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Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and heterogeneous interstitial lung disease with a median survival of 2–5 years. Though the diagnosis has been improved due to newly published guidelines, the recognition of the prognosis of IPF remains a challenge. Recently, several studies attempted to build prognostic models by extracting predictive variates from pulmonary function data, basic information, or chest computed tomography (CT) and CT-derived parameters with clinical characteristics. Artificial intelligence (AI) algorithms, including principal component analysis, support vector machine, random survival forest, and convolutional neural network, could be applied to the procedure of IPF prognostic model, that is, region of interest extraction, image feature selection, clinical feature selection, and model construction. Compared to human visualization, AI algorithms show a higher efficiency in calculating and extracting deep features and a lower inter-observer variation. Thus, this review provides a comprehensive CT evaluation of IPF prognostic models and discusses the role of AI in constructing IPF prognostic models. The potential improvements of AI in CT assessments, including time-series CT analysis, optimization of AI algorithms, utilization of multi-modal data, and discovery of new biomarkers through unsupervised algorithms, could be introduced to make a more accurate and convenient assessment for the prognosis of IPF patients. This review describes the status quo and future direction of AI applications in CT analysis for prognostic models of IPF. Take home message The review summarizes the applications of CT and AI algorithms for prognostic models in IPF and procedures of model construction. It reveals the current limitations and prospects of AI-aid models, and helps clinicians to recognize the AI algorithms and apply them to more clinical work.

Abstract Background miR-182 promoter hypermethylation frequently occurs in various tumors, including acute myeloid leukemia, and leads to low expression of miR-182. However, whether adult acute lymphocyte leukemia (ALL) cells have high miR-182 promoter methylation has not been determined. Methods To assess the methylation status of the miR-182 promoter, methylation and unmethylation-specific PCR analysis, bisulfite-sequencing analysis, and MethylTarget™ assays were performed to measure the frequency of methylation at the miR-182 promoter. Bone marrow cells were isolated from miR-182 knockout (182KO) and 182 wild type (182WT) mice to construct BCR-ABL (P190) and Notch-induced murine B-ALL and T-ALL models, respectively. Primary ALL samples were performed to investigate synergistic effects of the hypomethylation agents (HMAs) and the BCL2 inhibitor venetoclax (Ven) in vitro. Results miR-182 (miR-182-5P) expression was substantially lower in ALL blasts than in normal controls (NCs) because of DNA hypermethylation at the miR-182 promoter in ALL blasts but not in normal controls (NCs). Knockout of miR-182 (182KO) markedly accelerated ALL development, facilitated the infiltration, and shortened the OS in a BCR-ABL (P190)-induced murine B-ALL model. Furthermore, the 182KO ALL cell population was enriched with more leukemia-initiating cells (CD43+B220+ cells, LICs) and presented higher leukemogenic activity than the 182WT ALL population. Furthermore, depletion of miR-182 reduced the OS in a Notch-induced murine T-ALL model, suggesting that miR-182 knockout accelerates ALL development. Mechanistically, overexpression of miR-182 inhibited proliferation and induced apoptosis by directly targeting PBX3 and BCL2, two well-known oncogenes, that are key targets of miR-182. Most importantly, DAC in combination with Ven had synergistic effects on ALL cells with miR-182 promoter hypermethylation, but not on ALL cells with miR-182 promoter hypomethylation. Conclusions Collectively, we identified miR-182 as a tumor suppressor gene in ALL cells and low expression of miR-182 because of hypermethylation facilitates the malignant phenotype of ALL cells. DAC + Ven cotreatment might has been applied in the clinical try for ALL patients with miR-182 promoter hypermethylation. Furthermore, the methylation frequency at the miR-182 promoter should be a potential biomarker for DAC + Ven treatment in ALL patients.

Abstract X-ray computed tomography (XCT) and X-ray fluorescence (XRF) imaging are two non-invasive imaging techniques to study cellular structures and chemical element distributions, respectively. However, correlative X-ray computed tomography and fluorescence imaging for the same cell have yet to be routinely realized due to challenges in sample preparation and X-ray radiation damage. Here we report an integrated experimental and computational workflow for achieving correlative multi-modality X-ray imaging of a single cell. The method consists of the preparation of radiation-resistant single-cell samples using live-cell imaging-assisted chemical fixation and freeze-drying procedures, targeting and labeling cells for correlative XCT and XRF measurement, and computational reconstruction of the correlative and multi-modality images. With XCT, cellular structures including the overall structure and intracellular organelles are visualized, while XRF imaging reveals the distribution of multiple chemical elements within the same cell. Our correlative method demonstrates the feasibility and broad applicability of using X-rays to understand cellular structures and the roles of chemical elements and related proteins in signaling and other biological processes.

The continuous emergence of highly immune-evasive SARS-CoV-2 variants has challenged vaccine efficacy. A vaccine that can provide broad protection is desirable. We evaluated the immunogenicity of a series of monovalent and bivalent adenovirus-vectored vaccines containing the spikes of Wildtype (WT), Beta, Delta, Omicron subvariants BA.1, BA.2, BA.2.12.1, BA.2.13, BA.3, BA.5, BQ.1.1, and XBB. Vaccination in mice using monovalent vaccines elicited the highest neutralizing titers against each self-matched strain, but against other variants were reduced 2− to 73-fold. A bivalent vaccine consisting of WT and BA.5 broadened the neutralizing breadth against pre-Omicron and Omicron subvariants except XBB. Among bivalent vaccines based on the strains before the emergence of XBB, a bivalent vaccine consisting of BA.2 and BA.5 elicited the most potent neutralizing antibodies against Omicron subvariants, including XBB. In mice primed with injected WT vaccine, intranasal booster with a bivalent vaccine containing XBB and BA.5 could elicit broad serum and respiratory mucosal neutralizing antibodies against all late Omicron subvariants, including XBB. In mice that had been sequentially vaccinated with WT and BA.5, intranasal booster with a monovalent XBB vaccine elicited greater serum and mucosal XBB neutralizing antibodies than bivalent vaccines containing XBB. Both monovalent and bivalent XBB vaccines induced neutralizing antibodies against EG.5. Unlike the antibody response, which is highly variant-specific, mice receiving either monovalent or bivalent vaccines elicited comparable T-cell responses against all variants. Furthermore, intranasal but not intramuscular booster induced antigen-specific lung resident T cells. This study provides insights into the design of the COVID-19 vaccine and vaccination strategies.

ABSTRACTNeutralizing antibodies are a key component in protective humoral immunity against SARS-CoV-2. Currently, available technologies cannot track epitope-specific antibodies in global antibody repertoires. Thus, the comprehensive repertoire of spike-specific neutralizing antibodies elicited by SARS-CoV-2 infection is not fully understood. We therefore combined high-throughput immunoglobulin heavy chain (IgH) repertoire sequencing, and structural and bioinformatics analysis to establish an antibodyomics pipeline, which enables tracking spike-specific antibody lineages that target certain neutralizing epitopes. We mapped the neutralizing epitopes on the spike and determined the epitope-preferential antibody lineages. This analysis also revealed numerous overlaps between immunodominant neutralizing antibody-binding sites and mutation hotspots on spikes as observed so far in SARS-CoV-2 variants. By clustering 2677 spike-specific antibodies with 360 million IgH sequences that we sequenced, a total of 329 shared spike-specific antibody clonotypes were identified from 33 COVID-19 convalescents and 24 SARS-CoV-2-naïve individuals. Epitope mapping showed that the shared antibody responses target not only neutralizing epitopes on RBD and NTD but also non-neutralizing epitopes on S2. The immunodominance of neutralizing antibody response is determined by the occurrence of specific precursors in human naïve B-cell repertoires. We identified that only 28 out of the 329 shared spike-specific antibody clonotypes persisted for at least 12 months. Among them, long-lived IGHV3-53 antibodies are likely to evolve cross-reactivity to Omicron variants through accumulating somatic hypermutations. Altogether, we created a comprehensive atlas of spike-targeting antibody lineages in COVID-19 convalescents and antibody precursors in human naïve B cell repertoires, providing a valuable reference for future vaccine design and evaluation.

There is a relative lack of research aimed at developing a comprehensive index system for low-carbon development of power systems in load-intensive cities in China. First, this paper outlined the main challenges faced in the urban power system development process and determined development goals and key indexes that combined the macro goals and requirements of constructing new power systems with the development characteristics and trends of load-intensive urban power systems. Second, a comprehensive index system and evaluation method for the low-carbon development of power systems was proposed to consider the perspectives of safety, efficiency, clean energy, low carbon, and flexibility. Finally, the effectiveness of the proposed index system and evaluation method was verified by taking the development of actual power systems in ultra-large-load-intensive cities as an example, providing support for the development decision making of actual urban power system construction and transformation.

IntroductionIn Northeast China, Dorper and Australian White rams are commonly crossbred with small-tailed Han (STH) ewes to improve the offspring's meat yield and quality. However, the differences in traits and the flavor between the crossbred sheep and STH sheep remain unclear. In addition, the candidate genes potentially influencing the meat quality in the three sheep breeds require further verification.MethodsA total of 18 2-month-old healthy rams were raised over a period of 5 months, which included 6 STH, 6 Dorper and small-tailed Han crossbred (Do × STH), and 6 Australian white and small-tailed Han crossbred (Au × STH) offspring. The differences in slaughter, meat quality traits, fatty acid and amino acid composition in the muscular longissimus dorsi (MLD), and volatile compounds in the semitendinosus muscle were compared between the sheep breeds. The candidate genes related to intramuscular fat (IMF) content and fatty acids were validated.ResultsThe results of this study revealed that the crossbred sheep had higher body weight, carcass weight, bone weight, net meat weight, and IMF content than the STH sheep (p < 0.05). The Do × STH offspring had a higher pH value (24 h), moisture content, and cooking percentage; they also had redder and brighter meat color. The content of myristate, palmitic, and margaric acids in the crossbred sheep was higher than that in the STH sheep (p < 0.05). The Do × STH offspring had the highest saturated fatty acid content (p < 0.05). The Au × STH offspring had the highest protein content (p < 0.05). The arachidonic acid and amino acid (Asp, Ala, Ile, Leu, Lys, Thr, and essential amino acid) contents were higher in the STH sheep than in the crossbred sheep (p < 0.05). The odor activity value (OAV) analysis showed that most of the aldehydes in the Au × STH offspring had higher values. The PDK4 gene expression was positively associated with the IMF content and was negatively correlated with the linoleic acid content in the Do × STH sheep (p < 0.05). The TMEM273 gene expression was positively associated with linoleic and arachidonic acid contents and was negatively correlated with oleic and palmitic acid contents in the Do × STH sheep (p < 0.05).DiscussionThe results showed the differences between the crossbred sheep and STH sheep and provided the candidate genes related to meat quality in sheep.

The Arctic fox (Vulpes lagopus) is a species indigenous to the Arctic and has developed unique lipid metabolism, but the mechanisms remain unclear. Here, the significantly increased body weight of Arctic foxes was consistent with the significantly increased serum very-low-density lipoprotein (VLDL), and the 40% crude fat diet further increased the Arctic fox body weight. The enhanced body weight gain stems primarily from increased subcutaneous adipose tissue accumulation. The adipose triacylglycerol and phosphatidylethanolamine were significantly greater in Arctic foxes. The adipose fatty-acid synthase content was significantly lower in Arctic foxes, highlighting the main role of exogenous fatty-acids in fat accumulation. Considering the same diet, liver-derived fat dominates adipose expansion in Arctic foxes. Liver transcriptome analysis revealed greater fat and VLDL synthesis in Arctic foxes, consistent with the greater VLDL. Glucose homeostasis wasn’t impacted in Arctic foxes. And the free fatty-acids in adipose, which promote insulin resistance, also did not differ between groups. However, the hepatic glycogen was greater in Arctic foxes and transcriptome analysis revealed upregulated glycogen synthesis, improving glucose homeostasis. These results suggest that the superior fat accumulation capacity and distinct characteristics of hepatic and adipose lipid and glucose metabolism facilitate glucose homeostasis and massive fat accumulation in Arctic foxes.

Abstract Background Ferroptosis is a new form of nonapoptotic and iron-dependent type of cell death. Glutathione peroxidase-4 (GPX4) plays an essential role in anti-ferroptosis by reducing lipid peroxidation. Although acute myeloid leukemia (AML) cells, especially relapsed and refractory (R/R)-AML, present high GPX4 levels and enzyme activities, pharmacological inhibition of GPX4 alone has limited application in AML. Thus, whether inhibition of GPX4 combined with other therapeutic reagents has effective application in AML is largely unknown. Methods Lipid reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) assays were used to assess ferroptosis in AML cells treated with the hypomethylating agent (HMA) decitabine (DAC), ferroptosis-inducer (FIN) RAS-selective lethal 3 (RSL3), or their combination. Combination index (CI) analysis was used to assess the synergistic activity of DAC + RSL3 against AML cells. Finally, we evaluated the synergistic activity of DAC + RSL3 in murine AML and a human R/R-AML-xenografted NSG model in vivo. Results We first assessed GPX4 expression and found that GPX4 levels were higher in AML cells, especially those with MLL rearrangements, than in NCs. Knockdown of GPX4 by shRNA and indirect inhibition of GPX4 enzyme activity by RSL3 robustly induced ferroptosis in AML cells. To reduce the dose of RSL3 and avoid side effects, low doses of DAC (0.5 µM) and RSL3 (0.05 µM) synergistically facilitate ferroptosis by inhibiting the AMP-activated protein kinase (AMPK)-SLC7A11-GPX4 axis. Knockdown of AMPK by shRNA enhanced ferroptosis, and overexpression of SLC7A11 and GPX4 rescued DAC + RSL3-induced anti-leukemogenesis. Mechanistically, DAC increased the expression of MAGEA6 by reducing MAGEA6 promoter hypermethylation. Overexpression of MAGEA6 induced the degradation of AMPK, suggesting that DAC inhibits the AMPK-SLC7A11-GPX4 axis by increasing MAGEA6 expression. In addition, DAC + RSL3 synergistically reduced leukemic burden and extended overall survival compared with either DAC or RSL3 treatment in the MLL-AF9-transformed murine model. Finally, DAC + RSL3 synergistically reduced viability in untreated and R/R-AML cells and extended overall survival in two R/R-AML-xenografted NSG mouse models. Conclusions Our study first identify vulnerability to ferroptosis by regulating MAGEA6-AMPK-SLC7A11-GPX4 signaling pathway. Combined treatment with HMAs and FINs provides a potential therapeutic choice for AML patients, especially for R/R-AML.

Ginger, as a rich herb resource in China, has played an important role in food and medicine since ancient times. It is also known as a medicinal and edible homologous plant that possesses unique medical and nutritional values. Ginger polysaccharide is considered one of the most important bio-active components in ginger, which have attracted many attentions for various of bioactivities. In this review, the methods of extraction and purification of polysaccharide, as well as structural characteristics are discussed, what’s more, functional properties including antioxidant, immunity regulatory, anti-tumor and their influencing factors are reviewed. It is expected to provide valuable reference for further research and industrial application of ginger polysaccharide.

BackgroundOccupational commitment (OC) is a multidimensional construct that predicts turnover intentions. The interindividual variability of nurses’ OC merits further exploration. Therefore, this study aims to examine patterns of OC and its relationship with psychological empowerment and job crafting in nurses.MethodsA sample of 1,061 nurses was recruited from February 2022 to April 2022 by using a stratified four-stage cluster sampling procedure. A self-report survey included the Psychological Empowerment Scale, Job Crafting Scale, and Occupational Commitment Scale. Latent profile analysis (LPA) was used to examine the patterns of OC. Associations of the latent class membership with individual characteristics, psychological empowerment and job crafting were examined using multinomial logistic regression.ResultsThree patterns of OC were identified: (1) “Low OC group” (n = 224, 21.1%); (2) “Moderate OC group” (n = 665, 62.7%); (3) “High OC group” (n = 172, 16.2%). Nurses with higher education, fewer years of service, working in medicine, lower psychological empowerment and lower job crafting had a higher likelihood of belonging to Class 1 (Low OC group). In contrast, nurses working in emergency and with higher psychological empowerment and job crafting were more likely to belong to Class 3 (High OC group).ConclusionThe findings revealed the heterogeneity of occupational commitment among nurses in China and could guide the identification and early intervention of nurses with low level of occupational commitment.

IntroductionThe mental health of university students is influenced by a variety of factors, including self-esteem and personality traits, with resilience playing a crucial role in mediating and moderating these relationships. This study investigates the intricate dynamics affecting mental well-being in Chinese university students, focusing on the roles of self-esteem, personality traits, and the interventional effects of resilience.MethodsA cross-sectional survey was conducted with 689 students, aged on average 20.3 years, between April and July 2022. The Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS) was used to assess mental well-being, while resilience, personality traits, and self-esteem were evaluated using the revised Connor-Davidson Resilience Scale (CD-RISC), the Chinese version of the Big Five Inventory-2 (BFI-2), and the Texas Social Behavior Inventory (TSBI), respectively.ResultsAnalysis revealed significant correlations between self-esteem, personality traits, and both resilience and mental well-being. Resilience was found to partially mediate the relationship between self-esteem and mental well-being and fully mediate certain aspects of the relationship between personality traits and mental well-being. Additionally, tenacity and autonomy were identified as moderators in the link between specific personality traits and mental well-being.DiscussionThe findings highlight the complex interplay between self-esteem, personality traits, resilience, and mental well-being, underscoring the critical role of resilience. This insight is pivotal for developing targeted interventions to bolster mental well-being among university students, emphasizing the need for multifaceted support strategies to enhance student mental health.

Klebsiella pneumoniae (K. pneumoniae) is a common bacterium that can cause iatrogenic infection. Recently, the rise of antibiotic resistance among K. pneumoniae strains is one key factor associated with antibiotic treatment failure. Hencefore, there is an urgent need for effective K. pneumoniae vaccines. This study aimed to design a multi-epitope vaccine (MEV) candidate against K. pneumonia by utilizing an immunoinformatics method. In this study, we obtained 15 cytotoxic T lymphocyte epitopes, 10 helper T lymphocyte epitopes, 6 linear B-cell epitopes, and 2 conformational B-cell epitopes for further research. Then, we designed a multi-epitope vaccine composed of a total of 743 amino acids, containing the epitopes linked by GPGPG flexible links and an EAAAK linker to the Cholera Toxin Subunit B coadjuvant.The observed properties of the MEV, including non-allergenicity, high antigenicity, and hydrophilicity, are noteworthy. The improvements in the tertiary structure through structural refinement and disulfide bonding, coupled with promising molecular interactions revealed by molecular dynamics simulations with TLR4, position the MEV as a strong candidate for further investigation against K. pneumoniae.

Abstract Background Breast cancer‐related lymphedema (BCRL) is one of the common postoperative complications that severely affects the functions of the arm and quality of life. Since lymphedema is difficult to treat and prone to recurrence, early prevention of lymphedema is crucial. Methods Patient diagnosed with breast cancer (N = 108) were randomized to the intervention (n = 52) or control group (n = 56). In the intervention group, patients were provided the lymphedema prevention program based on the theory of knowledge–attitude–practice during the perioperative period and the first three chemotherapy sessions (mainly includes health education, seminars, knowledge manuals, sports guidance, peer education, and WeChat group).The limb volume, handgrip strength, arm function, and quality of life were measured in all patients at the baseline, 9 weeks (T1), and 18 weeks (T2) after surgery. Results The incidence of lymphedema in the Intervention group was numerically lower than in the control group after implementing the lymphedema prevention program, but the difference was not statistically significant (T1: 1.9% vs. 3.8%, p = 1.000; T2: 3.6% vs. 7.1%, p = 0.744). However, compared with the control group, the intervention group showed there was less deterioration in handgrip strength (T1 [t = −2.512, p

Clubroot disease, caused by Plasmodiophora brassicae, is a serious soil-borne disease in Brassica crops worldwide. It seriously occurs in conducive soils of southern China, while never happens in some areas of northern China with suppressive soils. To understanding the differences, we measured the soil suppressiveness, chemical properties, and microbial communities in suppressive and conducive soils by bioassay and sequencing of 16S and 18S rRNA amplicons. The biological basis of clubroot suppressiveness was supported by the ability to remove it by pasteurization. The pH value and calcium content in the suppressive soils were higher than those in the conducive soils. Suppressive soils were associated with higher fungal diversity and bacterial abundance. The fungal phyla Chytridiomycota, Olpidiomycota, and Mucoromycota and the bacterial phyla Acidobacteriota and Gemmatimonadota were enriched in suppressive soils. More abundant beneficial microbes, including Chaetomium and Lysobacter, were found in the suppressive soils than in the conducive soils. Molecular ecological network analysis revealed that the fungal network of suppressive soils was more complex than that of conducive soils. Our results indicate that plant health is closely related to soil physicochemical and biological properties. This study is of great significance for developing strategies for clubtroot disease prevention and control.

ABSTRACT Latent viral reservoir is recognized as the major obstacle to achieving a functional cure for HIV infection. We previously reported that arsenic trioxide (As2O3) combined with antiretroviral therapy (ART) can reactivate the viral reservoir and delay viral rebound after ART interruption in chronically simian immunodeficiency virus (SIV)-infected macaques. In this study, we further investigated the effect of As2O3 independent of ART in chronically SIV-infected macaques. We found that As2O3-only treatment significantly increased the CD4/CD8 ratio, improved SIV-specific T cell responses, and reactivated viral latency in chronically SIVmac239-infected macaques. RNA-sequencing analysis revealed that As2O3 treatment downregulated the expression levels of genes related to HIV entry and infection, while the expression levels of genes related to transcription initiation, cell apoptosis, and host restriction factors were significantly upregulated. Importantly, we found that As2O3 treatment specifically induced apoptosis of SIV-infected CD4+ T cells. These findings revealed that As2O3 might not only impact viral latency, but also induce the apoptosis of HIV-infected cells and thus block the secondary infection of bystanders. Moreover, we investigated the therapeutic potential of this regimen in acutely SIVmac239-infected macaques and found that As2O3 + ART treatment effectively restored the CD4+ T cell count, delayed disease progression, and improved survival in acutely SIV-infected macaques. In sum, this work provides new insights to develop As2O3 as a component of the “shock-and-kill” strategy toward HIV functional cure. IMPORTANCE Although antiretroviral therapy (ART) can effectively suppress the viral load of AIDS patients, it cannot functionally cure HIV infection due to the existence of HIV reservoir. Strategies toward HIV functional cure are still highly anticipated to ultimately end the pandemic of AIDS. Herein, we investigated the direct role of As2O3 independent of ART in chronically SIV-infected macaques and explored the underlying mechanisms of the potential of As2O3 in the treatment of HIV/SIV infection. Meanwhile, we investigated the therapeutic effects of ART+As2O3 in acutely SIVmac239-infected macaques. This study showed that As2O3 has the potential to be launched into the “shock-and-kill” strategy to suppress HIV/SIV reservoir due to its latency-reversing and apoptosis-inducing properties.

Summary: The slime mould algorithm (SMA) is a population-based swarm intelligence optimization algorithm that simulates the oscillatory foraging behavior of slime moulds. To overcome its drawbacks of slow convergence speed and premature convergence, this paper proposes an improved algorithm named PSMADE, which integrates the differential evolution algorithm (DE) and the Powell mechanism. PSMADE utilizes crossover and mutation operations of DE to enhance individual diversity and improve global search capability. Additionally, it incorporates the Powell mechanism with a taboo table to strengthen local search and facilitate convergence toward better solutions. The performance of PSMADE is evaluated by comparing it with 14 metaheuristic algorithms (MA) and 15 improved MAs on the CEC 2014 benchmarks, as well as solving four constrained real-world engineering problems. Experimental results demonstrate that PSMADE effectively compensates for the limitations of SMA and exhibits outstanding performance in solving various complex problems, showing potential as an effective problem-solving tool.

Oxidative stress, inflammatory response, and gut-liver axis dysbiosis have been suggested as the primarily involved in the pathogenesis of alcoholic liver injury. Previous research established that yeast extract (YE) has antioxidant, immune-boosting or microbiota-regulating properties. However, there is currently lack of information regarding the efficacy of YE on alcoholic liver injury. This study seeks to obtain data that will help to address this research gap using a Wistar male rat experimental model. Histologic and biochemical analysis results showed that the groups treated with both low-dose yeast extract (YEL) and high-dose yeast extract (YEH) had lower degrees of alcohol-induced liver injury. The abundance of Peptococcus and Ruminococcus reduced in the low-dose yeast extract (YEL) group, while that of Peptococcus, Romboutsia, Parasutterella, and Faecalibaculum reduced in the high-dose (YEH) group. Furthermore, Spearman analysis showed that the gut microbes were significantly associated with several liver-related indicators. For the analysis of differential metabolites and enriched pathways in the YEL group, the abundance of lysophosphatidylcholine (16:0/0:0) significantly increased, and then the levels of histamine, adenosine and 5′ -adenine nucleotide were remarkedly elevated in the YEH group. These findings suggest that both high and low doses of YE can have different protective effects on liver injury in alcoholic liver disease (ALD) rats, in addition to improving gut microbiota disorder. Besides, high-dose YE has been found to be more effective than low-dose YE in metabolic regulation, as well as in dealing with oxidative stress and inflammatory responses.

Clubroot (Plasmodiophora brassicae) is an important soilborne disease that causes severe damage to cruciferous crops in China. This study aims to compare the differences in chemical properties and microbiomes between healthy and clubroot-diseased soils. To reveal the difference, we measured soil chemical properties and microbial communities by sequencing 18S and 16S rRNA amplicons. The available potassium in the diseased soils was higher than in the healthy soils. The fungal diversity in the healthy soils was significantly higher than in the diseased soils. Ascomycota and Proteobacteria were the most dominant fungal phylum and bacteria phylum in all soil samples, respectively. Plant-beneficial microorganisms, such as Chaetomium and Sphingomonas, were more abundant in the healthy soils than in the diseased soils. Co-occurrence network analysis found that the healthy soil networks were more complex and stable than the diseased soils. The link number, network density, and clustering coefficient of the healthy soil networks were higher than those of the diseased soil networks. Our results indicate that the microbial community diversity and network structure of the clubroot-diseased soils were different from those of the healthy soils. This study is of great significance in exploring the biological control strategies of clubroot disease.

Toll-like receptors (TLRs) play key roles in activating immune responses during infection. In this study, we identified TLR genes in Manila clam at the genome-wide level and characterized it into 9 types according to the Ruditapes philippinarum genome annotation, including TLR1 (1–10), TLR2 (1–10), TLR2–2 (1–5), TLR3 (1–3), TLR4 (1–9), TLR5, TLR6 (1–5), TLR7 (1–2), and TLR13 (1–4). The length of TLR proteins varied from 128 to 1257 amino acids. The molecular weights and theoretical isoelectric point (pI) values ranged from 14.63 to 143.32 kDa and 4.47 to 9.45, respectively. TLR genes showed universal expression levels in adductor muscle (AM), mantle (M), foot (F), gill (GI), pipe (P), digestive gland (DG), gonad (GO) and labial palp (L). Transcriptome analysis revealed that the expression level of TLR4, TLR5, TLR7 and TLR13 genes are significantly highly expressed in resistant individuals of Manila clam under Vibrio anguillarum challenge, indicating these TLR genes may play significant roles in response to invading pathogens. The results obtained in this work will provide valuable insights into the immune function of TLR gene in R. philippinarum.

CRISPR/Cas technology originated from the immune mechanism of archaea and bacteria and was awarded the Nobel Prize in Chemistry in 2020 for its success in gene editing. Molecular diagnostics is highly valued globally for its development as a new generation of diagnostic technology. An increasing number of studies have shown that CRISPR/Cas technology can be integrated with biosensors and bioassays for molecular diagnostics. CRISPR-based detection has attracted much attention as highly specific and sensitive sensors with easily programmable and device-independent capabilities. The nucleic acid-based detection approach is one of the most sensitive and specific diagnostic methods. With further research, it holds promise for detecting other biomarkers such as small molecules and proteins. Therefore, it is worthwhile to explore the prospects of CRISPR technology in biosensing and summarize its application strategies in molecular diagnostics. This review provides a synopsis of CRISPR biosensing strategies and recent advances from nucleic acids to other non-nucleic small molecules or analytes such as proteins and presents the challenges and perspectives of CRISPR biosensors and bioassays.

A long-term high-fat diet causes hepatic steatosis, which further leads to oxidative stress and inflammation. In this study, we firstly investigated the regulation effects of different amounts of quinoa on hepatic steatosis, oxidative stress, and inflammation of rats fed a high-fat diet, then the gut microbiota was dynamically determined. Sprague–Dawley (SD, male) rats were randomized into four groups: normal controls (NC, fed standard chow), model groups (HF, fed a high-fat diet), low quinoa intake (HF + LQ), and high quinoa intake (HF + HQ) groups, which were supplemented with 9% and 27% quinoa in the high-fat feed (equivalent to 100 g/day and 300 g/day human intake, respectively). The results showed that quinoa intake significantly inhibited the hepatomegaly and splenomegaly, ameliorated hepatic steatosis pathologically; effectively rescued the decrease in the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) and the increase in malondialdehyde (MDA). The levels of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), transforming growth factor-β (TGF-β), and leptin in rats of two quinoa groups were close to those of the NC group. Besides, high quinoa intake significantly increased the relative abundance of Akkermansia, and low quinoa intake significantly increased the relative abundance of Blautia at the genus level. The relative abundances of Blautia and Dorea in rats in the HF + HQ group were lower than those in rats in the HF + LQ group. In addition, the relative abundances of Clostridium and Turicibacter of rats in the two quinoa intervention groups were lower than those of rats in the HF group after 12 weeks of intervention. In summary, quinoa exhibits a series of beneficial effects in the prevention of nonalcoholic fatty liver disease (NAFLD) and is suggested to be a component of a daily diet for the prevention of NAFLD.

The spontaneous combustion of coal gangue dumps after reclamation causes severe harm to the ecological environment surrounding mining areas. Using remote sensing technology to determine vegetation heat stress levels is an important way to evaluate the probability of a spontaneous combustion disaster. The canopy spectra and chlorophyll fluorescence (ChlF) parameters of alfalfa were collected through pot experiments to simulate different heat stress levels. Time series analyses of three ChlF (chlorophyll fluorescence) parameters showed that the regularity of the quantum efficiency of photosystem II (PSII) in light-adapted conditions (Fv′/Fm′) was stronger during the monitoring period. The correlation coefficients between the three ChlF parameters and the canopy raw spectrum, first derivative spectrum, and vegetation indices were calculated, and the spectral features were found to be more correlated. Lasso regression was used to further screen spectral features, and the optimal spectral features were the raw spectral value at 741 nm (abbreviated as RS (741)) and NDVI (652, 671). To discriminate among heat stress levels accurately and automatically, we built a time convolution neural network. The classification results showed that when the sequence length is 3, the heat stress is divided into three categories, and the model obtains the highest accuracy. In combination with relevant research conclusions on the temperature distribution law of spontaneous combustion in coal gangue dumps, three heat stress levels can be used to assess the potential of spontaneous combustion in coal gangue dumps after reclamation. The research results provide an important theoretical basis and technical support for early warnings regarding spontaneous combustion disasters in reclaimed coal gangue dumps.

Ultraviolet B (UV-B) irradiation has been demonstrated to play a synergistic effect with wounding in enhancing the accumulation of phenolic antioxidants in carrots. However, little is known about the molecular mechanisms of UV-B treatment on wounded carrots. In this study, wounded carrots were exposed to different doses of UV-B light, then stored at 15 °C for 2 d. The results showed that the content of phenolic compounds in 1 KJ m−2 UV-B–treated samples was 415% and 247% higher than that of whole and wounded carrots, respectively. Based on this, 1 KJ m−2 was selected as the optimal dose of UV-B treatment and used for further analysis. In addition, UV-B treatment greatly enhanced the enzyme activity of phenylalanine ammonia lyase (PAL) and the contents of phenolic profiles, especially 3-O-caffeoylquinic acid (3-CQA). Transcriptome analysis found that UV-B treatment could accelerate the KEGG pathways involved in signal transduction and secondary substance metabolism. The differentially expressed genes (DEGs) in phenolics biosynthesis–related metabolic processes of shikimate pathway and phenylpropanoid biosynthesis were extensively upregulated by UV-B treatment. Our results provided fundamental information for a better understanding of the molecular regulation mechanism of UV-B treatment in promoting the accumulation of phenolic compounds in wounded carrots.

Pimpinellin is a coumarin-like compound extracted from the root of Toddalia asiatica. Its effects on platelet function has not been investigated. This study found that pimpinellin pretreatment effectively inhibited collagen-induced platelet aggregation, but did not alter ADP- and thrombin-induced aggregation. Platelets pretreated with pimpinellin showed reduced α granule (CD62) level and secretion of dense granule (ATP release). Pimpinellin-treated platelets also exhibited decreased clot reaction and TxB2 production. Pimpinellin pretreatment suppressed adhesion and spreading of human platelets on the fibrinogen coated surface. Analysis of tail bleeding time of mice administered with pimpinellin (40 mg/kg) revealed that pimpinellin did not change tail bleeding time significantly, number of blood cells, and APTT and PT levels. Pimpinellin inhibited collagen-induced ex vivo aggregation of mice platelets. Immunoblotting results showed that pimpinellin suppressed collagen-induced phosphorylation of PI3K-Akt-Gsk3β and PKC/MAPK in platelets.

In this study, we examined whether vowel length affected the perceptual and emotional evaluations of Japanese sound-symbolic words. The perceptual and emotional features of Japanese sound-symbolic words, which included short and long vowels, were evaluated by 209 native Japanese speakers. The results showed that subjective evaluations of familiarity, visual imageability, auditory imageability, tactile imageability, emotional valence, arousal, and length were significantly higher for sound-symbolic words with long vowels compared to those with short vowels. Additionally, a subjective evaluation of speed was significantly higher for written Japanese sound-symbolic words with short vowels than for those with long vowels. The current findings suggest that vowel length in written Japanese sound-symbolic words increases the perceptually and emotionally subjective evaluations of Japanese sound-symbolic words.

Organizational external behavior changes are caused by the internal structure and interactions. External behaviors are also known as the behavioral events of an organization. Detecting event-related changes in organizational networks could efficiently be used to monitor the dynamics of organizational behaviors. Although many different methods have been used to detect changes in organizational networks, these methods usually ignore the correlation between the internal structure and external events. Event-related change detection considers the correlation and could be used for event recognition based on social network modeling and supervised classification. Detecting event-related changes could be effectively useful in providing early warnings and faster responses to both positive and negative organizational activities. In this study, event-related change in an organizational network was defined, and artificial neural network models were used to quantitatively determine whether and when a change occurred. To achieve a higher accuracy, Back Propagation Neural Networks (BPNNs) were optimized using Genetic Algorithms (GAs) and Particle Swarm Optimization (PSO). We showed the feasibility of the proposed method by comparing its performance with that of other methods using two cases. The results suggested that the proposed method could identify organizational events based on a correlation between the organizational networks and events. The results also suggested that the proposed method not only has a higher precision but also has a better robustness than the previously used techniques.

Objective: This study aimed to reveal the age-related changes in prevalence and symptom characteristics in kidney deficiency syndrome (KDS) with varied health status. Methods: This cross-sectional observational study was conducted in6 hospitals. Investigators queried participants aged 20–79 about their health, including symptoms if any, and completed questionnaires to collect participants responses. Prevalence, severity, and frequency of KDS and other relevant parameters were observed and recorded. Comparative analysis of countable variables, including prevalence, was performed by frequency analysis and χ2 test and expressed as a composite ratio. Comparative analysis of quantitative scores of the severity and frequency of symptoms was performed by the rank-sum test. Regression analysis of the correlation of KDS with potential contributing factors was performed by non-conditional binary logistic stepwise regression of numerical variables. Results: Prevalence of KDS in healthy and unhealthy participants correlated with increasing age (P 0.05). Age, health status, lower back pain, shin soreness or heel pain, tinnitus or deafness, hair loss or loose teeth, incomplete bladder emptying or incontinence, and sexual dysfunction or infertility were potential factors contributing to KDS (P 1. Moreover, the distribution of typical KDS-related symptoms showed dramatic regularities. Conclusion: Prevalence and symptom characteristics of KDS were found to increase consistently with increasing age and deteriorating health status. Kidney deficiency may be an important mechanism of aging in the subhealthy and chronic disease states.

The multi-layered cell envelope structure of Gram-negative bacteria represents significant physical and chemical barriers for short-tailed phages to inject phage DNA into the host cytoplasm. Here we show that a DNA-injection protein of bacteriophage Sf6, gp12, forms a 465-kDa, decameric assembly in vitro. The electron microscopic structure of the gp12 assembly shows a ~150-Å, mushroom-like architecture consisting of a crown domain and a tube-like domain, which embraces a 25-Å-wide channel that could precisely accommodate dsDNA. The constricted channel suggests that gp12 mediates rapid, uni-directional injection of phage DNA into host cells by providing a molecular conduit for DNA translocation. The assembly exhibits a 10-fold symmetry, which may be a common feature among DNA-injection proteins of P22-like phages and may suggest a symmetry mismatch with respect to the 6-fold symmetric phage tail. The gp12 monomer is highly flexible in solution, supporting a mechanism for translocation of the protein through the conduit of the phage tail toward the host cell envelope, where it assembles into a DNA-injection device.

Agent based simulation method has become a prominent approach in computational modeling and analysis of public emergency management in social science research. The group emotions evolution, information diffusion, and collective behavior selection make extreme incidents studies a complex system problem, which requires new methods for incidents management and strategy evaluation. This paper studies the group emotion evolution and intervention strategy effectiveness using agent based simulation method. By employing a computational experimentation methodology, we construct the group emotion evolution as a complex system and test the effects of three strategies. In addition, the events-chain model is proposed to model the accumulation influence of the temporal successive events. Each strategy is examined through three simulation experiments, including two make-up scenarios and a real case study. We show how various strategies could impact the group emotion evolution in terms of the complex emergence and emotion accumulation influence in extreme events. This paper also provides an effective method of how to use agent-based simulation for the study of complex collective behavior evolution problem in extreme incidents, emergency, and security study domains.

Given the extremely high inter-patient heterogeneity of acute myeloid leukemia (AML), the identification of biomarkers for prognostic assessment and therapeutic guidance is critical. Cell surface markers (CSMs) have been shown to play an important role in AML leukemogenesis and progression. In the current study, we evaluated the prognostic potential of all human CSMs in 130 AML patients from The Cancer Genome Atlas (TCGA) based on differential gene expression analysis and univariable Cox proportional hazards regression analysis. By using multi-model analysis, including Adaptive LASSO regression, LASSO regression, and Elastic Net, we constructed a 9-CSMs prognostic model for risk stratification of the AML patients. The predictive value of the 9-CSMs risk score was further validated at the transcriptome and proteome levels. Multivariable Cox regression analysis showed that the risk score was an independent prognostic factor for the AML patients. The AML patients with high 9-CSMs risk scores had a shorter overall and event-free survival time than those with low scores. Notably, single-cell RNA-sequencing analysis indicated that patients with high 9-CSMs risk scores exhibited chemotherapy resistance. Furthermore, PI3K inhibitors were identified as potential treatments for these high-risk patients. In conclusion, we constructed a 9-CSMs prognostic model that served as an independent prognostic factor for the survival of AML patients and held the potential for guiding drug therapy. [ABSTRACT FROM AUTHOR]