Mediating effects of BMI on the association between DNA methylation regions and 24-h blood pressure in African Americans.

BACKGROUND: DNA methylation is an important epigenetic mechanism that may influence blood pressure (BP) regulation and hypertension risk. Obesity, a major lifestyle factor associated with hypertension, may interact with DNA methylation to affect BP. However, the indirect effect of DNA methylation on 24-hBP measurements mediated by obesity-related phenotypes such as BMI has not been investigated. METHODS: Causal mediation analysis was applied to examine the mediating role of BMI in the relation between DNA methylation and 24-h BP phenotypes, including SBP, DBP and mean arterial blood pressure (MAP), in 281 African American participants. RESULTS: Analysis of 38 215 DNA methylation regions, derived from 1,549,368 CpG sites across the genome, identified up to 138 methylation regions that were significantly associated with 24-h BP measurements through BMI mediation. Among them, 38 (19.2%) methylation regions were concurrently associated with SBP, DBP and MAP. Genes associated with BMI-mediated methylation regions are potentially involved in various chronic diseases such as coronary artery disease and renal disease, which are often caused or exacerbated by hypertension. Notably, three genes (CDH4, NOTCH1 and COLGALT1) showed both direct associations with 24-h BP measurements and indirect associations through BMI after adjusting for age and sex covariates. CONCLUSION: Our findings suggest that DNA methylation may contribute to the regulation of 24-h BP in African Americans both directly and indirectly through BMI mediation.

Assessment of environmental exposure to betamethasone on the reproductive function of female Japanese medaka (Oryzias latipes).

Betamethasone has been extensively used in medicine in recent years and poses potential hazards to aquatic organisms. This study investigated the reproductive toxic effects of betamethasone exposure in fish, employing female Japanese medaka (Oryzias latipes) as a model. Betamethasone exposure at environmentally relevant concentrations (0, 20, 200, and 2000 ng/L) for a period of 15 weeks resulted in its high accumulation in the ovary, leading to abnormal oogenesis in female Japanese medaka. The production of gonadotropins (LH and FSH) in the pituitary gland was inhibited, and sex steroid biosynthesis in the ovary was significantly influenced at the transcriptional level. The imbalance of androgens and estrogens resulted in a decrease in the E2/T ratio and hepatic VTG synthesis, and the suppression of estrogen receptor signaling was also induced. Furthermore, betamethasone exposure delayed spawning and reduced fertility in the F0 generation, and had detrimental effects on the fertilization rate and hatchability of the F1 generation. Our results showed that environmental betamethasone had the potential to adversely affect female fertility and steroid hormone dynamics in fish.

Acetylation-dependent deubiquitinase USP26 stabilizes BAG3 to promote breast cancer progression.

Deubiquitylases (DUBs) have emerged as promising targets for cancer therapy due to their role in stabilizing substrate proteins within the ubiquitin machinery. Here, we identified ubiquitin-specific protease 26 (USP26) as an oncogene via screening prognostic DUBs in breast cancer. Through in vitro and in vivo experiments, we found that depletion of USP26 inhibited breast cancer cell proliferation and invasion, and suppressed tumor growth and metastasis in nude mice. Further investigation identified co-chaperone Bcl-2-associated athanogene 3 (BAG3) as the direct substrate of USP26, and ectopic expression of BAG3 partially reversed antitumor effect induced by USP26 knockdown. Mechanistically, the lysine acetyltransferase Tip60 targeted USP26 at K134 for acetylation, which enhanced USP26 binding affinity to BAG3, leading to BAG3 deubiquitination and increased protein stability. Importantly, we employed a structure-based virtual screening and discovered a drug-like molecule called 5813669 that targets USP26, destabilizing BAG3 and effectively mitigating tumor growth and metastasis in vivo. Clinically, high expression levels of USP26 were correlated with elevated BAG3 levels and poor prognosis in breast cancer patients. Overall, our findings highlight the critical role of USP26 in BAG3 protein stabilization and provide a promising therapeutic target for breast cancer.

Haploid identification in maize.

Doubled haploid (DH) line production through in vivo maternal haploid induction is widely adopted in maize breeding programs. The established protocol for DH production includes four steps namely in vivo maternal haploid induction, haploid identification, genome doubling of haploid, and self-fertilization of doubled haploids. Since modern haploid inducers still produce relatively small portion of haploids among undesirable hybrid kernels, haploid identification is typically laborious, costly, and time-consuming, making this step the second foremost in the DH technique. This manuscript reviews numerous methods for haploid identification from different approaches including the innate differences in haploids and diploids, biomarkers integrated in haploid inducers, and automated seed sorting. The phenotypic differentiation, genetic basis, advantages, and limitations of each biomarker system are highlighted. Several approaches of automated seed sorting from different research groups are also discussed regarding the platform or instrument used, sorting time, accuracy, advantages, limitations, and challenges before they go through commercialization. The past haploid selection was focusing on finding the distinguishable marker systems with the key to effectiveness. The current haploid selection is adopting multiple reliable biomarker systems with the key to efficiency while seeking the possibility for automation. Fully automated high-throughput haploid sorting would be promising in near future with the key to robustness with retaining the feasible level of accuracy. The system that can meet between three major constraints (time, workforce, and budget) and the sorting scale would be the best option.

Fine mapping of major QTL qshgd1 for spontaneous haploid genome doubling in maize (Zea mays L.).

KEY MESSAGE: A large-effect QTL was fine mapped, which revealed 79 gene models, with 10 promising candidate genes, along with a novel inversion. In commercial maize breeding, doubled haploid (DH) technology is arguably the most efficient resource for rapidly developing novel, completely homozygous lines. However, the DH strategy, using in vivo haploid induction, currently requires the use of mutagenic agents which can be not only hazardous, but laborious. This study focuses on an alternative approach to develop DH lines-spontaneous haploid genome duplication (SHGD) via naturally restored haploid male fertility (HMF). Inbred lines A427 and Wf9, the former with high HMF and the latter with low HMF, were selected to fine-map a large-effect QTL associated with SHGD-qshgd1. SHGD alleles were derived from A427, with novel haploid recombinant groups having varying levels of the A427 chromosomal region recovered. The chromosomal region of interest is composed of 45 megabases (Mb) of genetic information on chromosome 5. Significant differences between haploid recombinant groups for HMF were identified, signaling the possibility of mapping the QTL more closely. Due to suppression of recombination from the proximity of the centromere, and a newly discovered inversion region, the associated QTL was only confined to a 25 Mb region, within which only a single recombinant was observed among ca. 9,000 BC1 individuals. Nevertheless, 79 gene models were identified within this 25 Mb region. Additionally, 10 promising candidate genes, based on RNA-seq data, are described for future evaluation, while the narrowed down genome region is accessible for straightforward introgression into elite germplasm by BC methods.

Classification of exercise fatigue levels by multi-class SVM from ECG and HRV.

Among the various physiological signals, electrocardiogram (ECG) is a valid criterion for the classification of various exercise fatigue. In this study, we combine features extracted by deep neural networks with linear features from ECG and heart rate variability (HRV) for exercise fatigue classification. First, the ECG signals are converted into 2-D images by using the short-term Fourier transform (STFT), and image features are extracted by the visual geometry group (VGG) . The extracted image and linear features of ECG and HRV are sent to the different types of classifiers to distinguish distinct exercise fatigue level. To validate performance, the proposed methods are tested on (i) an open-source EPHNOGRAM dataset and (ii) a self-collected dataset (n = 51). The results reveal that the classification based on the concatenated features has the highest accuracy, and the calculation time of the system is also significantly reduced. This demonstrates that the proposed novel hybrid approach can be used to assist in improving the accuracy and timeliness of exercise fatigue classification in a real-time exercise environment. The experimental results show that the proposed method outperforms other recent state-of-the-art methods in terms of accuracy 96.90%, sensitivity 96.90%, F1-score of 0.9687 in EPHNOGRAM and accuracy 92.17%, sensitivity 92.63%, F1-score of 0.9213 in self-collected dataset.

The nematode Caenorhabditis elegans enhances tolerance to landfill leachate stress by increasing trehalose synthesis.

The burgeoning issue of landfill leachate, exacerbated by urbanization, necessitates evaluating its biological impact, traditionally overshadowed by physical and chemical assessments. This study harnesses Caenorhabditis elegans, a model organism, to elucidate the physiological toxicity of landfill leachate subjected to different treatment processes: nanofiltration reverse osmosis tail water (NFRO), membrane bioreactor (MBR), and raw leachate (RAW). Our investigation focuses on the modulation of sugar metabolism, particularly trehalose-a disaccharide serving dual functions as an energy source and an anti-adversity molecule in invertebrates. Upon exposure, C. elegans showcased a 60-70% reduction in glucose and glycogen levels alongside a significant trehalose increase, highlighting an adaptive response to environmental stress by augmenting trehalose synthesis. Notably, trehalose-related genes in the NFRO group were up-regulated, contrasting with the MBR and RAW groups, where trehalose synthesis genes outpaced decomposition genes by 20-30 times. These findings suggest that C. elegans predominantly counters landfill leachate-induced stress through trehalose accumulation. This research not only provides insights into the differential impact of leachate treatment methods on C. elegans but also proposes a molecular framework for assessing the environmental repercussions of landfill leachate, contributing to the development of novel strategies for pollution mitigation and environmental preservation.

Triblock PolyA-Mediated Protein Biosensor Based on a Size-Matching Proximity Hybridization Analysis.

The antibodies in the natural biological world utilize bivalency/multivalency to achieve a higher affinity for antigen capture. However, mimicking this mechanism on the electrochemical sensing interface and enhancing biological affinity through precise spatial arrangement of bivalent aptamer probes still pose a challenge. In this study, we have developed a novel self-assembly layer (SAM) incorporating triblock polyA DNA to enable accurate organization of the aptamer probes on the interface, constructing a "lock-and-key-like" proximity hybridization assay (PHA) biosensor. The polyA fragment acts as an anchoring block with a strong affinity for the gold surface. Importantly, it connects the two DNA probes, facilitating one-to-one spatial proximity and enabling a controllable surface arrangement. By precisely adjusting the length of the polyA fragment, we can tailor the distance between the probes to match the molecular dimensions of the target protein. This design effectively enhances the affinity of the aptamers. Notably, our biosensor demonstrates exceptional specificity and sensitivity in detecting PDGF-BB, as confirmed through successful validation using human serum samples. Overall, our biosensor presents a novel and versatile interface for proximity assays, offering a significantly improved surface arrangement and detection performance.

Does the neighborhood built and social environment reduce long-term care costs for Japanese older people? The JAGES2010-2019 cohort study.

Japan's population has been aging steadily, evidenced by it spending JPY 11 trillion (USD 110 billion) on annual long-term care (LTC) costs in 2021. In this context, understanding the factors influencing LTC costs has become increasingly vital. Although studies have reported positive relationships between neighborhood environment and health outcomes, the connection between LTC costs and neighborhood environment remains unclear. To address this gap in the literature, this cohort study, conducted from 2010 to 2019 across seven Japanese municipalities and involving 34,982 older people, examined the relationship between eight neighborhood environment elements and the mean monthly cumulate costs (MMCC) of LTC. The results showed that older people who reported the presence of fresh food stores nearby and dangerous places for walking alone at night in the neighborhood had lower MMCC, by JPY 1,367.6 and 1,383.3 per month, respectively, than respondents who did not report the presence of these neighborhood elements. Meanwhile, older people whose neighborhoods had easily accessible facilities had higher MMCC of JPY 739.4. This study's key findings reveal significant relationships between neighborhood environment elements and LTC costs and can be used to support developments in urban design to support healthy aging and reduced LTC costs.

Taking spontaneous plants as a natural strategy for vegetation restoration in construction and demolition waste landfills: a case study in Suzhou, China.

Construction and demolition waste (CDW) landfills around the city have caused serious damage to the ecological environment and menaced the public health. Restoration of closed CDW landfills is critical to compensate for the degraded ecosystem and ensure safety in further development and utilization. Vegetation restoration is an essential part of the restoration of CDW landfills, in which the use of spontaneous plants is the foundation of the nature-based strategy. In this study, Fenghuangshan CDW landfill in Suzhou, China, was selected as the research site, and the species composition and diversity of the spontaneous plants were analyzed. Moreover, the types of habitats and growth indexes of 8 species with high frequency and 18 species with medium frequency in the CDW landfill were investigated, and a comprehensive evaluation of growth rate and expansion capacity of the 26 species was conducted. The results showed that, herbs were the main type of the spontaneous plants in the CDW landfill. The species and quantities of the spontaneous plants in the CDW landfill were obviously fewer than those in the surrounding areas of the CDW landfill, and the Shannon-Wiener index and Pielou index of the spontaneous plants were lower compared with the surrounding areas of the CDW landfill. Meanwhile, the differences of dominant families and the distribution of origins, life forms and growth types between these two fields were insignificant. The heliophilous and drought tolerance species were widely distributed in the CDW landfill while the shade-tolerant or hygrophilous species were few. The relatively large comprehensive evaluation indexes of Elymus dahuricus, Daucus carota, Sonchus asper, Geranium carolinianum, Rumex acetosa, Metaplexis japonica, Carex breviculmis, Erigeron canadensis, Trigonotis peduncularis, Lamium amplexicaule reflected their high growth rates and strong expansion capacity, demonstrating their great potentiality in the vegetation restoration of CDW landfills as indispensable components of the nature-based solution.

Double layered asymmetrical hydrogels enhanced by thermosensitive microgels for high-performance mechanosensors and actuators.

Thermosensitive hydrogels have found extensive applications in soft devices, but they often suffer from limited functionalities, low response rate and small response amplitude. In this work, double layered asymmetrical hydrogels composed of a thermosensitive layer and a non-thermosensitive layer are developed to simultaneously achieve high-performance mechanosensing and actuating properties in a single hydrogel. In thermosensitive layer, thermosensitive microgels are introduced to construct hierarchical structure, which accounts for the enhanced thermosensitive behaviors by cooperative responsiveness. In non-thermosensitive layer, poly(acrylamide-co-acrylic acid) (P(AM-co-AA)) hydrogel is constructed. KCl is introduced as conductive component. Mechanosensors for monitoring various mechanical stimuli in daily life have been fabricated utilizing such hydrogels and high gauge factors (GF) have been achieved, 0.38 for resistive strain sensors, 9.40 kPa-1 for piezoresistive pressure sensors and 3.92 kPa-1 for capacitive pressure sensors. Because of the asymmetrical structure, such hydrogels also exhibit outstanding actuating properties with a fast response rate of 863°/min and a bending amplitude about 360°. Interestingly, grasping-releasing of target objects utilizing an octopus-shaped hydrogel actuator and temperature alerting based on hydrogel actuator are also demonstrated. Overall, the double layered asymmetrical ionic hydrogels have provided a new clue to construct hydrogel devices with multiple functionalities and enhanced response properties.

Use of municipal solid waste incineration (MSWI) bottom ash as a permeable subgrade material: An experimental and mechanism study.

As a traditional method of waste treatment, municipal solid waste incineration (MSWI) has become one of the main methods of urban waste treatment. However, as a byproduct of MSWI, a large amount of MSWI bottom ash is not reused in current practice. This study innovatively posits MSWI bottom ash as an eco-friendly adsorbent rather than a pollutant, exploring its potential application as a permeable subgrade material. The results reveal that MSWI bottom ash exhibits promising properties to serve as a permeable subgrade material to achieve the permeability and improve the sustainability for subgrade. Due to the arrangement of its particles, it shows excellent performance in shear strength and permeability, which are comparable to or surpass those of sandy soils. The average pore width of 14.200 nm allows heavy metal substances to be encapsulated within the matrix, significantly reducing their leachability, thereby aligning with environmental friendliness standards. Its adsorption capacity is about 6.60 mg/g, and the adsorption capacity per volume is 3.66 times and 2.04 times that of fly ash and clay, respectively. The mechanism analysis shows that the adsorption process is monolayer heterogeneous adsorption. This paper presents a novel perspective on reusing MSWI bottom ash and provides evidence supporting its effective utilization as a permeable subgrade material, offering substantial environmental benefits through enhanced adsorption ability.Implications: Municipal solid waste incineration (MSWI) is a common method for municipal solid waste treatment, while the MSWI bottom ash is often not reused. This paper explored the explores the feasibility of using MSWI bottom ash as a permeable road base material. The results show that the particle arrangement enables excellent shear strength and permeability, comparable to sandy soil. It meets safety requirements for the leaching of heavy metals and acts as an adsorbent for pollutants leaching from permeable pavements. Furthermore, the mechanisms underlying these behaviors of MSWI were confirmed by microstructural and mineralogical analyses. These indicate that MSWI bottom ash has great potential as a permeable road base material. This paper provides a clear understanding of the physical, mechanical and environmental properties of MSWI bottom ash, which can promote its reuse in practice.

Thermal stratification controls taste and odour compounds by regulating the phytoplankton community in a large subtropical water source reservoir (Xin'anjiang Reservoir).

2-Methylisoborneol (2-MIB) and geosmin are compounds released by algae that significantly degrade reservoir water quality, posing a threat to both the safety of drinking water and the quality of aquatic products sourced from these environments. However, few studies have explored how enhanced thermal stratification affects the occurrence and regulation of odorants in large drinking water reservoirs. Through systematic monitoring and investigation of Xin'anjiang Reservoir, we found that enhanced thermal stratification promotes filamentous cyanobacteria, particularly Leptolyngbya sp., as the primary contributor to 2-MIB production within the 1-10 m layer of the water column. The highest 2-MIB concentration, 92.5 ng/L, was recorded in the riverine region, which was 2.54 and 14.52 times higher than that in the transitional and central parts of the reservoir, respectively. Temperature indirectly impacted algal growth and odorant production by modulating TN/TP ratios. Geosmin concentration responded rapidly to relatively low TN/TP ratios (< 25). Our findings suggest that phosphorus control in estuaries should be enhanced during thermal stratification period. In summary, our study provides valuable insights to inform pragmatic water intake strategies and the distribution and release of odorants caused by thermal stratification. This is particularly relevant in the context of future global warming and extremely high temperatures during the warm season.

Holistic quality evaluation method of Epimedii Folium based on NIR spectroscopy and chemometrics.

INTRODUCTION: There are some problems in the quality control of Epimedii Folium (leaves of Epimedium brevicornum Maxim.), such as the mixed use of Epimedii Folium from different harvesting periods and regions, incomplete quality evaluation, and time-consuming analysis methods. OBJECTIVE: Near-infrared (NIR) spectroscopy was conducted to establish a rapid overall quality evaluation method for Epimedii Folium. MATERIALS AND METHODS: Quantitative models of the total solid, moisture, total flavonoid, and flavonol glycoside (Epimedin A, Epimedin B, Epimedin C, Icariin) contents of Epimedii Folium were established by partial least squares regression (PLSR). The root mean square error (RMSE) and correlation coefficient (R) were used to evaluate the performance of models. The qualitative models of Epimedii Folium from different geographic origins and harvest periods were established based on K-nearest neighbor (KNN), back-propagation neural network (BPNN), and random forest (RF). Accuracy and Kappa values were used to evaluate the performance of models. A new multivariable signal conversion strategy was proposed, which combines NIR spectroscopy with the PLSR model to predict the absorbance values of retention time points in the high-performance liquid chromatography (HPLC) fingerprint to obtain the predicted HPLC fingerprint. The Pearson correlation coefficient and cosine coefficient were used to evaluate the similarity between real and predicted HPLC fingerprints. RESULTS: Qualitative models, quantitative models, and the similarity between real and predicted HPLC fingerprints are satisfactory. CONCLUSION: The method serves as a fast and green analytical quality evaluation method of Epimedii Folium and can replace traditional methods to achieve the overall quality evaluation of Epimedii Folium.

Comprehensive evaluation of antibiotics pollution the Yangtze River basin, China: Emission, multimedia fate and risk assessment.

Antibiotics have attracted global attention because of their potential ecological and health risks. The emission, multimedia fate and risk of 18 selected antibiotics in the entire Yangtze River basin were evaluated by using a level Ⅳ fugacity model. High antibiotic emissions were found in the middle and lower reaches of the Yangtze River basin. The total antibiotic emissions in the Yangtze River basin exceeded 1600 tons per year between 2013 and 2021. The spatial distribution of antibiotics concentration was the upper Yangtze River > middle Yangtze River > lower Yangtze River, which is positively correlated with animal husbandry size in the basin. Temperature and precipitation increases may decrease the antibiotic concentrations in the environment. Transfer fluxes showed that source emission inputs, advection processes, and degradation fluxes contributed more to the total input and output. High ecological risks in the water environment were found in 2018, 2019, 2020, and 2021. The comprehensive health risk assessment through drinking water and fish consumption routes showed that a small part of the Yangtze River basin is at medium risk, and children have a relatively high degree of health risk. This study provides a scientific basis for the pollution control of antibiotics at the basin scale.

Aldehyde dehydrogenase 2-mediated aldehyde metabolism promotes tumor immune evasion by regulating the NOD/VISTA axis.

BACKGROUND: Aldehyde dehydrogenase 2 (ALDH2) is a crucial enzyme involved in endogenous aldehyde detoxification and has been implicated in tumor progression. However, its role in tumor immune evasion remains unclear. METHODS: Here, we analyzed the relationship between ALDH2 expression and antitumor immune features in multiple cancers. ALDH2 knockout tumor cells were then established using CRISPR/Cas9 system. In immunocompetent breast cancer EMT6 and melanoma B16-F10 mouse models, we investigated the impact of ALDH2 blockade on cytotoxic T lymphocyte function and tumor immune microenvironment by flow cytometry, mass cytometry, Luminex liquid suspension chip detection, and immunohistochemistry. Furthermore, RNA sequencing, flow cytometry, western blot, chromatin immunoprecipitation assay, and luciferase reporter assays were employed to explore the detailed mechanism of ALDH2 involved in tumor immune evasion. Lastly, the synergistic therapeutic efficacy of blocking ALDH2 by genetic depletion or its inhibitor disulfiram in combination with immune checkpoint blockade (ICB) was investigated in mouse models. RESULTS: In our study, we uncovered a positive correlation between the expression level of ALDH2 and T-cell dysfunction in multiple cancers. Furthermore, blocking ALDH2 significantly suppressed tumor growth by enhancing cytotoxic activity of CD8+ T cells and reshaping the immune landscape and cytokine milieu of tumors in vivo. Mechanistically, inhibiting ALDH2-mediated metabolism of aldehyde downregulated the expression of V-domain Ig suppressor of T-cell activation (VISTA) via inactivating the nucleotide oligomerization domain (NOD)/nuclear factor kappa-B (NF-κB) signaling pathway. As a result, the cytotoxic function of CD8+ T cells was revitalized. Importantly, ALDH2 blockade markedly reinforced the efficacy of ICB treatment. CONCLUSIONS: Our data delineate that ALDH2-mediated aldehyde metabolism drives tumor immune evasion by activating the NOD/NF-κB/VISTA axis. Targeting ALDH2 provides an effective combinatorial therapeutic strategy for immunotherapy.

Anisomeles indica Extracts and Their Constituents Suppress the Protein Expression of ACE2 and TMPRSS2 In Vivo and In Vitro.

Coronavirus disease 2019 (COVID-19), stemming from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a profound global impact. This highly contagious pneumonia remains a significant ongoing threat. Uncertainties persist about the virus's effects on human health, underscoring the need for treatments and prevention. Current research highlights angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) as key targets against SARS-CoV-2. The virus relies on ACE2 to enter cells and TMPRSS2 to activate its spike protein. Inhibiting ACE2 and TMPRSS2 expression can help prevent and treat SARS-CoV-2 infections. Anisomeles indica (L.) Kuntze, a medicinal plant in traditional Chinese medicine, shows various promising pharmacological properties. In this study, ethanolic extracts of A. indica were examined both in vivo (250 and 500 µM) and in vitro (500 µM). Through Western blotting analysis, a significant reduction in the expression levels of ACE2 and TMPRSS2 proteins was observed in HepG2 (human hepatocellular carcinoma) cells and HEK 293T (human embryonic kidney) cell lines without inducing cellular damage. The principal constituents of A. indica, namely, ovatodiolide (5 and 10 µM), anisomlic acid (5 and 10 µM), and apigenin (12.5 and 25 µM), were also found to produce the same effect. Furthermore, immunohistochemical analysis of mouse liver, kidney, and lung tissues demonstrated a decrease in ACE2 and TMPRSS2 protein expression levels. Consequently, this article suggests that A. indica and its constituents have the potential to reduce ACE2 and TMPRSS2 protein expression levels, thus aiding in the prevention of SARS-CoV-2 infections.

Theoretical one-dimensional porous media model for microbial growth on pore plugging and permeability evolution and its verification.

The growth, reproduction, and metabolic activities of microorganisms can lead to blockages within porous media, a phenomenon commonly observed in landfill engineering. Termed as microbial plugging, this phenomenon is significantly influenced by the inherent permeability characteristics of the system. In this study, we propose a simulation model based on the Monod equation to elucidate the clogging process caused by microorganisms in one-dimensional pore channels. Our primary focus is on the application of this model in landfill bioreactor systems. We demonstrate that microbial clogging in these systems is predominantly affected by factors such as the maximum environmental carrying capacity and pore size. These factors are directly influenced by the presence of solid waste within the landfill. By offering a theoretical foundation for mitigating microbial clogging in pore channels of landfill bioreactor systems, this research has the potential to contribute to the development of more efficient and effective waste management practices.Implications: Microbial plugging is a hot research topic in the field of environmental geotechnical engineering. Previous papers often only considered the reduction of pore volumes, while neglecting the role of clogging and the uneven distribution of permeability. In this paper, we established a permeability model for porous media that considers microbial growth and plugging. This model can reflect the temporal variation of permeability with microbial growth and predict the spatial distribution of permeability. This paper can promote on the utilization of microbial plugging technology in landfills or solid waste.

Built Environments and Frailty in Older Adults: The JAGES Longitudinal Study Using Mediation Analysis.

OBJECTIVES: The purpose of this study was to investigate the association between subjective built environment and the onset of frailty in older adults living in the community. In addition, we examined whether daily walking time, depressive symptoms, and social support from neighbors and friends are mediating factors. DESIGN: This was a longitudinal study using prospective cohort data from the 2013 Japan Gerontological Evaluation Study. SETTING AND PARTICIPANTS: Participants included 38,829 older adults who were not frail recruited from 22 cities and towns. METHODS: The dependent variable, frailty, was assessed using the Kihon checklist. The explanatory variables were 5 items for the subjective built environment. The mediating variables were walking time of at least 30 minutes per day, a Geriatric Depression Scale (GDS) score of at least 5 points, and social support from neighbors and friends. We performed a causal mediation analysis of mediating effects between each built environment and frailty onset. Furthermore, the proportion of mediation was estimated. RESULTS: After 3 years of follow-up, frailty emerged in 2232 adults (6.7%) in 2016. Access to parks and sidewalks, access to fresh food stores, houses or facilities where people feel free to drop in, and fascinating views, or buildings reduced the onset of frailty. Mediators significantly associated with the built environment and onset of frailty were access to parks and sidewalks (walking time: 5.9%, GDS: 22.9%, social support: 5.9%), access to fresh food stores (GDS: 31.9%, social support: 4.0%), hills and steps (GDS: 20.6%), houses or facilities where people feel free to drop in (walking time: 4.0%, GDS 28.0%, social support: 10.4%), and fascinating views, or buildings (walking time: 7.8%, GDS: 42.1%, social support: 12.0%). CONCLUSIONS AND IMPLICATIONS: We found that walking time, depression, and social support were mediating factors in the relationship between built environment and the onset of frailty.

Extraction technology, components analysis and anti-inflammatory activity in vitro of total flavonoids extract from Artemisia anomala S. Moore.

Artemisia anomala S. Moore exerts many pharmacological activities, including the removing of the blood stasis, relieving of the fever and analgesia, reducing the swelling and dampness. In this study, the extraction technology, chemical compositions and anti-inflammatory effect in vitro and mechanism of total flavonoids extract from Artemisia anomala S. Moore were studied. The optimal yield rate of total flavonoids extract was optimized by single factor experiments and response surface method, and the chemical constituents were analyzed by UPLC-QTOF-MS method; and the anti-inflammatory activity of the extract was evaluated with lipopolysaccharide induced RAW 264.7 cells. The highest extraction rate was 2.02% under these conditions of the concentration of ethanol 50%, the ultrasonic extraction time 30 min, and the ratio of solvent volume to material weight 20:1 (ml/g). In addition, the main components of total flavonoid extract were preliminarily identified and deduced based on mass spectrometry information and relevant literatures, and its stronger anti-inflammatory activity was demonstrated by reducing the phagocytosis, the content of nitric oxide and the level of related cytokines (tumor necrosis factor-α, interleukin-10, interleukin-6). Furthermore, it was further revealed that the anti-inflammatory effect of the extract was closely connected with the activation of TLR4-MyD88-NF-κB signalling pathway. This study indicated that the total flavonoids extract from Artemisia anomala S. Moore may be a better candidate anti-inflammatory natural medicine.