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IntroductionTendinopathy, the most common form of chronic tendon disorder, leads to persistent tendon pain and loss of function. Profiling the heterogeneous cellular composition in the tendon microenvironment helps to elucidate rational molecular mechanisms of tendinopathy.Methods and resultsIn this study, through a multi-modal analysis, a single-cell RNA- and ATAC-seq integrated tendinopathy landscape was generated for the first time. We found that a specific cell subpopulation with low PRDX2 expression exhibited a higher level of inflammation, lower proliferation and migration ability, which not only promoted tendon injury but also led to microenvironment deterioration. Mechanistically, a motif enrichment analysis of chromatin accessibility showed that FOXO1 was an upstream regulator of PRDX2 transcription, and we confirmed that functional blockade of FOXO1 activity induced PRDX2 silencing. The TNF signaling pathway was significantly activated in the PRDX2-low group, and TNF inhibition effectively restored diseased cell degradation.DiscussionWe revealed an essential role of diseased cells in tendinopathy and proposed the FOXO1-PRDX2-TNF axis is a potential regulatory mechanism for the treatment of tendinopathy.

Citrus chlorotic dwarf-associated virus (CCDaV) is a Citlodavirus species in the Geminiviridae family that causes tremendous economic loss to the citrus industry in China. Some proteins encoded by geminiviruses are crucial for the interaction between the virus and its host plant. However, the exact functions of CCDaV-encoded proteins such as CCDaV-RepA have not been investigated. This study presents evidence that CCDaV-RepA elicits a hypersensitive response (HR)-like cell death in Nicotiana benthamiana that was accompanied by the production of H2O2 and ion leakage, which suggested that CCDaV-RepA is a potential recognition target for inducing host defense responses. Furthermore, the rolling-circle replication motifs of CCDaV-RepA are associated with triggering HR-like cell death in N. benthamiana. Confocal microscopy and deletion mutagenesis assays showed that CCDaV-RepA was located in the nucleus, while the first eight amino acids (aa) at the N terminus and two regions located between aa residues 122-263 and 220-264 of RepA were not associated with nuclear localization. Tobacco rattle virus-induced gene silencing of the key signaling cascade components revealed that HR-like cell death induced by RepA was inhibited in WRKY1-silenced N. benthamiana. Moreover, WRKY1 expression was upregulated in RepA-GFP infiltrated Overall, the results suggest that NbWRKY1 positively regulated CCDaV-RepA -induced cell death in N. benthamiana. These findings provide novel information for further research on the interactions between CCDaV and the host plant.

Lipid metabolism disorders may considerably contribute to the formation and development of atherosclerosis (AS). Traditional Chinese medicine has received considerable attention in recent years owing to its ability to treat lipid metabolism disorders using multiple components and targets. Verbena officinalis (VO), a Chinese herbal medicine, exhibits anti-inflammatory, analgesic, immunomodulatory, and neuroprotective effects. Evidence suggests that VO regulates lipid metabolism; however, its role in AS remains unclear. In the present study, an integrated network pharmacology approach, molecular docking, and molecular dynamics simulation (MDS) were applied to examine the mechanism of VO against AS. Analysis revealed 209 potential targets for the 11 main ingredients in VO. Further, 2698 mechanistic targets for AS were identified, including 147 intersection targets between VO and AS. Quercetin, luteolin, and kaempferol were considered key ingredients for the treatment of AS based on a potential ingredient target–AS target network. GO analysis revealed that biological processes were primarily associated with responses to xenobiotic stimuli, cellular responses to lipids, and responses to hormones. Cell components were predominantly focused on the membrane microdomain, membrane raft, and caveola nucleus. Molecular functions were mainly focused on DNA-binding transcription factor binding, RNA polymerase II-specific DNA-binding transcription factor binding, and transcription factor binding. KEGG pathway enrichment analysis identified pathways in cancer, fluid shear stress, and atherosclerosis, with lipid and atherosclerosis being the most significantly enriched pathways. Molecular docking revealed that three key ingredients in VO (i.e., quercetin, luteolin, and kaempferol) strongly interacted with three potential targets (i.e., AKT1, IL-6, and TNF-α). Further, MDS revealed that quercetin had a stronger binding affinity for AKT1. These findings suggest that VO has beneficial effects on AS via these potential targets that are closely related to the lipid and atherosclerosis pathways. Our study utilized a new computer-aided drug design to identify key ingredients, potential targets, various biological processes, and multiple pathways associated with the clinical roles of VO in AS, which provides a comprehensive and systemic pharmacological explanation for the anti-atherosclerotic activity of VO.

Aiming to answer an interesting question on why some radio sources can be detected by Fermi-LAT but others cannot, we compare several parameters of Fermi-detected Fanaroff-Riley radio galaxies (FFRs) and non-Fermi-detected sources (NFFRs), including the optical absolute magnitude, 1.4 GHz radio luminosity, radio loudness, core dominance parameter, Doppler factor, and the mass of the central black hole. Significant differences are ascertained within these parameters between FFRs and NFFRs. Our findings suggest that FFRs are jet-dominant while NFFRs are disk-dominant sources, and NFFRs have a weaker beaming effect. Additionally, we predict the observed γ-ray flux for NFFRs, establishing that the reason why some NFFRs are not detectable arises from their γ-ray flux being below the sensitivity detection threshold of Fermi. We also discuss two sub-types of Fanaroff-Riley galaxies, namely FR I and FR II sources. We first propose a “changing-look” phenomenon in these radio sources and also investigate why FR IIs seem to be exclusive in γ-ray emission.

Abstract Identifying the general mechanics behind the equilibration of a complex isolated quantum system towards a state described by only a few parameters has been the focus of attention in non-equilibrium thermodynamics. And several experimentally unproven conjectures are proposed for the statistical description of quantum (non-)integrable models. The plausible eigenstate thermalization hypothesis (ETH), which suggests that each energy eigenstate itself is thermal, plays a crucial role in understanding the quantum thermalization in non-integrable systems; it is commonly believed that it does not exist in integrable systems. Nevertheless, integrable systems can still relax to the generalized Gibbs ensemble. From a microscopic perspective, understanding the origin of this generalized thermalization that occurs in an isolated integrable system is a fundamental open question lacking experimental investigations. Herein, we experimentally investigated the spin subsystem relaxation in an isolated spin–orbit coupling quantum system. By applying the quantum state engineering technique, we initialized the system with various distribution widths in the mutual eigenbasis of the conserved quantities. Then, we compared the steady state of the spin subsystem reached in a long-time coherent dynamics to the prediction of a generalized version of ETH and the underlying mechanism of the generalized thermalization is experimentally verified for the first time. Our results facilitate understanding the origin of quantum statistical mechanics.

Abstract A method was used to fabricate a fully inkjet-printed gas sensor matrix on photographic paper. An electrode matrix comprising 36 interdigital electrodes in a high-density layout that is easy to integrate has been fabricated using a combination of insulating ink and commercial silver ink. Molecular-imprinted polymer (MIP) inks were then made using a simple solution mixing method, and these inks were printed together with carbon black ink on the electrode matrix to complete production of the sensor. Finally, experimental dynamic sensing of volatile organic compounds verifies that for detection of gases corresponding to the MIP template molecules, the MIP layer offers improvements in both sensitivity and selectivity when compared with non-imprinted polymer layers. The matrix can produce a response of more than 20% to 3 ppm propenoic acid gas through adjustment of the printing times for the carbon black layer and the MIP layer.

Opposite anthropogenic aerosol emission trends in Asia can lead to different responses of the climate. Here, we examined the responses of the East Asian summer monsoon (EASM) to changes in Asian anthropogenic aerosol emissions during 2006–2014 using a global aerosol/atmospheric chemistry–climate coupled model (BCC_AGCM2.0_CUACE/Aero) with two sets of emission inventories: the Community Emissions Data System (CEDS) inventory adopted by the Coupled Model Intercomparison Project Phase 6 (CMIP6) and the inventory developed at Peking University (PKU). The changes in Asian anthropogenic aerosol emissions during 2006–2014 between the two inventories were remarkably different, particularly in eastern China where completely opposite trends were observed (i.e., increase in the CEDS inventory, but significant reduction in the PKU inventory). The perturbation simulations with the Asian anthropogenic aerosol forcing from the two inventories showed opposite changes in aerosol optical depth, aerosol effective radiative forcing, cloud liquid water path, and total cloud cover in eastern China. The simulated ‘dipole-type’ changes (i.e., increase in India but decrease in China) in Asian aerosols and the resulting changes in local radiation budget under the PKU inventory were consistent with the corresponding observations. The summer surface temperatures over eastern China decreased by 0–0.4 K because of the Asian anthropogenic aerosol forcing under the CEDS inventory, while they increased by 0.1–0.8 K under the PKU inventory. The weakening of the EASM index caused by the Asian aerosol forcing under the PKU inventory was twofold greater than that under the CEDS inventory (−0.4 vs. −0.2). The Asian ‘dipole-type’ aerosol forcing contributed to the observed summer ‘southern drought and northern flood’ phenomenon in eastern China during 2006–2014. The slow ocean-mediated response to the regional ‘dipole-type’ aerosol forcing dominated the weakening of the EASM circulation and the precipitation changes in eastern China in the total response. This study further confirms that the biases in anthropogenic aerosol emissions over Asia can affect the CMIP6-based regional climate attribution.

The effects of Mooney viscosity of raw rubbers (Mv) of SBR 1500 and SBR 1586 on the properties of SBR 1500 and SBR 1586, such as Mooney viscosity of rubber compounds (Mb), modulus at 300% 25 min (M25), modulus at 300% 35 min (M35), modulus at 300% 50 min (M50), tensile strength (Ts) and elongation at break (Eb) of vulcanizates were investigated. The results showed that with the increase of Mv, Mb, M25, M35, M50, Ts and Eb of SBR 1500 and SBR1586 all increased linearly. When Mv increased by 1 unit, Mb, M25, M35, M50, Ts and Eb of SBR 1500 increased by 1.17, 0.11 MPa, 0.27 MPa, 0.56 MPa, 0.16 MPa and 2.8% respectively, and Mb, M25, M35, M50, Ts and Eb of SBR 1586 increased by 1.00, 0.08 MPa, 0.10 MPa, 0.57 MPa, 0.20 MPa and 3.8%. When the increase ranges of Mv of SBR 1500 and SBR 1586 were the same, the growth rates of Mb, M25 and M35 of SBR 1500 were higher than those of SBR 1586, and the growth rate of M50 of SBR 1500 was equal to that of SBR 1586, while Ts and Eb of of SBR 1500 were lower than those of SBR 1586.

First-principles density-functional theory calculations were performed to reveal the effect of surface polarization and structural deformation on the formation and stabilization of the polaron in two-dimensional Ruddlesden–Popper perovskites. Our results revealed that the orientational distribution of organic cations induces surface polarization. The surface dipole moment can be well featured by the c axis distances between N and the nearest I atoms. Structural deformation and surface dipole moments result in separate real-space distributions of hole and electron polarons. Our results also reveal that the structural deformation of the [PbI6] sublattices and surface polarization are closely related to the reorientation of organic cations and can be effectively modulated by it. This reorientation significantly impacts the stabilization of polarons. Our understandings provide insight into the nature of polarons in two-dimensional Ruddlesden–Popper perovskites and general guidance for the proper selection of organic cations in two-dimensional perovskites for suitable applications in photovoltaic and optoelectronic devices. [ABSTRACT FROM AUTHOR]

Abnormal stratifin (SFN) expression is closely related to the progression of several human cancers, but the potential roles of SFN in hepatocellular carcinoma (HCC) remain largely unknown. In this study, we found that SFN was upregulated in HCC cell lines and tissues and was positively associated with tumor size, poor differentiation, Tumor Node Metastasis (TNM) stage, and vascular invasion. In addition, high expression levels of SFN were associated with poor overall survival and disease-free survival. Biologically, downregulation of SFN suppressed tumor cell proliferation, epithelial–mesenchymal transition (EMT), invasion, and migration in vitro and tumor growth in vivo. However, overexpression of SFN promoted cell proliferation, EMT, invasion, and migration in vitro and tumor growth in vivo. Mechanistically, overexpression of SFN activated the Wnt/β-catenin pathway by promoting Glycogen synthase kinase-3 beta (GSK-3β) phosphorylation, decreasing β-catenin phosphorylation, promoting β-catenin transport into the nucleus, and enhancing the expression of c-Myc, whereas depletion of SFN inhibited the Wnt/β-catenin pathway. In addition, TOPFlash/FOPFlash reporter assays showed that overexpression or downregulation of SFN obviously increased or decreased, respectively, the activity of the Wnt/β-catenin pathway. Our results indicated that SFN plays an important role in HCC, possibly providing a prognostic factor and therapeutic target for HCC.

ObjectiveTo compare the diagnostic value of four tools—the Global Leadership Initiative on Malnutrition (GLIM) criteria, the subjective global assessment (SGA), patient-generated subjective global assessment (PG-SGA), and prognostic nutritional index (PNI) in malnutrition among hospitalized patients undergoing hepatobiliary-pancreatic surgery. Meanwhile, to observe the nutritional intervention of these patients.MethodsPresent study was a cross-sectional study, including 506 hospitalized patients who underwent hepatobiliary-pancreatic surgery between December 2020 and February 2022 at Ningbo Medical Center Lihuili Hospital, China. The incidence rate of malnutrition was diagnosed using the four tools. The consistency of the four tools was analyzed by Cohen's kappa statistic. Data, including nutritional characteristics and nutritional interventions, were collected. The nutritional intervention was observed according to the principles of Five Steps Nutritional Treatment.ResultsThe prevalence was 36.75, 44.58, and 60.24%, as diagnosed by the GLIM, PG-SGA, and PNI, respectively, among 332 tumor patients. Among the 174 non-tumor patients, the prevalence was 9.77, 10.92, and 32.18% as diagnosed by the GLIM, SGA, and PNI. The diagnostic concordance of PG-SGA and GLIM was higher (Kappa = 0.814,