Baicalin inhibits the replication of the hepatitis B virus by targeting TRIM25.

Objective: Baicalin, which is a key bioactive constituent obtained from Scutellaria baicalensis, has been utilized in traditional Chinese medicine for many centuries. Although it has been reported that Baicalin (BA) can inhibit the replication of the Hepatitis B virus (HBV), the exact mechanism behind this process remains unclear. Interferon-stimulated genes (ISGs) are crucial in the process of antiviral defense. We aim to investigate whether BA can regulate the expression of ISGs, and thereby potentially modulate the replication of HBV. Methods: The study involved the use of CRISPR/Cas9 technology to perform knockout experiments on TRIM25 and IFIT3 genes. The expression of these genes was confirmed through techniques such as immunoblotting or Q-PCR. The levels of HBsAg and HBeAg were measured using ELISA, and the expression of interferon-stimulated genes was detected using a luciferase assay. Results: It is interesting to note that several ISGs belonging to the TRIM family, including TRIM5, TRIM25, and TRIM14, were induced after BA treatment. On the other hand, members of the IFIT family were reduced by BA stimulation. Additionally, BA-mediated HBV inhibition was found to be significantly restored in HepG2 cells where TRIM25 was knocked out. Additional research into the mechanism of action of BA found that prolonged treatment with BA activated the JAK/STAT signaling pathway while simultaneously inhibiting the NF-kB pathway. Conclusion: The findings of our study indicate that TRIM25 has a significant impact on the regulation of HBV replication following BA treatment, providing additional insight into the mechanisms by which BA exerts its antiviral effects.

Low-Friction Hybrid Hydrogel with Excellent Mechanical Properties for Simulating Articular Cartilage Movement.

Hydrogels, which can withstand large deformations and have stable chemical properties, are considered a potential material for cartilage repair. However, hydrogels still face some challenges regarding their mechanical properties, tribological behavior, and biocompatibility. Thus, we synthesized a hybrid hydrogel by means of chemical cross-linking and transesterification using glycerol ethoxylate (GE) and zwitterionic polysulfobetaine methacrylate (PSBMA) as raw materials. The hybrid hydrogel showed excellent compressive stress at approximately 3.50 MPa and low loss factors (0.023-0.049). Moreover, because GE has good water binding properties, helping to form a stable hydration layer and maintain low energy dissipation, a low friction coefficient (µ ≈ 0.028) was obtained with the "soft-soft contact mode" of a hydrogel hemisphere and hydrogel disc under reciprocating motion. In vitro cytotoxicity, skin sensitization, and irritation reaction tests were carried out to show good biocompatibility of the GE-PSBMA hybrid hydrogel. In this study, a hybrid hydrogel with no potential cytotoxicity, strong compressive capacity, and excellent lubricity was obtained to provide a potential alternative for developing polymer hybrids, as well as demonstrating an idea for the application of hybrid hydrogels in cartilage replacement.

Endothelial SIRPα signaling controls VE-cadherin endocytosis for thymic homing of progenitor cells.

Thymic homing of hematopoietic progenitor cells (HPCs) is tightly regulated for proper T cell development. Previously we have identified a subset of specialized thymic portal endothelial cells (TPECs), which is important for thymic HPC homing. However, the underlying molecular mechanism still remains unknown. Here, we found that signal regulatory protein alpha (SIRPα) is preferentially expressed on TPECs. Disruption of CD47-SIRPα signaling in mice resulted in reduced number of thymic early T cell progenitors (ETPs), impaired thymic HPC homing, and altered early development of thymocytes. Mechanistically, Sirpa-deficient ECs and Cd47-deficient bone marrow progenitor cells or T lymphocytes demonstrated impaired transendothelial migration (TEM). Specifically, SIRPα intracellular ITIM motif-initiated downstream signaling in ECs was found to be required for TEM in an SHP2- and Src-dependent manner. Furthermore, CD47 signaling from migrating cells and SIRPα intracellular signaling were found to be required for VE-cadherin endocytosis in ECs. Thus, our study reveals a novel role of endothelial SIRPα signaling for thymic HPC homing for T cell development.

Can acupuncture improve sleep quality and anxiety among women during perimenopause?: A protocol for systematic review and meta-analysis.

BACKGROUND: The decrease in estrogen levels during the perimenopausal period can cause women to have various symptoms such as insomnia, emotional anxiety, and even depression. Therefore, whether the green therapy of acupuncture can improve the sleep quality and anxiety of perimenopausal women has attracted more and more attention. The purpose of this systematic evaluation was to assess the efficacy of acupuncture on insomnia and anxiety in perimenopausal women. METHODS: We will search for clinical observational pilot studies or cohort studies of acupuncture for insomnia, anxiety, or depression included in PubMed, Cochrane Library, Embase, Web of science, China Knowledge Network (CNKI), Wanfang, VIP and China Biomedical Database (CBM), etc. The search period will be from the establishment of the database until November 2021. Two researchers will independently perform literature screening, data extraction, and quality assessment. Finally, data analysis will be performed using Revman and Stata software. RESULTS: The purpose of this study was to evaluate the effectiveness and safety of acupuncture therapy for the treatment of insomnia, anxiety, and depression in perimenopausal women. CONCLUSION: This study will provide new evidence on the effectiveness and safety of acupuncture for the treatment of insomnia, anxiety, and depression in perimenopausal women, and provide additional options for clinicians and patients to improve insomnia and anxiety. REGISTRATION NUMBER: INPLASY2021120012.

Functions of lncRNA DUXAP8 in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) poses a serious threat to public health due to its significant morbidity and mortality rates. The processes of NSCLC formation and development are quite complex and involve numerous regulatory biomolecules. Long non-coding RNAs (lncRNAs) have attracted attention since they have been found to play critical roles in the tumorigenesis of various human malignancies. Recently, double homeobox A pseudogene 8 (DUXAP8) was identified as an oncogenic lncRNA that is overexpressed in different tumor types. In NSCLC, high expression of DUXAP8 is associated with poor prognosis in patients. The regulatory mechanism underlying the oncogenic effects of DUXAP8 can be divided into transcriptional level and post-transcriptional level. DUXAP8 promotes proliferation, epithelial-mesenchymal transition, and aerobic glycolysis in NSCLC cells. Moreover, DUXAP8 shows potential for the diagnosis and treatment of NSCLC. Herein, we review the molecular mechanisms underlying the DUXAP8-mediated phenotypes of NSCLC as well as its potential clinical applications.

Thymic Egress Is Regulated by T Cell-Derived LTßR Signal and via Distinct Thymic Portal Endothelial Cells.

Thymic blood vessels at the perivascular space (PVS) are the critical site for both homing of hematopoietic progenitor cells (HPCs) and egress of mature thymocytes. It has been intriguing how different opposite migrations can happen in the same place. A subset of specialized thymic portal endothelial cells (TPECs) associated with PVS has been identified to function as the entry site for HPCs. However, the cellular basis and mechanism underlying egress of mature thymocytes has not been well defined. In this study, using various conventional and conditional gene-deficient mouse models, we first confirmed the role of endothelial lymphotoxin beta receptor (LTßR) for thymic egress and ruled out the role of LTßR from epithelial cells or dendritic cells. In addition, we found that T cell-derived ligands lymphotoxin (LT) and LIGHT are required for thymic egress, suggesting a crosstalk between T cells and endothelial cells (ECs) for thymic egress control. Furthermore, immunofluorescence staining analysis interestingly showed that TPECs are also the exit site for mature thymocytes. Single-cell transcriptomic analysis of thymic endothelial cells suggested that TPECs are heterogeneous and can be further divided into two subsets depending on BST-1 expression level. Importantly, BST-1hi population is associated with thymic egressing thymocytes while BST-1lo/- population is associated with HPC settling. Thus, we have defined a LT/LIGHT-LTßR signaling-mediated cellular crosstalk regulating thymic egress and uncovered distinct subsets of TPECs controlling thymic homing and egress, respectively.

Zwitterionic Hydrogel Incorporated Graphene Oxide Nanosheets with Improved Strength and Lubricity.

Graphene oxide (GO) has been evaluated as a multifunctional cross-linker or reinforcement agent in composite hydrogels. In this study, a nanocomposite hydrogel consisting of GO nanosheets and zwitterionic poly(sulfobetaine methacrylate) (PSBMA) was synthesized in an aqueous system via chemical and physical cross-linking effects. GO nanosheets were well dispersed in the hydrogels and effectively cross-linked into the sulfobetaine methacrylate (SBMA) polymer chains through the electrostatic interactions. The PSBMA hydrogel exhibited a significant enhancement in the compressive stress (close to a 5-fold increase) and a remarkable reduction in the coefficient of friction (COF) (corresponding to a decline of 52-76%) after the embedding of GO nanosheets. These improvements indicate the existence of synergetic interaction and good compatibility between GO nanosheets and the PSBMA hydrogel matrix, which results in an intertwined network structure with higher load-bearing capacity and better lubrication properties. This study provides potential in the development of new graphene-polymer composites, which is beneficial for cartilage replacement with high mechanical properties and excellent lubrication characteristics.

Langerhans Cells Control Lymphatic Vessel Function during Inflammation via LIGHT-LTßR Signaling.

The lymphatic vasculature is an important route for dendritic cell (DC) or tumor cell migration from peripheral tissues to draining lymph nodes (DLNs). However, the underlying molecular and cellular mechanisms remain poorly understood. In this study, using conventional bone marrow chimeric mice and additional UVB radiation, we found that deficiency of LIGHT but not lymphotoxin (LT) α1ß2, likely on radioresistant Langerhans cells (LCs), resulted in impaired skin DC migration to DLNs during LPS-induced inflammation. In addition, LT ß receptor (LTßR), but not herpes virus entry mediator, was found to be the receptor of LIGHT controlling DC migration. Furthermore, conditional deficiency of LTßR in Tie2 cre or Lyve1 cre mice, but not in LTßR-deficient bone marrow chimeric mice, impaired DC migration, suggesting an important role of LTßR in radioresistant lymphatic endothelial cells (LECs), although the role of LTßR in blood endothelial cells remains intriguing. Mechanistically, the gene expression of both CCL21 and CCL19 was found to be reduced in skin LECs isolated from LC-LIGHT-conditionally deficient or Lyve1 cre Ltbr fl/fl mice compared with their controls upon LPS stimulation. Soluble recombinant LIGHT was able to upregulate CCL21 and CCL19 gene expression on SVEC4-10 endothelial cells. Doxycycline, an inhibitor of soluble LIGHT release in the inflamed skin, impaired skin CCL21 and CCL19 expression and DC migration. In addition, melanoma cell metastasis to DLNs was also inhibited in LC-LIGHT-conditionally deficient or Lyve1 cre Ltbr fl/fl mice. Together, our data suggest, to our knowledge, a previously unrecognized scenario in which LCs activate LECs via the LIGHT-LTßR signaling axis to promote DC migration or tumor cell metastasis.

Investigation of the lubrication properties and synergistic interaction of biocompatible liposome-polymer complexes applicable to artificial joints.

Achievement of efficient biolubrication is essential for the design of artificial joints with long lifetimes. This study examines the frictional behaviors and adsorption structures of liposomes and liposome complexes with biocompatible polymers to reveal the underlying lubrication mechanisms between biomimetic bearing surfaces of polyetheretherketone (PEEK) and silicon nitride (Si3N4). The liposomes with increasing carbon chain lengths exhibit the remarkable lubrication capabilities that correlate strongly with the structural integrity of small unilamellar vesicles adsorbed on the Si3N4 surfaces, while the bilayer structures weaken the stability of vesicles against rupture and cause the increase of friction. The synergistic interaction of liposomes and biocompatible negative-charged polymer leads to the formation of a boundary-lubricating layer with high-density liposome-polymer complex structures that can efficiently improve the lubrication properties of liposomes. Our findings might have implications for future biolubrication investigations on biocompatible liposome-polymer complexes applicable to artificial joints at the specified macroscale conditions.

Origin of hydration lubrication of zwitterions on graphene.

Formation of a hydration layer on charge sites can support normal pressure, and meanwhile it retains excellent fluidity to provide efficient boundary lubrication; however, it is limited to the sliding system between two similarly charged surfaces. In the present study, we report extremely low friction as the zwitterions in a lipid bilayer slide on the topmost graphene layer of graphite across pure water, with the friction coefficient falling to the level of 0.001, which provides direct evidence that hydration lubrication is effective even between such dissimilar surfaces. The origin of hydration lubrication on graphene was studied by atomic force microscopy and molecular dynamics simulation simultaneously. It reveals that a subnanometer hydration layer is confined between zwitterions and graphene, which remains as a liquid phase under normal pressure. The shear occurs between water molecules and graphene because of the extremely low shear strength of the water/graphene interface, which contributes to extremely low friction. Our finding demonstrates that the formation of a hydration layer is possible to lubricate layered materials efficiently, which has potential implications for designing efficient boundary lubrication with layered materials.

Large herbivores influence plant litter decomposition by altering soil properties and plant quality in a meadow steppe.

Large herbivores act as a major driver of plant litter decomposition in grasslands. The modifications of soil biotic and abiotic properties, as well as the changes in quality (C/N ratio) of plant litter, are two key pathways by which large herbivores can affect litter decomposition. Yet we know little about the relative role of these two mechanisms in mediating decomposition. Here, by combining a large-scale and a small-scale field manipulative experiment, we examined how livestock (cattle and sheep) grazing affects standing litter decomposition of a dominant grass, Leymus chinensis in grasslands in northeast China. We found that livestock grazing affected litter decay rate both by its influences on soil property (soil moisture, nutrient content, and microbial communities) and on plant litter quality (C/N ratio). Due to their distinct body size and diet preference, cattle and sheep affected soil property and litter quality, thus litter decay rate, differently by causing varying disturbance regimes and by feeding on different dominant species. Our study provides evidence that herbivore grazing can influence litter decomposition by modifying soil conditions and litter quality independently. Therefore, choosing the proper large herbivore(s) in grazing regimes may be important in maintaining nutrient cycling in grassland ecosystems.

Differential Roles of LTßR in Endothelial Cell Subsets for Lymph Node Organogenesis and Maturation.

Cellular cross-talk mediated by lymphotoxin αß-lymphotoxin ß receptor (LTßR) signaling plays a critical role in lymph node (LN) development. Although the major role of LTßR signaling has long been considered to occur in mesenchymal lymphoid tissue organizer cells, a recent study using a VE-cadherincreLtbrfl/fl mouse model suggested that endothelial LTßR signaling contributes to the formation of LNs. However, the detailed roles of LTßR in different endothelial cells (ECs) in LN development remain unknown. Using various cre transgenic mouse models (Tekcre , a strain targeting ECs, and Lyve1cre , mainly targeting lymphatic ECs), we observed that specific LTßR ablation in Tekcre+ or Lyve1cre+ cells is not required for LN formation. Moreover, double-cre-mediated LTßR depletion does not interrupt LN formation. Nevertheless, TekcreLtbrfl/fl mice exhibit reduced lymphoid tissue inducer cell accumulation at the LN anlagen and impaired LN maturation. Interestingly, a subset of ECs (VE-cadherin+Tekcre-low/neg ECs) was found to be enriched in transcripts related to hematopoietic cell recruitment and transendothelial migration, resembling LN high ECs in adult animals. Furthermore, endothelial Tek was observed to negatively regulate hematopoietic cell transmigration. Taken together, our data suggest that although Tekcre+ endothelial LTßR is required for the accumulation of hematopoietic cells and full LN maturation, LTßR in VE-cadherin+Tekcre-low/neg ECs in embryos might represent a critical portal-determining factor for LN formation.

Superlubricity of 1-Ethyl-3-methylimidazolium trifluoromethanesulfonate Ionic Liquid Induced by Tribochemical Reactions.

The robust liquid superlubricity of a room-temperature ionic liquid induced by tribochemical reactions is explored in this study. Here, 1-ethyl-3-methylimidazolium trifluoromethanesulfonate ([EMIM]TFS) could realize stable superlubricity (µ < 0.01) with water at the interfaces of Si3N4/SiO2. A superlow and steady friction coefficient of 0.002-0.004 could be achieved under neutral conditions (pH of 6.9 ± 0.1) after 600 s of running-in process. Various factors that could affect superlubricity were explored, including concentration of [EMIM]TFS, sliding speed, applied load, and volume of the lubricant. The results reveal that superlubricity can be achieved with [EMIM]TFS aqueous solution under a broad scope of conditions. The results of surface analysis show that a steady composite tribochemical layer comprising [EMIM]TFS, silica, ammonia-containing compounds, and sulfides was formed by tribochemical reactions between [EMIM]TFS and Si3N4 during the running-in period. The film thickness calculation reveals that the achieved superlubricity is in a mixed lubrication regime that comprises boundary lubrication and thin film lubrication. The superlubricity state is governed by a firm composite tribochemical layer, a molecular adsorption layer (electric double layer of [EMIM]TFS), and a fluid layer. The liquid superlubricity achieved by the ionic liquid is helpful for the development of new ionic liquids with superlubricity characteristics and is of great significance for scientific understanding as well as engineering applications.

LTßR controls thymic portal endothelial cells for haematopoietic progenitor cell homing and T-cell regeneration.

Continuous thymic homing of haematopoietic progenitor cells (HPCs) via the blood is critical for normal T-cell development. However, the nature and the differentiation programme of specialized thymic endothelial cells (ECs) controlling this process remain poorly understood. Here using conditional gene-deficient mice, we find that lymphotoxin beta receptor (LTßR) directly controls thymic ECs to guide HPC homing. Interestingly, T-cell deficiency or conditional ablation of T-cell-engaged LTßR signalling results in a defect in thymic HPC homing, suggesting the feedback regulation of thymic progenitor homing by thymic products. Furthermore, we identify and characterize a special thymic portal EC population with features that guide HPC homing. LTßR is essential for the differentiation and homeostasis of these thymic portal ECs. Finally, we show that LTßR is required for T-cell regeneration on irradiation-induced thymic injury. Together, these results uncover a cellular and molecular pathway that governs thymic EC differentiation for HPC homing.

Positive interactions between large herbivores and grasshoppers, and their consequences for grassland plant diversity.

Although the influence of positive interactions on plant and sessile communities has been well documented, surprisingly little is known about their role in structuring terrestrial animal communities. We evaluated beneficial interactions between two distantly related herbivore taxa, large vertebrate grazers (sheep) and smaller insect grazers (grasshoppers), using a set of field experiments in eastern Eurasian steppe of China. Grazing by large herbivores caused significantly higher grasshopper density, and this pattern persisted until the end of the experiment. Grasshoppers, in turn, increased the foraging time of larger herbivores, but such response occurred only during the peak of growing season (August). These reciprocal interactions were driven by differential herbivore foraging preferences for plant resources; namely, large herbivores preferred Artemisia forbs, whereas grasshoppers preferred Leymus grass. The enhancement of grasshopper density in areas grazed by large herbivores likely resulted from the selective consumption of Artemisia forbs by vertebrate grazers, which may potentially improve the host finding of grasshoppers. Likewise, grasshoppers appeared to benefit large herbivores by decreasing the cover and density of the dominant grass Leymus chinensis, which hampers large herbivores' access to palatable forbs. Moreover, we found that large herbivores grazing alone may significantly decrease plant diversity, yet grasshoppers appeared to mediate such negative effects when they grazed with large herbivores. Our results suggest that the positive, reciprocal interactions in terrestrial herbivore communities may be more prevalent and complex than previously thought.

LIGHT regulates inflamed draining lymph node hypertrophy.

Lymph node (LN) hypertrophy, the increased cellularity of LNs, is the major indication of the initiation and expansion of the immune response against infection, vaccination, cancer, or autoimmunity. The mechanisms underlying LN hypertrophy remain poorly defined. In this article, we demonstrate that LIGHT (homologous to lymphotoxins, exhibits inducible expression, and competes with HSV glycoprotein D for HVEM, a receptor expressed by lymphocytes) (TNFSF14) is a novel factor essential for LN hypertrophy after CFA immunization. Mechanistically, LIGHT is required for the influx of lymphocytes into but not egress out of LNs. In addition, LIGHT is required for dendritic cell migration from the skin to draining LNs. Compared with wild type mice, LIGHT(-)(/)(-) mice express lower levels of chemokines in skin and addressins in LN vascular endothelial cells after CFA immunization. We unexpectedly observed that LIGHT from radioresistant rather than radiosensitive cells, likely Langerhans cells, is required for LN hypertrophy. Importantly, Ag-specific T cell responses were impaired in draining LNs of LIGHT(-)(/)(-) mice, suggesting the importance of LIGHT regulation of LN hypertrophy in the generation of an adaptive immune response. Collectively, our data reveal a novel cellular and molecular mechanism for the regulation of LN hypertrophy and its potential impact on the generation of an optimal adaptive immune response.

[Construction of shRNA eukaryotic expression vectors of pkm2 gene and their effect on drug resistant cell line of acute promyelocytic leukemia].

This study was aimed to construct the shRNA eukaryotic expression vectors of M2-pyruvate kinase gene (pkm2) and to investigate the effects of pkm2 gene interference on the drug resistance of acute promyelocytic leukemia (APL) cells in vitro. Three specific shRNAs of pkm2 gene were designed and cloned into PBSU6 vector containing a U6 promotor. The constructed plasmids were identified and proved by the restriction sequence analysis. Then the effect of pkm2-shRNA on the protein expression of endogenous PKM2 was detected in NB4R2 cells, a drug resistant cell line of APL by Western blot. The alteration of NB4R2 cell differentiation with the interference of pkm2 gene was also validated by nitroblue tetrazolium (NBT) reduction test. The results showed that three specific shRNA eukaryotic expression vectors targeting pkm2 were successfully constructed. The efficiency of pkm2 gene silence was proved at protein level. The interference of pkm2 gene could significantly enhance the cell differentiation in the drug resistant NB4R2 cell line. It is concluded that the DNA vector containing pkm2 targeting shRNA remarkably promotes the differentiation of NB4R2 cells, showing the prospects of developing the gene target drug.