Plasma thrombomodulin as a candidate biomarker for the diagnosis and prognosis of HBV-related acute-on-chronic liver failure.

Background and Aim: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a complicated syndrome with high short-term mortality. Effective biomarkers are required for its early diagnosis and prognosis. This study aimed to determine the diagnostic and prognostic value of thrombomodulin (TM) in patients with HBV-ACLF. Methods: The expression of TM during disease progression was evaluated through transcriptomics analysis. The plasma TM concentrations of 393 subjects with HBV-ACLF (n=213), acute-on-chronic hepatic dysfunction (ACHD, n=50), liver cirrhosis (LC, n=50) or chronic hepatitis B (CHB, n=50), and normal controls (NC, n=30) from a prospective multicenter cohort, were measured to verify the diagnostic and prognostic significance of plasma TM for HBV-ACLF patients by enzyme-linked immunosorbent assay (ELISA). Results: TM mRNA was highly expressed in the HBV-ACLF group compared with the ACHD group (AUROC=0.710). High expression of TM predicted poor prognosis for HBV-ACLF patients at 28/90 days (AUROCs=0.823/0.788). Functional analysis showed that TM was significantly associated with complement activation and the inflammatory signaling pathway. External validation confirmed its high diagnostic accuracy for HBV-ACLF patients (AUROC=0.796). Plasma TM concentrations were correlated with organ failure, including coagulation and kidney failure. Plasma TM concentrations showed a potential prognostic value for 28-day mortality rates (AUROC=0.702). Risk stratification specifically identified HBV-ACLF patients with a high risk of death as having a plasma TM concentration of ≥8.4 ng/mL. Conclusion: This study reveals that the plasma TM can be a candidate biomarker for early diagnosis and prognosis of HBV-ACLF, and might play a vital role in coagulation and inflammation.

Trophic interactions in soil micro-food webs drive ecosystem multifunctionality along tree species richness.

Rapid biodiversity losses under global climate change threaten forest ecosystem functions. However, our understanding of the patterns and drivers of multiple ecosystem functions across biodiversity gradients remains equivocal. To address this important knowledge gap, we measured simultaneous responses of multiple ecosystem functions (nutrient cycling, soil carbon stocks, organic matter decomposition, plant productivity) to a tree species richness gradient of 1, 4, 8, 16, and 32 species in a young subtropical forest. We found that tree species richness had negligible effects on nutrient cycling, organic matter decomposition, and plant productivity, but soil carbon stocks and ecosystem multifunctionality significantly increased with tree species richness. Linear mixed-effect models showed that soil organisms, particularly arbuscular mycorrhizal fungi (AMF) and soil nematodes, elicited the greatest relative effects on ecosystem multifunctionality. Structural equation models revealed indirect effects of tree species richness on ecosystem multifunctionality mediated by trophic interactions in soil micro-food webs. Specifically, we found a significant negative effect of gram-positive bacteria on soil nematode abundance (a top-down effect), and a significant positive effect of AMF biomass on soil nematode abundance (a bottom-up effect). Overall, our study emphasizes the significance of a multitrophic perspective in elucidating biodiversity-multifunctionality relationships and highlights the conservation of functioning soil micro-food webs to maintain multiple ecosystem functions.

A novel mutation in IAA16 is associated with dicamba resistance in Chenopodium album.

BACKGROUND: Resistance to dicamba in Chenopodium album was first documented over a decade ago, however, the molecular basis of dicamba resistance in this species has not been elucidated. In this research, the resistance mechanism in a dicamba-resistant C. album phenotype was investigated using a transcriptomics (RNA-sequence) approach. RESULTS: The dose-response assay showed that the resistant (R) phenotype was nearly 25-fold more resistant to dicamba than a susceptible (S) phenotype of C. album. Also, dicamba treatment significantly induced transcription of the known auxin-responsive genes, Gretchen Hagen 3 (GH3), small auxin-up RNAs (SAURs), and 1-aminocyclopropane-1-carboxylate synthase (ACS) genes in the susceptible phenotype. Comparing the transcripts of auxin TIR/AFB receptors and auxin/indole-3-acetic acid (AUX/IAA) proteins identified from C. album transcriptomic analysis revealed that the R phenotype contained a novel mutation at the first codon of the GWPPV degron motif of IAA16, resulting in an amino acid substitution of glycine (G) with aspartic acid (D). Sequencing the IAA16 gene in other R and S individuals further confirmed that all the R individuals contained the mutation. CONCLUSION: In this research, we describe the dicamba resistance mechanism in the only case of dicamba-resistant C. album reported to date. Prior work has shown that the dicamba resistance allele confers significant growth defects to the R phenotype investigated here, suggesting that dicamba-resistant C. album carrying this novel mutation in the IAA16 gene may not persist at high frequencies upon removal of dicamba application. © 2024 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Intramuscular endometriosis of the forearm: a case report.

Endometriosis is a disorder that commonly affects females of reproductive age and is defined as the presence of endometrial glands or stroma outside the uterine cavity. Patients typically present with cyclical pain during menses. Endometriosis can be characterized as endopelvic or extrapelvic depending on the sites involved. We report a case of a 40-year-old, right-hand-dominant, female who presented with a painful mass in her right proximal forearm. She was ultimately diagnosed with intramuscular endometriosis and underwent surgical excision.

A review of microplastic transport in coastal zones.

Transport of microplastics (MPs) in coastal zones is influenced not only by their own characteristics, but also by the hydrodynamic conditions and coastal environment. In this article, we first summarized the source, distribution and abundance of MPs in coastal zones around the world through the induction of in-situ observation literature, and then comprehensively reviewed the different transports of MPs in coastal zones, including sedimentation, vertical mixing, resuspension, drift and biofouling. Afterwards, we conducted a comparative analysis of relevant experimental literature, and found that the current experimental research on microplastic transport mainly focused on the settling velocity under static water and the transport distribution under dynamic water. Based on the relevant literature on numerical simulation of microplastic transport in coastal zones, it was also found that the Euler-Lagrange method is the most widely used. The main influencing factor in the Euler method is hydrodynamic, while the Lagrange method and Euler-Lagrange method is hydrodynamic and microplastic particle characteristics. Tides in hydrodynamics are mentioned the most frequently, and the role of turbulence in almost all the literature. The density of MPs is the most influencing factor on transport results, followed by size, while shape is only studied in small-scale models. Some literature has also found that the influence of biofilms is mainly reflected in the changes in the density and size of MPs.

Peptide-Functionalized Inorganic Oxide Nanomaterials for Solid Cancer Imaging and Therapy.

The diagnosis and treatment of solid tumors have undergone significant advancements marked by a trend toward increased specificity and integration of imaging and therapeutic functions. The multifaceted nature of inorganic oxide nanomaterials (IONs), which boast optical, magnetic, ultrasonic, and biochemical modulatory properties, makes them ideal building blocks for developing multifunctional nanoplatforms. A promising class of materials that have emerged in this context are peptide-functionalized inorganic oxide nanomaterials (PFIONs), which have demonstrated excellent performance in multifunctional imaging and therapy, making them potential candidates for advancing solid tumor diagnosis and treatment. Owing to the functionalities of peptides in tumor targeting, penetration, responsiveness, and therapy, well-designed PFIONs can specifically accumulate and release therapeutic or imaging agents at the solid tumor sites, enabling precise imaging and effective treatment. This review provides an overview of the recent advances in the use of PFIONs for the imaging and treatment of solid tumors, highlighting the superiority of imaging and therapeutic integration as well as synergistic treatment. Moreover, the review discusses the challenges and prospects of PFIONs in depth, aiming to promote the intersection of the interdisciplinary to facilitate their clinical translation and the development of personalized diagnostic and therapeutic systems by optimizing the material systems.

Strategies for utilizing covalent organic frameworks as host materials for the integration and delivery of bioactives.

Covalent organic frameworks (COFs), a new and developing class of porous framework materials, are considered a type of promising carrier for the integration and delivery of bioactives, which have diverse fascinating merits, such as a large specific surface area, designable and specific porosity, stable and orderly framework structure, and various active sites. However, owing to the significant differences among bioactives (including drugs, proteins, nucleic acid, and exosomes), such as size, structure, and physicochemical properties, the interaction between COFs and bioactives also varies. In this review, we firstly summarize three strategies for the construction of single or hybrid COF-based matrices for the delivery of cargos, including encapsulation, covalent binding, and coordination bonding. Besides, their smart response release behaviors are also categorized. Subsequently, the applications of cargo@COF biocomposites in biomedicine are comprehensively summarized, including tumor therapy, central nervous system (CNS) modulation, biomarker analysis, bioimaging, and anti-bacterial therapy. Finally, the challenges and opportunities in this field are briefly discussed.

High-throughput virtual screening to identify potential small molecule inhibitors of the Zα domain of the adenosine deaminases acting on RNA 1(ADAR1).

Changes in RNA editing are closely associated with diseases such as cancer, viral infections, and autoimmune disorders. Adenosine deaminase (ADAR1), which acts on RNA 1, plays a key role in adenosine to inosine editing and is a potential therapeutic target for these various diseases. The p150 subtype of ADAR1 is the only one that contains a Zα domain that binds to both Z-DNA and Z-RNA. The Zα domain modulates immune responses and may be suitable targets for antiviral therapy and cancer immunotherapy. In this study, we attempted to utilize molecular docking to identify potential inhibitors that bind to the ADAR1 Zα domain. The virtual docking method screened the potential activity of more than 100,000 compounds on the Zα domain of ADAR1 and filtered to obtain the highest scoring results.We identified 71 compounds promising to bind to ADAR1 and confirmed that two of them, lithospermic acid and Regaloside B, interacts with the ADAR1 Zα domain by surface plasmonic resonance technique. The molecular dynamics calculation of the complex of lithospermic acid and ADAR1 also showed that the binding effect of lithospermic acid to ADAR1 was stable.This study provides a new perspective for the search of ADAR1 inhibitors, and further studies on the anti-ADAR11 activity of these compounds have broad prospects.

OsNAC74 affects grain protein content and various biological traits by regulating OsAAP6 expression in rice.

The grain protein content is an important quality trait in cereals, and the expression level of the OsAAP6 can significantly affect the grain protein content in rice. Through site-directed mutagenesis, we found that the position from -7 to -12 bp upstream of the transcription start site of the OsAAP6 was the functional variation site. By using the yeast single hybrid test, point-to-point in yeast, and the local surface plasmon resonance test, the OsNAC74 was screened and verified to be a regulator upstream of OsAAP6. The OsNAC74 is a constitutively expressed gene whose product is located on the cell membrane. The OsAAP6 and the genes related to the seed storage in the Osnac74 mutants were downregulated, and grain protein content was significantly reduced. In addition, OsNAC74 had a significant impact on quality traits such as grain chalkiness and gel consistency in rice. Although the Osnac74 mutant seeds were relatively small, the individual plant yield was not decreased. Therefore, OsNAC74 is an important regulatory factor with multiple biological functions. This study provides important information for the later use of OsNAC74 gene for molecular design and breeding in rice. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01433-w.

Linkages of soil CO2 emission with plant functional traits in young subtropical plantations.

Soil respiration is a key process in forest biogeochemical cycling. Exploring the relationship between plant functional traits and soil respiration can help understand the effects of tree species conversion on soil carbon cycling. In this study, we selected 15 common subtropical tree species planted in the logging site of second-generation Chinese fir forest to measure soil CO2 emission fluxes, soil physicochemical properties, leaf and root functional traits of each species, and explored the effects of plant functional traits on soil respiration. The results showed that the annual flux of soil CO2 emissions varied from 7.93 to 22.52 Mg CO2·hm-2, with the highest value under Castanopsis carlesii (22.52 Mg CO2·hm-2) and the lowest value under Taxus wallichiana (7.93 Mg CO2·hm-2). Results of stepwise regression analysis showed that the annual flux of soil CO2 emission decreased with the increases of leaf nitrogen content and fine root diameter, and increased with increasing leaf non-structural carbohydrate. In the structural equation model, leaf non-structural carbohydrate had a direct and significant positive effect on soil CO2 emission fluxes, while leaf nitrogen content and fine root diameter had a direct negative effect by decreasing soil pH and soluble organic nitrogen content. Plantations of different tree species would affect soil CO2 emission directly by changing functional traits related to water and nutrient acquisition or indirectly through soil properties. When creating plantations, we should select tree species based on the relationship between plant functional traits and ecosystem functions, with a view to improving forest productivity and soil carbon sequestration potential.

A refined management system focusing on medication dispensing errors: A 14-year retrospective study of a hospital outpatient pharmacy.

Objectives: This study aimed to evaluate the efficiency of a 14-year refined management system for the reduction of dispensing errors in a large-scale hospital outpatient pharmacy and to determine the effects of person-related and environment-related factors on the occurrence of dispensing errors. Methods: A retrospective study was performed. Data on dispensing errors, inventory and account management from 2008 to 2021 were collected from the electronic system and evaluated using the direct observation method and the Plan-Do-Check-Act (PDCA) cycle. Results: The consistency of the inventory and accounts increased substantially (from 86.93 % to 99.75 %) with the implementation of the refined management program. From 2008 to 2021, the total number of dispensing errors was reduced by approximately 96.1 %. The number of dispensing errors in quantity and name was reduced by approximately 98.2 % and 95.07 %, respectively. A remarkable reduction in the error rate was achieved (from 0.014 % to 0.00002 %), and the rate of dispensing errors was significantly reduced (0.019 % vs. 0.0003 %, p < 0.001). Across all medication dispensing errors, human-related errors decreased substantially (208 vs. 7, p < 0.05), as did non-human-related errors also (202 vs. 9, p < 0.05). There was a correlation between the occurrence of errors and pharmacists' sex (females generally made fewer errors than males), age (more errors were made by those aged 31-40 years), and working years (more errors were made by those with more than 11 years of work experience) from 2016 to 2021. The technicians improved during this procedure. Conclusions: Refined management using the PDCA cycle was helpful in preventing dispensing errors and improving medication safety for patients.

Hollow Cu2-xSe-based nanocatalysts for combined photothermal and chemodynamic therapy in the second near-infrared window.

Chemodynamic therapy (CDT) and photothermal therapy (PTT) have gained popularity due to their non-invasive characteristics and satisfying therapeutic expectations. A Cu-based nanomaterial serving as a Fenton-like nanocatalyst for CDT together with a photothermal agent for simultaneous PTT seems to be a powerful strategy. In this work, the morphological effect of Cu2-xSe nanoparticles on CDT and PTT was systematically investigated. In particular, the hollow octahedral Cu2-xSe nanoparticles exhibited higher photothermal and chemodynamic performance than that of spherical or cubic Cu2-xSe nanoparticles in the second near-infrared (NIR-II) window. In addition, the octahedral Cu2-xSe nanoparticles were further loaded with the autophagy inhibitor chloroquine (CQ) and connected with the targeting neuropeptide Y ligand, and shown to work as a novel therapeutic platform (Cu2-xSe@CQ@NPY), holding an immense potential to achieve synergetic enhancement of CDT/PTT with a positive therapeutic outcome for breast cancer.

Innovative Strategy for the Control of Citrus Canker: Inhibitors Targeting the Type III Secretion System of Xanthomonas citri Subsp. citri.

To find potential type III secretion system (T3SS) inhibitors against citrus canker caused by Xanthomonas citri subsp. citri (Xcc), a new series of 5-phenyl-2-furan carboxylic acid derivatives stitched with 2-mercapto-1,3,4-thiadiazole were designed and synthesized. Among the 30 compounds synthesized, 14 compounds significantly inhibited the promoter activity of a harpin gene hpa1. Eight of the 14 compounds did not affect the growth of Xcc, but significantly reduced the hypersensitive response (HR) of tobacco and decreased the pathogenicity of Xcc on citrus plants. Subsequent studies have demonstrated that these inhibitory molecules effectively suppress the T3SS of Xcc and significantly impair the pathogen's ability to subvert citrus immunity, resulting in a reduction in the level of disease progression. As a result, our work has identified a series of potentially attractive agents for the control of citrus canker.

E3 ubiquitin ligase Siah1 aggravates NAFLD through Scp2 ubiquitination.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver disorders and accompanied by multiple metabolic dysfunctions. Although excessive lipid accumulation in hepatocytes has been identified as a crucial mediator of NAFLD development, the underlying mechanisms are very complicated and remain largely unknown. In this study, we reported that upregulated expression of the seven in absentia homolog 1 (Siah1) in the liver exacerbated NAFLD progression. Conversely, Siah1 downregulation markedly alleviated the high fat diet-induced accumulation of hepatic fat and expression of genes related to lipid metabolism in vitro and in vivo. The mechanistic study revealed that Siah1 interacted with sterol carrier protein 2 (Scp2) and promotes its ubiquitination and degradation, suggesting that Siah1 is an important activator of Scp2 ubiquitination in the context of NAFLD. Our results demonstrated that Siah1 regulated the lipid accumulation in NAFLD by interacting with Scp2. Thus, this study presents Siah1 as a promising therapeutic target in the development of NAFLD.

Transcriptomics unveils immune metabolic disruption and a novel biomarker of mortality in patients with HBV-related acute-on-chronic liver failure.

Background & Aims: HBV-related acute-on-chronic liver failure (HBV-ACLF) is a complex syndrome associated with high short-term mortality. This study aims to reveal the molecular basis and identify novel HBV-ACLF biomarkers. Methods: Seventy patients with HBV-ACLF and different short-term (28 days) outcomes underwent transcriptome sequencing using peripheral blood mononuclear cells. Candidate biomarkers were confirmed in two external cohorts using ELISA. Results: Cellular composition analysis with peripheral blood mononuclear cell transcriptomics showed that the proportions of monocytes, T cells and natural killer cells were significantly correlated with 28-day mortality. Significant metabolic dysregulation of carbohydrate, energy and amino acid metabolism was observed in ACLF non-survivors. V-set and immunoglobulin domain-containing 4 (VSIG4) was the most robust predictor of patient survival (adjusted p = 1.74 × 10-16; variable importance in the projection = 1.21; AUROC = 0.89) and was significantly correlated with pathways involved in the progression of ACLF, including inflammation, oxidative phosphorylation, tricarboxylic acid cycle and T-cell activation/differentiation. Plasma VSIG4 analysis externally validated its diagnostic value in ACLF (compared with chronic liver disease and healthy groups, AUROC = 0.983). The prognostic performance for 28-/90-day mortality (AUROCs = 0.769/0.767) was comparable to that of three commonly used scores (COSSH-ACLFs, 0.867/0.884; CLIF-C ACLFs, 0.840/0.835; MELD-Na, 0.710/0.737). Plasma VSIG4 level, as an independent predictor, could be used to improve the prognostic performance of clinical scores. Risk stratification based on VSIG4 expression levels (>122 µg/ml) identified patients with ACLF at a high risk of death. The generality of VSIG4 in other etiologies was validated. Conclusions: This study reveals that immune-metabolism disorder underlies poor ACLF outcomes. VSIG4 may be helpful as a diagnostic and prognostic biomarker in clinical practice. Impact and implications: Acute-on-chronic liver failure (ACLF) is a lethal clinical syndrome associated with high mortality. We found significant immune cell alterations and metabolic dysregulation that were linked to high mortality in patients with HBV-ACLF based on transcriptomics using peripheral blood mononuclear cells. We identified VSIG4 (V-set and immunoglobulin domain-containing 4) as a diagnostic and prognostic biomarker in ACLF, which could specifically identify patients with ACLF at a high risk of death.

A novel strategy to control Pseudomonas syringae through inhibition of type III secretion system.

Pseudomonas syringae (P. syringae) is a highly prevalent Gram-negative pathogen with over 60 pathogenic variants that cause yield losses of up to 80% in various crops. Traditional control methods mainly involve the application of antibiotics to inactivate pathogenic bacteria, but large-scale application of antibiotics has led to the development of bacterial resistance. Gram-negative pathogens including P. syringae commonly use the type III secretion system (T3SS) as a transport channel to deliver effector proteins into host cells, disrupting host defences and facilitating virulence, providing a novel target for antibacterial drug development. In this study, we constructed a high-throughput screening reporter system based on our previous work to screen for imidazole, oxazole and thiazole compounds. The screening indicated that the three compounds (II-14, II-15 and II-24) significantly inhibited hrpW and hrpL gene promoter activity without influencing the growth of P. syringae, and the inhibitory activity was better than that of the positive control sulforaphane (4-methylsulfinylbutyl isothiocyanate, SFN) at 50 µM. Three compounds suppressed the transcript levels of representative T3SS genes to different degrees, suggesting that the compounds may suppress the expression of T3SS by modulating the HrpR/S-HrpL regulatory pathway. Inoculation experiments indicated that all three compounds suppressed the pathogenicity of Pseudomonas syringae pv. tomato DC3000 in tomato and Pseudomonas syringae pv. phaseolicola 1448A in bean to varying degrees. One representative compound, II-15, significantly inhibited the secretion of the Pst DC3000 AvrPto effector protein. These findings provide a theoretical basis for the development of novel P. syringae T3SS inhibitors for application in disease prevention and control.

Genomic landscape and expression profile of consensus molecular subtype four of colorectal cancer.

Background: Compared to other subtypes, the CMS4 subtype is associated with lacking of effective treatments and poorer survival rates. Methods: A total of 24 patients with CRC were included in this study. DNA and RNA sequencing were performed to acquire somatic mutations and gene expression, respectively. MATH was used to quantify intratumoral heterogeneity. PPI and survival analyses were performed to identify hub DEGs. Reactome and KEGG analyses were performed to analyze the pathways of mutated or DEGs. Single-sample gene set enrichment analysis and Xcell were used to categorize the infiltration of immune cells. Results: The CMS4 patients had a poorer PFS than CMS2/3. CTNNB1 and CCNE1 were common mutated genes in the CMS4 subtype, which were enriched in Wnt and cell cycle signaling pathways, respectively. The MATH score of CMS4 subtype was lower. SLC17A6 was a hub DEG. M2 macrophages were more infiltrated in the tumor microenvironment of CMS4 subtype. The CMS4 subtype tended to have an immunosuppressive microenvironment. Conclusion: This study suggested new perspectives for exploring therapeutic strategies for the CMS4 subtype CRC.

A potential novel biomarker: comprehensive analysis of prognostic value and immune implication of CES3 in colonic adenocarcinoma.

PURPOSE: Colon cancer is the most common malignant tumor in the intestine. Abnormal Carboxylesterases 3 (CES3) expression had been reported to be correlated to multiple tumor progression. However, the association among CES3 expression and prognostic value and immune effects in colonic adenocarcinoma (COAD) were unclear. PATIENTS AND METHODS: The transcription and expression data of CES3 and corresponding clinical information was downloaded from The Cancer Genome Atlas (TCGA). The CES3 protein expression and the prognostic value were verified based on tissue microarray data. The Cancer immune group Atlas (TCIA), Tumor Immune Dysfunction and Exclusion (TIDE) algorithm and the GSE78220 immunotherapy cohort were used to forecast immunotherapy efficacy. Finally, a prognostic immune signature was constructed and verified. RESULTS: Compared with normal colon tissues, the expression of mRNA and protein levels of CES3 were downregulated in tumor tissues. CES3 expression was associated with TIICs. Hihg-CES3 COAD patients had better efficacy of concurrent immunotherapy. CES3-related immune genes (CRIs) were identified and were then used to construct prognostic immune signature and had been successfully verified in GES39582. CONCLUSION: CES3 might be a potential immune-related gene and promising prognostic biomarker in COAD.

Novel Ethyl-3-Aryl-2-Nitroacrylate Derivatives as Potential T3SS Inhibitors against Xanthomonas oryzae pv. oryzae on Rice.

Bacterial leaf blight (BLB) caused by Xanthomonas oryzae pv. oryzae (Xoo) is a highly destructive bacterial disease. Traditional prevention methods have utilized antibiotics to target bacterial growth, which has accelerated the emergence of resistant strains. New prevention techniques are developing agents such as type III secretion system (T3SS) inhibitors that target bacterial virulence factors without affecting bacterial growth. To explore novel T3SS inhibitors, a series of ethyl-3-aryl-2-nitroacrylate derivatives were designed and synthesized. Preliminary screening of T3SS inhibitors was based on the inhibition of the hpa1 gene promoter and showed no effect on bacterial growth. Compounds B9 and B10, obtained in the primary screening, significantly inhibited the hypersensitive response (HR) in tobacco and the expression of T3SS genes in the hrp cluster including key regulatory genes. In vivo bioassays showed that T3SS inhibitors obviously inhibited BLB and appeared to be more effective when combined with quorum quenching bacteria F20.