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Abstract The Lateral Organ Boundaries Domain (LBD) proteins, an exclusive family of transcription factors (TFs) found solely in plants, play pivotal roles in lateral organogenesis, stress adaptation, secondary growth, and hormonal signaling responses. In this study, a total of 55 PtLBD TFs from Populus trichocarpa were identified and systematically classified into two subfamilies, designated as subfamily-I and subfamily-II with seven distinct groups based on phylogenetic analysis. Gene structure detection indicated that the difference of phase numbers linking adjacent exons contribute to the variations in splicing patterns among different PtLBD groups. Numerous transcription factor binding sites and cis-elements pertinent to hormone signaling pathways and stress response mechanisms were identified within the upstream promoter regions of the PtLBD genes. Thirty-five PtLBDs were found to be engaged in either tandem or segmental duplications, and genomic collinearity analysis revealed a stronger alignment between PtLBD genes and eudicots plants compared to their relationship with monocots. GO enrichment and temporal-spatio expression patterns showed that PtLBD7 from subfamily-I and PtLBD20 from subfamily-II, along with other 13 PtLBDs, were involved in plant growth and development biological processes. The multilayered hierarchical gene networks (ML-hGRN) mediated by PtLBD7 and PtLBD20 indicated that PtLBDs were mainly function in poplar growth and stress tolerance through a multifaceted and intricate regulatory machinery. This study lays a solid groundwork for delving deeper into the roles and underlying mechanisms of LBD transcription factors in poplar, specifically those related to plant hormones and stress tolerance.

This study investigates hybrid stainless steel (SS) 316L/Inconel 625 (IN625) materials via DED for hydrofluoric acid (HF) corrosion resistance. 20% SS 316L + 80% IN625 (20% 316L) exhibits low uniform corrosion (0.35 mm/y) and improved local corrosion performance. High Cr2O3 content in its passive film ensures uniform corrosion resistance. The thermodynamic analysis combined with microstructure observation shows reduced Nb content in 20% 316L's Laves phase, enhancing resistance to micro-galvanic local corrosion. This study provides insights into the design and manufacturing technology of corrosion-resistant materials in harsh corrosive environments.

Abstract Background Due to the complexity of the metabolic pathway network of active ingredients, precise targeted synthesis of any active ingredient on a synthetic network is a huge challenge. Based on a complete analysis of the active ingredient pathway in a species, this goal can be achieved by elucidating the functional differences of each enzyme in the pathway and achieving this goal through different combinations. Lignans are a class of phytoestrogens that are present abundantly in plants and play a role in various physiological activities of plants due to their structural diversity. In addition, lignans offer various medicinal benefits to humans. Despite their value, the low concentration of lignans in plants limits their extraction and utilization. Recently, synthetic biology approaches have been explored for lignan production, but achieving the synthesis of most lignans, especially the more valuable lignan glycosides, across the entire synthetic network remains incomplete. Results By evaluating various gene construction methods and sequences, we determined that the pCDF-Duet-Prx02-PsVAO gene construction was the most effective for the production of (+)-pinoresinol, yielding up to 698.9 mg/L after shake-flask fermentation. Based on the stable production of (+)-pinoresinol, we synthesized downstream metabolites in vivo. By comparing different fermentation methods, including “one-cell, one-pot” and “multicellular one-pot”, we determined that the “multicellular one-pot” method was more effective for producing (+)-lariciresinol, (-)-secoisolariciresinol, (-)-matairesinol, and their glycoside products. The “multicellular one-pot” fermentation yielded 434.08 mg/L of (+)-lariciresinol, 96.81 mg/L of (-)-secoisolariciresinol, and 45.14 mg/L of (-)-matairesinol. Subsequently, ultilizing the strict substrate recognition pecificities of UDP-glycosyltransferase (UGT) incorporating the native uridine diphosphate glucose (UDPG) Module for in vivo synthesis of glycoside products resulted in the following yields: (+)-pinoresinol glucoside: 1.71 mg/L, (+)-lariciresinol-4-O-d-glucopyranoside: 1.3 mg/L, (+)-lariciresinol-4’-O-d-glucopyranoside: 836 µg/L, (-)-secoisolariciresinol monoglucoside: 103.77 µg/L, (-)-matairesinol-4-O-d-glucopyranoside: 86.79 µg/L, and (-)-matairesinol-4’-O-d-glucopyranoside: 74.5 µg/L. Conclusions By using various construction and fermentation methods, we successfully synthesized 10 products of the lignan pathway in Isatis indigotica Fort in Escherichia coli, with eugenol as substrate. Additionally, we obtained a diverse range of lignan products by combining different modules, setting a foundation for future high-yield lignan production.

Background Acute kidney injury (AKI) represents a diverse range of conditions characterized by high incidence and mortality rates, and it is mainly associated with immune-mediated mechanisms and mitochondrial metabolism dysfunction. Cuproptosis, a recently identified form of programmed cell death dependent on copper, is closely linked to mitochondrial respiration and contributes to various diseases. Our study aimed to investigate the involvement of cuproptosis-related genes (CRGs) in AKI.Methods Identification of CRGs was conducted using differential expression analysis, and subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using human sequencing profiles. Utilizing CIBERSORT algorithm, receiver operating characteristic (ROC) curve analysis, nomogram development, and decision curve analysis (DCA), the association among immune scores, CRGs, and the diagnostic value of these genes was explored.Results Notably, six CRGs (FDX1, DLD, DLAT, DBT, PDHA1, and ATP7A) were identified as significant differentiators between AKI and non-AKI groups. The ROC curve, based on these six genes, demonstrated an AUC value of 0.917, which was further validated using an additional dataset with an AUC value of 0.902. Nomogram and DCA further confirmed the accuracy of the model in predicting the risk of AKI.Conclusion This study elucidated the role of cuproptosis in AKI and revealed the association between CRGs and infiltrated immune cells through comprehensive bioinformatic techniques. The six-gene cuproptosis-related signature exhibited remarkable predictive efficiency for AKI.

ABSTRACTThe increasing incidence of diseases caused by Coxsackievirus A6 (CV-A6) and the presence of various mutants in the population present significant public health challenges. Given the concurrent development of multiple vaccines in China, it is challenging to objectively and accurately evaluate the level of neutralizing antibody response to different vaccines. The choice of the detection strain is a crucial factor that influences the detection of neutralizing antibodies. In this study, the National Institutes for Food and Drug Control collected a prototype strain (Gdula), one subgenotype D1, as well as 13 CV-A6 candidate vaccine strains and candidate detection strains (subgenotype D3) from various institutions and manufacturers involved in research and development. We evaluated cross-neutralization activity using plasma from naturally infected adults (n = 30) and serum from rats immunized with the aforementioned CV-A6 strains. Although there were differences between the geometric mean titer (GMT) ranges of human plasma and murine sera, the overall trends were similar. A significant effect of each strain on the neutralizing antibody test (MAX/MIN 48.0 ∼16410.3) was observed. Among all strains, neutralization of the S112 strain by 15 different sera resulted in higher neutralizing antibody titers (GMTS112 = 132.0) and more consistent responses across different genotypic immune sera (MAX/MIN = 48.0). Therefore, S112 may serve as a detection strain for NtAb testing in various vaccines, minimizing bias and making it suitable for evaluating the immunogenicity of the CV-A6 vaccine.

AbstractTargeting Heat shock protein 90 (HSP90) C-terminus is an important strategy to develop HSP90 inhibitors without inducing heat shock response. The development of C-terminal inhibitors, however, is hampered by a lack of understanding regarding the interaction between the HSP90 C-terminus and the present inhibitors. We collected seven classical and structurally diverse HSP90 C-terminal inhibitors and constructed a ligand-based pharmacophore model. The subsequent virtual screening and structural optimisation led to the identification of 2-heteroarylthio-N-arylacetamides as novel HSP90 C-terminal inhibitors. 9 and 27 exhibited strong antitumour activity in vitro by inhibiting proliferation and inducing apoptosis in multiple cancer cell lines. These compounds disrupted the interaction between HSP90 C-terminus and peptidylprolyl isomerase D, exerting a stronger inhibitory effect than novobiocin. 27 significantly induced the degradation of HSP90 clients without triggering heat shock response. In an in vivo study using 4T1 mice breast cancer models, 9 showed a potent antitumour effect without obvious toxicity.

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BackgroundTo examine the associations of serum sodium and frailty with the risk of mild cognitive impairment (MCI) among hospitalized older adults with chronic diseases.MethodsA cross-sectional study was conducted in 403 hospitalized older adults with chronic diseases. Serum sodium concentration was assessed by the ion-selective electrode method, frailty status was evaluated by the FRAIL scale, and MCI was determined by the Montreal Cognitive Assessment (MoCA). Multiple logistic regression models were used to estimate the associations of serum sodium and frailty with MCI.ResultsParticipants with the lowest tertile of serum sodium had a higher risk of MCI than those in the middle tertile group (OR = 1.75, 95% CI: 1.01–3.04). Below 143 mmol/L, the risk of MCI was 1.38 (95% CI: 1.03–1.84) for per 1 SD decrease in serum sodium. Compared with the robust group, frailty was significantly associated with an increased risk of MCI (OR = 3.94, 95% CI: 1.92–8.10). Moreover, in comparison with participants with the middle tertile of serum sodium and who were robust/prefrail, those with frailty and either the lowest (OR = 5.53, 95% CI: 2.08–14.67) or the highest tertile of serum sodium (OR = 3.48, 95% CI: 1.20–10.05) had higher risks of MCI.ConclusionBoth lower and higher serum sodium impose a significantly higher risk for MCI in older adults with frailty. This could inform the design of clinical trials and the development of guidelines and recommendations for correcting serum sodium and frailty in hospitalized older adults with chronic diseases.

Objective The present study aimed to investigate the effect of β-nicotinamide mononucleotide (NMN) supplementation on ram sperm quality during storage at 4°C in vitro. Methods Tris-citric acid-glucose solution containing different doses of NMN (0, 30, 60, 90, and 120 μM) was used to dilute semen collected from rams and it was stored at 4°C. Sperm motility, plasma membrane integrity as well as acrosome integrity were evaluated at 0, 24, and 48 h time points after storage at 4°C. In addition, sperm mitochondrial activity, lipid peroxidation (LPO), malondialdehyde (MDA) content, reactive oxygen species (ROS) content, glutathione (GSH) content, superoxide dismutase (SOD) activity, and apoptosis were measured at 48 h time point after storage at 4°C. Results Results demonstrate that the values obtained for sperm motility, acrosome integrity, and plasma membrane integrity in the NMN treatments were significantly higher than control (p

Enhancing the high-temperature oxidation resistance of nickel-based alloys is critical for expanding their industrial applications. Herein, we report a novel strategy for enhancing the high-temperature oxidation resistance of the GH4169 nickel-based alloy by adding small amounts of 304L stainless steel using selective laser melting technology. The oxidation property of GH4169 with various 304L additions (2 wt.%, 4 wt.%, and 6 wt.%) at 900 °C for 45 h was investigated. Results show that the addition of 304L significantly improves the oxidation resistance of GH4169. The thickness of the oxide film and the intergranular oxidation depth of GH4169 with 6 wt.% 304L added are reduced by 61% and 69%, respectively. The addition of 304L increases Cr and decreases Ni in the matrix, which facilitates the formation of a more compact oxide film. The Nb in Laves phase will be increased with 304L addition, which effectively inhibits oxygen penetration and metallic element diffusion.

Superoxide dismutase (SOD) is widely present in plants and plays a crucial role in defending against oxidative stress and preventing tissue damage. This study discovered that the PagSOD2a gene in 84K poplar (Populus alba × P. glandulosa) exhibits a distinct capacity to be induced in response to salt stress. To delve into the pivotal role of PagSOD2a in conferring salt tolerance, the entire PagSOD2a fragment was successfully cloned from 84K poplar and the potential function of PagSOD2a was explored using bioinformatics and subcellular localization. PagSOD2a was found to encode a CuZn-SOD protein localized in chloroplasts. Furthermore, six CuZn-SOD family members were identified in poplar, with closely related members displaying similar gene structures, indicating evolutionary conservation. Morphological and physiological indexes of transgenic 84K poplar overexpressing PagSOD2a (OE) were compared with non-transgenic wild-type (WT) plants under salt stress. The OE lines (OE1 and OE3) showed improved growth performance, characterized by increased plant height and fresh weight, along with reduced malondialdehyde (MDA) content and electrolyte leakage rate under salt stress. Meanwhile, overexpression of PagSOD2a significantly augmented CuZn-SOD and total SOD enzyme activities, leading to a reduction in superoxide anion accumulation and an enhancement of salt tolerance. Additionally, co-expression and multilayered hierarchical gene regulatory network (ML-hGRN) mediated by PagSOD2a constructed using transcriptome data revealed that PagSOD2a gene may be directly regulated by SPL13, NGA1b and FRS5, as well as indirectly regulated by MYB102 and WRKY6, in response to salt stress. These findings provide a theoretical and material foundation for further elucidating the function of PagSOD2a under salt stress and for developing salt-tolerant poplar varieties.

Abstract The inter-subspecific indica-japonica hybrid rice confer potential higher yield than the widely used indica-indica intra-subspecific hybrid rice. Nevertheless, the utilization of this strong heterosis is currently hindered by asynchronous diurnal floret opening time (DFOT) of indica and japonica parental lines. Here, we identify OsMYB8 as a key regulator of rice DFOT. OsMYB8 induces the transcription of JA-Ile synthetase OsJAR1, thereby regulating the expression of genes related to cell osmolality and cell wall remodeling in lodicules to promote floret opening. Natural variations of OsMYB8 promoter contribute to its differential expression, thus differential transcription of OsJAR1 and accumulation of JA-Ile in lodicules of indica and japonica subspecies. Furthermore, introgression of the indica haplotype of OsMYB8 into japonica effectively promotes DFOT in japonica. Our findings reveal an OsMYB8-OsJAR1 module that regulates differential DFOT in indica and japonica, and provide a strategy for breeding early DFOT japonica to facilitate breeding of indica-japonica hybrids.

Liver fibrosis, characterized by scar tissue formation, can ultimately result in liver failure. It's a major cause of morbidity and mortality globally, often associated with chronic liver diseases like hepatitis or alcoholic and non-alcoholic fatty liver diseases. However, current treatment options are limited, highlighting the urgent need for the development of new therapies. As a reversible regulatory mechanism, epigenetic modification is implicated in many biological processes, including liver fibrosis. Exploring the epigenetic mechanisms involved in liver fibrosis could provide valuable insights into developing new treatments for chronic liver diseases, although the current evidence is still controversial. This review provides a comprehensive summary of the regulatory mechanisms and critical targets of epigenetic modifications, including DNA methylation, histone modification, and RNA modification, in liver fibrotic diseases. The potential cooperation of different epigenetic modifications in promoting fibrogenesis was also highlighted. Finally, available agonists or inhibitors regulating these epigenetic mechanisms and their potential application in preventing liver fibrosis were discussed. In summary, elucidating specific druggable epigenetic targets and developing more selective and specific candidate medicines may represent a promising approach with bright prospects for the treatment of chronic liver diseases.

Abstract Clonal hematopoiesis (CH) can be caused by either single gene mutations (eg point mutations in JAK2 causing CHIP) or mosaic chromosomal alterations (e.g., loss of heterozygosity at chromosome 9p). CH is associated with a significantly increased risk of hematologic malignancies. However, the absolute rate of transformation on an annualized basis is low. Improved prognostication of transformation risk is urgently needed for routine clinical practice. We hypothesized that the co-occurrence of CHIP and mCAs at the same locus (e.g., transforming a heterozygous JAK2 CHIP mutation into a homozygous mutation through concomitant loss of heterozygosity at chromosome 9) might have important prognostic implications for malignancy transformation risk. We tested this hypothesis using our discovery cohort, the UK Biobank (n = 451,180), and subsequently validated it in the BioVU cohort (n = 91,335). We find that individuals with a concurrent somatic mutation and mCA were at significantly increased risk of hematologic malignancy (for example, In BioVU cohort incidence of hematologic malignancies is higher in individuals with co-occurring JAK2 V617F and 9p CN-LOH; HR = 54.76, 95% CI = 33.92–88.41, P

Earth-rock dam failures account for the largest proportion of all dam failure accidents. There are many factors inducing accidents in hydroelectric projects, and the relationships between them are intricate and complex. Therefore, it is crucial to explore the relationship between the influencing factors and identify the key factors leading to accidents. Through an analysis of the factors influencing earth rock dam failures, an index system for failure influence factors was constructed in this paper. Considering complexity and integration in influence factors analysis, a DEMATEL-ISM model (Decision Making Trial and Evaluation Laboratory; Interpretive Structural Model) analysis method was employed to examine the internal relationship among various factors based on the influence degree between them, and a MICMAC model (Matrix Impacts Cross-reference Multiplication Applied to a Classification methodology) was introduced to analyze the hierarchical relationship between various factors. The results showed that The results show that the seismic capacity and flood discharge capacity of the dam body are the key influencing factors of dam safety during the operation of the earth-rock dams. The comprehensive method employed in this paper overcame the complexity of evaluation results and was capable of more directly presenting relationships of factors. As suggested by these results, the analysis model employed in this paper has great significance for preparing a flexible-efficient management scheme for earth-rock dams.

Early weaning leads to weaning stress in calves, which hinders healthy growth and development. As an excellent sweetener applied in food, steviol glycosides (STE) has also been shown to exhibit positive biological activity in monogastric animals. Therefore, this study aimed to evaluate the impact of incorporating STE as a dietary supplement on rumen development, fermentation, and microbiota of rumen in weaned calves. This study selected 24 healthy Holstein bull calves and randomly allocated them into two groups (CON and STE). The results indicated that supplementation STE group improved rumen development in weaned calves, as demonstrated by a marked increase in the weight of the rumen, as well as the length and surface area of the rumen papilla. Compared with the CON group, the concentrations of total volatile fatty acids (TVFA), propionate, butyrate, and valerate were higher in the STE group. Moreover, STE treatment increased the relative abundance of Firmicutes and Actinobacteria at the phylum level. At the genus level, the STE group showed a significantly increased relative abundance of Succiniclasticum, Lachnospiraceae_NK3A20_group, and Olsenella, and a decreased relative abundance of Acinetobacter compared to the CON group. Pusillimonas, Lachnospiraceae_NK3A20_group, Olsenella, and Succiniclasticum were significantly enriched in rumen chyme after supplementation with STE, as demonstrated by LEfSe analysis. Overall, our findings revealed that rumen bacterial communities altered in response to the dietary supplementation with STE, and some bacterial taxa in these communities may have positive effects on rumen development during this period.

ObjectiveTo evaluate the diagnostic value of metagenomic sequencing technology based on Illumina and Nanopore sequencing platforms for patients with suspected lower respiratory tract infection whose pathogen could not be identified by conventional microbiological tests.MethodsPatients admitted to the Respiratory and Critical Care Medicine in Shanghai Ruijin Hospital were retrospectively studied from August 2021 to March 2022. Alveolar lavage or sputum was retained in patients with clinically suspected lower respiratory tract infection who were negative in conventional tests. Bronchoalveolar lavage fluid (BALF) samples were obtained using bronchoscopy. Sputum samples were collected, while BALF samples were not available due to bronchoscopy contraindications. Samples collected from enrolled patients were simultaneously sent for metagenomic sequencing on both platforms.ResultsThirty-eight patients with suspected LRTI were enrolled in this study, consisting of 36 parts of alveolar lavage and 2 parts of sputum. According to the infection diagnosis, 31 patients were confirmed to be infected with pathogens, while 7 patients were diagnosed with non-infectious disease. With regard to the diagnosis of infectious diseases, the sensitivity and specificity of Illumina and Nanopore to diagnose infection in patients were 80.6% vs. 93.5% and 42.9 vs. 28.6%, respectively. In patients diagnosed with bacterial, Mycobacterium, and fungal infections, the positive rates of Illumina and Nanopore sequencer were 71.4% vs. 78.6%, 36.4% vs. 90.9%, and 50% vs. 62.5%, respectively. In terms of pathogen diagnosis, the sensitivity and specificity of pathogens detected by Illumina and Nanopore were 55.6% vs. 77.8% and 42.9% vs. 28.6%, respectively. Among the patients treated with antibiotics in the last 2 weeks, 61.1% (11/18) and 77.8% (14/18) cases of pathogens were accurately detected by Illumina and Nanopore, respectively, among which 8 cases were detected jointly. The consistency between Illumina and diagnosis was 63.9% (23/36), while the consistency between Nanopore and diagnosis was 83.3% (30/36). Between Illumina and Nanopore sequencing methods, the consistency ratio was 55% (22/42) based on pathogen diagnosis.ConclusionBoth platforms play a certain value in infection diagnosis and pathogen diagnosis of CMT-negative suspected LRTI patients, providing a theoretical basis for clinical accurate diagnosis and symptomatic treatment. The Nanopore platform demonstrated potential advantages in the identification of Mycobacterium and could further provide another powerful approach for patients with suspected Mycobacterium infection.

Abstract Background Diabetic encephalopathy (DE) is a complication of diabetes that leads to cognitive and behavioral decline. Utilizing safe and effective complementary and alternative medications for its management is a wise choice. Previous studies have shown that GuanXinNing Tablet (GXNT), an oral preparation primarily derived from two Chinese herbs, Salvia miltiorrhiza Bge. and Ligusticum chuanxiong Hort., exerts a beneficial neuroprotective effect. In this study, we explored the protective effects of GXNT on DE in male Zucker diabetic fatty (ZDF) rats induced by a high-fat diet, aiming to ascertain its significance and potential mechanisms. Methods ZDF rats were induced to develop type 2 diabetes (T2DM) with DE by a high-fat diet and treated with GXNT for 8 weeks until they were 20 weeks old. Throughout the experiment, the animals’ vital parameters, such as body weight, were continuously monitored. Cognitive function was evaluated using the Y maze test. Biochemical kits were employed to analyze blood glucose, lipids, and vascular endothelial-related factors. Cerebrovascular lesions were assessed using magnetic resonance angiography (MRA) imaging. Brain lesions were evaluated using hematoxylin and eosin (H&E) staining and ultrastructure observation. IgG and albumin (ALB) leakage were detected using immunofluorescence. Results GXNT demonstrated an enhancement in the overall well-being of the animals. It notably improved cognitive and behavioral abilities, as demonstrated by extended retention time in the novel heterogeneous arm during the Y-maze test. GXNT effectively regulated glucose and lipid metabolism, reducing fasting and postprandial blood glucose, glycated hemoglobin (HbA1c), and total cholesterol (TC) levels. Additionally, it exhibited a protective effect on the vascular endothelium by reducing the serum TXB2/PGI2 ratio while elevating NO and PGI2 levels. Moreover, GXNT ameliorated stenosis and occlusion in cerebral vessel branches, increased the number of microvessels and neurons around the hippocampus, and improved microvascular occlusion in the cerebral cortex, along with addressing perivascular cell abnormalities. Immunofluorescence staining showed a decrease in the fluorescence intensity of IgG and ALB in the cerebral cortex. Conclusions GXNT demonstrated a highly satisfactory protective effect on DE in ZDF rats. Its mechanism of action could be based on the regulation of glucolipid metabolism and its protective effect on the vascular endothelium.

Abstract Revealing spatio-temporal evolution regularity in the spatial diffusion of epidemics is helpful for preventing and controlling the spread of epidemics. Based on the real-time COVID-19 datasets by prefecture-level cities, this paper is devoted to exploring the multifractal scaling in spatial diffusion pattern of COVID-19 pandemic and its evolution characteristics in Chinese mainland. The ArcGIS technology and box-counting method are employed to extract spatial data and the least square regression based on rescaling probability (μ-weight method) is used to calculate fractal parameters. The results show multifractal distribution of COVID-19 pandemic in China. The generalized correlation dimension spectrums are inverse S-shaped curves, but the fractal dimension values significantly exceed the Euclidean dimension of embedding space when moment order q«0. The local singularity spectrums are asymmetric unimodal curves, which slant to right. The fractal dimension growth curves are shown as quasi S-shaped curves. From these spectrums and growth curves, the main conclusions can be drawn as follows: First, self-similar patterns developed in the process of COVID-19 pandemic, which seems to be dominated by multifractal scaling law. Second, the spatial pattern of COVID-19 across China can be characterized by global clustering with local disordered diffusion. Third, the spatial diffusion process of COVID-19 in China experienced four stages, i.e., initial stage, the rapid diffusion stage, the hierarchical diffusion stage, and finally the contraction stage. This study suggests that multifractal theory can be utilized to characterize spatio-temporal diffusion of COVID-19 pandemic, and the case analyses may be instructive for further exploring natural laws of spatial diffusion.

Abstract Background Anaerobic fungi are effective fibre-degrading microorganisms in the digestive tract of horses. However, our understanding of their diversity and community structure is limited, especially in different parts of the gastrointestinal tract. Results For the first time, high-throughput sequencing technology was used to analyse and predict fungal microbial diversity in different parts of the gastrointestinal tract of Mongolian horses. The results revealed that the richness and diversity of fungi in the hindgut of Mongolian horses were much higher than those in the foregut. The foregut was dominated by Basidiomycota and Ascomycota, whereas the hindgut was dominated by Neocallimastigomycota and Basidiomycota. At the genus level, the relative abundance of many pathogenic fungi (Cryptococcus, Cladosporium, Alternaria, and Sarocladium) in the foregut was significantly higher than that in the posterior gut, indicating that Mongolian horses have strong disease resistance. The prediction of fungal function also showed significant differences in the fungal flora between the foregut and the hindgut. The fungi in Mongolian horses’ foreguts were mainly pathologically nutritive and contained many animal and plant pathogens, particularly in the small intestine (jejunum and ileum). This indicates that the foregut may be the most important immune site in the digestive system of Mongolian horses, which explains the high disease resistance of Mongolian horses. The number of unassigned functional groups in the posterior gut was significantly higher than that in the anterior gut, indicating that the functions of fungal groups in the posterior gut have not been fully explored, and further studies are required in the future. Conclusions Analysis of high-throughput sequencing results revealed that the fungal composition varied greatly among different gastrointestinal tract segments in Mongolian horses, whose hindgut contains many anaerobic fungi involved in plant cellulose degradation. This provides important basic data for studying fungal diversity in the digestive system of healthy horses, which can be used for the health assessment of horses and provides clues for further research on the disease resistance and digestive capacity of horses, as well as a reference for the early diagnosis of intestinal diseases and innovative treatment methods.

Abstract Background Aging is an important pathogenic factor of age-related diseases and has brought huge health threat and economic burden to the society. Dendrobium nobile Lindl., a valuable herb in China, promotes longevity according to the record of ancient Chinese materia medica. This study aimed to discover the material basis of D. nobile as an anti-aging herb and elucidate its action mechanism. Methods K6001 yeast replicative lifespan assay was used to guide the isolation of D. nobile. The chronological lifespan assay of YOM36 yeast was further conducted to confirm the anti-aging activity of dendrobine. The mechanism in which dendrobine exerts anti-aging effect was determined by conducting anti-oxidative stress assay, quantitative real-time PCR, Western blot, measurements of anti-oxidant enzymes activities, determination of nuclear translocation of Rim15 and Msn2, and replicative lifespan assays of Δsod1, Δsod2, Δcat, Δgpx, Δatg2, Δatg32, and Δrim15 yeasts. Results Under the guidance of K6001 yeast replicative lifespan system, dendrobine with anti-aging effect was isolated from D. nobile. The replicative and chronological lifespans of yeast were extended upon dendrobine treatment. In the study of action mechanism, dendrobine improved the survival rate of yeast under oxidative stress, decreased the levels of reactive oxygen species and malondialdehyde, and enhanced the enzyme activities and gene expression of superoxide dismutase and catalase, but it failed to elongate the replicative lifespans of Δsod1, Δsod2, Δcat, and Δgpx yeast mutants. Meanwhile, dendrobine enhanced autophagy occurrence in yeast but had no effect on the replicative lifespans of Δatg2 and Δatg32 yeast mutants. Moreover, the inhibition of Sch9 phosphorylation and the promotion of nuclear translocation of Rim15 and Msn2 were observed after treatment with denrobine. However, the effect of dendrobine disappeared from the Δrim15 yeast mutant after lifespan extension, oxidative stress reduction, and autophagy enhancement. Conclusions Dendrobine exerts anti-aging activity in yeast via the modification of oxidative stress and autophagy through the Sch9/Rim15/Msn2 signaling pathway. Our work provides a scientific basis for the exploitation of D. nobile as an anti-aging herb.

Objective: To better develop high-value products from deer antlers, this study determined the optimal process conditions for the enzymatic digestion of deer antler peptides by alkaline proteases and evaluated their in vitro anti-blue light activity. Methods: Select four factors: digestion temperature, substrate ratio, digestion time and pH, three levels of each factor, based on unifactor experiment optimization, the yield of the enzyme digestion of the deer antler peptide was obtained, and the content of the deer antler peptide was determined. The survival rate of the Human immortal keratinocyte line (HaCat) cultured with different concentrations of deer antler peptide was measured by the CCK-8 method. The method of ELISA was used to analyze the secretion levels of Superoxide dismutase (SOD) and reduced Glutathione-reduced (GSH) secretion levels. The UV method calculated the ability of antler peptides to scavenge DPPH free radicals and OH free radicals. Results: The optimum conditions for the enzymatic digestion of antler peptides were determined to be 45 °C, 5 h, pH8.5, and a 6% enzyme-substrate ratio. The extraction rate of antler peptide was 52.7% at this time. With different concentrations (12.5, 25, 50, 75, 100 μg/mL), the proliferation activity of HaCat cells was reduced, and the cell survival rate was increased, significant difference (P

Aging is often accompanied by irreversible decline in body function, which causes a large number of age-related diseases and brings a huge economic burden to society and families. Many traditional Chinese medicines have been known to extend lifespan, but it has still been a challenge to isolate a single active molecule from them and verify the mechanism of anti-aging action. Drugs that inhibit senescence-associated secretory phenotypes (SASPs) are called “senomorphics”. In this study, arctigenin (ATG), a senomorphic, was screened from the Chinese medicine Fructus arctii using K6001 yeast replicative lifespan. Autophagy, oxidative stress, and telomerase activity are key mechanisms related to aging. We found that ATG may act through multiple mechanisms to become an effective anti-aging molecule. In exploring the effect of ATG on autophagy, it was clearly observed that ATG significantly enhanced autophagy in yeast. We further verified that ATG can enhance autophagy by targeting protein phosphatase 2A (PP2A), leading to an increased lifespan. Meanwhile, we evaluated the antioxidant capacity of ATG and found that ATG increased the activities of the antioxidant enzymes, thereby reducing reactive oxygen species (ROS) and malondialdehyde (MDA) levels to improve the survival of yeast under oxidative stress. In addition, ATG was able to increase telomerase activity by enhancing the expression of EST1, EST2, and EST3 genes in yeast. In conclusion, ATG exerts anti-aging effects through induction of autophagy, antioxidative stress, and enhancement of telomerase activity in yeast, which is recognized as a potential molecule with promising anti-aging effects, deserving in-depth research in the future.

DREB has been reported to be involved in plant growth and response to environmental factors. However, the function of DREB in growth and development has not been elucidated in alfalfa (Medicago sativa L.), a perennial tetraploid forage cultivated worldwide. In this study, an ortholog of MtDREB1C was characterized from alfalfa and named MsDREB1C accordingly. MsDREB1C was significantly induced by abiotic stress. The transcription factor MsDREB1C resided in the nucleus and had self-transactivation activity. The MsDREB1C overexpression (OE) alfalfa displayed growth retardation under both long-day and short-day conditions, which was supported by decreased MsGA20ox and upregulated MsGA2ox in the OE lines. Consistently, a decrease in active gibberellin (GA) was detected, suggesting a negative effect of MsDREB1C on GA accumulation in alfalfa. Interestingly, the forage quality of the OE lines was better than that of WT lines, with higher crude protein and lower lignin content, which was supported by an increase in the leaf–stem ratio (LSR) and repression of several lignin-synthesis genes (MsNST, MsPAL1, MsC4H, and Ms4CL). Therefore, this study revealed the effects of MsDREB1C overexpression on growth and forage quality via modifying GA accumulation and lignin synthesis, respectively. Our findings provide a valuable candidate for improving the critical agronomic traits of alfalfa, such as overwintering and feeding value of the forage.

Objective: To compare the effect of fermentation on the chemical constituents of Gastrodia Tuder Halimasch Powder (GTHP), to establish its fingerprinting and multicomponent content determination, and to provide a basis for the processing, handling, and clinical application of this herb. Methods: Ultra-high-performance liquid chromatography-quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) was used to conduct a preliminary analysis of the chemical constituents in GTHP before and after fermentation. High-performance liquid chromatography (HPLC) was used to determine some major differential components of GTHP and establish fingerprints. Cluster analysis (CA), and principal component analysis (PCA) were employed for comprehensive evaluation. Results: Seventy-nine compounds were identified, including flavonoids, organic acids, nucleosides, terpenoids, and others. The CA and PCA results showed that ten samples were divided into three groups. Through standard control and HPLC analysis, 10 compounds were identified from 22 peaks, namely uracil, guanosine, adenosine, 5-hydroxymethylfurfural (5-HMF), daidzin, genistin, glycitein, daidzein, genistein, and ergosterol. After fermentation, GTHP exhibited significantly higher contents of uracil, guanosine, adenosine, 5-hydroxymethylfurfural, and ergosterol and significantly lower genistein and daidzein contents. Conclusions: The UHPLC-Q-Orbitrap HRMS and HPLC methods can effectively identify a variety of chemical components before and after the fermentation of GTHP. This study provides a valuable reference for further research on the rational clinical application and quality control improvement of GTHP.

As a typical chlorophenol, 2,4,6-trichlorophenol (2,4,6-TCP) is highly toxic and difficult to degrade. Here, we prepared a novel material (Cu/HAP@sBC) by combining copper-based hydroxyapatite with biochar, which removes 2,4,6-TCP via activated persulfate (PS). Cu/HAP@sBC was tested using various characterization methods. In addition, the removal of 2,4,6-TCP was up to 100% after 60 min, and the Cu/HAP@sBC/PS system had a broad pH application range (3−10). Based on the results, SO4−•, •OH, •O2−, and 1O2 were the main reactive species. Finally, the possible degradation pathways of 2,4,6-TCP were explored based on the intermediates identified by high-performance liquid chromatography-mass spectrometry (LC-MS).

Background: Almonertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is commonly used as a first-line treatment for non-small cell lung cancer (NSCLC) patients with EGFR T790M mutations. Rivaroxaban and apixaban are a selective, direct factor Xa inhibitor used to treat venous thromboembolism (VTE), which is a frequent complication of NSCLC. Rivaroxaban and apixaban are substrates of CYP3A4, P-gp and BCRP, whereas almonertinib is an inhibitor of P-gp and BCRP. Rivaroxaban or apixaban are often prescribed together with almonertinib in NSCLC patients, but clear information on pharmacokinetic drug interaction is lacking. Therefore, this study aimed to unravel the extent of interactions between almonertinib-rivaroxaban and almonertinib apixaban in rats, and whether the pharmacokinetic interaction can be mitigated by rivaroxaban and apixaban dose adjustment.Methods: Rats were divided into ten groups (n = 6) that received rivaroxaban (2 mg/kg) (group 1), apixaban (0.5 mg/kg) (group 2), almonertinib (15 mg/kg) (group 3, group 4), almonertinib with rivaroxaban (2 mg/kg) (group 5), almonertinib with rivaroxaban (1 mg/kg) (group 6), almonertinib with apixaban (0.5 mg/kg) (group 7), almonertinib with apixaban (0.25 mg/kg) (group 8), rivaroxaban (2 mg/kg) with almonertinib (group 9), apixaban (0.5 mg/kg) with almonertinib (group 10). The concentrations of drugs were determined by an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The levels of messenger RNA were determined using quantitative real-time polymerase chain reaction (qRT-PCR).Results and Discussion: The results indicate that almonertinib increased the Cmax and AUC0-t of 2 mg/kg rivaroxaban by 3.30 and 3.60-fold, 1 mg/kg rivaroxaban by 1.28 and 1.90-fold. Almonertinib increased the Cmax and AUC0-t of 0.5 mg/kg apixaban by 2.69 and 2.87-fold, 0.25 mg/kg apixaban by 2.19 and 2.06-fold. In addition, rivaroxaban also increased systemic exposure to almonertinib. The results of qRT-PCR showed that almonertinib reduced the expression of Cyp3a1 in liver and intestine, and Abcb1a, Abcg2 in intestine and kidney. The pharmacokinetic results suggest that it is important to take special care of the interactions of these drugs in clinical applications.

The molecular chaperone HSP90 plays an essential role in cancer occurrence and development. Therefore, it is an important target for the development of anticancer drugs. 1,3-Dibenzyl-2-aryl imidazolidine (8) is a previously reported inhibitor of HSP90; however, its anticancer activity is poor. In this work, chemical modification of 8 led to the discovery of 2,4-diarylimidazoles and 2,4-bis(benzyloxy)-5-arylpyrimidines as two types of novel HSP90 N-terminal inhibitors. 16l and 22k exhibited antiproliferative activity against multiple breast cancer cell lines with IC50 values at the low micromolar level. 16l and 22k induced significant degradation of the client proteins AKT and ERK and a lower level of the heat shock response in comparison with tanespimycin (17-AAG). 22k exhibited a strong affinity for the HSP90α N-terminus with an IC50 value of 0.21 μM. A molecular docking study revealed that 16l and 22k successfully bind to the geldanamycin binding site at the N-terminus of HSP90α.

Context Atorvastatin (ATV) and QiShenYiQi pills (QSYQ), a Chinese patent medicine, are often co-prescribed to Chinese cardiovascular patients. The effects of QSYQ on the pharmacokinetics of ATV have not been studied. Objective We investigated the influence of QSYQ on the pharmacokinetics of ATV and its metabolites upon oral or intravenous administration of ATV to rats. Materials and methods Sprague-Dawley rats (n = 5/group) were pre-treated with oral QSYQ (675 mg/kg) or vehicle control for 7 days and then orally administrated ATV (10 mg/kg) or intravenously administrated ATV (2 mg/kg). Serum concentrations of ATV and metabolites were determined by ultra-high performance liquid chromatography tandem mass spectrometry. Expression of metabolic enzymes and transporters in jejunum and ileum were measured by quantitative real-time PCR and Western blot. Results QSYQ resulted in an increase of AUC0-12 h of ATV from 226.67 ± 42.11 to 408.70 ± 161.75 ng/mL/h and of Cmax of ATV from 101.46 ± 26.18 to 198.00 ± 51.69 ng/mL and in an increased of para-hydroxy atorvastatin from 9.07 ± 6.20 to 23.10 ± 8.70 ng/mL in rats administered ATV orally. No change was observed in rats treated intravenously. The expression of multidrug resistance-associated protein 2 mRNA and protein decreased in ileum, and the mRNA of P-glycoprotein decreased in jejunum, though no change in protein expression was found. Discussion and conclusions QSYQ increased bioavailability of ATV administered orally through inhibiting the expression of Mrp2 in ileum. Clinicians should pay close attention to potential drug-drug interactions between ATV and QSYQ.

As coal mines continue to deepen high-intensity mining, the two disasters of coal seam rock burst and spontaneous combustion obviously have a trend of compound occurrence. How to achieve the integrated prevention and control of the two disasters is an important guarantee to realize coal mine safety. As a result, it is very important to select a coal seam water injection additive that can not only reduce the bursting liability, but also prolong the spontaneous combustion period of coal. In this paper, the chelating wetting agent was chosen to soak the coal, and the mass changed and carbon-containing functional groups during the coal oxidation process were studied by thermogravimetric and X-ray photoelectron spectroscopy, and tested the strength of coal by uniaxial compression experiment, and the scanning electron microscopy and low-temperature N2 adsorption were used to analyze the pore structure of coal. The experiment results show that the mass of the raw coal, the mass of the coal soaked in FeSO4 solution, and the mass of the coal soaked in the chelating wetting agent were reduced by 30.01%, 34.62% and 19.00%, respectively. The amount of the carbon–carbon bond and carbon–hydrogen bond decrease and the amount of carbon–oxygen bond increase in the chelating wetting agent soaking coal were less than in the water soaking coal and FeSO4 solution soaking coal. After soaking in the chelating wetting agent, the mechanical properties of the coal were changed, and the uniaxial compressive strength was reduced by 52.55%. The fractal dimension of the coal surface increased from 1.8448 to 1.8575, the average pore diameter in the coal was increased, the specific surface area was reduced, and the number of mesopores also increased. The above results can provide an important theoretical basis for the integrated prevention and control of rock burst-spontaneous combustion compound disaster.

Abstract Irrigation with mine water not only improves water resource utilization rates and alleviates water shortages but can also promote crop growth and yields. However, long-term irrigation with mine water can significantly change the physicochemical properties of soil due to its unique mineral content. In this study, two groups of experiments were conducted (pot experiments and soilless cultivation) using mine water from the Fushun mining area to explore its effects on the physiological and photosynthetic characteristics of ryegrass, as well as soil properties. Mine water irrigation inhibited all of the indicators evaluated in this study, whereas a mixture of clean water and mine water had a stimulatory effect. Interestingly, this stimulatory effect was weakened as the proportion of mine water increased but reached its maximum when the ratio was 2:1. Moreover, the inhibitory effect of the irrigation water was weakened as the proportion of clean water increased. The contents of K+, Na+, Ca2+ and Mg2+ in soil were higher than those in the soil matrix, and the content of the nutrient elements N, P and K, and metal cations increased gradually as the mine water ratio increased, and the electrical conductivity increased significantly. Moreover, the pH of the soil decreased steadily (i.e. acidity increased) with increased soil salinity. Our findings indicated that a mixture of mine water from Fushun mining area and clean water at a 1:2 ratio could improve the physiological, growth, and photosynthetic characteristics of ryegrass by enhancing soil quality. Our study thus provides an experimental precedent for the utilization of mine water in ecological restoration and agricultural irrigation, and could therefore serve as a basis for the development of novel strategies for environmental restoration and the utilization of water resources.

Assessing the health status of old trees is crucial for the effective protection and health management of old trees. In this study, we utilized an unmanned aerial vehicle (UAV) equipped with multispectral cameras to capture images for the rapid assessment of the health status of old trees. All trees were classified according to health status into three classes: healthy, declining, and severe declining trees, based on the above-ground parts of the trees. Two traditional machine learning algorithms, Support Vector Machines (SVM) and Random Forest (RF), were employed to assess their health status. Both algorithms incorporated selected variables, as well as additional variables (aspect and canopy area). The results indicated that the inclusion of these additional variables improved the overall accuracy of the models by 8.3% to 13.9%, with kappa values ranging from 0.166 and 0.233. Among the models tested, the A-RF model (RF with aspect and canopy area variables) demonstrated the highest overall accuracy (75%) and kappa (0.571), making it the optimal choice for assessing the health condition of old trees. Overall, this research presents a novel and cost-effective approach to assessing the health status of old trees.

Alfalfa (M. sativa), a perennial legume forage, is known for its high yield and good quality. As a long-day plant, it is sensitive to changes in the day length, which affects the flowering time and plant growth, and limits alfalfa yield. Photoperiod-mediated delayed flowering in alfalfa helps to extend the vegetative growth period and increase the yield. We isolated a blue-light phytohormone gene from the alfalfa genome that is an ortholog of soybean FKF1 and named it MsFKF1. Gene expression analyses showed that MsFKF1 responds to blue light and the circadian clock in alfalfa. We found that MsFKF1 regulates the flowering time through the plant circadian clock pathway by inhibiting the transcription of E1 and COL, thus suppressing FLOWERING LOCUS T a1 (FTa1) transcription. In addition, transgenic lines exhibited higher plant height and accumulated more biomass in comparison to wild-type plants. However, the increased fiber (NDF and ADF) and lignin content also led to a reduction in the digestibility of the forage. The key genes related to GA biosynthesis, GA20OX1, increased in the transgenic lines, while GA2OX1 decreased for the inactive GA transformation. These findings offer novel insights on the function of MsFKF1 in the regulation of the flowering time and plant height in cultivated M. sativa. These insights into MsFKF1’s roles in alfalfa offer potential strategies for molecular breeding aimed at optimizing flowering time and biomass yield.

Abstract Photocages are a class of substances containing photosensitive groups, also known as “photoremovable protecting groups”, from which target substances are released upon exposure to specific wavelengths of light. The substances released in the light‐promoted processes have chemical or biological properties that enable them to carry specifically designed functions. As a result, photocages can be utilized in various fields such as chemistry, biology, and medicine. In this paper, progress made in research carried out in recent years aimed at developing photocage molecules with different photosensitive moieties is reviewed.

Colorectal cancer (CRC) is ranked as the second leading cause of cancer-related death worldwide. Many abnormally expressed long non-coding RNAs (lncRNAs) in CRC were identified with the development of next-generation sequencing, most functions of which are largely unclear. In this study, we report that the lncRNA SLC7A11-AS1 was significantly overexpressed in CRC by analyzing TCGA database and 6 pairs of clinical samples. High SLC7A11-AS1 level was related to poor CRC overall survival and SLC7A11-AS1 knockdown could inhibit the proliferation, migration and invasion of CRC cell lines. Furthermore, we found there was a positive correlation between the expression of SLC7A11-AS1 and its’ sense transcript SLC7A11. In HCT-8 cells, SLC7A11-AS1 knockdown decreased expression of both SLC7A11 and the nuclear level of NRF2, which happens to be the activator of SLC7A11 transcription. Interestingly, in SLC7A11-AS1 overexpressed CRC tissues, SLC7A11 and NRF2 were also upregulated. Moreover, the ROS levels increased with SLC7A11-AS1 knockdown in HCT-8 cells. And the down regulated expression of SLC7A11 and lower ROS level causing by SLC7A11-AS1 knocked down could be relieved by overexpressed NRF2. These results suggested that upregulated SLC7A11-AS1 might promote the formation and progression of CRC by increasing the expression of NRF2 and SLC7A11, which decreases the ROS level in cancer cells. Therefore, SLC7A11-AS1 could be a potential therapeutic target and diagnostic marker of CRC.

Abstract Background IgA nephropathy (IgAN), which has been reported as the most prevalent glomerulonephritis globally, is the major contributor to end-stage renal diseases. This bioinformatics study aimed to explore glomerulotubular crosstalk genes and dysregulated pathways relating to the pathogenesis of IgAN. Methods The microarray datasets from the Gene Expression Omnibus (GEO) database were searched. Weighted gene co-expression network analysis (WGCNA) and differentially expressed genes (DEGs) of both glomeruli and tubulointerstitium were conducted individually. The co-expression gene modules of glomeruli and tubulointerstitium were compared via gene function enrichment analysis. Subsequently, the crosstalk co-expression network was constructed via the STRING database and key genes were mined from the crosstalk network. Finally, key genes were validated using another GEO dataset (GSE99340) containing RNA-seq data of IgAN and lupus nephritis, and their potential diagnostic values were shown using receiver operating characteristic (ROC) analysis. Results Five hundred eighty-three DEGs and eight modules were identified in glomerular samples, while 272 DEGs and four modules were in tubulointerstitial samples. There were 119 overlapping DEGs between the two groups. Among the distinctive modules, four modules in glomeruli and one module in tubulointerstitium were positively associated with IgAN. While four modules in glomeruli and two modules in tubulointerstitium were negatively associated with IgAN. The top ten key genes screened by CytoHubba were ITGAM, ALB, TYROBP, ITGB2, CYBB, HCK, CSF1R, LAPTM5, FN1, and CTSS. Compared with lupus nephritis, there were significant differences in the expression levels of CYBB, CTSS and TYROBP (P

Camellia oleifera is a vital economic crop of southern China. Accurate mapping and monitoring of Camellia oleifera plantations are essential for promoting sustainable operations within the Camellia oleifera industry. However, traditional remote sensing interpretation methods are no longer feasible for the large-scale extraction of plantation areas. This study proposes a novel deep learning-based method that utilizes GF-2 remote sensing imagery to achieve precise mapping and efficient monitoring of Camellia oleifera plantations. First, we conducted a comparative analysis of the performance of various semantic segmentation models using a self-compiled dataset of Camellia oleifera plantations. Subsequently, we proceeded to validate the prediction results obtained from the most effective deep-learning network model for Camellia oleifera plantations in Hengyang City. Finally, we incorporated DEM data to analyze the spatial distribution patterns. The findings indicate that the U-Net++ network model outperforms other semantic segmentation methods when applied to our self-generated dataset of Camellia oleifera plantations. It achieves a recall rate of 0.89, a precision rate of 0.92, and an mIOU of 0.83, demonstrating the effectiveness of the proposed method in identifying and monitoring Camellia oleifera plantations. By combining the predicted results with the data from DEM, we discovered that these plantations are typically situated at elevations ranging from 50 to 200 m, with slopes below 25°, and facing south or southeast. Moreover, a significant positive spatial correlation and clustering phenomenon are observed among the townships in Hengyang City. The method proposed in this study facilitates rapid and precise identification and monitoring of Camellia oleifera plantations, offering significant theoretical support and a scientific foundation for the management and ecological conservation of Camellia oleifera plantations.

This study explored the microbial population dynamics of Accumulibacter (Acc) at low temperature and metabolic shift to limiting polyphosphate (Poly-P) in enhanced biological phosphorus removal (EBPR) system. The Accumulibacter-enriched EBPR systems, fed with acetate (HAc) and propionate (HPr) at 10 ± 1 °C respectively, were operated for 60 days in two identical SBR reactors (SBR-1 and SBR-2). The phosphorus removal performance in two systems was stable at 10 ± 1 °C, while the microbial community structure changed. Compared with the population structure in seed sludge, Accumulibacter clades reduced in the HAc system, while Acc I increased significantly in the HPr system. Low temperature was beneficial to the formation of granular sludge in the EBPR system, and the sludge granulation in the HAc system was more homogeneous than that in the HPr system. Accumulibacter in the HPr system can get ATP through glycogen accumulating metabolism (GAM) under limiting Poly-P condition at 10 ± 1 °C, while that in the HAc system cannot. This work suggests that poly-P levels can affect the metabolic pathway of Accumulibacter in EBPR systems under low temperature. HIGHLIGHTS Low temperature was more beneficial to the proliferation of Acc I feeding with HPr.; Sludge granulation was achieved in the EBPR system at 10 ± 1 °C.; Acc in HPr system can behave as GAM under the limiting Poly-P at 10 ± 1 °C.;

Introduction: The neurological impairment of survivors after ischemic stroke poses a serious risk to their quality of life and health. Effective therapeutic options are still lacking. Neural stem cells (NSCs) promote neurogenesis via secreted extracellular vesicles (NSC-EVs), which would be a potential therapeutic option, but the insufficient quantity of NSC-EVs in vivo restrains clinical application. Buyang Huanwu Decoction (BHD), a classic traditional Chinese medicine (TCM) decoction, is promising to alleviate neurological impairment after ischemic stroke. It was speculated that BHD might promote neurological recovery through the NSC-EVs.Methods: The medicated plasma of BHD (MP-BHD) was prepared to precondition NSCs and isolate EVs (BHD-NSC-EVs). Middle cerebral artery occlusion (MCAO) models and primary NSCs were administered to evaluate the therapeutic effect. Next-generation sequencing was performed to explore the mechanism.Results: The BHD-NSC-EVs more significantly accelerated neurological recovery after MCAO and promoted NSCs proliferation and differentiation than BHD and NSC-EVs alone. MP-BHD enhanced the largescale generation of BHD-NSC-EVs, which encapsulated functional miRNA and may play critical roles in neurogenesis.Discussion: In replacing BHD or NSCs, the preconditioned NSC-EVs present a more efficient therapeutic strategy for ischemic stroke. Based on the clinical efficacy of TCM, the preconditioning of NSC-derived EVs via the MP of TCM herbs would presents a newly promising therapeutic strategy for neurological diseases.

Purpose: As polygenic risk scores (PRSs) enter clinical practice, health care providers’ and the publics’ comprehension of PRS results are of great importance; yet, they are poorly understood. We present the Vanderbilt polygenic risk scores knowledge scale (Vanderbilt PRS-KS), a tool to quantify PRS knowledge. Methods: The Vanderbilt PRS-KS was developed by a team of genetic counselors and physicians to cover key conceptual facts pertaining to PRSs. We recruited (n = 500) individuals with demographics representative of a U.S. sample and graduate-level health care students (n = 74) at a large academic medical center to participate in this validation study. We evaluated the Vanderbilt PRS-KS’s psychometric properties using confirmatory factor analysis and item response theory. Results: The 7-item Vanderbilt PRS-KS correlated to a single latent construct on confirmatory factor analysis (Λ = 0.31-0.61). The scale showed promising reliability (Cronbach’s α = 0.66) with item response theory summed scores of ≥2 to ≤5, demonstrating reliability >0.70. The Vanderbilt PRS-KS significantly correlated with genetic knowledge and applied PRS knowledge (r = 0.55 and r = 0.29), and graduate-level health care students scored significantly higher compared with the U.S. representative sample (P < .01). Conclusion: The Vanderbilt PRS-KS is a rigorously validated measure to quantify PRS knowledge. Clinicians should tailor future PRS knowledge interventions to the identified knowledge gaps, including PRS inheritance, equity of performance in different ethnicities, and integration with other health determinants.

Plant phenomics aims to perform high-throughput, rapid, and accurate measurement of plant traits, facilitating the identification of desirable traits and optimal genotypes for crop breeding. Salvia miltiorrhiza (Danshen) roots possess remarkable therapeutic effect on cardiovascular diseases, with huge market demands. Although great advances have been made in metabolic studies of the bioactive metabolites, investigation for S. miltiorrhiza roots on other physiological aspects is poor. Here, we developed a framework that utilizes image feature extraction software for in-depth phenotyping of S. miltiorrhiza roots. By employing multiple software programs, S. miltiorrhiza roots were described from 3 aspects: agronomic traits, anatomy traits, and root system architecture. Through K-means clustering based on the diameter ranges of each root branch, all roots were categorized into 3 groups, with primary root-associated key traits. As a proof of concept, we examined the phenotypic components in a series of randomly collected S. miltiorrhiza roots, demonstrating that the total surface of root was the best parameter for the biomass prediction with high linear regression correlation (R2 = 0.8312), which was sufficient for subsequently estimating the production of bioactive metabolites without content determination. This study provides an important approach for further grading of medicinal materials and breeding practices.

Based on 2010-2019 Chinese logistics listed companies as research samples, the paper used the binary Logit model measuring degree of financing constraints. The Kernel density function and Markov chain model are used to forecast China listed companies financing logistics dynamic constraints and business performance growth. Furthermore the stock of knowledge was chosen as a threshold variable to explore the impact of financing constraints on corporate performance growth of listed logistics enterprises. We find that the degree of financing constraints of logistics enterprises in our country has not been significantly eased. Corporate performance has not changed significantly and there are no obvious spatial gap and polarization with the passage of time. The impact of financing constraints on the corporate performance growth of logistics enterprises in China has a double threshold effect of knowledge stock, and has an inhibitory effect that first increases and then decreases. This is because in the short term, the investment of knowledge stock by enterprises can crowd out more corporate liquidity, and in the long run, it is related to the conversion rate of the knowledge stock itself. Because of the uneven regional distribution of resources and differences in the degree of economic development, there is a growing disincentive effect in central China as the stock of knowledge accumulates.

Nonalcoholic fatty liver disease (NAFLD) has become one of the most prominent causes of chronic liver diseases and malignancies. However, few therapy has been approved. Radix Bupleuri (RB) is the most frequently used herbal medicine for the treatment of liver diseases. In the current study, we aim to systemically evaluate the therapeutic effects of saikosaponin A (SSa) and saikosaponin D (SSd), the major bioactive monomers in RB, against NAFLD and to investigate the underlying mechanisms. Our results demonstrated that both SSa and SSd improved diet-induced NAFLD. Integrative lipidomic and transcriptomic analysis revealed that SSa and SSd modulated glycerolipid metabolism by regulating related genes, like Lipe and Lipg. SSd profoundly suppressed the fatty acid biosynthesis by downregulating Fasn and Acaca expression and promoted fatty acid degradation by inducing Acox1 and Cpt1a expression. Bioinformatic analysis further predicted the implication of master transcription factors, including peroxisome proliferator-activated receptor alpha (PPARα), in the protective effects of SSa and SSd. These results were further confirmed in vitro in mouse primary hepatocytes. In summary, our study uncoded the complicated mechanisms underlying the promising anti-steatosis activities of saikosaponins (SSs), and provided critical evidence inspiring the discovery of innovative therapies based on SSa and SSd for the treatment of NAFLD and related complications.

BackgroundFructose consumption is a potential risk factor for hyperuricemia because uric acid (UA) is a byproduct of fructose metabolism caused by the rapid consumption of adenosine triphosphate and accumulation of adenosine monophosphate (AMP) and other purine nucleotides. Additionally, a clinical experiment with four gout patients demonstrated that intravenous infusion of fructose increased the purine de novo synthesis rate, which implied fructose-induced hyperuricemia might be related to purine nucleotide synthesis. Moreover, the mechanistic (mammalian) target of rapamycin (mTOR) is a key protein both involved in fructose metabolism and purine de novo synthesis. The present study was conducted to elucidate how fructose influences mTOR and purine de novo synthesis in a hepatic cell line and livers of mice.Materials and methodsRNA-sequencing in NCTC 1469 cells treated with 0- and 25-mM fructose for 24 h and metabolomics analysis on the livers of mice fed with 0- and 30-g/kg fructose for 2 weeks were assessed. Gene and protein expression of phosphoribosyl pyrophosphate synthase (PRPSAP1), Glutamine PRPP aminotransferase (PPAT), adenyl succinate lyase (ADSL), adenyl succinate synthetase isozyme-1 (Adss1), inosine-5’-monophosphate dehydrogenase (IMPDH), and guanine monophosphate synthetase (GMPS) was measured. The location of PRPSAP1 and PPAT in the liver was assessed by an immunofluorescence assay.ResultsMetabolite profiling showed that the level of AMP, adenine, adenosine, hypoxanthine, and guanine was increased significantly. RNA-sequencing showed that gene expression of phosphoribosyl pyrophosphate synthase (PRPS2), phosphoribosyl glycinamide formyl transferase (GART), AICAR transformylase (ATIC), ADSL, Adss1, and IMPDH were raised, and gene expression of adenosine monophosphate deaminase 3 (AMPD3), adenosine deaminase (ADA), 5’,3’-nucleotidase, cytosolic (NT5C), and xanthine oxidoreductase (XOR) was also increased significantly. Fructose increased the gene expression, protein expression, and fluorescence intensity of PRPSAP1 and PPAT in mice livers by increasing mTOR expression. Fructose increased the expression and activity of XOR, decreased the expression of uricase, and increased the serum level of UA.ConclusionThis study demonstrated that the increased purine de novo synthesis may be a crucial mechanism for fructose-induced hyperuricemia.

Traditional Chinese medicine (TCM) has unique advantages in preventing and treating depression based on holistic concepts and syndrome differentiation and treatment. Liver depression and spleen deficiency are the main syndrome of depression. Danzhi Xiaoyao powder has the efficacy of soothing the liver and relieving depression, nourishing blood, and strengthening spleen. Present studies have proven that it has antidepressant efficacy for the syndrome of liver depression and spleen deficiency. The basic research on pharmacodynamic substances has found that the main active ingredients of Danzhi Xiaoyao powder in the treatment of depression include bupleurum saponin, paeonol, gardenoside, angelica polysaccharide, sulfate polysaccharide, paeoniflorin, albiflorin, atractylone, etc. In clinical practice, Danzhi Xiaoyao powder is often modified to make it more suitable according to the characteristics of pathogenesis and changes in the disease condition. Our research group has found that “brain and spirit failure and liver failing to disperse” are the main pathogenesis of depression. Based on the theory of “liver–brain cotreatment,” the treatment principle of “dispersing the liver and relieving depression, strengthening brain and benefiting intelligence” was put forward. On the basis of Danzhi Xiaoyao powder, Shichangpu (Acori Tatarinowii Rhizoma) was added to enlighten the mind and Yuanzhi (Polygalae Radix) to calm the mind and benefit intelligence. The modified Danzhi Xiaoyao powder was formulated, and its clinical effects on depression were remarkable. Animal experiments also confirmed that modified Danzhi Xiaoyao powder can significantly improve the depression-like behavior of depression model rats and the mechanism may be related to the regulation of the hypothalamic–pituitary–adrenal axis, the increase of the content of 5-hydroxytryptamine, and norepinephrine, which provides a reference for the further promotion of the clinical application of modified Danzhi Xiaoyao powder in the treatment of depression.

Cadmium (Cd) is a harmful heavy metal that is risky for plant growth and human health. The zinc-finger transcription factor ZAT10 is highly conserved with ZAT6 and ZAT12, which are involved in Cd tolerance in plants. However, the definite function of ZAT10 in Cd tolerance remains uncertain. Here, we demonstrated that ZAT10 negatively regulated Cd uptake and enhanced Cd detoxification in Arabidopsis. The expression of ZAT10 in plants is induced by Cd treatment. The zat10 mutant plants exhibited a greater sensitivity to Cd stress and accumulated more Cd in both shoot and root. Further investigations revealed that ZAT10 repressed the transcriptional activity of IRT1, which encodes a key metal transporter involved in Cd uptake. Meanwhile, ZAT10 positively regulated four heavy metal detoxification-related genes: NAS1, NAS2, IRT2, and MTP3. We further found that ZAT10 interacts with FIT, but their regulatory relationship is still unclear. In addition, ZAT10 directly bound to its own promoter and repressed its transcription as a negative feedback regulation. Collectively, our findings provided new insights into the dual functions of ZAT10 on Cd uptake and detoxification in plants and pointed to ZAT10 as a potential gene resource for Cd tolerance improvement in plants.

A continuous-flow Anaerobic/Anoxic/Oxic (A2/O) system was operated at different organic concentrations to systematically investigate the effect on the nutrient removal, secretion characteristics of extracellular polymer, phosphorus forms transformation and changes in functional flora in this system. The results showed that high organic loading was more conducive to promote the secretion of extracellular polymeric substance (EPS), the increase of polysaccharide content was more obvious compared with protein, the impact of organic loading on the components of loosely bound EPS (LB-EPS) was higher than that of tight-bound EPS (TB-EPS). Phosphorus in sludge floc mainly existed in the form of inorganic phosphorus (IP), and IP mainly existed in the form of apatite inorganic phosphorus (AP). High organic load showed higher phosphorus storage in EPS, and the phosphorus content in EPS was positively correlated with the content of EPS. Non-apatite phosphorus (NAIP) content played an important role in the extracellular dephosphorization. The abundance of Nitrosomonas and Nitrospira responsible for nitrification decreased with the increase in organic loading. The group of denitrifiers was large, and Azospira was the most abundant genus among them. Dechloromonas, Acinetobacter, Povalibacter, Chryseolinea and Pirellula were the functional genera closely associated with phosphorus removal. HIGHLIGHTS High organic loading promoted the secretion of EPS, the impact of organic loading on the components of LB-EPS was higher than that of TB-EPS.; NAIP played an important role in the extracellular phosphorus removal.; Influent organic loading shaped the bacterial community structure.; The core functional genera in N and P removal were identified by correlation analysis.;

With the rapid growth of the aviation industry, there is a need for a large number of flight crew. How to select suitable prospective pilots in a cost-efficient manner has become an important research question. In the current study, 23 pilots were recruited from China Eastern Airlines, and 23 novices were from the community of Tsinghua University. A novel approach incorporating machine learning and virtual reality technology was applied to distinguish features between these participants with different flight skills. Results indicate that SVM with the MIC feature selection method consistently achieved the highest prediction performance on all metrics with an accuracy of 0.93, an AUC of 0.96, and an F1 of 0.93, which outperforms four other classifier algorithms and two other feature selection methods. From the perspective of feature selection methods, the MIC method can select features with a nonlinear relationship to sampling labels instead of a simple filter-out. Our new implementation of the SVM + MIC algorithm outperforms all existing pilot selection algorithms and perhaps provides the first implementation based on eye tracking and flight dynamics data. This study’s VR simulation platforms and algorithms can be used for pilot selection, training, and personnel selection in other fields (e.g., astronauts).

Water inrush in karst tunnels will cause casualties and economic losses. Thus, it is significant to objectively assess the water inrush risk level and adopt valid preventive measures to reduce losses from this disaster. The relationship between the factors affecting water inrush in the dynamic coupling system is strong nonlinear, so the attribute recognition model, which lessens the mutation points and error and causes the evaluation results to be more reasonable and accurate, is improved nonlinearly in this paper. Firstly, the assessment system was established by selecting seven factors: formation lithology, unfavorable geological conditions, attitude of rock formation, landform and physiognomy, contact zones of dissolvable and insoluble rock, layer and interlayer fissures, and groundwater level. Secondly, the multi-factor interaction matrix, C-OWA operator, and variable weight theory are used to calculate the constant weight and variable weight of each evaluation index. In addition, the linear attribute measurement function of the attribute identification model is optimized by using the non-linear trigonometric function to distinguish the risk level of the water inrush. Finally, the proposed model was successfully used in Qiyueshan Tunnel. The evaluation results of the risk level are more accurate than other methods, and they are in agreement with the excavation results. The proposed model provides a valuable reference for the risk assessment and project management of tunnel construction.