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Abstract Background The subjective sign of a serious pandemic in human work and life is mathematical neural tinnitus. fNIRS (functional near-infrared spectroscopy) is a new non-invasive brain imaging technology for studying the neurological activity of the human cerebral cortex. It is based on neural coupling effects. This research uses the fNIRS approach to detect differences in the neurological activity of the cerebral skin in the sound stimulation mission in order to better discriminate between the sensational neurological tinnitus. Methods In the fNIRS brain imaging method, 14 sensorineural tinnitus sufferers and 14 healthy controls listened to varied noise and quiet for fNIRS data collection. Linear fitting was employed in MATLAB to eliminate slow drifts during preprocessing and event-related design analysis. The false discovery rate (FDR) procedure was applied in IBM SPSS Statistics 26.0 to control the false positive rate in multiple comparison analyses. Results When the ill group and the healthy control group were stimulated by pink noise, there was a significant difference in blood oxygen concentration (P

Abstract Background Primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) variant syndrome (VS) exhibit a complex overlap of AIH features with PBC, leading to poorer prognoses than those with PBC or AIH alone. The biomarkers associated with drug response and potential molecular mechanisms in this syndrome have not been fully elucidated. Methods Whole-transcriptome sequencing was employed to discern differentially expressed (DE) RNAs within good responders (GR) and poor responders (PR) among patients with PBC/AIH VS. Subsequent gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted for the identified DE RNAs. Plasma metabolomics was employed to delineate the metabolic profiles distinguishing PR and GR groups. The quantification of immune cell profiles and associated cytokines was achieved through flow cytometry and immunoassay technology. Uni- and multivariable logistic regression analyses were conducted to construct a predictive model for insufficient biochemical response. The performance of the model was assessed by computing the area under the receiver operating characteristic (AUC) curve, sensitivity, and specificity. Findings The analysis identified 224 differentially expressed (DE) mRNAs, 189 DE long non-coding RNAs, 39 DE circular RNAs, and 63 DE microRNAs. Functional pathway analysis revealed enrichment in lipid metabolic pathways and immune response. Metabolomics disclosed dysregulated lipid metabolism and identified PC (18:2/18:2) and PC (16:0/20:3) as predictors. CD4+ T helper (Th) cells, including Th2 cells and regulatory T cells (Tregs), were upregulated in the GR group. Pro-inflammatory cytokines (IFN-γ, TNF-α, IL-9, and IL-17) were downregulated in the GR group, while anti-inflammatory cytokines (IL-10, IL-4, IL-5, and IL-22) were elevated. Regulatory networks were constructed, identifying CACNA1H and ACAA1 as target genes. A predictive model based on these indicators demonstrated an AUC of 0.986 in the primary cohort and an AUC of 0.940 in the validation cohort for predicting complete biochemical response. Conclusion A combined model integrating genomic, metabolic, and cytokinomic features demonstrated high accuracy in predicting insufficient biochemical response in patients with PBC/AIH VS. Early recognition of individuals at elevated risk for insufficient response allows for the prompt initiation of additional treatments.

Grain weight is one of the key components of wheat (Triticum aestivum L.) yield. Genetic manipulation of grain weight is an efficient approach for improving yield potential in breeding programs. A recombinant inbred line (RIL) population derived from a cross between W7268 and Chuanyu 12 (CY12) was employed to detect quantitative trait loci (QTLs) for thousand-grain weight (TGW), grain length (GL), grain width (GW), and the ratio of grain length to width (GLW) in six environments. Seven major QTLs, QGl.cib-2D, QGw.cib-2D, QGw.cib-3B, QGw.cib-4B.1, QGlw.cib-2D.1, QTgw.cib-2D.1 and QTgw.cib-3B.1, were consistently identified in at least four environments and the best linear unbiased estimation (BLUE) datasets, and they explained 2.61 to 34.85% of the phenotypic variance. Significant interactions were detected between the two major TGW QTLs and three major GW loci. In addition, QTgw.cib-3B.1 and QGw.cib-3B were co-located, and the improved TGW at this locus was contributed by GW. Unlike other loci, QTgw.cib-3B.1/QGw.cib-3B had no effect on grain number per spike (GNS). They were further validated in advanced lines using Kompetitive Allele Specific PCR (KASP) markers, and a comparison analysis indicated that QTgw.cib-3B.1/QGw.cib-3B is likely a novel locus. Six haplotypes were identified in the region of this QTL and their distribution frequencies varied between the landraces and cultivars. According to gene annotation, spatial expression patterns, ortholog analysis and sequence variation, the candidate gene of QTgw.cib-3B.1/QGw.cib-3B was predicted. Collectively, the major QTLs and KASP markers reported here provide valuable information for elucidating the genetic architecture of grain weight and for molecular marker-assisted breeding in grain yield improvement.

We aimed to explore the effect of salidroside (SAL) on meat quality, antioxidant capacity, and lipid metabolism in broilers. The results demonstrated that SAL significantly reduced the yellowness (b*), shear force, cooking loss, drip loss, MDA, TBARS, and carbonyl content in breast (P

The relationship between the local structures and the thermodynamic properties of metallic liquids has been a fundamental issue, which significantly impacts the comprehensive performances of metallic materials. The temperature-induced structure evolution in CoxBy alloy liquids, involving CoB, Co2B, Co3B, and Co23B6, was investigated using ab initio molecular dynamics simulations. The results show that the clusters of icosahedral-like polyhedrons are found predominantly in all alloys at low temperature, while the heating induces the decrease in ideal icosahedral and the increase in defected icosahedral. At high temperature, the polyhedron clusters decrease significantly and the ideal icosahedra transforms into smaller short-range polyhedrons, signifying the temperature-induced chemical structure change from long-range to short-range ordering. The aggregation of B atoms at high temperature is confirmed by atomic configuration, charge density, and B-centered Voronoi polyhedrons, and the α-Co single phase is observed below 1600 K. This study is helpful for understanding the local structure variability in eutectic Co-B alloys and guiding solidification path in theory.

Grain hardness (Gh) is important for wheat processing and end-product quality. Puroindolines polymorphism explains over 60% of Gh variation and the novel genetic factors remain to be exploited. In this study, a total of 153 quantitative trait loci (QTLs), clustered into 12 genomic intervals (C1-C12), for 13 quality-related traits were identified using a recombinant inbred line population derived from the cross of Zhongkemai138 (ZKM138) and Chuanmai44 (CM44). Among them, C7 (harboring eight QTLs for different quality-related traits) and C8 (mainly harboring QGh.cib-5D.1 for Gh) were attributed to the famous genes, Rht-D1 and Pina, respectively, indicating that the correlation of involved traits was supported by the pleotropic or linked genes. Notably, a novel major stable QTL for Gh was detected in the C12, QGh.cib-7D, with ZKM138-derived allele increasing grain hardness, which was simultaneously mapped by the BSE-Seq method. The geographic pattern and transmissibility of this locus revealed that the increasing-Gh allele is highly frequently present in 85.79% of 373 worldwide wheat varieties and presented 99.31% transmissibility in 144 ZKM138-derivatives, indicating the non-negative effect on yield performance and that its indirect passive selection has happened during the actual breeding process. Thus, the contribution of this new Gh-related locus was highlighted in consideration of improving the efficiency and accuracy of the soft/hard material selection in the molecular marker-assisted process. Further, TraesCS7D02G099400, TraesCS7D02G098000, and TraesCS7D02G099500 were initially deduced to be the most potential candidate genes of QGh.cib-7D. Collectively, this study provided valuable information of elucidating the genetic architecture of Gh for wheat quality improvement.

Grain number per spike (GNS) is a crucial component of grain yield and plays a significant role in improving wheat yield. To identify quantitative trait loci (QTL) associated with GNS, a recombinant inbred line (RIL) population derived from the cross of Zhongkemai 13F10 and Chuanmai 42 was employed to conduct QTL mapping across eight environments. Based on the bulked segregant exome sequencing (BSE-Seq), genomic regions associated with GNS were detected on chromosomes 5A and 6A. According to the constructed genetic maps, two major QTL QGns.cib-5A (LOD = 4.35–8.16, PVE = 8.46–14.43%) and QGns.cib-6A (LOD = 3.82–30.80, PVE = 5.44–12.38%) were detected in five and four environments, respectively. QGns.cib-6A is a QTL cluster for other seven yield-related traits. QGns.cib-5A and QGns.cib-6A were further validated using linked Kompetitive Allele Specific PCR (KASP) markers in different genetic backgrounds. QGns.cib-5A exhibited pleiotropic effects on productive tiller number (PTN), spike length (SL), fertile spikelet number per spike (FSN), and ratio of grain length to grain width (GL/GW) but did not significantly affect thousand grain weight (TGW). Haplotype analysis revealed that QGns.cib-5A and QGns.cib-6A were the targets of artificial selection during wheat improvement. Candidate genes for QGns.cib-5A and QGns.cib-6A were predicted by analyzing gene annotation, spatiotemporal expression patterns, and orthologous and sequence differences. These findings will be valuable for fine mapping and map-based cloning of genes underlying QGns.cib-5A and QGns.cib-6A.

Abstract Background Hepatic ischemia–reperfusion injury (IRI) in donation after cardiac death (DCD) donors is a major determinant of transplantation success. Endoplasmic reticulum (ER) stress plays a key role in hepatic IRI, with potential involvement of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway and the antiapoptotic protein hematopoietic-lineage substrate-1-associated protein X-1 (HAX1). In this study, we aimed to investigate the effects of hypothermic oxygenated perfusion (HOPE), an organ preservation modality, on ER stress and apoptosis during hepatic IRI in a DCD rat model. Methods To investigate whether HOPE could improve IRI in DCD livers, levels of different related proteins were examined by western blotting and quantitative real-time polymerase chain reaction. Further expression analyses, immunohistochemical analyses, immunofluorescence staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, and transmission electron microscopy were conducted to analyze the effects of HOPE on ER stress and apoptosis. To clarify the role of the JAK2/STAT3 pathway and HAX1 in this process, AG490 inhibitor, JAX1 plasmid transfection, co-immunoprecipitation (CO-IP), and flow cytometry analyses were conducted. Results HOPE reduced liver injury and inflammation while alleviating ER stress and apoptosis in the DCD rat model. Mechanistically, HOPE inhibited unfolded protein responses by activating the JAK2/STAT3 pathway, thus reducing ER stress and apoptosis. Moreover, the activated JAK2/STAT3 pathway upregulated HAX1, promoting the interaction between HAX1 and SERCA2b to maintain ER calcium homeostasis. Upregulated HAX1 also modulated ER stress and apoptosis by inhibiting the inositol-requiring enzyme 1 (IRE1) pathway. Conclusions JAK2/STAT3-mediated upregulation of HAX1 during HOPE alleviates hepatic ER stress and apoptosis, indicating the JAK2/STAT3/HAX1 pathway as a potential target for IRI management during DCD liver transplantation. Graphical Abstract

Abstract Background Artificial ovary (AO) is an alternative approach to provide physiological hormone to post-menopausal women. The therapeutic effects of AO constructed using alginate (ALG) hydrogels are limited by their low angiogenic potential, rigidity, and non-degradability. To address these limitations, biodegradable chitin-based (CTP) hydrogels that promote cell proliferation and vascularization were synthesized, as supportive matrix. Methods In vitro, follicles isolated from 10–12-days-old mice were cultured in 2D, ALG hydrogels, and CTP hydrogels. After 12 days of culture, follicle growth, steroid hormone levels, oocyte meiotic competence, and expression of folliculogenesis-related genes were monitored. Additionally, follicles isolated from 10–12-days-old mice were encapsulated in CTP and ALG hydrogels and transplanted into the peritoneal pockets of ovariectomised (OVX) mice. After transplantation, steroid hormone levels, body weight, rectal temperature, and visceral fat of the mice were monitored every two weeks. At 6 and 10 weeks after transplantation, the uterus, vagina, and femur were collected for histological examination. Results The follicles developed normally in CTP hydrogels under in vitro culture conditions. Additionally, follicular diametre and survival rate, oestrogen production, and expression of folliculogenesis-related genes were significantly higher than those in ALG hydrogels. After one week of transplantation, the numbers of CD34-positive vessels and Ki-67-positive cells in CTP hydrogels were significantly higher than those in ALG hydrogels (P

Grain size and weight are key components of wheat yield. Exploitation of major underlying quantitative trait loci (QTL) can improve yield potential in wheat breeding. A recombinant inbred line (RIL) population was constructed to detect QTL for thousand-grain weight (TGW), grain length (GL) and grain width (GW) across eight environments. Genomic regions associated with grain size and grain weight were identified on chromosomes 4A and 6A using bulked segregant exome sequencing (BSE-Seq) analysis. After constructing genetic maps, six major QTL detected in at least four individual environments and in best linear unbiased estimator (BLUE) datasets, explained 7.50%–23.45% of the phenotypic variation. Except for QGl.cib-4A, the other five QTL were co-located in two regions, namely QTgw/Gw.cib-4A and QTgw/Gw/Gl.cib-6A. Interactions of these QTL were analyzed. Unlike QTgw/Gw/Gl.cib-6A, QTgw/Gw.cib-4A and QGl.cib-4A had no effect on grain number per spike (GNS). The QTL were validated in a second cross using Kompetitive Allele Specific PCR (KASP) markers. Since QTgw/Gw.cib-4A was probably a novel locus, it and the KASP markers reported here can be used in wheat breeding. TraesCS4A03G0191200 was predicted to be potential candidate gene for QTgw/Gw.cib-4A based on the sequence differences, spatiotemporal expression patterns, gene annotation and haplotype analysis. Our findings will be useful for fine mapping and for marker-assisted selection in wheat grain yield improvement.

Tinnitus is an auditory phantom percept that affects the perception of sound in the patient’s ears, and the incidence of prolonged tinnitus is as high as ten to fifteen percent. Acupuncture is a unique treatment method in Chinese medicine, and it has great advantages in the treatment of tinnitus. However, tinnitus is a subjective symptom of patients, and there is currently no objective detection method to reflect the improvement effect of acupuncture on tinnitus. We used functional near-infrared spectroscopy (fNIRS) to explore the effect of acupuncture on the cerebral cortex of tinnitus patients. We collected the scores of the tinnitus disorder inventory (THI), tinnitus evaluation questionnaire (TEQ), hamilton anxiety scale (HAMA), and hamilton depression scale (HAMD) of eighteen subjects before and after acupuncture treatment, and the fNIRS signals of these subjects in sound-evoked activity before and after acupuncture treatment. According to the fNIRS detection results of tinnitus patients, acupuncture increased the concentration of oxygenated hemoglobin in the temporal lobe of tinnitus patients, and affected the activation of the auditory cortex. The study may reflect the neural mechanisms of acupuncture treatment for tinnitus and ultimately help to provide an objective evaluation method for the therapeutic effect of acupuncture treatment for tinnitus.

In this work, a surface dispersed heterojunction of BiVO4-nanoparticle@WO3-nanoflake was successfully prepared by hydrothermal combined with solvothermal method. We optimized the morphology of the WO3 nanoflakes and BiVO4 nanoparticles by controlling the synthesis conditions to get the uniform BiVO4 loaded on the surface of WO3 arrays. The phase composition and morphology evolution with different reaction precursors were investigated in detail. When used as photoanodes, the WO3/BiVO4 composite exhibits superior activity with photocurrent at 3.53 mA cm−2 for photoelectrochemical (PEC) water oxidation, which is twice that of pure WO3 photoanode. The superior surface dispersion structure of the BiVO4-nanoparticle@WO3-nanoflake heterojunction ensures a large effective heterojunction area and relieves the interfacial hole accumulation at the same time, which contributes to the improved photocurrents together with the stability of the WO3/BiVO4 photoanodes.

ABSTRACTMetal-organic framework materials (MOFs) have been widely studied because of their adjustable composition and controllable structure in the field of microwave absorption (MA). Therein, Prussian blue analogs (PBA) have attracted the attention of researchers with ultra-high metal content. However, the attenuation ability of microwave for PBA-based composites is still unsatisfactory up to now. Therefore, the NiFe/CoFe@C composites were prepared by carbonizing polymetallic PBA (NiCoFe PBA) materials in this work, and the influence of different metal alloy components on MA was explored by adjusting the ratio of metal ions (Ni2+/Co2+). Moreover, the NiFe/CoFe@C composites have rich interfaces and enhance the polarization loss due to the introduction of Ni and it has an optimal performance at 2.7 mm that is the reflection loss (RL) is −41.49 dB and an effective absorption bandwidth (EAB) is 7.12 GHz with 1/1 (Ni2+/Co2+). The above data provides a research idea for obtaining light and efficient absorbers.

Soil acidity reduces base cations required for plant growth and may result in phytotoxic concentrations of soluble aluminum. Liming acidic soils is generally promoted as an effective management practice to increase soil pH, base cation concentrations, and ameliorate toxicity caused by aluminum and manganese. Through a global literature review using data published from field experiments on liming, the objective of this paper is to understand the effects of liming on soil pH, crop yields, and economic profitability. The results show that liming positively influenced crop yields and soil pH, implying that various lime sources can increase soil pH and crop productivity. The effect sizes of liming on crop yields when lime was incorporated into soils were higher than surface application irrespective of tillage practice. Liming under no-tillage (NT) compared to conventional tillage (CT) management showed higher effect sizes for crop yields. Liming increased effect sizes for crop yields in fertilized compared with unfertilized trials. Gypsum, calcium hydroxide and calcium carbonate showed higher effect sizes when compared with Cement Klin Dust (CKD), dolomite and wood ash. The results show that liming increased yields for all crops except potatoes and oats. Liming generally increases soil pH and changes in soil pH increased with higher lime application rates and yield increases were proportional to the magnitude of increases in soil pH. The profitability of liming differed with crop type and liming rate, being more profitable at lower liming rates. Overall, this meta-analysis shows that liming decreases soil acidity and improves crop yields. Attaining maximum gains from liming agricultural crops under acidic soil conditions requires an understanding of the appropriate lime rates required for specific crops and soil types to ensure overall profitability for producers and sustainable improvement of soil health.

Metal-organic frameworks (MOFs) and covalent organic frameworks (COFs) as the novel porous materials have the merits of diverse, adjustable functionality, high porosity and surface area, which have great application prospects in the gas storage, separation and catalysis. In addition, their derivates make up for the insufficient of electronic conductivity and chemical stability of MOFs and COFs, and provide a new ideal for accurate control of material structure. Up to now, many efficient electrocatalysts have been designed based on MOFs, COFs and their derivates for O2 reduction/evolution reactions (ORR/OER) and CO2 reduction/evolution reactions (CO2RR/CO2ER) in the metal-air batteries. In this review, the latest development of MOFs, COFs and their derivates in the metal-air batteries is summarized, and we discuss the structural characteristics of these materials and their corresponding mechanisms of action. By comprehensively reviewing the advantages, challenges and prospects of MOFs and COFs, we hope that the organic framework materials will shed more profound insights into the development of electrocatalysis and energy storage in the future.

Agrifood systems account for 31% of global greenhouse gas emissions. Substantial emissions reduction in agrifood systems is critical to achieving the temperature goal set by the Paris Agreement. A key challenge in reducing GHG emissions in the agrifood value chain is the imbalanced allocation of benefits and costs associated with emissions reduction among agrifood value chain participants. However, only a few studies have examined agrifood emissions reduction from a value chain perspective, especially using dynamic methods to investigate participants' long-term emissions reduction strategies. This paper helps fill this gap in the existing literature by examining the impact of collaborations among agrifood value chain participants on correcting those misallocations and reducing emissions in agrifood systems. We develop a dynamic differential game model to examine participants' long-term emissions reduction strategies in a three-stage agrifood value chain. We use the Hamilton-Jacobi-Bellman equation to derive the Nash equilibrium emissions reduction strategies under non-cooperative, cost-sharing, and cooperative mechanisms. We then conduct numerical analysis and sensitivity analysis to validate our model. Our results show that collaboration among value chain participants leads to higher emissions reduction efforts and profits for the entire value chain. Specifically, based on our numerical results, the cooperative mechanism results in the greatest emissions reduction effort by the three participants, which leads to a total that is nearly three times higher than that of the non-cooperative mechanism and close to two times higher than the cost-sharing mechanism. The cooperative mechanism also recorded the highest profits for the entire value chain, surpassing the non-cooperative and cost-sharing mechanisms by around 37% and 16%, respectively. Our results provide valuable insights for policymakers and agrifood industry stakeholders to develop strategies and policies encouraging emissions reduction collaborations in the agrifood value chain and reduce emissions in the agrifood systems.

Flag leaf size is a crucial trait influencing plant architecture and yield potential in wheat. A recombinant inbred line (RIL) population derived from the cross of W7268 and Chuanyu 12 was employed to identify quantitative trait loci (QTL) controlling flag leaf length (FLL), flag leaf width (FLW), and flag leaf area (FLA) in six environments and the best linear unbiased estimator (BLUE) datasets. Using a 55 K SNP-based genetic map, six major and stable QTL were detected with 6.33–53.12% of explained phenotypic variation. Except for QFlw.cib-4B.3, the other five major QTL were co-located within two intervals on chromosomes 2B and 2D, namely QFll/Fla.cib-2B and QFll/Flw/Fla.cib-2D, respectively. Their interactions and effects on the corresponding traits and yield-related traits were also assessed based on flanking markers. QFll/Fla.cib-2B showed pleiotropic effects on spikelet number per spike (SNS). QFlw.cib-4B.3 and QFll/Flw/Fla.cib-2D had effects on grain number per spike (GNS) and thousand-grain weight (TGW). Comparison analysis suggested that QFll/Fla.cib-2B was likely a new locus. Two candidate genes, TraesCS2B03G0222800 and TraesCS2B03G0230000, associated with leaf development within the interval of QFll/Fla.cib-2B were identified based on expression-pattern analysis, gene annotation, ortholog analysis, and sequence variation. The major QTL and markers reported here provide valuable information for understanding the genetic mechanism underlying flag leaf size as well as breeding utilization in wheat.

Abstract Background Emergence of new pathogen strains of Magnaporthe oryzae is a major reason for recurrent failure of the resistance mediated by a single resistance gene (Pi) in rice. Stacking various Pi genes in the genome through marker-assisted selection is thus an effective strategy in rice breeding for achieving durable resistance against the pathogen. However, the effect of pyramiding of multiple Pi genes using transgenesis still remains largely unknown. Results Three Pi genes Pib, Pi25 and Pi54 were transferred together into two rice varieties, the indica variety Kasalath and the japonica variety Zhenghan 10. Transgenic plants of both Kasalath and Zhenghan 10 expressing the Pi transgenes showed imparted pathogen resistance. All the transgenic lines of both cultivars also exhibited shorter growth periods with flowering 2–4 days early, and shorter plant heights with smaller panicle. Thus, pyramiding of the Pi genes resulted in reduced grain yields in both rice cultivars. However, tiller numbers and grain weight were generally similar between the pyramided lines and corresponding parents. A global analysis of gene expression by RNA-Seq suggested that both enhancement and, to a lesser extent, inhibition of gene transcription occurred in the pyramided plants. A total of 264 and 544 differentially expressed genes (DEGs) were identified in Kasalath and Zhenghan 10, respectively. Analysis of the DEGs suggested that presence of the Pi transgenes did not alter gene expression only related to disease resistance, but also impacted many gene transcriptions in the pathways for plant growth and development, in which several were common for both Kasalath and Zhenghan 10. Conclusion Pyramiding of the Pi genes Pib, Pi25 and Pi54 via transgenesis is a potentially promising approach for improving rice resistance to the pathogen Magnaporthe oryzae. However, pleiotropic effects of the Pi genes could potentially result in yield loss. These findings support the idea that immunity is often associated with yield penalties. Rational combination of the Pi genes based on the genetic background may be important to balance yield and disease resistance.

Autoimmune hepatitis (AIH) is an autoimmune disease caused by disruption of liver immune homeostasis. Genetic studies have revealed the predisposition of AIH with the human leukocyte antigen (HLA) region. Recently, metabolomics integrated with genomics has identified many genetic loci of biomedical interest. However, there is no related report in AIH. In the present study, we found that HLA-DRB1*04:05 was linked to the clinical features and prognosis of AIH in Chinese patients. Furthermore, our patients were divided into DRB1*04:05 positive and DRB1*04:05 negative groups and the metabolic profiling was done by HPLC/MS. We chose inosine, one of the highly altered metabolites, to explore the effect on an acute severe hepatitis murine model. The results showed that inosine treatment attenuated hepatocyte apoptosis, enhanced antioxidant ability and inhibited the activation and glycolysis of CD4+ T cell. We propose that inosine participates in the regulation of AIH through its protective effect on hepatocytes and inhibition of overactivated immune cells, which might provide a potential novel approach in treating acute form of AIH.

Acute-on-chronic liver failure (ACLF) usually develops based on acute decompensation (AD) of cirrhosis and is characterized by intense systemic inflammation, multiple organ failure, and high short-term mortality. Validated biomarkers for the diagnosis and prognosis of ACLF remain to be clarified. Metabolomics is an emerging method used to measure low-molecular-weight metabolites and is currently frequently implemented to understand pathophysiological processes involved in disease progression, as well as to search for new diagnostic or prognostic biomarkers of various disorders. The characterization of metabolites in ACLF has recently been described via metabolomics. The role of metabolites in the pathogenesis of ACLF deserves further investigation and improvement and could be the basis for the development of new diagnostic and therapeutic strategies. In this review, we focused on the contributions of metabolomics on uncovering metabolic profiles in patients with ACLF, the key metabolic pathways that are involved in the progression of ACLF, and the potential metabolite-associated therapeutic targets for ACLF.

Wheat is one of the most important staple crops for supplying nutrition and energy to people world. A new genetic map based on the Wheat 55 K SNP array was constructed using recombinant inbred lines derived from a cross between Zhongkemai138 and Kechengmai2 to explore the genetic foundation for wheat grain features. This new map covered 2,155.72 cM across the 21 wheat chromosomes with 11,455 markers. And 2,846 specific markers for this genetic map and 148 coincident markers among different maps were documented, which was helpful for improving and updating wheat genetic and genomic information. Using this map, a total of 68 additive QTLs and 82 pairs of epistatic QTLs were detected for grain features including yield, nutrient composition, and quality-related traits by QTLNetwork 2.1 and IciMapping 4.1 software. Fourteen additive QTLs and one pair of epistatic QTLs could be detected by both software programs and thus regarded as stable QTLs here, all of which explained higher phenotypic variance and thus could be utilized for wheat grain improvement. Additionally, thirteen additive QTLs were clustered into three genomic intervals (C4D.2, C5D, and C6D2), each of which had at least two stable QTLs. Among them, C4D.2 and C5D have been attributed to the famous dwarfing gene Rht2 and the hardness locus Pina, respectively, while endowed with main effects on eight grain yield/quality related traits and epistatically interacted with each other to control moisture content, indicating that the correlation of involved traits was supported by the pleotropic of individual genes but also regulated by the gene interaction networks. Additionally, the stable additive effect of C6D2 (QMc.cib-6D2 and QTw.cib-6D2) on moisture content was also highlighted, potentially affected by a novel locus, and validated by its flanking Kompetitive Allele-Specific PCR marker, and TraesCS6D02G109500, encoding aleurone layer morphogenesis protein, was deduced to be one of the candidate genes for this locus. This result observed at the QTL level the possible contribution of grain water content to the balances among yield, nutrients, and quality properties and reported a possible new locus controlling grain moisture content as well as its linked molecular marker for further grain feature improvement.

Mining novel and less utilized thousand grain weight (TGW) related genes are useful for improving wheat yield. In this study, a recombinant inbred line population from a cross between Zhongkemai 138 (ZKM138, high TGW) and Chuanmai 44 (CM44, low TGW) was used to construct a new Wheat 50K SNP array-derived genetic map that spanned 1,936.59 cM and contained 4, 139 markers. Based on this map, ninety-one quantitative trait loci (QTL) were detected for eight grain-related traits in six environments. Among 58 QTLs, whose superior alleles were contributed by ZKM138, QTgw.cib-6A was a noticeable major stable QTL and was also highlighted by bulked segregant analysis with RNA sequencing (BSR-Seq). It had a pyramiding effect on TGW enhancement but no significant trade-off effect on grain number per spike or tiller number, with two other QTLs (QTgw.cib-2A.2 and QTgw.cib-6D), possibly explaining the excellent grain performance of ZKM138. After comparison with known loci, QTgw.cib-6A was deduced to be a novel locus that differed from nearby TaGW2 and TaBT1. Seven simple sequence repeat (SSR) and thirty-nine kompetitive allele-specific PCR (KASP) markers were finally developed to narrow the candidate interval of QTgw.cib-6A to 4.1 Mb. Only six genes in this interval were regarded as the most likely candidate genes. QTgw.cib-6A was further validated in different genetic backgrounds and presented 88.6% transmissibility of the ZKM138-genotype and a 16.4% increase of TGW in ZKM138 derivatives. And the geographic pattern of this locus revealed that its superior allele is present in only 6.47% of 433 Chinese modern wheat varieties, indicating its potential contribution to further high-yield breeding.

Anther development is crucial for controlling crop fertility. To elucidate the underlying mechanisms of reproductive development of highland barley (called Qingke in Chinese), two main Qingke cultivars, Zangqing 2000 and Ximala 22, were utilized. Transcriptome analysis showed that lipid, sugar and phenylpropane metabolisms might be the major pathways associated with Qingke male fertility by analyzing the possible common DEGs before anther maturation in both varieties. Additionally, 26 genes related to crop genic male sterility were screened to identify homologous genes for Qingke male sterile lines. Among them, HORVU.MOREX.r3.7HG0634780 (HvtOSC12), an oxidosqualene cyclase, was highlighted as a candidate gene for affecting Qingke male fertility, as it is highly and especially expressed before Qingke anther maturation. Furthermore, HvtOSC12 (including promoter sequence) was cloned by homology-based cloning. The further bioinformatic analysis deduced that MYBs might be one of the transcription factors affecting expression of HvtOSC12 by responding to environmental changes. These results might lay a foundation for the potential applications for the creation of environment-sensitive genic male sterility in Qingke.

Spike compactness (SC) and length (SL) are the components of spike morphology and are strongly related to grain yield in wheat (Triticum aestivum L.). To investigate quantitative trait loci (QTL) associated with SC and SL, a recombinant inbred lines (RIL) population derived from the cross of Bailangmai (BLM, a Tibet landrace) and Chuanyu 20 (CY20, an improved variety) was employed in six environments. Three genomic regions responsible for SC and SL traits were identified on chromosomes 2A and 2D using bulked segregant exome sequencing (BSE-Seq). By constructing genetic maps, six major QTL were repeatedly detected in more than four environments and the best linear unbiased estimation (BLUE) datasets, explaining 7.00–28.56% of the phenotypic variation and the logarithm of the odd (LOD) score varying from 2.50 to 13.22. They were co-located on three loci, designed as QSc/Sl.cib-2AS, QSc/Sl.cib-2AL, and QSc/Sl.cib-2D, respectively. Based on the flanking markers, their interactions and effects on the corresponding trait and other agronomic traits were also analyzed. Comparison analysis showed that QSc/Sl.cib-2AS and QSc/Sl.cib-2AL were possibly two novel loci for SC and SL. QSc/Sl.cib-2AS and QSc/Sl.cib-2D showed pleiotropic effects on plant height and grain morphology, while QSc/Sl.cib-2AL showed effects on spikelet number per spike (SNS) and grain width (GW). Based on the gene annotation, orthologous search, and spatiotemporal expression patterns of genes, TraesCS2A03G0410600 and TraesCS2A03G0422300 for QSc/Sl.cib-2AS, and TraesCS2D03G1129300 and TraesCS2D03G1131500 for QSc/Sl.cib-2D were considered as potential candidate genes, respectively. These results will be useful for fine mapping and developing new varieties with high yield in the future.

Mesenchymal stem cells (MSCs), as the most common cell source for stem cell therapy, play an important role in the modulation of innate and adaptive immune responses and have been widely used in clinical trials to treat autoimmune and inflammatory diseases. Recent experimental and clinical studies have shown that MSC-derived extracellular vesicles (MSC-EVs) can inhibit the activation and proliferation of a variety of proinflammatory cells, such as Th1, Th17 and M1 macrophages, reducing the secretion of proinflammatory cytokines, while promoting the proliferation of anti-inflammatory cells, such as M2 macrophages and Tregs, and increasing the secretion of anti-inflammatory cytokines, thus playing a role in immune regulation and exhibiting immunomodulatory functions. Besides MSC-EVs are more convenient and less immunogenic than MSCs. There is growing interest in the role of MSC-EVs in liver diseases owing to the intrinsic liver tropism of MSC-EVs. In this review, we focus on the immunomodulatory effects of MSC-EVs and summarize the pivotal roles of MSC-EVs as a cell-free therapy in liver diseases, including NAFLD, AIH, acute liver failure, liver fibrosis and hepatic ischemia–reperfusion injury. Moreover, we provide a concise overview of the potential use and limits of MSC-EVs in clinical application.

p-Hydroxybenzoic acid (p-HBA), which exists extensively in plants, is well known for its anti-inflammatory effects, but various adverse side effects have also been reported. Previous research has found that acid translated to its sodium salt improves the safety profile of compounds. Therefore, we hypothesized that p-HBA translated to sodium p-hydroxybenzoate would improve its safety profile. In the present study, we evaluated the toxicity of sodium p-hydroxybenzoate after 90 days of repeated oral toxicity experiments according to OECD guidelines in male and female Sprague–Dawley rats. Sodium p-hydroxybenzoate was administered orally to SD rats at doses of 0, 125, 250, and 500 mg/kg body weight (BW)/day for 90 days. All animals survived to the end of the study, and no sodium p-hydroxybenzoate treatment-associated mortality or clinical changes were observed during the study period. Sodium p-hydroxybenzoate did not promote any clinical signs of toxicologically relevant effects, including changes in body weight, food intake and urinalysis parameters, in male or female SD rats. Dose-related alterations in hematological parameters, organ weights and histopathological findings in hepatic tissue were examined in animals of both sexes in the 500 mg/kg BW/day group. Based on the study, the no-observed-adverse-effect level (NOAEL) for sodium p-hydroxybenzoate was determined to be 250 mg/kg BW/day in both male and female rats.

Liver diseases, such as viral hepatitis, alcoholic hepatitis and cirrhosis, nonalcoholic steatohepatitis, and hepatocellular carcinoma place a heavy burden on many patients worldwide. However, the treatment of many liver diseases is currently insufficient, and the treatment may be associated with strong side effects. Therapies for liver diseases targeting the molecular and cellular levels that minimize adverse reactions and maximize therapeutic effects are in high demand. Immune cells are intimately involved in the occurrence, development, and prognosis of liver diseases. The immune response in the liver can be suppressed, leading to tolerance in homeostasis. When infection or tissue damage occurs, immunity in the liver is activated rapidly. As small membrane vesicles derived from diverse cells, exosomes carry multiple cargoes to exert their regulatory effects on recipient cells under physiological or pathological conditions. Exosomes from different immune cells exert different effects on liver diseases. This review describes the biology of exosomes and focuses on the effects of exosomes from different immune cells on pathogenesis, diagnosis, and prognosis and their therapeutic potential in liver diseases.

The Yin'gen-E'ji'naqi Basin is located in the central and western part of the Inner Mongolia autonomous region, with an area of about 123×103 km2. It is a continental rift basin with a low exploration degree in North China. Due to the influence of complex surface and underground conditions, only the geological characteristics of the Chagan, Tiancao, Hari and other sags around the basin were studied during the early stage, which proved that each sag had the conditions for oil and gas accumulation, but the overall exploration potential was low. In recent years, on the basis of previous studies and combined with more field geology surveys, seismic and drilling data, the formation and evolution of the basin and the resource potential were re-evaluated. The Yin'gen-E'ji'naqi Basin basement was formed from the end of Permian to the Early Triassic, mainly composed of accretion-collision mélange, with moderate-shallow metamorphism generally occurring. Since the Mesozoic, affected by the Yanshanian and Himalayan movements, the basin has undergone six stages of structural evolution, with the characteristics of residual and reformed basins. The remaining Lower Cretaceous Bayin Gobi Formation is mainly distributed in the central and northern part of the basin, and is the main hydrocarbon generation and reservoir system. The total resources of the basin are estimated to be about 1.364 billion tons. Under the influence of strong late transformations, preservation conditions are the key factors for hydrocarbon accumulation. The tectonic activities in the northern part of the basin are relatively weak, and the effective source rocks in Bayin Gobi Formation remain in the depression area, which is the development area of overpressure oil and gas reservoirs and has become the key area for further exploration.

A data identifier (DID) is an essential tag or label in all kinds of databases—particularly those related to integrated computational materials engineering (ICME), inheritable integrated intelligent manufacturing (I3M), and the Industrial Internet of Things. With the guidance and quick acceleration of the development of advanced materials, as envisioned by official documents worldwide, more investigations are required to construct relative numerical standards for material informatics. This work proposes a universal DID format consisting of a set of build chains, which aligns with the classical form of identifier in both international and national standards, such as ISO/IEC 29168-1:2000, GB/T 27766–2011, GA/T 543.2–2011, GM/T 0006–2012, GJB 7365–2011, SL 325–2014, SL 607–2018, WS 363.2–2011, and QX/T 39–2005. Each build chain is made up of capital letters and numbers, with no symbols. Moreover, the total length of each build chain is not restricted, which follows the formation of the Universal Coded Character Set in the international standard of ISO/IEC 10646. Based on these rules, the proposed DID is flexible and convenient for extending and sharing in and between various cloud-based platforms. Accordingly, classical two-dimensional (2D) codes, including the Hanxin Code, Lots Perception Matrix (LP) Code, Quick Response (QR) code, Grid Matrix (GM) code, and Data Matrix (DM) Code, can be constructed and precisely recognized and/or decoded by either smart phones or specific machines. By utilizing these 2D codes as the fingerprints of a set of data linked with its cloud-based platforms, progress and updates in the composition–processing–structure–property–performance workflow process can be tracked spontaneously, paving a path to accelerate the discovery and manufacture of advanced materials and enhance research productivity, performance, and collaboration.

Autoimmune hepatitis (AIH) is a chronic liver disease caused by disruption of liver immune homeostasis. The effect of dendritic cells (DCs) on the pathogenesis of AIH is not fully understood. Long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs) have been shown to play critical roles in the regulation of cell function. In this study, we analyzed the immunophenotypic characteristics of DCs in the peripheral blood. The percentage of mature DCs was higher in AIH patients than in healthy controls (HCs), and the proportion of mature DCs decreased after treatment. We isolated monocyte-derived DCs (moDCs) from the peripheral blood, obtained whole RNA-sequencing (RNA-seq) data for the moDCs from the two groups, and identified differentially expressed (DE) lncRNAs, circRNAs, miRNAs and mRNAs. In addition, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses for the DE mRNAs and constructed competing endogenous RNA (ceRNA) networks. ENST00000543334, hsa_circ_0000279, and hsa_circ_0005076 were selected and validated by RT-qPCR. These results provide a possible molecular mechanism of DCs in the pathogenesis of AIH and identify some potential therapeutic targets.

Parents’ knowledge, attitudes, and beliefs about attention-deficit/hyperactivity disorder (ADHD) are crucial in the selection of the treatment strategy and how to care for children with ADHD. However, little is known about parents’ conception in mainland China. A semi-structured questionnaire was used to assess this information with 25 true/false questions regarding ADHD, and other questions investigating the methods of acquiring ADHD-related information, treatment preference, and concerns about ADHD treatment strategy. We found that the average score of all the participants was 17.42 ± 2.69 (total of 25 points) for the questionnaire on knowledge, attitudes, and beliefs about ADHD. This indicated that the parents had insufficient knowledge of this disease profile. They always accessed specialized information through mobile internet. For the treatment options, the investigated parents chose psychotherapy treatment rather than medications, in that they worried about the side effects of medication and expected to find alternative treatment strategies. The present investigation demonstrated that most parents lack knowledge about ADHD in treatment decision making in China. Medical professionals should provide parents with evidence-based ADHD-related information to help them understand this disease.

Optimal kernel size and shape were critical in improving the wheat yield potential and processing quality. A traditional and conditional QTL analysis for kernel-related traits was performed using 152 recombinant inbred lines derived from a cross between Zhongkemai 138 (ZKM138) and Kechengmai 2, whose kernel size showed significant differences. A total of 48 traditional QTLs (LOD: 3.69–14.20) were identified, with twenty-six QTLs distributed across five genomic regions. Each had at least one major stable QTL for kernel-related traits. We deduced from the co-location and conditional QTL analysis results that R3D and R4B.1 primarily controlled kernel shape, while R4D, R6A, and R6D2 primarily contributed to kernel size and the final thousand-kernel weight, potentially providing the genetic basis for the ZKM138’s high TKW and large-kernel performance. R4D may be involved with Rht2, and the possible regulatory effects of the other four QTL clusters are more likely to be influenced by unknown genes. The KASP markers validated their effect on kernel-related traits, and they were used to analyze the transmissibility and distribution of superior genotypes in ZKM138 derivatives and global wheat cultivars, respectively. These findings may serve as a reference for future genetic improvement of the ideal kernel morphology.

Autoimmune hepatitis (AIH) is an inflammatory liver disease caused by a dysregulated immune response. Although the pathogenesis of AIH remains unclear, impaired regulatory T cells (Tregs) have been considered a driver of AIH development. Unlike autoreactive T cells, Tregs mainly utilize oxidative phosphorylation (OXPHOS) as their energy supply. Elevated glycolysis has been reported to limit the suppressive functions of Tregs. However, whether glucose metabolism reprogramming in Tregs is involved in AIH etiology remains unknown. The aim of this study was to examine alternations in Treg numbers and functions in AIH patients and concanavalin A (Con A)-induced hepatitis, while exploring associations between impaired Tregs and glucose metabolism. The frequency of Tregs was decreased in the peripheral blood but increased in liver biopsies of AIH patients. Moreover, immunosuppressive therapy rescued circulating Tregs in AIH. In Con A-induced immune hepatitis, enhanced intrahepatic Treg accumulation was observed over time, accompanied by reduced splenic Treg numbers. To investigate whether functional impairment of Tregs occurs in AIH, Tregs were isolated from experimental AIH (EAH) model mice and normal controls and the former displayed downregulated mRNA levels of FOXP3, CTLA4, CD103, TIGIT, CD39, and CD73. EAH model-derived Tregs also produced fewer anti-inflammatory mediators (TGF-β and IL-35) than control Tregs. Moreover, enhanced glycolysis and reduced OXPHOS were found in Tregs from EAH model mice, as reflected by elevated levels of key glycolytic enzymes (HK2, PK-M2, and LDH-A) and a decreased ATP concentration. This study revealed a decreased peripheral Treg frequency and abnormal intrahepatic Treg infiltration in AIH. It is first reported that glucose metabolism reprogramming is associated with decreases and functional impairments in the Treg population, promoting AIH development. Targeting glucose metabolism may provide novel insights for the treatment of AIH.

We investigate how phytosanitary regulations related to apple maggot could affect optimal pest control strategies and profits for apple producers potentially located in apple maggot quarantine areas. We estimate producer profits by an orchard's quarantine status subject to a phytosanitary regulation requiring an additional cold storage period, reflecting the import requirements of China and British Columbia (Canada). Interestingly, we find that the increased cost burden generated by the additional cold storage from quarantine areas has an unintended consequence of raising the number of chemical applications, suggesting a substitution effect between pesticide application and cold storage.

Abstract By adopting the first-principle methods based on the density functional theory, we studied the structural, electronic, and magnetic properties of defected monolayer WSe2 with vacancies and the influences of external strain on the defected configurations. Our calculations show that the two W atom vacancies (VW2) and one W atom and its nearby three pairs of Se atom vacancies (VWSe6) both induce magnetism into monolayer WSe2 with magnetic moments of 2 and 6 μB, respectively. The magnetic moments are mainly contributed by the atoms around the vacancies. Particularly, monolayer WSe2 with VW2 is half-metallic. Additionally, one Se and one W atom vacancies (VSe, VW), two Se atom vacancies (VSe-Se), and one W atom and the nearby three Se atoms on the same layer vacancy (VWSe3)-doped monolayer WSe2 remain as non-magnetic semiconducting. But the impure electronic states attributed from the W d and Se p orbitals around the vacancies locate around the Fermi level and narrow down the energy gaps. Meanwhile, our calculations indicate that the tensile strain of 0~7% not only manipulates the electronic properties of defected monolayer WSe2 with vacancies by narrowing down their energy gaps, but also controls the magnetic moments of VW-, VW2-, and VWSe6-doped monolayer WSe2.

Abstract Background Common wheat (Triticum aestivum L.) is one of the most important food crops worldwide. Wheat spike-layer uniformity related traits (SLURTs) were complex traits that directly affect yield potential and appearance. In this study, quantitative trait locus (QTL) for five SLURTs among inter-tillers were first documented using a recombinant inbred line (RIL) mapping population derived from a cross between Kenong9204 and Jing411 (represented by KJ-RILs). Genetic relationships between SLURTs and yield were characterized in detail. Results The trait phenotypic performances for the 188 KJ-RILs and their parents were evaluated in eight different environments. The genetic data included in a high-density genetic map derived from the Affymetrix 660 K SNP Array and the corresponding genotypes in each lines. Of 99 putative additive QTL 11 were stable across environments and 57 showed significant additive-by-environment interaction effects. These QTL individually explained 1.05–39.62% of the phenotypic variance, with log of odds (LOD) values ranging from 2.00 to 34.01. Genetic relationships between SLURTs and yield indicated that plants with slight uneven spike spatial distribution should be an ideotype for super high-yield in wheat. Conclusions The present study will provide assistance in understanding the genetic relationships between SLURTs and yield potential. The 11 stable QTL for SLURTs identified herein may facilitate breeding new wheat varieties with scientifically reasonable spike-layer distribution by marker assisted selection.

Greenish leaf variation has been reported widely as a trait of great interest in wheat for improving photosynthesis. Zhongkenuomai No.1 (ZKNM1), a mutant with recoverable leaf spots, was regarded as a suitable material for studying chlorophyll synthesis-related mechanisms. In this study, transcriptome and DNA methylation analyses were conducted in ZKNM1 leaves to determine the transcriptional regulatory mechanism of leaf spot development. Ultimately, 890 differentially expressed genes (DEGs) were discovered, with chlorophyll biosynthesis pathway genes downregulated and chlorophyll degradation pathway genes upregulated, possibly acting as a double block to chlorophyll accumulation. Among them, HEMA1s (Glutamyl-tRNA reductase family proteins) and PORAs (protochlorophyllide oxidoreductase A) were the most important controlled genes. Furthermore, a genome-wide methylation analysis indicates that a hypermethylated region is present 1690 bp upstream of the transcriptional start sites in spot tissues (SPs), and 131 DNA methylation-mediated DEGs were identified, one of which encoded a putative resistance gene (TraesCS1A02G009500) and was a hub gene in interaction network modules. In the sample groups with leaf spots (SPs), this gene may be involved in the photosynthetic processes. The findings indicated that dynamic variations in DNA methylation play key roles in gene regulation to govern leaf spot development.

Background. Some autoimmune hepatitis (AIH) patients have elevated serum IgG4 levels, and the clinical characteristics of such patients are currently incompletely characterized. Aim. To analyze the clinical features and possible pathogenesis of AIH with elevated serum IgG4 levels. Methods. According to their serum IgG4 value, patients were divided into elevated IgG4 (IgG4 > 1.35 g/l) and normal IgG4 (IgG4 ≤ 1.35 g/l) groups. Results. Among the 152 patients included in this study, those in the elevated IgG4 group had the following characteristics: older onset age (56 ± 11.43 years vs. 49.49 ± 13.04 years, P=0.005), higher proportion of males (34.15% vs. 12.61%, P=0.002), higher prevalence of cirrhosis (56.10% vs. 36.04%, P=0.026), lower prevalence of extrahepatic autoimmune diseases (9.76% vs. 27.3%, P=0.023), and higher levels of IL-17 and IL-22 (P

Aim. To compare the response between the current recommended dosage 13–15 mg/kg/d and 20 mg/kg/d dose of ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC) patients who do not respond completely to a standard dose of UDCA. Methods. We included 73 patients with poor response and randomized them into two groups to investigate whether increasing the dosage of UDCA was beneficial to nonresponders. Patients assigned to the 13–15 mg/kg/d group continued with standard therapy, and participants in the 18–22 mg/kg/d group switched to the higher dosage (18–22 mg/kg/d), with a follow-up of 12 months for both groups. The primary endpoints were the rate of response at 6 months and drug side effects. Results. According to the Paris 2 criteria, patients receiving 18–22 mg/kg/d UDCA achieved a response rate of 59.4% compared with 36.1% in the standard dosage group (P=0.046) at 6 months, respectively. At 12 months, the high-UDCA-dosage group achieved a response rate of 59.4% compared with 47.2% in the standard dosage group (P=0.295), respectively. Additionally, the risk score predicted by the UK-PBC model was lower in high-dosage UDCA-treated patients than in the standard dosage group (all P

Autoimmune liver diseases (AILDs) are a group of liver disorders composed of autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) characterized by chronic hepatic and biliary inflammation. Although several genetic factors, such as HLA alleles, TNFA, and CTLA-4, have been reported in the pathogenesis of AILDs, many details remain unknown. In recent years, microRNAs (miRNAs) have emerged as crucial components in the diagnosis and therapeutic applications of various autoimmune diseases, including systemic lupus erythematosus (SLE), glomerulonephritis, and AILDs. MiRNAs comprise a class of small, noncoding molecules of 19-–25 nucleotides that modulate multiple genes by suppressing or degrading target mRNAs. Altered miRNA profiles have been identified in serum, immune cells, and live tissues from AILD patients. Elevated serum miR-21 and miR-122 levels in AIH patients as well as decreased miR-200c levels in PSC patients indicate their diagnostic utility. Highly expressed miR-122 and miR-378f as well as downregulated miR-4311 and miR-4714-3p in serum samples from refractory PBC patients suggest their potential to evaluate treatment efficacy. Moreover, miRNAs have been reported to participate in AILD development. Increased miR-506 levels may impair bile secretion in PBC by inhibiting Cl-/HCO3-anion exchanger 2 (AE2) and type III inositol 1,4,5-trisphosphate receptor-3 (InsP3R3). Additionally, different miRNA mimics or antagonists, such as atagomiR-155 and miR-223 mimics, have been widely applied in experimental AILD murine models with great efficacy. Here, we provide an overview of miRNAs in AILDs, aiming to summarize their potential roles in diagnosis and therapeutic interventions, and we discuss the challenges and future applications of miRNAs in clinical practice.

Exosomes are small discoid extracellular vesicles (EVs) originating from endosomes that are 30–150 nm in diameter and have a double lipid layer. They participate in the immune response, cell migration, cell differentiation, and tumor invasion and mediate intercellular communication, regulating the biological activity of receptor cells through the proteins, nucleic acids, and lipids that they carry. Exosomes also play vital roles in the diagnosis and treatment of liver diseases. Macrophages, which show unique phenotypes and functions in complex microenvironments, can be divided into M1 and M2 subtypes. M1 macrophages function in immune surveillance, and M2 macrophages downregulate the immune response. Recent studies have shown that macrophages are involved in non-alcoholic fatty liver disease, liver fibrosis, and hepatocellular carcinoma. Moreover, several studies have demonstrated that liver diseases are associated with exosomes derived from or transferred to macrophages. This review focuses on the participation of macrophages and exosomes in liver diseases.

Total glucosides of paeony (TGP), an active mixture extracted from paeony root, has anti-inflammatory and immunoregulatory effects and is widely used for the treatment of autoimmune diseases such as rheumatoid arthritis. However, the role of TGP in autoimmune hepatitis (AIH) is still unknown. In this study, we aimed to investigate the effect of TGP in autoimmune liver disease (AILD) patients and in concanavalin A (Con A)-induced experimental autoimmune hepatitis (EAH). Changes in biochemical parameters of AILD patients showed that treatment with TGP exerts significant protective effects on liver function, as reflected by decreased levels of serum alanine transaminase, aspartate transaminase, γ-glutamyl transpeptidase and total bilirubin. In EAH mice, we found that pretreatment with TGP reduced the levels of serum liver enzyme levels, histopathological damage and hepatocyte apoptosis. Importantly, flow cytometry analysis showed that pretreatment with TGP reduced the infiltration of mature dendritic cells in the liver. In vitro, TGP pretreatment ameliorated the Con A-induced mitochondrial membrane potential decline, reactive oxygen species increase, and apoptosis increase in hepatocytes. In addition, the levels of Bax, Cleaved Caspase-3 and cytoplasmic Cytochrome C decreased during this process, whereas those of Bcl-2 and mitochondrial Cytochrome C increased. Therefore, TGP might decrease hepatocyte apoptosis through the mitochondrial apoptotic pathway. Moreover, the maturation of bone marrow dendritic cells was also inhibited by TGP treatment. In conclusion, TGP treatment ameliorates AIH by regulating hepatocyte apoptosis and DC maturation. TGP is a potential compound for AIH treatment.

Colored wheat is a valuable resource that is rich in anthocyanins and minerals and thus contributes additional nutritional value to a healthy human diet. However, the effects of nitrogen fertilization on anthocyanin content (AC) and the balance between quality and yield still merit discussion. In this study, blue, purple, and common-colored wheat genotypes were used to investigate three nutrient quality traits, seven processing quality traits, three yield traits and seven grain morphology traits at three nitrogen levels in two years to excavate their possible plasticity under low-nitrogen stress and the tradeoffs among these traits. The highest AC was found in the blue genotypes followed by the purple genotypes. Analysis of variance (ANOVA) showed that AC could be significantly increased by reducing N application, especially in the purple genotypes. Therefore, growing colored wheat with low nitrogen input could allow efficient harvesting of grain with higher AC. However, the other nutrient quality traits and most processing quality traits were observed to decrease under low-nitrogen (LN) stress. Additionally, a correlation analysis indicated that the nutrient quality traits had stable tradeoffs with thousand kernel weight at all N levels because of the significantly negative correlations among them. Therefore, the additive main effect and multiplicative interaction (AMMI) model was used to further identify the most suitable colored genotypes with the best yield potential and also nutrient quality relative characteristics under LN stress. The blue lines Lanmai2999 and purple varieties Zhongkezinuomai 168 were found to be specifically adapted to LN stress with the highest AC values and showed stable performance in the other nutrient quality- and yield-related features. To further investigate the possible mechanism of anthocyanin accumulation in response to reduced N application, the expression of four genes (TaCHS, TaFDR, TaCHI and TaANS) involved in the anthocyanin synthesis pathway was evaluated. All four genes were downregulated under high nitrogen fertilizer application, indicating that anthocyanin synthesis in colored wheat might be inhibited by nitrogen fertilizer. Therefore, this research provided information for optimizing nitrogen fertilizer management in producing colored wheat and also demonstrated that it is efficient and economical to plant colored wheat genotypes in nitrogen-poor areas for use in a healthy human diet, improving the benefits of wheat planting and facilitating nitrogen pollution control.

Autoimmune hepatitis (AIH) is characterized by massive immune cell-mediated hepatocyte destruction. Glucocorticoids, particularly methylprednisolone (MP), are the most effective treatment for AIH; however, the mechanism underlying the effects of glucocorticoid treatment has not been fully elucidated. The present study explored the effects of MP on damaged hepatocytes in mice with concanavalin A (ConA)−induced experimental autoimmune hepatitis (EAH). C57BL/6 mice were divided into three groups: a normal control group (injected with normal saline), a ConA (20 mg/kg) group, and a ConA + MP (3.12 mg/kg) group. The serum levels of liver enzymes, cytokines, activated T cells, and apoptosis− and autophagy−associated marker proteins were determined 12 h after ConA injection. Human hepatocyte cell line LO2 was used to verify the effects of ConA and MP in vitro. MP treatment significantly decreased inflammatory reactions in the serum and liver tissues and activated the Akt/mTOR signaling pathway to inhibit apoptosis and autophagy in hepatocytes in vivo. Transmission electron microscopy (TEM) revealed fewer autophagosomes in the MP-treated group than in the ConA-treated group. MP treatment obviously suppressed apoptosis and mitochondrial membrane potential (ΔΨm) loss in hepatocytes in vitro. Furthermore, ConA treatment increased the levels of LC3-II, p62/SQSTM1, and Beclin-1, while bafilomycin A1 did not augment the levels of LC3-II. MP treatment decreased the levels of LC3-II, p62/SQSTM1, and Beclin-1 and upregulated the levels of phosphorylated (p)-Akt and p-mTOR. In conclusion, MP ameliorated mitochondria-mediated apoptosis and autophagy dysfunction in ConA-induced hepatocyte injury in vivo and in vitro via the Akt/mTOR signaling pathway.

Background/Aims: Autoimmune hepatitis (AIH) is a chronic necroinflammatory disease of the liver whose pathogenic mechanisms have not yet been elucidated. Moreover, the current treatment used for the vast majority of AIH patients is largely dependent on immunosuppressant administration and liver transplantation. However, research on the pathogenesis of AIH and effective new treatments for AIH have been hampered by a lack of animal models that accurately reproduce the human condition. Methods: AIH models created by concanavalin A (ConA) injections at different times and doses. The levels of ALT, AST, LDH and inflammatory cytokines were examined at various times after 20 mg/kg ConA was administered by ELISA using commercially available kits. Moreover, liver pathological changes were observed by flow cytometry (FCM) and H&E staining. Results: Our experiments demonstrated that the levels of ALT, AST, LDH and several inflammatory cytokines, including TNF-α, IFN-γ, and IL-6, were higher in the 20 mg/kg 12 h ConA group than in the other groups. Importantly, the numbers of activated CD4+ and CD8+ T lymphocytes in the blood, spleen and liver were calculated. These results showed that ConA (20 mg/kg for 12 h)-induced hepatitis was similar to that in clinical AIH patients. Furthermore, we found that the number of MDSCs in the blood was significantly increased in the ConA (20 mg/kg for 12 h) group compared with controls. Our findings indicated that ConA (20 mg/kg for 12 h)-induced hepatitis could be used as an experimental murine model that mirrors most of the pathogenic properties of human type I AIH. Conclusion: This model [ConA (20 mg/kg for 12 h)] provides a valuable tool for studying AIH immunopathogenesis and rapidly assessing novel therapeutic approaches.

Abstract Background The content of grain protein (GPC) in cereals is an important part of total protein in human food. Exploring and utilizing new GPC genes is one of the most effective approaches for wheat quality breeding. Results Three homoeologues of TaAAP6(−3A, 3B, 3D)were cloned by homology cloning from OsAAP6.Temporal and spatial expression analysis showed that TaAAP6homoeologues were preferentially expressed in developing grains, and TaAAP6-3B may play a major role in regulating GPC in wheat. Association analysis indicated thatTaAAP6-3B-I is significantly correlated with higher GPC than that of TaAAP6-3B-II for 115 wheat lines in all five environments. TaAAP6-3B-I, the favored allele of TaAAP6-3B, was preferentially expressed in preliminary developing grain stage. Two functional markers were developed to discriminate 197F2populations and the result showed that TaAAP6-3B-I (high-protein content) was completely dominant. Two cis-regulatory elements appear to be associated with high GPC were found in the 5’UTR of TaAAP6-3B-I.The change of the TaAAP6-3B locus types indicated that the gene was subjected to selection pressures during long process of artificial selection. Conclusions TaAAP6-3B is a regulator of GPC and its favored allele TaAAP6-3B-I exhibits an obvious potential application in wheat high-GPC breeding.