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This study aimed to analyze the structure of polysaccharides from eight different Dendrobium species and their protective effects on gastric mucosa. Ultraviolet (UV) analysis showed that the contents of eight polysaccharides ranged from 51.89 ± 6.91% to 80.57 ± 11.63%; the degree of acetylation ranged from 0.17 ± 0.03 to 0.48 ± 0.03. High-performance liquid chromatography (HPLC) results showed that these polysaccharides were mainly composed of mannose (Man) and glucose (Glc) with a small amount of galactose (Gal) and arabinose (Ara), and the monosaccharide ratios of different Dendrobium species were different. High-performance size exclusion chromatography—multi angle light scattering—refractive index detector (HPSEC-MALS-RID) showed that the molecular weight (Mw) of all Dendrobium polysaccharides was >1 × 105 Da; D. huoshanense had the lowest molecular weight. Subsequently, an ethanol injured GES-1 cell model was constructed to evaluate the gastric mucosal protective potential of polysaccharides from eight different Dendrobium species. The results showed that the protective effect of the low concentration 50 μg/mL DHP treatment group was similar to that of the control group (p > 0.05), and the cell viability could reach 97.32% of that of the control group. Based on the polysaccharide composition, different kinds of Dendrobium have different degrees of migration and repair effects on GES-1 damaged cells, and the effect of DHP is slightly better than that of other varieties (83.13 ± 1.05%). Additionally, Dendrobium polysaccharides alleviated ethanol-induced oxidative stress and inflammatory response in gastric mucosal cells by enhancing the activity of antioxidant enzymes (superoxide dismutase, glutathione peroxidase, catalase) and reducing the levels of malondialdehyde and reactive oxygen species. Overall, DHP can most effectively protect gastric mucosa. These findings enhance our understanding of the relationship between the structure and biological activity of Dendrobium polysaccharides, providing a foundation for the quality control of Dendrobium. Furthermore, these findings offer theoretical support for the development of Dendrobium polysaccharides as nutraceuticals to treat digestive system diseases. [ABSTRACT FROM AUTHOR]

Traditional Chinese medicine (TCM) is considered to be one of the most comprehensive and influential form of traditional medicine. It plays an important role in clinical treatment and adjuvant therapy for cancer. However, the complex composition of TCM presents challenges to the comprehensive and systematic understanding of its antitumor mechanisms, which hinders further development of TCM with antitumor effects. Omics technologies can immensely help in elucidating the mechanism of action of drugs. They utilize high-throughput sequencing and detection techniques to provide deeper insights into biological systems, revealing the intricate mechanisms through which TCM combats tumors. Multi-omics approaches can be used to elucidate the interrelationships among different omics layers by integrating data from various omics disciplines. By analyzing a large amount of data, these approaches further unravel the complex network of mechanisms underlying the antitumor effects of TCM and explain the mutual regulations across different molecular levels. In this study, we presented a comprehensive overview of the recent progress in single-omics and multi-omics research focused on elucidating the mechanisms underlying the antitumor effects of TCM. We discussed the significance of omics technologies in advancing research on the antitumor properties of TCM and also provided novel research perspectives and methodologies for further advancing this research field. [ABSTRACT FROM AUTHOR]

Background: Equine herpesvirus type 1 (EHV-1) is commonly associated with horse abortion. Currently, there are no reported cases of abortion resulting from EHV-1 infection in donkeys. Results: This was the first survey-based study of Chinese donkeys. The presence of EHV-1 was identified by PCR. This survey was conducted in Chabuchar County, North Xinjiang, China, in 2020. A donkey EHV-1 strain (Chabuchar/2020) was successfully isolated in MDBK cells. Seventy-two of 100 donkey sera were able to neutralize the isolated EHV-1. Moreover, the ORF33 sequence of the donkey-origin EHV-1 Chabuchar/2020 strain showed high levels of similarity in both its nucleotide (99.7‒100%) and amino acid (99.5‒100%) sequences, with those of horse EHV-1 strains. EHV-1 Chabuchar/2020 showed significant consistency and was classified within cluster 1 of horse EHV-1 strains. Further, analysis of the expected ORF30 nucleotide sequence revealed that donkey EHV-1 strains contained guanine at position 2254, resulting in a change to aspartic acid at position 752 of the viral DNA polymerase. Therefore, these strains were classified as horse neuropathogenic strains. Lastly, a phylogenetic tree was constructed using the partial ORF68 nucleotide sequences, showing that the identified donkey EHV-1 strain and the EHV-1 strain found in aborted Yili horses in China comprised a novel independent VIII group. Conclusion: This study showed the first isolation and identification of EHV-1 as an etiological agent of abortions in donkeys. Further analysis of the ORF33, ORF30, and ORF68 sequences indicated that the donkey EHV-1 contained the neuropathogenic genotype of strains in the VIII group. It is thus important to be aware of EHV-1 infection in the donkey population, even though the virus has only been identified in donkey abortions in China. [ABSTRACT FROM AUTHOR]

Porcine reproductive and respiratory syndrome virus (PRRSV), a member of the Arteriviridae family, represents a persistent menace to the global pig industry, causing reproductive failure and respiratory disease in pigs. In this study, we delved into the role of histone deacetylases (HDAC2) during PRRSV infection. Our findings revealed that HDAC2 expression is downregulated upon PRRSV infection. Notably, suppressing HDAC2 activity through specific small interfering RNA led to an increase in virus production, whereas overexpressing HDAC2 effectively inhibited PRRSV replication by boosting the expression of IFN-regulated antiviral molecules. Furthermore, we identified the virus's nonstructural protein 11 (nsp11) as a key player in reducing HDAC2 levels. Mutagenic analyses of PRRSV nsp11 revealed that its antagonistic effect on the antiviral activity of HDAC2 is dependent on its endonuclease activity. In summary, our research uncovered a novel immune evasion mechanism employed by PRRSV, providing crucial insights into the pathogenesis of this virus and guiding the development of innovative prevention strategies against PRRSV infection. [ABSTRACT FROM AUTHOR]

Background: Biogeochemical processing of metals including the fabrication of novel nanomaterials from metal contaminated waste streams by microbial cells is an area of intense interest in the environmental sciences. Results: Here we focus on the fate of Ce during the microbial reduction of a suite of Ce-bearing ferrihydrites with between 0.2 and 4.2 mol% Ce. Cerium K-edge X-ray absorption near edge structure (XANES) analyses showed that trivalent and tetravalent cerium co-existed, with a higher proportion of tetravalent cerium observed with increasing Ce-bearing of the ferrihydrite. The subsurface metal-reducing bacterium Geobacter sulfurreducens was used to bioreduce Ce-bearing ferrihydrite, and with 0.2 mol% and 0.5 mol% Ce, an Fe(II)-bearing mineral, magnetite (Fe(II)(III)2O4), formed alongside a small amount of goethite (FeOOH). At higher Ce-doping (1.4 mol% and 4.2 mol%) Fe(III) bioreduction was inhibited and goethite dominated the final products. During microbial Fe(III) reduction Ce was not released to solution, suggesting Ce remained associated with the Fe minerals during redox cycling, even at high Ce loadings. In addition, Fe L2,3 X-ray magnetic circular dichroism (XMCD) analyses suggested that Ce partially incorporated into the Fe(III) crystallographic sites in the magnetite. The use of Ce-bearing biomagnetite prepared in this study was tested for hydrogen fuel cell catalyst applications. Platinum/carbon black electrodes were fabricated, containing 10% biomagnetite with 0.2 mol% Ce in the catalyst. The addition of bioreduced Ce-magnetite improved the electrode durability when compared to a normal Pt/CB catalyst. Conclusion: Different concentrations of Ce can inhibit the bioreduction of Fe(III) minerals, resulting in the formation of different bioreduction products. Bioprocessing of Fe-minerals to form Ce-containing magnetite (potentially from waste sources) offers a sustainable route to the production of fuel cell catalysts with improved performance. [ABSTRACT FROM AUTHOR]

Background: Varicellovirus equidalpha1 (formerly Equid alphaherpesvirus 1, EqAHV-1) is among the most important viruses responsible for respiratory disease outbreaks among horses throughout the world. No reports to date have detailed the association between EqAHV-1 and respiratory disease among horses in China. This study described one such outbreak among a population of horses in north Xinjiang that occurred from April 2021 - May 2023. Results: qPCR revealed that EqAHV-1 was detectable in all samples and this virus was identified as a possible source of respiratory disease, although a limited subset of these samples were also positive for EqAHV-2, EqAHV-4, and EqAHV-5. In total, three EqAHV-1 strains responsible for causing respiratory illness in horses were isolated successfully, and full-length ORF33 sequence comparisonsand phylogenetic analyses indicated that these isolates may have originated from EqAHV-1 strains detected in Yili horse abortions. ORF30 sequence data additionally suggested that these strains were neuropathic, as evidenced by the presence of a guanine residue at nucleotide position 2254 corresponding to the aspartic acid present at position 752 in the DNA polymerase encoded by this virus. Conclusion: This study is the first report of an outbreak of respiratory disease among horses in China caused by EqAHV-1. ORF30 sequence characterization revealed that these EqAHV-1 strains harbored a neuropathogenic genotype. Given the detection of this virus in horses suffering from respiratory disease, concern is warranted with respect to this neuropathogenic EqAHV-1 outbreak. [ABSTRACT FROM AUTHOR]

Background: Usenamine A, a novel natural compound initially isolated from the lichen Usnea longissima, has exhibited promising efficacy against hepatoma in prior investigation. Nevertheless, the underlying mechanisms responsible for its antihepatoma effects remain unclear. Furthermore, the role of the AKT/mechanistic target of the rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT3)/inhibitor of differentiation/DNA binding 1 (ID1) signaling axis in hepatocellular carcinoma (HCC), and the potential anti-HCC effects of drugs targeting this pathway are not well understood. Methods: CCK-8 assay was used to investigate the effects of usenamine A on the proliferation of human HCC cells. Moreover, the effects of usenamine A on the invasion ability of human HCC cells were evaluated by transwell assay. In addition, expression profiling analysis, quantitative real-time PCR, immunoblotting, immunohistochemistry (IHC) analysis, RNAi, immunoprecipitation, and chromatin immunoprecipitation (ChIP) assay were used to explore the effects of usenamine A on the newly identified AKT/mTOR/STAT3/ID1 signaling axis in human HCC cells. Results: Usenamine A inhibited the proliferation and invasion of human HCC cell lines (HepG2 and SK-HEP-1). Through the analysis of gene expression profiling, we identified that usenamine A suppressed the expression of ID1 in human HCC cells. Furthermore, immunoprecipitation experiments revealed that usenamine A facilitated the degradation of the ID1 protein via the ubiquitin–proteasome pathway. Moreover, usenamine A inhibited the activity of STAT3 in human HCC cells. ChIP analysis demonstrated that STAT3 positively regulated ID1 expression at the transcriptional level in human HCC cells. The STAT3/ID1 axis played a role in mediating the anti-proliferative and anti-invasive impacts of usenamine A on human HCC cells. Additionally, usenamine A suppressed the STAT3/ID1 axis through AKT/mTOR signaling in human HCC cells. Conclusion: Usenamine A displayed robust anti-HCC potential, partly attributed to its capacity to downregulate the AKT/mTOR/STAT3/ID1 signaling pathway and promote ubiquitin–proteasome-mediated ID1 degradation. Usenamine A has the potential to be developed as a therapeutic agent for HCC cases characterized by abnormal AKT/mTOR/STAT3/ID1 signaling, and targeting the AKT/mTOR/STAT3 signaling pathway may be a viable option for treating patients with HCC exhibiting elevated ID1 expression. [ABSTRACT FROM AUTHOR]

The accurate prediction of binding free energy is a major challenge in structure-based drug design. Quantum mechanics (QM)-based approaches show promising potential in predicting ligand–protein binding affinity by accurately describing the behavior and structure of electrons. However, traditional QM calculations face computational limitations, hindering their practical application in drug design. Nevertheless, the fragment molecular orbital (FMO) method has gained widespread application in drug design due to its ability to reduce computational costs and achieve efficient ab initio QM calculations. Although the FMO method has demonstrated its reliability in calculating the gas phase potential energy, the binding of proteins and ligands also involves other contributing energy terms, such as solvent effects, the 'deformation energy' of a ligand's bioactive conformations, and entropy. Particularly in cases involving ionized fragments, the calculation of solvation free energy becomes particularly crucial. We conducted an evaluation of some previously reported implicit solvent methods on the same data set to assess their potential for improving the performance of the FMO method. Herein, we develop a new QM-based binding free energy calculation method called FMOScore, which enhances the performance of the FMO method. The FMOScore method incorporates linear fitting of various terms, including gas-phase potential energy, deformation energy, and solvation free energy. Compared to other widely used traditional prediction methods such as FEP+, MM/PBSA, MM/GBSA, and Autodock vina, FMOScore showed good performance in prediction accuracies. By constructing a retrospective case study, it was observed that incorporating calculations for solvation free energy and deformation energy can further enhance the precision of FMO predictions for binding affinity. Furthermore, using FMOScore-guided lead optimization against Src homology-2-containing protein tyrosine phosphatase 2 (SHP-2), we discovered a novel and potent allosteric SHP-2 inhibitor (compound 8). [ABSTRACT FROM AUTHOR]

Ferroptosis is a non-apoptotic form of regulated cell death characterized by iron-dependent lipid peroxidation. It can be triggered by various mechanisms, including the glutathione peroxidase 4 (GPX4)-glutathione (GSH) axis, iron metabolism, lipid metabolism, the GTP cyclohydrolase 1 (GCH1)-tetrahydrobiopterin (BH4) pathway, and the ferroptosis suppressor protein 1 (FSP1)-coenzyme Q10 axis. The redox balance is disrupted when ferroptosis occurs in cells, which is fatal to cancer cells. Additionally, some tumor-associated genes are involved in ferroptosis. Hence, targeting ferroptosis might be an effective strategy for treating cancer. Several small-molecule compounds exhibit anti-tumor effects through ferroptosis, including sorafenib and altretamine, which induce ferroptosis by inhibiting System-Xc and GPX4 respectively, but many problems, such as poor druggability, still exist. Some studies have shown that many traditional Chinese medicine (TCM) induce ferroptosis by inhibiting GPX4, solute carrier family 7 member 11 (SLC7A11), and nuclear factor (erythroid-derived 2)-like 2 (Nrf2), or by increasing the expression of Acyl-CoA synthetase long-chain family member 4 (ACSL4), transferrin (TF), and transferrin receptor 1 (TFR1). These changes can lead to the lysosomal degradation of ferritin, accumulation of iron, lipid peroxidation and the production of reactive oxygen species (ROS), which in turn can promote anti-tumor activities or synergistic effects with chemotherapeutic drugs. In this study, we elucidated the underlying mechanisms of ferroptosis, and the anti-tumor pharmacology of TCM targeting ferroptosis including prescriptions, Chinese herbs, extracts, and natural compounds. Our findings might act as valuable reference for research on anti-tumor drugs targeting ferroptosis, especially those drugs developed from TCM. [ABSTRACT FROM AUTHOR]

Air pollution, via ambient PM2.5, is a big threat to public health since it associates with increased hospitalisation, incidence rate and mortality of cardiopulmonary injury. However, the potential mediators of pulmonary injury in PM2.5‐induced cardiovascular disorder are not fully understood. To investigate a potential cross talk between lung and heart upon PM2.5 exposure, intratracheal instillation in vivo, organ culture ex vivo and human bronchial epithelial cells (Beas‐2B) culture in vitro experiments were performed respectively. The exposed supernatants of Beas‐2B were collected to treat primary neonatal rat cardiomyocytes (NRCMs). Upon intratracheal instillation, subacute PM2.5 exposure caused cardiac dysfunction, which was time‐dependent secondary to lung injury in mice, thereby demonstrating a cross‐talk between lungs and heart potentially mediated via small extracellular vesicles (sEV). We isolated sEV from PM2.5‐exposed mice serum and Beas‐2B supernatants to analyse the change of sEV subpopulations in response to PM2.5. Single particle interferometric reflectance imaging sensing analysis (SP‐IRIS) demonstrated that PM2.5 increased CD63/CD81/CD9 positive particles. Our results indicated that respiratory system‐derived sEV containing miR‐421 contributed to cardiac dysfunction post‐PM2.5 exposure. Inhibition of miR‐421 by AAV9‐miR421‐sponge could significantly reverse PM2.5‐induced cardiac dysfunction in mice. We identified that cardiac angiotensin converting enzyme 2 (ACE2) was a downstream target of sEV‐miR421, and induced myocardial cell apoptosis and cardiac dysfunction. In addition, we observed that GW4869 (an inhibitor of sEV release) or diminazene aceturate (DIZE, an activator of ACE2) treatment could attenuate PM2.5‐induced cardiac dysfunction in vivo. Taken together, our results suggest that PM2.5 exposure promotes sEV‐linked miR421 release after lung injury and hereby contributes to PM2.5‐induced cardiac dysfunction via suppressing ACE2. [ABSTRACT FROM AUTHOR]

[Figure: see text]. [ABSTRACT FROM AUTHOR]

Ligands are an imperative part of targeted drug delivery systems, and choosing a ligand with high affinity is a subject of considerable interest. In this study, we first synthesized a 12-residue peptide (TK) that interacts with integrin α6β1overexpressed on colonic cancer cells. The molecular binding affinity assay indicated that TK had a high binding affinity for integrin α6β1. The results of cellular and tumor spheroid uptake suggested that TK peptide not only increases Caco-2 cells uptake, but also effectively increases penetration of the tumor spheroids. TK-conjugated PEG-PLA was synthesized to prepare a novel PEG-PLA micelles loading DOX or coumarin-6 (TK-MS/DOX or TK-MS/C6). The obtained TK-MS/DOX exhibited uniform, spherical shape with a size of 23.80 ± 0.32 nm and zeta potential of 12.21 ± 0.31 mV. The release behavior of DOX from micelles were observed no significant changes after TK modification, however, the release profile exhibited pH-sensitive properties. Compared with MS/DOX, TK-MS/DOX exhibited significantly stronger cytotoxicity for Caco-2. Confocal laser microscopy and flow cytometry data further indicated that the targeting micelles not only had higher uptake by Caco-2 cells, but also more effectively penetrated the tumor spheroids. Therefore, TK peptide appears to be suitable as a targeting ligand with potential applications in colonic targeted therapy. [ABSTRACT FROM PUBLISHER]

[Display omitted] • QFASA was used for the first time to identify sources of indoor organic pollutants. • OPFR concentrations and lipid content in house dust were significantly related. • Clothing was the predominant contributing vector introducing indoor OPFRs. • QFASA can accurately predict most of OPFR concentrations in clothing. Indoor dust has been used as a proxy for estimating human indoor pollutant exposure risks, yet source identification remains challenging. This study tentatively investigated whether quantitative fatty acid signature analysis (QFASA) of dust, could be applied to indicate sources and their respective contributions for a major class of indoor organic pollutants organophosphate flame retardants (OPFRs). We observed significant correlations between OPFR concentrations and lipid content (p < 0.05) in house dusts. Using 15 signature fatty acids (FAs) in various indoor sources and the QFASA model, we found that clothing (39.1% in Australia and 36.5% in China) was the predominant contributing vector of dust OPFR followed by cooking oil and pet hair. Among these sources, clothing materials were proposed to be important vectors introducing organic pollutants to the indoor environment. Our QFASA contribution estimation analyses allowed for accurate prediction of most OPFR concentrations in clothing, validating our findings that clothing materials may serve as important carrier for OPFRs in indoor migration. This is the first study attempting to identify sources of organic pollutants using QFASA in an indoor setting and will provide important insight into the transfer of organic pollutants in indoor environment. [ABSTRACT FROM AUTHOR]

Z-scheme Cu 2 O-(rGO-TiO 2) photocatalyst was successfully synthesized via a simple three-step approach for 2,2′,4,4′-tretrabromodiphenyl ether (BDE47) reductive removal under simulated solar irradiation. Unlike the traditional heterojunction, the addition of reduced graphene oxide (rGO) enhanced the redox ability of Cu 2 O-TiO 2 by increasing charge transfer. When modifying Cu 2 O films by adding 1% rGO and coating with 70% TiO 2 , the resulting Cu 2 O-(rGO-TiO 2) exhibited the best photocatalytic activity for BDE47 removal. The charge transfers of Cu 2 O-(rGO-TiO 2) were proven to follow a Z-scheme pathway through the electron paramagnetic resonance analysis. The degradation pathways of BDE47 were elucidated by identifying intermediate products via gas chromatography-mass spectrometry (GC-MS) and gas chromatography (GC). Photo-electrons (e−) generated from the conduction band of Cu 2 O and hydrogen protons (H0) reduced from H+ in water were the main contributing elements for the removal of BDE47, which response to the ortho and para debromination. Ortho-Br of BDE47 was attacked by e− and BDE28 was the dominant debromination product on the first stage. Then e− and H0 attacked ortho-Br and para-Br of BDE28 to form BDE15 and BDE8, respectively. The concentration of BDE8 was higher than that of BDE15, suggesting that H0 played the most important role on the second debromination stage. An effective Cu 2 O-(rGO-TiO 2)-based Z-scheme system for BDE47 debromination was proposed in this study, which may contribute to the development of novel green technologies. Image 1 • Z-scheme system of Cu 2 O-(rGO-TiO 2) is designed and prepared. • Efficient removal of 2,2′,4,4′-tetrabromodiphenyl ether with Cu 2 O-(rGO-TiO 2) under simulated sunlight. • rGO significantly enhanced photocatalytic performance. • Mechanism and debromination pathway of BDE47 are proposed. [ABSTRACT FROM AUTHOR]