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Abstract Rheumatoid arthritis (RA) is a debilitating autoimmune disease characterized by chronic joint inflammation and cartilage damage. Current therapeutic strategies often result in side effects, necessitating the development of targeted and safer treatment options. This study introduces a novel nanotherapeutic system, 2-APB@DGP-MM, which utilizes macrophage membrane (MM)-encapsulated nanoparticles (NPs) for the targeted delivery of 2-Aminoethyl diphenylborinate (2-APB) to inflamed joints more effectively. The NPs are designed with a matrix metalloproteinase (MMP)-cleavable peptide, allowing for MMP-responsive drug release within RA microenvironment. Comprehensive in vitro and in vivo assays confirmed the successful synthesis and loading of 2-APB into the DSPE-GPLGVRGC-PEG (DGP) NPs, as well as their ability to repolarize macrophages from a pro-inflammatory M1 to an anti-inflammatory M2 phenotype. The NPs demonstrated high biocompatibility, low cytotoxicity, and enhanced cellular uptake. In a collagen-induced arthritis (CIA) mouse model, intra-articular injection of 2-APB@DGP-MM significantly reduced synovial inflammation and cartilage destruction. Histological analysis corroborated these findings, demonstrating marked improvements in joint structure and delayed disease progression. Above all, the 2-APB@DGP-MM nanotherapeutic system offers a promising and safe approach for RA treatment by modulating macrophage polarization and delivering effective agents to inflamed joints. Graphical Abstract

Pyroptosis induced by lipopolysaccharide (LPS) has an obvious impact on intestinal inflammation and immune regulation. Enterotoxigenic Escherichia coli (ETEC) K88 has been proved to induce inflammatory responses in several models, but whether E. coli K88 participates in the same process of pyroptotic cell death as LPS remains to be identified. We conducted a pilot experiment to confirm that E. coli K88, instead of Escherichia coli O157 and Salmonella typhimurium, promotes the secretion of interleukin-1 beta (IL-1β) and interleukin-18 (IL-18) in macrophages. Further experiments were carried out to dissect the molecular mechanism both in vitro and in vivo. The Enzyme-Linked Immunosorbent Assay (ELISA) results suggested that E. coli K88 treatment increased the expression of pro-inflammatory cytokines IL-18 and IL-1β in both C57BL/6 mice and the supernatant of J774A.1 cells. Intestinal morphology observations revealed that E. coli K88 treatment mainly induced inflammation in the colon. Real-time PCR and Western blot analysis showed that the mRNA and protein expressions of pyroptosis-related factors, such as NLRP3, ASC, and Caspase1, were significantly upregulated by E. coli K88 treatment. The RNA-seq results confirmed that the effect was associated with the activation of NLRP3, ASC, Caspase1, GSDMD, IL-18, and IL-1β, and might also be related to inflammatory bowel disease and the tumor necrosis factor pathway. The pyroptosis-activated effect of E. coli K88 was significantly blocked by NLRP3 siRNA. Our data suggested that E. coli K88 caused inflammation by triggering pyroptosis, which provides a theoretical basis for the prevention and treatment of ETEC in intestinal infection.

Abstract The biosynthetic process of selenium nanoparticles (SeNPs) by specific bacterial strain, whose growth directly affects the synthesis efficiency, has attracted great attentions. We previously reported that Bacillus paralicheniformis SR14, a SeNPs-producing bacteria, could improve intestinal antioxidative function in vitro. To further analyze the biological characteristics of SR14, whole genome sequencing was used to reveal the genetic characteristics in selenite reduction and sugar utilization. The results reviewed that the genome size of SR14 was 4,448,062 bp, with a GC content of 45.95%. A total of 4300 genes into 49 biological pathways was annotated to the KEGG database. EC: 1.1.1.49 (glucose-6-phosphate 1-dehydrogenase) and EC: 5.3.1.9 (glucose-6-phosphate isomerase), were found to play a potential role in glucose degradation and EC:2.7.1.4 (fructokinase) might be involved in the fructose metabolism. Growth profile and selenite-reducing ability of SR14 under different sugar supplements were determined and the results reviewed that glucose had a better promoting effect on the reduction of selenite and growth of bacteria than fructose, sucrose, and maltose. Moreover, RT-qPCR experiment proved that glucose supplement remarkably promoted the expressions of thioredoxin, fumarate reductase, and the glutathione peroxidase in SR14. Analysis of mRNA expression showed levels of glucose-6-phosphate dehydrogenase and fructokinase significantly upregulated under the supplement of glucose. Overall, our data demonstrated the genomic characteristics of SR14 and preliminarily determined that glucose supplement was most beneficial for strain growth and SeNPs synthesis.

The aim of the present study is to evaluate the absolute content and accumulation patterns of flavonoid components; to give insight into the accumulation relationships among flavonoid components; to explore the correlation between the content of flavonoid components and the expression of flavonoid biosynthesis genes in Tartary buckwheat seeds; and to construct a biosynthetic pathway on the major flavonoid components in Tartary buckwheat seeds. In total, 61 flavonoid components were absolutely quantified in five Tartary buckwheat varieties, of which 41 existed in all varieties. The content of most flavonoids varied significantly among different varieties or within the same variety. Rutin, quercetin, nicotiflorin, and kaempferol were the dominant flavonoid components in the Tartary buckwheat seeds, accounting for 73.05–81.79% of the total flavonoids. Significantly positive or negative correlations with content accumulation were found between some flavonoid components. Thirty-six flavonoid components displayed four different accumulation patterns in the developing Tartary buckwheat seeds. Seventeen structural genes for flavonoid biosynthesis displayed a significantly positive correlation with the accumulation of most flavonoid components during the development of Tartary buckwheat seeds, and the F3′5′H-3 gene might be the most crucial contributor in determining the total flavonoid content in Tartary buckwheat seeds. A schematic of the biosynthesis pathways for 30 major flavonoids in Tartary buckwheat seeds was constructed. These findings provide an outlook of the flavonoid components and their biosynthesis in Tartary buckwheat seeds and have potential applications in breeding new cultivars with higher flavonoid contents.

Abstract The Wuyi‐Yunkai Orogen experienced a polyphase tectonomagmatism and is a key region for deciphering the alteration and thermal structure of the South China Block lithosphere. Herein, an electrical resistivity model of the lithosphere is presented via the three‐dimensional inversion of broadband (0.003–3600 s) magnetotelluric (MT) data collected along a 380‐km‐long profile comprising 62 MT sites across the Wuyi‐Yunkai Orogen, and the robustness of this model is critically evaluated through a series of sensitivity tests. The resistivity model reveals that the upper crust of the Cathaysia Block and the Wuyi‐Yunkai Orogen is dominated by high‐resistivity sedimentary cover interposed with low‐resistivity features, mainly along fault zones. High‐resistivity bodies and strong conductors in the upper crust are interpreted as magmatic rocks and tectonic mélanges, respectively. Another feature of this resistivity model is the presence of zones featuring enhanced electrical conductivity (

The utilization of geothermal energy has gradually increased in northern China because of its unique advantages as a heating supply. However, the sustainable exploitation of geothermal energy usually requires a comprehensive investigation of the geothermal water circulation pattern prevailing at a proposed site. During the exploitation of geothermal energy resources at Nanpu Sag in northern China, thermal anomalies were found to exist in two adjacent regions: the Caofeidian and the Matouying. To reconcile the anomalies and to examine both the source of recharge water and the geothermal systems’ circulation dynamics, a comprehensive investigation was performed using multiple chemical and isotopic tracers (δ2H, δ18O, 87Sr/86Sr, δ13C, and 14C). The total dissolved solids (TDS) of the geothermal water are approximately 750 mg/L and 1,250 mg/L, respectively. The geothermal water isotopes at the two sites are also different, with average values of -9.3‰ and -8.2‰ for δ18O and -73.4‰ and -71‰ for δ2H, respectively. Moreover, the 87Sr/86Sr ratio of geothermal water at Matouying is 0.7185, which is much greater than that of Caofeidian, with an average value of 0.7088. All the results confirm the difference between the two geothermal systems and may explain the two circulation patterns of deep groundwater at Caofeidian and Matouying. The reservoir temperature obtained from theoretical chemical geothermometers is estimated to be 83–92°C at the Caofeidian and 107–137°C at the Matouying, respectively. The corrected 14C age implies a low circulation rate that would allow sufficient time to heat the water at Caofeidian. In addition, we propose a geothermal conceptual model in our study area. This model could provide key information regarding the geothermal sustainable exploitation and the effective management of geothermal resources.

Assessment of available geothermal resources in the deep oil field is important to the synergy exploitation of oil and geothermal resources. A revised volumetric approach is proposed in this work for evaluating deep geothermal potential in an active oil field by integrating a 3D geological model into a hydrothermal (HT)-coupled numerical model. Based on the analysis of the geological data and geothermal conditions, a 3D geological model is established with respect to the study area, which is discretized into grids or elements represented in the geological model. An HT-coupled numerical model was applied based on the static geological model to approximate the natural-state model of the geothermal reservoir, where the thermal distribution information can be extracted. Then the geothermal resource in each small grid element is calculated using a volumetric method, and the overall geothermal resource of the reservoirs can be obtained by making an integration over each element of the geological model. A further parametric study is carried out to investigate the influence of oil and gas saturations on the overall heat resources. The 3D geological model can provide detailed information on the reservoir volume, while the HT natural-state numerical model addressed the temperature distribution in the reservoir by taking into account complex geological structures and contrast heterogeneity. Therefore, integrating the 3D geological modeling and HT numerical model into the geothermal resource assessment improved its accuracy and helped to identify the distribution map of the available geothermal resources, which indicate optimal locations for further development and utilization of the geothermal resources. The Caofeidian new town Jidong oil field serves as an example to depict the calculation workflow. The simulation results demonstrate in the Caofeidian new town geothermal reservoir that the total amount of geothermal resources, using the proposed calculation method, is found to be 1.23e+18 J, and the total geothermal fluid volume is 8.97e+8 m3. Moreover, this approach clearly identifies the regions with the highest potential for geothermal resources. We believe this approach provides an alternative method for geothermal potential assessment in oil fields, which can be also applied globally.

Liver injury is a common complication of inflammatory bowel disease (IBD). However, the mechanisms of liver injury development are not clear in IBD patients. Gut microbiota is thought to be engaged in IBD pathogenesis. Here, by an integrated analysis of host transcriptome and colonic microbiome, we have attempted to reveal the mechanism of liver injury in colitis mice. In this study, dextran sulfate sodium (DSS) -induced mice colitis model was constructed. Liver transcriptome showed significant up- and down-regulation of pathways linked to immune response and lipid metabolism, respectively. Whilst the colon transcriptome exhibited dramatic alterations in immune response and pathways associated with cell growth and death. The microbiota of DSS-treated mice underwent strong transitions. Correlation analyses identified genes associated with liver and colon injury, whose expression was associated with the abundance of liver and gut health-related bacteria. Collectively, the results indicate that the liver injury in colitis mice may be related to the intestinal dysbiosis and host-microbiota interactions. These findings may provide new insights for identifying potential targets for the treatment of IBD and its induced liver injury.

Large areas of Yanshan period granites with high heat production values (3–10 μW/m3) and mantle plume around Hainan province co-exist in Igneous Rocks Regions of South China (IRRSC). Surface manifestations are mainly warm/hot springs with temperatures below 90 °C and no typical phenomenon of high temperature resources have been observed. The main objective of this paper is to discuss the existence of high temperature geothermal resources and their possible locations under this kind of geothermal and tectonic background by analysis of high temperature heat sources, borehole temperature measurement, and reservoir temperature estimation. Two possible partial melts of the magma chamber were detected as high temperature heat sources in the Southern Leizhou Peninsular and North Hainan Island at a depth of 8–15 km. Other low resistivity zones in the upper crust are more likely caused by fluid in the formations or faults but not high temperature heat sources. This was also verified by borehole temperature measurement in these two areas, with maximum formation temperatures of 211°C and 185°C found, respectively. Reservoir temperatures from fluid geothermometers show lower temperatures of between 110–160°C for typical geothermal fields over the IRRSC but not in the Southern Leizhou Peninsular and Northern Hainan Island. In all, high temperature geothermal resources may be found in the Southern Leizhou Peninsular and on Northern Hainan Island.

Liver segmentation from CT is regarded as a prerequisite for computer-assisted clinical applications. However, automatic liver segmentation technology still faces challenges due to the variable shapes and low contrast. In this paper, a patient-specific probabilistic atlas (PA)-based method combing modified distance regularized level set for liver segmentation is proposed. Firstly, the similarities between training atlases and testing patient image are calculated, resulting in a series of weighted atlas, which are used to generate the patient-specific PA. Then, a most likely liver region (MLLR) can be determined based on the patient-specific PA. Finally, the refinement is performed by the modified distance regularized level set model, which takes advantage of both edge and region information as balloon force. We evaluated our proposed scheme based on 35 public datasets, and experimental result shows that the proposed method can be deployed for robust and precise liver segmentation, to replace the tedious and time-consuming manual method.

To provide a safe and effective supplement of the essential trace element selenium, we focused on the biosynthesis of nanoselenium (SeNPs) via probiotics. A novel kind of exopolymer-functionalized nanoselenium (SeEPS), whose average size was 67.0 ± 0.6 nm, was produced by Bacillus subtilis SR41, whereas the control consisted of exopolymers without selenium (EPS). Chemical composition analysis, Fourier transform infrared (FTIR) spectroscopy and high-performance liquid chromatography (HPLC) confirmed that SeEPS and EPS shared similar polysaccharide characteristic groups, such as COO- and C=O, and contained not only 45.2–45.4% of sugars but also 23.5–24.7% of proteins and some lipids. Both SeEPS and EPS were primarily composed of mannose, amino glucose, ribose, glucose and galactose. Furthermore, to identify the biologically active component of SeEPS, three kinds of selenium particles with different stabilizers [Se(0), bovine serum albumin-Se and EPS-Se] were synthesized chemically, and their ability to scavenge free radicals in vitro was compared with that of SeEPS and EPS. The results revealed that EPS itself exhibited weak superoxide and hydroxyl radical scavenging abilities. Nevertheless, SeEPS had superior antioxidant properties compared to all other products, possibly due to the specific structure of SeNPs and exopolymers. Our results suggested that exopolymer-functionalized SeNPs with specific monosaccharide composition and structure could eventually find a potential application as an antioxidant.

The initiation and evolution of seismic activity in intraplate regions are controlled by heterogeneous stress and highly fractured rocks within the rock mass triggered by fluid migration. In this study, we imaged the electrical structure of the crust beneath the Ganzi fault using a three-dimensional magnetotelluric inversion technique, which is host to an assemblage of resistive and conductive features extending into the lower crust. It presents a near-vertical low-resistance zone that cuts through the brittle ductile transition zone, extends to the lower crust, and acts as a pathway for fluid migration from the crustal flow to the upper crustal depths. Conductors in the upper and lower crust are associated with saline fluids and 7% to 16% partial melting, respectively. The relationship between the earthquake epicenter and the surrounding electrical structure suggests that the intraplate seismicity is triggered by overpressure fluids, which are dependent on fluid volume changes generated by the decompression dehydration of partially molten material during upwelling and native fluid within the crustal flow.

Abstract In the present study, we examined the ability of Enterobacter cloacae Z0206 to reduce toxic sodium selenite and mechanism of this process. E. cloacae Z0206 was found to completely reduce up to 10 mM selenite to elemental selenium (Se°) and form selenium nanoparticles (SeNPs) under aerobic conditions. The selenite reducing effector of E. cloacae Z0206 cell was to be a membrane-localized enzyme. iTRAQ proteomic analysis revealed that selenite induced a significant increase in the expression of fumarate reductase. Furthermore, the addition of fumarate to the broth and knockout of fumarate reductase (frd) both significantly decreased the selenite reduction rate, which revealed a previously unrecognized role of E. cloacae Z0206 fumarate reductase in selenite reduction. In contrast, glutathione-mediated Painter-type reactions were not the main pathway of selenite reducing. In conclusion, E. cloacae Z0206 effectively reduced selenite to Se° using fumarate reductase and formed SeNPs; this capability may be employed to develop a bioreactor for treating Se pollution and for the biosynthesis of SeNPs in the future.

This study investigated the effects of dietary C. butyricum ZJU-F1 on the apparent digestibility of nutrients, intestinal barrier function, immune response, and microflora of weaned piglets, with the aim of providing a theoretical basis for the application of Clostridium butyricum as an alternative to antibiotics in weaned piglets. A total of 120 weanling piglets were randomly divided into four treatment groups, in which piglets were fed a basal diet supplemented with antibiotics (CON), Bacillus licheniformis (BL), Clostridium butyricum ZJU-F1 (CB), or Clostridium butyricum and Bacillus licheniformis (CB-BL), respectively. The results showed that CB and CB-BL treatment increased the intestinal digestibility of nutrients, decreased intestinal permeability, and increased intestinal tight junction protein and mucin expression, thus maintaining the integrity of the intestinal epithelial barrier. CB and CB-BL, as exogenous probiotics, were also found to stimulate the immune response of weaned piglets and improve the expression of antimicrobial peptides in the ileum. In addition, dietary CB and CB-BL increased the proportion of Lactobacillus. The levels of butyric acid, propionic acid, acetic acid, and total acid were significantly increased in the ceca of piglets fed CB and CB-BL. Furthermore, we validated the effects of C. butyricum ZJU-F1 on the intestinal barrier function and immune response in vitro and found C. butyricum ZJU-F1 improved intestinal function and enhanced the TLR-2-MyD88-NF-κB signaling.

Rice sheath blight, caused by Rhizoctonia solani, is one of the most devastating diseases for stable rice production in most rice-growing regions of the world. Currently, studies of the molecular mechanism of rice sheath blight resistance are scarce. Here, we used an RNA-seq approach to analyze the gene expression changes induced by the AG1 IA strain of R. solani in rice at 12, 24, 36, 48, and 72 h. By comparing the transcriptomes of TeQing (a moderately resistant cultivar) and Lemont (a susceptible cultivar) leaves, variable transcriptional responses under control and infection conditions were revealed. From these data, 4,802 differentially expressed genes (DEGs) were identified. Gene ontology and pathway enrichment analyses suggested that most DEGs and related metabolic pathways in both rice genotypes were common and spanned most biological activities after AG1 IA inoculation. The main difference between the resistant and susceptible plants was a difference in the timing of the response to AG1 IA infection. Photosynthesis, photorespiration, and jasmonic acid and phenylpropanoid metabolism play important roles in disease resistance, and the relative response of disease resistance-related pathways in TeQing leaves was more rapid than that of Lemont leaves at 12 h. Here, the transcription data include the most comprehensive list of genes and pathway candidates induced by AG1 IA that is available for rice and will serve as a resource for future studies into the molecular mechanisms of the responses of rice to AG1 IA.

To understand the phylogenetic position of Larimichthys polyactis within the family Sciaenidae and the phylogeny of this family, the organization of the mitochondrial genome of small yellow croaker was determined herein. The complete, 16,470 bp long, mitochondrial genome contains 37 mitochondrial genes (13 protein-coding, 2 ribosomal RNA and 22 transfer RNA genes), as well as a control region (CR), as in other bony fishes. Comparative analysis of initiation/termination codon usage in mitochondrial protein-coding genes of Percoidei species, indicated that COI in Sciaenidae entails an ATG/AGA codon usage different from other Percoidei fishes, where absence of a typical conserved domain or motif in the control regions is common. Partitioned Bayesian analysis of 618 bp of COI sequences data were used to infer the phylogenetic relationships within the family Sciaenidae. An improvement in harmonic mean -lnL was observed when specific models and parameter estimates were assumed for partitions of the total data. The phylogenetic analyses did not support the monophyly of Otolithes, Argyrosomus, and Argyrosominae. L. polyactis was found to be most closely related to Collichthys niveatus, whereby, according to molecular systematics studies, the relationships within the subfamily Pseudosciaenidae should be reconsidered.

In this paper, a novel 3D vector field convolution (VFC)-based B-spline deformation model is proposed for accurate and robust cartilage segmentation. Firstly, the anisotropic diffusion method is utilized for noise reduction, and the Sinc interpolation method is employed for resampling. Then, to extract the rough cartilage, features derived from Hessian matrix are chosen to enhance the cartilage, followed by binarizing the images via an optimal thresholding method. Finally, the proposed VFC-based B-spline deformation model is used to refine the rough segmentation. In the experiments, the proposed method was evaluated and demonstrated on 46 magnetic resonance images (MRI) (including 20 hip joints and 26 knee joints), and the results were compared with three state-of-the-art cartilage segmentation methods. Both qualitative and quantitative segmentation results indicate that the proposed method can be deployed for accurate and robust cartilage segmentation. Furthermore, from the segmentation results, patient-specific 3D models of the patient’s anatomy can be derived, which then can be utilized in a wide range of clinical applications, such as 3D visualization for surgical planning and guidance.

Major histocompatibility complex (MHC) has a central role in the adaptive immune system by presenting foreign peptide to the T-cell receptor. In order to study the molecular function and genomic characteristic of class II genes in teleost, the full lengths of MHC class IIA and IIB cDNA and genomic sequence were cloned from miiuy croaker (Miichthys miiuy). As in other teleost, four exons and three introns were identified in miiuy croaker class IIA gene; but the difference is that six exons and five introns were identified in the miiuy croaker class IIB gene. The deduced amino acid sequence of class IIA and class IIB had 26.3-85.7% and 11.0-88.8% identity with those of mammal and teleost, respectively. Real-time quantitative RT-PCR demonstrated that the MHC class IIA and IIB were ubiquitously expressed in ten normal tissues; expression levels of MHC genes were found first upregulated and then downregulated, and finally by a recovery to normal level throughout the pathogenic bacteria infection process. In addition, we report on the underlying mechanism that maintains sequences diversity among many fish species. A series of site-model tests implemented in the CODEML program revealed that positive Darwinian selection is likely the cause of the molecular evolution in the fish MHC class II genes.