A novel bispecific antibody targeting two overlapping epitopes in RBD improves neutralizing potency and breadth against SARS-CoV-2.

ABSTRACTSARS-CoV-2 has been evolving into a large number of variants, including the highly pathogenic Delta variant, and the currently prevalent Omicron subvariants with extensive evasion capability, which raises an urgent need to develop new broad-spectrum neutralizing antibodies. Herein, we engineer two IgG-(scFv)2 form bispecific antibodies with overlapping epitopes (bsAb1) or non-overlapping epitopes (bsAb2). Both bsAbs are significantly superior to the parental monoclonal antibodies in terms of their antigen-binding and virus-neutralizing activities against all tested circulating SARS-CoV-2 variants including currently dominant JN.1. The bsAb1 can efficiently neutralize all variants insensitive to parental monoclonal antibodies or the cocktail with IC50 lower than 20 ng/mL, even slightly better than bsAb2. Furthermore, the cryo-EM structures of bsAb1 in complex with the Omicron spike protein revealed that bsAb1 with overlapping epitopes effectively locked the S protein, which accounts for its conserved neutralization against Omicron variants. The bispecific antibody strategy engineered from overlapping epitopes provides a novel solution for dealing with viral immune evasion.

Occurrence and Flow Behavior for Oil Transport in Mixed Wetting Nanoscale Shale Bedding Fractures.

Shale reservoirs are characterized by an abundance of nanoscale porosities and microfractures. The states of fluid occurrence and flow behaviors within nanoconfined spaces necessitate novel research approaches, as traditional percolation mathematical models are inadequate for accurately depicting these phenomena. This study takes the Gulong shale reservoir in China as the subject of its research. Initially, the unique mixed wetting characteristics of the Gulong shale reservoir are examined and characterized using actual micropore images. Subsequently, the occurrence and flow behavior of oil within the nanoscale bedding fractures under various wettability scenarios are described through a combination of microscopic pore image and molecular dynamics simulations. Ultimately, a mathematical model is established that depicts the velocity distribution of oil and its apparent permeability. This study findings indicate that when the scale of the shale bedding fractures is less than 100 nm, the impact of the nanoconfinement effect is significant and cannot be overlooked. In this scenario, the state of oil occurrence and its flow behavior are influenced by the initial oil-wet surface area on the mixed wetting walls. The study quantifies the velocity and density distribution of oil in mixed wetting nanoscale shale bedding fractures through a mathematical model, providing a crucial theoretical basis for upscaling from the nanoscale to the macroscale.

Enhancing tunnel crack detection with linear seam using mixed stride convolution and attention mechanism.

Cracks in tunnel lining structures constitute a common and serious problem that jeopardizes the safety of traffic and the durability of the tunnel. The similarity between lining seams and cracks in terms of strength and morphological characteristics renders the detection of cracks in tunnel lining structures challenging. To address this issue, a new deep learning-based method for crack detection in tunnel lining structures is proposed. First, an improved attention mechanism is introduced for the morphological features of lining seams, which not only aggregates global spatial information but also features along two dimensions, height and width, to mine more long-distance feature information. Furthermore, a mixed strip convolution module leveraging four different directions of strip convolution is proposed. This module captures remote contextual information from various angles to avoid interference from background pixels. To evaluate the proposed approach, the two modules are integrated into a U-shaped network, and experiments are conducted on Tunnel200, a tunnel lining crack dataset, as well as the publicly available crack datasets Crack500 and DeepCrack. The results show that the approach outperforms existing methods and achieves superior performance on these datasets.

Effect of Physical Activity on the Association Between Diet and Constipation: Evidence From the National Health and Nutrition Examination Survey 2007-2010.

Background/Aims: Previous studies have shown that diet and physical activity can influence constipation. However, the combined effect of diet and physical activity on constipation remains unclear. Methods: Constipation was defined based on stool consistency and frequency, while overall diet quality was assessed using Healthy Eating Index (HEI)-2015 scores. Participants were categorized into low (metabolic equivalent [MET]-min/wk < 500) and high physical activity groups (MET-min/wk ≥ 500). The association between diet and constipation across physical activity groups was analyzed using survey logistic regression and restricted cubic splines. Results: Higher HEI-2015 scores were associated with reduced constipation risk in the high physical activity group when constipation was defined by stool consistency (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.97-0.99). However, in the low physical activity group, increased HEI-2015 scores did not significantly affect constipation risk (OR, 1.01; 95% CI, 0.97-1.05). Similar results were found when constipation was defined based on stool frequency. In the high physical activity group, increased HEI-2015 scores were significantly associated with a reduced constipation risk (OR, 0.96; 95% CI, 0.94-0.98). Conversely, in the low physical activity group, increased HEI-2015 scores did not affect the risk of constipation (OR, 0.96; 95% CI, 0.90-1.03). Conclusions: Our findings suggest that a higher HEI-2015 score is negatively associated with constipation among individuals with high physical activity levels but not among those with low physical activity levels. This association was consistent when different definitions of constipation were used. These results highlight the importance of combining healthy diet with regular physical activity to alleviate constipation.

Genome-wide identification of JAZ gene family members in autotetraploid cultivated alfalfa (Medicago sativa subsp. sativa) and expression analysis under salt stress.

BACKGROUND: Jasmonate ZIM-domain (JAZ) proteins, which act as negative regulators in the jasmonic acid (JA) signalling pathway, have significant implications for plant development and response to abiotic stress. RESULTS: Through a comprehensive genome-wide analysis, a total of 20 members of the JAZ gene family specific to alfalfa were identified in its genome. Phylogenetic analysis divided these 20 MsJAZ genes into five subgroups. Gene structure analysis, protein motif analysis, and 3D protein structure analysis revealed that alfalfa JAZ genes in the same evolutionary branch share similar exon‒intron, motif, and 3D structure compositions. Eight segmental duplication events were identified among these 20 MsJAZ genes through collinearity analysis. Among the 32 chromosomes of the autotetraploid cultivated alfalfa, there were 20 MsJAZ genes distributed on 17 chromosomes. Extensive stress-related cis-acting elements were detected in the upstream sequences of MsJAZ genes, suggesting that their response to stress has an underlying function. Furthermore, the expression levels of MsJAZ genes were examined across various tissues and under the influence of salt stress conditions, revealing tissue-specific expression and regulation by salt stress. Through RT‒qPCR experiments, it was discovered that the relative expression levels of these six MsJAZ genes increased under salt stress. CONCLUSIONS: In summary, our study represents the first comprehensive identification and analysis of the JAZ gene family in alfalfa. These results provide important information for exploring the mechanism of JAZ genes in alfalfa salt tolerance and identifying candidate genes for improving the salt tolerance of autotetraploid cultivated alfalfa via genetic engineering in the future.

Multiomics Analyses Reveal MsC3H29 Positively Regulates Flavonoid Biosynthesis to Improve Drought Resistance of Autotetraploid Cultivated Alfalfa (Medicago sativa L.).

Alfalfa (Medicago sativa subsp. sativa), the "queen of forage," is the most important perennial legume, with high productivity and an excellent nutritional profile. Medicago sativa subsp. falcata is a subspecies of the alfalfa complex and exhibits better drought tolerance. However, drought stress significantly hampers their development and yield. The molecular mechanisms underlying the aboveground and underground tissues of sativa and falcata responding to drought stress remain obscure. Here, we performed a comprehensive comparative analysis of the physiological and transcriptomic responses of sativa and falcata under drought stress. The results showed that photosynthesis was inhibited, and antioxidant enzymes were activated under drought stress. MsC3H29, a CCCH-type zinc finger protein, was identified as a hub gene through weighted gene coexpression network analysis (WGCNA) and was significantly induced by drought in underground tissue. The MsC3H29 protein was localized in the nucleus. Overexpression (OE) of MsC3H29 can increase the primary root length and fresh weight of transgenic alfalfa hairy roots, while RNA interference (RNAi) decreases them under drought stress. The 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) staining revealed that MsC3H29 promoted drought tolerance of alfalfa hairy roots through decreasing ROS accumulation. The targeted metabolome analysis showed that the overexpression of MsC3H29 resulted in higher levels of accumulation for flavonoid monomers, including vicenin, daidzein, apigenin, isorhamnetin, quercetin, and tricin, in transgenic alfalfa hairy roots before and after drought stress, while RNAi led to a reduction. Our study provided a key candidate gene for molecular breeding to improve drought resistance in alfalfa.

Echistatin/BYL-719 impedes epithelial-mesenchymal transition in pulmonary fibrosis induced by silica through modulation of the Integrin ß1/ILK/PI3K signaling pathway.

Silicosis is a chronic fibroproliferative lung disease caused by long-term inhalation of crystalline silica dust, characterized by the proliferation of fibroblasts and pulmonary interstitial fibrosis. Currently, there are no effective treatments available. Recent research suggests that the Integrin ß1/ILK/PI3K signaling pathway may be associated with the pathogenesis of silicosis fibrosis. In this study, we investigated the effects of Echistatin (Integrin ß1 inhibitor) and BYL-719 (PI3K inhibitor) on silicosis rats at 28 and 56 days after silica exposure. Histopathological analysis of rat lung tissue was performed using H&E staining and Masson staining. Immunohistochemistry, Western blotting, and qRT-PCR were employed to assess the expression of markers associated with epithelial-mesenchymal transition (EMT), fibrosis, and the Integrin ß1/ILK/PI3K pathway in lung tissue. The results showed that Echistatin, BYL 719 or their combination up-regulated the expression of E-cadherin and down-regulated the expression of Vimentin and extracellular matrix (ECM) components, including type I and type III collagen. The increase of Snail, AKT and ß-catenin in the downstream Integrin ß1/ILK/PI3K pathway was inhibited. These results indicate that Echistatin and BYL 719 can inhibit EMT and pulmonary fibrosis by blocking different stages of Integrinß1 /ILK/PI3K signaling pathway. This indicates that the Integrin ß1/ILK/PI3K signaling pathway is associated with silica-induced EMT and may serve as a potential therapeutic target for silicosis.

Activation of Sirtuin3 by honokiol ameliorates alveolar epithelial cell senescence in experimental silicosis via the cGAS-STING pathway.

BACKGROUND: Silicosis, characterized by interstitial lung inflammation and fibrosis, poses a significant health threat. ATII cells play a crucial role in alveolar epithelial repair and structural integrity maintenance. Inhibiting ATII cell senescence has shown promise in silicosis treatment. However, the mechanism behind silica-induced senescence remains elusive. METHODS: The study employed male C57BL/6 N mice and A549 human alveolar epithelial cells to investigate silicosis and its potential treatment. Silicosis was induced in mice via intratracheal instillation of crystalline silica particles, with honokiol administered intraperitoneally for 14 days. Silica-induced senescence in A549 cells was confirmed, and SIRT3 knockout and overexpression cell lines were generated. Various analyses were conducted, including immunoblotting, qRT-PCR, histology, and transmission electron microscopy. Statistical significance was determined using one-way ANOVA with Tukey's post-hoc test. RESULTS: This study elucidates how silica induces ATII cell senescence, emphasizing mtDNA damage. Notably, honokiol (HKL) emerges as a promising anti-senescence and anti-fibrosis agent, acting through sirt3. honokiol effectively attenuated senescence in ATII cells, dependent on sirt3 expression, while mitigating mtDNA damage. Sirt3, a class III histone deacetylase, regulates senescence and mitochondrial stress. HKL activates sirt3, protecting against pulmonary fibrosis and mitochondrial damage. Additionally, HKL downregulated cGAS expression in senescent ATII cells induced by silica, suggesting sirt3's role as an upstream regulator of the cGAS/STING signaling pathway. Moreover, honokiol treatment inhibited the activation of the NF-κB signaling pathway, associated with reduced oxidative stress and mtDNA damage. Notably, HKL enhanced the activity of SOD2, crucial for mitochondrial function, through sirt3-mediated deacetylation. Additionally, HKL promoted the deacetylation activity of sirt3, further safeguarding mtDNA integrity. CONCLUSIONS: This study uncovers a natural compound, HKL, with significant anti-fibrotic properties through activating sirt3, shedding light on silicosis pathogenesis and treatment avenues.

GSEA analysis identifies potential drug targets and their interaction networks in coronary microcirculation disorders.

Coronary microcirculation dysfunction (CMD) is one of the main causes of cardiovascular disease. Traditional treatment methods lack specificity, making it difficult to fully consider the differences in patient conditions and achieve effective treatment and intervention. The complexity and diversity of CMD require more standardized diagnosis and treatment plans to clarify the best treatment strategy and long-term outcomes. The existing treatment measures mainly focus on symptom management, including medication treatment, lifestyle intervention, and psychological therapy. However, the efficacy of these methods is not consistent for all patients, and the long-term efficacy is not yet clear. GSEA is a bioinformatics method used to interpret gene expression data, particularly for identifying the enrichment of predefined gene sets in gene expression data. In order to achieve personalized treatment and improve the quality and effectiveness of interventions, this article combined GSEA (Gene Set Enrichment Analysis) technology to conduct in-depth research on potential drug targets and their interaction networks in coronary microcirculation dysfunctions. This article first utilized the Coremine medical database, GeneCards, and DrugBank public databases to collect gene data. Then, filtering methods were used to preprocess the data, and GSEA was used to analyze the preprocessed gene expression data to identify and calculate pathways and enrichment scores related to CMD. Finally, protein sequence features were extracted through the calculation of autocorrelation features. To verify the effectiveness of GSEA, this article conducted experimental analysis from four aspects: precision, receiver operating characteristic (ROC) curve, correlation, and potential drug targets, and compared them with Gene Regulatory Networks (GRN) and Random Forest (RF) methods. The results showed that compared to the GRN and RF methods, the average precision of GSEA improved by 0.11. The conclusion indicated that GSEA helped identify and explore potential drug targets and their interaction networks, providing new ideas for personalized quality of CMD.

Enhanced Recovery Protocol Versus Conventional Care in Patients Undergoing Esophagectomy for Cancer: Advantages in Clinical and Patient-Reported Outcomes.

BACKGROUND: This study was designed to compare the clinical and patient-reported outcomes (PROs) between the enhanced recovery after surgery (ERAS) protocol and conventional care in patients undergoing esophagectomy for cancer, which have not previously been compared. METHODS: This single-center retrospective study included prospective PRO data from August 2019 to June 2021. Clinical outcomes included perioperative complications and postoperative length of stay (PLOS). Patient-reported outcomes were assessed by using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ-C30) and esophagus-specific module (QLQ-OES18) preoperatively to 6 months postoperatively. Mixed-effects models were used to longitudinally compare quality of life (QOL) scores between the two modes. RESULTS: Patients undergoing conventional care and ERAS were analyzed (n = 348 and 109, respectively). The ERAS group had fewer overall complications, pneumonia, arrhythmia, and a shorter PLOS than the conventional group, and outperformed the conventional group in five functional QLQ-C30 domains and five symptom QLQ-OES18 domains, including less dysphagia (p < 0.0001), trouble talking (p = 0.0006), and better eating (p < 0.0001). These advantages persisted for 3 months postoperatively. For the cervical circular stapled anastomosis, the initial domains and duration of benefit were reduced in the ERAS group. CONCLUSIONS: The ERAS protocol has significant advantages over conventional care in terms of clinical outcomes, lowering postoperative symptom burden, and improving functional QOL in patients who have undergone esophagectomy. Selection of the optimal technique for cervical anastomosis is a key operative component of ERAS that maintains the symptom domains and duration of the advantages of PROs.

Host-Guest Cocrystallization of Phenanthrene[2]arene Macrocycles Facilitating Structure Determination of Liquid Organic Molecules.

Single-crystal X-ray diffraction analysis has emerged as the most reliable method for determining the structures of organic molecules. However, numerous analytes, such as liquid organic molecules, pose challenges in crystallization, making their structures directly elusive via X-ray crystallography methods. Herein, we introduced the rapid cocrystallization of a macrocycle named phenanthrene[2]arene (PTA, host) with 15 liquid organic molecules (guests). The guest liquid organic molecules were successively cocrystallized with the aid of the PTA host. Moreover, the chemical structures of the liquid organic molecules could be determined through single-crystal X-ray diffraction analysis. PTA exhibited high adaptivity and was capable of encapsulating liquid organic molecules without forming covalent bonds or strong directional interactions. The results revealed that the adaptive crystals of PTA exhibited excellent cocrystallization capacity. Weak noncovalent interactions between the host and guest molecules were crucial for organizing the guests in an ordered pattern.

Highly Efficient and Selective Extraction of Gold from Thiosulfate Leaching Solution Using Functionalized Dicationic Ionic Liquids.

Thiosulfate leaching has been regarded as a promising alternative to cyanidation, but it still faces the challenge of the recovery of low content of gold from high concentrations of thiosulfate solutions. Liquid-liquid extraction is a method to address this issue but is still limited by the use of volatile and toxic organic solvents. To overcome this limitation, this work synthesized some functionalized dicationic ionic liquids (DILs) to serve as extraction solvents for the recovery of the gold-thiosulfate complex, [Au(S2O3)2]3-, from thiosulfate solutions. Experimental results indicated that the DILs showed higher extraction rates toward [Au(S2O3)2]3- compared with their monocationic-based counterparts, likely due to the stronger electrostatic interaction between the dications of the ILs and [Au(S2O3)2]3-. The transfer of [Au(S2O3)2]3- from the water phase to the IL phase was identified as an anion exchange and endothermic process. The rate of extraction was limited by the anion exchange process occurring at the IL-water interface. The extraction ability of ILs highly depended on the type of anion; specifically, the ILs with anions that had strong hydrogen-bonding ability exhibited high extraction ability toward [Au(S2O3)2]3-. Finally, DILs proved effective in the recovery of [Au(S2O3)2]3- from an actual gold leaching solution and exhibited high selectivity toward coexisting ions, indicating their potential as environmentally friendly solvents for gold recovery.

The Force-Frequency Characteristics of Quartz Wafers under a Cantilever Beam Structure.

This study investigated the force-frequency characteristics of quartz wafers inside a cantilever beam frame. Firstly, the force-frequency coefficient formula of quartz wafers with fixed ends under axial force was analyzed. Firstly, the formula for the force-frequency coefficient of quartz wafers with fixed ends under axial force was analyzed. A force-frequency coefficient formula suitable for cantilever beam structures was derived by considering the changes in surface stress and stiffness of quartz wafers with fixed ends and one end under force on the other. Subsequently, the formula's accuracy was verified by experiments, and the accuracy was more than 92%. In addition, strain simulation analysis was performed on three different shapes of quartz wafers, and experimental verification was carried out on two of them. The results revealed that trapezoidal quartz wafers and cantilever beam structures exhibited superior stress distribution to rectangular chips. Furthermore, by positioning electrodes at various locations on the surface of the quartz chip, it was observed that, as the electrodes moved closer to the fixed end, the force-frequency coefficient of the rectangular quartz chip increased, along with an increase in chip strain under the cantilever structure. In summary, this study provides a new approach for designing cantilever quartz resonator sensors in the future.

Identification and validation of two major QTL for grain number per spike on chromosomes 2B and 2D in bread wheat (Triticum aestivum L.).

KEY MESSAGE: Major QTL for grain number per spike were identified on chromosomes 2B and 2D. Haplotypes and candidate genes of QGns.cib-2B.1 were analyzed. Grain number per spike (GNS) is one of the main components of wheat yield. Genetic dissection of their regulatory factors is essential to improve the yield potential. In present study, a recombinant inbred line population comprising 180 lines developed from the cross between a high GNS line W7268 and a cultivar Chuanyu12 was employed to identify quantitative trait loci (QTL) associated with GNS across six environments. Two major QTL, QGns.cib-2B.1 and QGns.cib-2D.1, were detected in at least four environments with the phenotypic variations of 12.99-27.07% and 8.50-13.79%, respectively. And significant interactions were observed between the two major QTL. In addition, QGns.cib-2B.1 is a QTL cluster for GNS, grain number per spikelet and fertile tiller number, and they were validated in different genetic backgrounds using Kompetitive Allele Specific PCR (KASP) markers. QGns.cib-2B.1 showed pleotropic effects on other yield-related traits including plant height, spike length, and spikelet number per spike, but did not significantly affect thousand grain weight which suggested that it might be potentially applicable in breeding program. Comparison analysis suggested that QGns.cib-2B.1 might be a novel QTL. Furthermore, haplotype analysis of QGns.cib-2B.1 indicated that it is a hot spot of artificial selection during wheat improvement. Based on the expression patterns, gene annotation, orthologs analysis and sequence variations, the candidate genes of QGns.cib-2B.1 were predicted. Collectively, the major QTL and KASP markers reported here provided a wealth of information for the genetic basis of GNS and grain yield improvement.

Machine learning predicts the serum PFOA and PFOS levels in pregnant women: Enhancement of fatty acid status on model performance.

Human exposure to per- and polyfluoroalkyl substances (PFASs) has received considerable attention, particularly in pregnant women because of their dramatic changes in physiological status and dietary patterns. Predicting internal PFAS exposure in pregnant women, based on external and relevant parameters, has not been investigated. Here, machine learning (ML) models were developed to predict the serum concentrations of PFOA and PFOS in a large population of 588 pregnant participants. Dietary exposure characteristics, demographic parameters, and in particular, serum fatty acid (FA) data were used for the model development. The fitting results showed that the inclusion of FAs as covariates significantly improved the performance of the ML models, with the random forest (RF) model having the best predictive performance for PFOA (R2 = 0.33, MAE = 1.51 ng/mL, and RMSE = 1.89 ng/mL) and PFOS (R2 = 0.12, MAE = 2.65 ng/mL, and RMSE = 3.37 ng/mL). The feature importance analysis revealed that serum FAs greatly affected PFOA concentration in the pregnant women, with saturated FAs being associated with decreased PFOA levels and unsaturated FAs with increased levels. Comparison with one-compartment pharmacokinetic model further demonstrated the advantage of the ML models in predicting PFAS exposure in pregnant women. Our models correlate for the first time blood chemical concentrations with human FA status using ML, introducing a novel perspective on predicting PFAS levels in pregnant women. This study provides valuable insights concerning internal exposure of PFASs generated from external exposure, and contributes to risk assessment and management in pregnant populations.

Evodiamine encapsulated by hyaluronic acid modified zeolitic imidazolate framework-8 for tumor targeted therapy.

Evodiamine (EVO), a natural bioactive compound extracted from Evodia rutaecarpa, shows therapeutic ability against malignant melanoma. However, the poor solubility and bioavailability of EVO limit its clinical application. Metal-organic frameworks (MOFs) have shown excellent physical and chemical properties and are widely used as drug delivery systems. Among them, zeolitic imidazolate framework-8 (ZIF-8) is a research popular material because of its unique properties, such as hydrothermal stability, non-toxicity, biocompatibility, and pH sensitivity. In this study, in order to load EVO, a drug carrier that hyaluronic acid (HA) modified zeolitic imidazolate framework-8 (ZIF-8) is synthesized. This drug carrier has shown drug loading with 6.2 ± 0.6%, and the nano drugs (EVO@ZIF-8/HA) have good dispersibility. Owing to the decoration HA of EVO@ZIF-8, the potential of the nano drugs is reversed from the positive charge to the negative charge, which is beneficial to blood circulation in vivo. Furthermore, because the CD44-expressing in tumor cells is excessed, the endocytosis and accumulation of nano drugs in tumor cells are beneficial to improvement. Compared with free EVO, EVO@ZIF-8/HA has shown a significantly improved anti-tumor efficacy in vitro and in vivo. In summary, the drug carrier effectively addresses the challenges that are caused by the strong hydrophobicity and low bioavailability of EVO, thereby targeted tumor therapy of EVO can be achieved.

Ionic liquids functionalized chitosan: An effective, rapid and green adsorbent for gold recovery.

Thiosulfate has been considered as a more environmentally-friendly alternative to cyanide salts for the extraction of gold from gold ores and the development of affordable, green and efficient adsorbents for the isolation of gold-thiosulfate complex (Au(S2O3)23-) from the leaching solution remains a significant challenge. To address this issue, chitosan, a natural macromolecule, was selected as a carrier and chemically modified with ionic liquids. The ionic liquids modified chitosan showed greater adsorption capacity towards Au(S2O3)23- compared with pristine chitosan. The adsorption of Au(S2O3)23- on ionic liquid modified chitosan followed Freundlich isotherm and pseudo-second order kinetic models, involving an anion-exchange mechanism with liquid film diffusion as the rate-limiting step. The chitosan modified with butylimidazolium-based ionic liquid modified had an adsorption capacity of 5.0 mg g-1 for Au(S2O3)23- (10 mg L-1, pH 6, 2 g L-1 of adsorbent dosage), outperforming other reported adsorbents. The ionic liquid modified chitosan showed a high adsorption efficiency of up to 96.7 % for Au(S2O3)23- in an actual thiosulfate leaching solution with a desorption efficiency of 98.4 %, suggesting that the ionic liquid modified chitosan has the potential to be a eco-friendly, biocompatible and effective adsorbent for the recovery of Au(S2O3)23-.

Predictive Value of Serum Albumin, Iron, Ferritin, and Hepcidin for Antiviral Efficacy of IFNα Treatment in Patients with Chronic Hepatitis B.

OBJECTIVE: Interferon-α (IFNα) therapy has been an integral part of the current treatment for hepatitis B virus (HBV) infection. However, the exact effect of IFNα antiviral therapy on liver function and iron metabolism in patients with chronic hepatitis B (CHB) remains unclear. Here, we investigated the characteristics of changes in liver function and iron metabolism indexes in patients with chronic hepatitis B before and after IFNα treatment. Additionally, we determined their predictive value for the therapeutic response of IFNα treatment. METHODS: In this study, 34 patients with CHB before and after IFNα treatment were enrolled. Serum levels of virological indicators, liver function, and iron metabolism markers were detected and analyzed in each patient. ROC curve analysis was performed to compare the predictive value of serum liver function and iron metabolism markers for the therapeutic response of IFN α treatment. RESULTS: A significant decrease in serum HBV DNA (P<0.001) and HBsAg (P<0.001) was observed before and after IFNα treatment. Compared to the patients before IFNα treatment, patients after IFNα treatment showed a significant increase in serum albumin (ALB) (P<0.05) and a significant decrease in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (P=0.003 and P=0.034). These findings suggested that the synthetic function of the liver was improved, and liver inflammation was alleviated. Serum HEPC and serum ferritin (SF) levels in patients after IFNα treatment were significantly higher (P<0.001, P<0.001); however, serum iron (SI) levels were significantly lower (P=0.005) than those in patients before IFNα treatment. These findings indicate that IFNα treatment regulated iron metabolism homeostasis in CHB patients. Combined liver function and iron metabolism markers, including ALB, SI, SF, and HEPC, had the highest predictive value for the therapeutic response of IFNα treatment for CHB. CONCLUSION: IFNα treatment improved liver function and iron metabolism homeostasis in patients with CHB. Regular monitoring of serum ALB, SI, SF, and HEPC can help predict the therapeutic response of IFNα treatment for CHB.

Activation of the cGAS-STING pathway by viral dsDNA leading to M1 polarization of macrophages mediates antiviral activity against hepatitis B virus.

BACKGROUND AND AIMS: Activation of the cGAS-STING pathway induces the production of type I interferons, initiating the antiviral immune response, which contributes to the clearance of pathogens. Previous studies have shown that STING agonists promote hepatitis B virus (HBV) clearance; however, few studies have investigated the effect of activating the cGAS-STING pathway in macrophages on HBV. METHODS: The polarization status of HBV particle-stimulated RAW264.7 macrophages was analyzed. After stimulation with HBV particles, the analysis focused on determining whether the DNA sensors in RAW264.7 macrophages recognized the viral double-stranded DNA (dsDNA) and evaluating the activation of the cGAS-STING pathway. Coculture of mouse macrophages and hepatocytes harboring HBV was used to study the antiviral activity of HBV-stimulated RAW264.7 macrophages. RESULTS: After stimulation with HBV particles, HBV relaxed circular DNA (rcDNA) was detected in RAW264.7 macrophages, and the protein expression of phospho-STING, phospho-TBK1, and phospho-IRF3 in the STING pathway was increased, as shown by Western blot analysis, which revealed that M1 polarization of macrophages was caused by increased expression of CD86. RT-PCR analyses revealed elevated expression of M1 macrophage polarization-associated cytokines such as TNFα, IL-1ß, iNOS, and IFNα/ß. In the coculture experiment, both HBsAg and HBeAg expression levels were significantly decreased in AML12-HBV1.3 cells cocultured with the supernatants of HBV-stimulated RAW264.7 macrophages. CONCLUSION: The results suggest that macrophages can endocytose HBV particles. Additionally, viral dsDNA can be recognized by DNA pattern recognition receptors, which in turn activate the cGAS-STING pathway, promoting the M1 polarization of macrophages, while no significant M2 polarization is observed. Macrophages stimulated with HBV particles exhibit enhanced antiviral activity against HBV.