRACT Treponema pallidum (T. pallidum), the pathogen of syphilis, can invade organisms through mucous membranes or broken skin and proliferate in the host. It spreads rapidly and causes chronic systemic multi-organ damage. Currently, the invasion and pathogenesis of T. pallidum remain a mystery. In this study, we established a T. pallidum infection model in New Zealand rabbits, and the T. pallidum burden in various tissues and organs was detected to investigate the dynamic spread of T. pallidum in different organs. Our results indicated that the T. pallidum burden in rabbits was in a cyclic and repeated dynamic process of decreasing and increasing after infection. In addition, the localization of lipoprotein Tp0971 was confirmed by using the gel microdroplet method. We found that Tp0971 might be a membrane lipoprotein that exists in the inner and outer membranes of T. pallidum. The immune-protective effect of the T. pallidum infection-dependent antigen Tp0971 was evaluated. Tp0971/CpG can induce high levels of Tp0971-specific antibodies, delay skin damage, and promote healing at the infected sites of T. pallidum in New Zealand rabbits. This indicated that Tp0971 may serve as a vaccine antigen candidate. Our results provide new ideas for future research on the proliferation, spread mechanism, and vaccine development of T. pallidum. IMPORTANCE The past two decades have seen a worldwide resurgence in infections caused by Treponema pallidum (T. pallidum) subsp. pallidum, the syphilis spirochete. The well-recognized capacity of the syphilis spirochete for early dissemination and immune evasion has earned it the designation “the stealth pathogen.” There are many hurdles to studying syphilis pathogenesis, most notably the difficulty of culturing and genetically manipulating T. pallidum, as well as the absence of an effective vaccine for T. pallidum prevention. T. pallidum infection in humans is a complex and lengthy process. In this study, we investigated the invasion process and the function of the infection-dependent antigen Tp0971 as an immunogen to inhibit the dissemination of T. pallidum in an animal infection model. This enables a better understanding of the specific pathogenic mechanism of this pathogen, syphilis pathogenesis, and vaccine research.

The aim of this study was to explore the relationship between two genetic variants (rs2275913 and rs3748067) of interleukin-17A (IL-17A) and the risk of ovarian endometriosis in northern Chinese women. This study was performed in 316 patients with ovarian endometriosis and 328 female control subjects. The genotypes of the two polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The mRNA expression of IL-17A was detected by quantitative real-time PCR (qRT-PCR). There was a significant difference in the genotype distributions of the rs2275913 polymorphism between the patients and control subjects (p = .006). Compared with the GG genotype of rs2275913, the AA genotype was correlated with a higher susceptibility to the development of ovarian endometriosis (OR = 2.28, 95% confidence interval (CI) = 1.37–3.80). Furthermore, the levels of IL-17A mRNA were higher in the ectopic endometrium from ovarian endometriosis patients carrying the rs2275913 AA genotype than in those carrying the rs2275913 GG genotype (p = .007). This study suggested that the rs2275913 polymorphism at the promoter region of IL-17A may be a functional genetic variant, and the rs2275913 AA genotype is associated with a higher risk of developing ovarian endometriosis in northern Chinese women.IMPACT STATEMENT What is already known on this subject? Interleukin-17A (IL-17A) is a crucial proinflammatory and angiogenic cytokine that has been shown to participate in the pathogenesis of chronic inflammatory and autoimmune diseases. Genetic variants in IL-17A may alter the expression of the IL-17A, and are associated with the susceptibility to a wide range of human diseases. What do the results of this study add? This study suggested that the rs2275913 polymorphism at the promoter region of IL-17A may be a functional genetic variant that affects the expression of IL-17A mRNA in ectopic endometrial tissues. The AA genotype of rs2275913 was associated with a higher risk of developing ovarian endometriosis in northern Chinese women. What are the implications of these findings for clinical practice and/or further research? IL-17A may be a potential biomarker for early diagnosis and gene-targeted therapy of ovarian endometriosis.