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A viscous feature is beneficial for a solid electrolyte with respect to assembling solid‐state batteries, which can change the solid‐solid contacts from point to face. Here, novel halide‐based deep eutectic solid electrolytes (DESEs) prepared by a facile ball milling method is reported. The mixture of halides triggers the deep eutectic phenomena by intermolecular interactions, leading to diverse morphologies and viscous statuses in terms of composition. Chemical‐ and micro‐structure analyses via the cryogenic technique reveal that the LiCl and LiF nanoparticles are dispersed in an amorphous halide matrix, which endow freely mobile ions for fast ion transport. The optimized DESE thus achieves low activation energy and high ionic conductivity of 16 mS cm−1 at room temperature, one of the highest values among various electrolytes so far. By integrating with the active materials to form a composite cathode, the viscous DESE yields a super‐dense composite pellet which possesses intensively enhanced ionic conductivity in contrast to those formed by the sulfide‐based electrolyte additives, demonstrating an attractive application prospect. [ABSTRACT FROM AUTHOR]

The severe parasitic interface reaction and dendrite growth retard the practical applications of all‐solid‐state (ASS) Na batteries with sulfide solid electrolytes (SEs). Here, a novel composite SE is proposed, with a high ionic conductivity, composed of Na3SbS4 (NSS) and oxysulfide glass. The study reveals that the P2S7‐aOa and PS4‐aOa units in oxysulfide play various roles: The former is deoxidized to release free O ions, which reacts with the anode via migrating to form oxides, favoring an improved interface stability. The latter is highly stable upon cycling, thereby maintaining an ion transport network. Meanwhile, NSS acts as a dendrite predator via reacting with penetrated Na. These advantages enable the resulting ASS Na battery with superior long‐term cycling performance at a high current density at room temperature, one of the best results so far. This discovery sheds light on innovative advanced SE materials through an oxysulfide‐based composite design. [ABSTRACT FROM AUTHOR]

This study compared lipid profiles and volatile composition in marinated eggs from different species (chicken, quail, and pigeon) using LC‐ESI‐MS/MS, and GC–MS, respectively. The three marinated eggs showed significant differences in phosphatidylcholine, phosphatidylethanolamine (PE), and neutral lipid profiles of the three marinated eggs. Pigeon‐eggs contained the highest content of PE but the lowest content of triglycerides. Seventy‐six potential lipid metabolites such as Cer(d18:1/21:0), DG(15:0/18:2), and PE‐O(16:1/18:2) were selected for the discrimination of all three groups. Pigeon‐eggs contained the highest contents of C18:2 and C22:6, as well as n‐3 and n‐6 PUFA than quail‐eggs and chicken‐eggs. Major compounds including 2‐Nonanone, 1‐Octen‐3‐ol, and cyclic octaatomic sulfur have greatly contributed to the distinction of eggs from different species. The highest levels of aldehydes, acids, and ketones were found in chicken‐eggs. This study reported that lipidomic and volatile composition analysis are promising approaches for discriminating of marinated eggs from different species. Novelty impact statement: This is the first study that aiming at comparing the lipid profiles and volatile composition in marinated eggs from different species (chicken, quail, and pigeon) using LC‐ESI‐MS/MS and GC–MS. Pigeon‐eggs contained the highest contents of glycerol phospholipid, n‐3, and n‐6 PUFA. The predominating volatile compositions of marinated eggs were alcohols aldehydes acids and ketones. Therefore, this study provides a better understanding of the quality of marinated eggs, and help customers to better choose higher nutritional values of marinated eggs. [ABSTRACT FROM AUTHOR]

This paper presents an approach to determine optimal grasping poses for dual-arm space robot cooperatively grasping an uncooperative satellite. Aiming at better manipulating the satellite after capture, it is necessary to plan properly grasping poses on the satellite for dual-arm end-effectors to maximize the manipulability of space robot. In this paper, global manipulability based on capability map is applied as the quality index to seek optimal grasping poses. First, the technique to generate cooperative workspace for a closed chain system is introduced fusing the workspace of each single-arm with self-collision avoidance. Second, several general manipulability indices, such as dexterity, manipulability measure and task compatibility, are extended to the entire cooperative workspace to construct capability maps. Next, global manipulability is evaluated for dual-arm space robot cooperative manipulation based on the capability maps. Following this, the optimal grasping poses among all feasible grasping poses on the satellite are obtained by the global manipulability. Finally, a simulation study is carried out to verify the feasibility of the proposed approach based on a redundant dual-arm space robotic system. • Planning optimal grasping poses for dual-arm space robot by global manipulability. • Manipulability measure and task compatibility are extended to space closed chain system. • Cooperative workspace satisfying closure constraint generates by single-arm workspace. • Capability map for dual-arm cooperative manipulation is constructed. • Global manipulability is analyzed based on Capability map. [ABSTRACT FROM AUTHOR]

• Angular momentum transfer is used to design the detumbling and stabilization strategy. • Reaction wheels absorb extra momentum with maximum torque capabilities. • Dynamic coupling and dynamic allocation are used to design manipulator's motion. • Parameter scaling accelerates the convergence speed of the estimated parameters. After capturing a tumbling target, the combined system must be stabilized as soon as possible to ensure the safety of operation tasks. In this paper, a detumbling and stabilization strategy based on angular momentum distribution is proposed for the post-capture space robotic system. Compared with previous works, the proposed approach considers joint velocity limits, which is more suitable for practical cases. Through proper motion planning of the manipulator, the angular momentum of the target and the manipulator is transferred into the reaction wheel while keeping the attitude of the base stabilized. Simultaneously, joint velocity limits are addressed by a dynamic allocation method. Furthermore, a modified identification model with a scaling factor which can provide better converge performance is used to obtained the unknown parameters of the tumbling target, and thus the accurate angular momentum of the target can be obtained for the motion planning after a transition phase. A simulation study is conducted to verify the feasibility and effectiveness of the proposed strategy. [ABSTRACT FROM AUTHOR]

In this work, four structurally similar flavonols (galangin, kaempferol, quercetin and myricetin) were coated on the surface of (11-mercaptoundecyl)- N , N , N -trimethylammonium bromide (MUTAB)‑gold nanoparticles (AuNPs) by two-step phase transfer and self-assembly, and the cationic MUTAB- AuNPs coated with flavonols (flavonol-MUTAB-AuNPs) were designed. Free radical scavenging and antibacterial experiments show that flavonol-MUTAB-AuNPs greatly improve the scavenging effect on DPPH, hydroxyl and superoxide anion radicals, and significantly enhance the inhibition effect on Staphylococcus aureus and Escherichia coli compared with flavonols and AuNPs. Then γ-globulin, fibrinogen, trypsin and pepsin were selected as representative proteins and their interaction with flavonol-MUTAB-AuNPs were investigated by various spectroscopic techniques. The fluorescence quenching mechanism of these four proteins by flavonol-MUTAB-AuNPs is static quenching. The binding constants K a between them are in the range of 103 to 106. The interaction between them is endothermic, entropy-driven spontaneous process, and the main non-covalent force is the hydrophobic interaction. The effect of flavonol-MUTAB-AuNPs on the structure of the four proteins were investigated using UV–vis absorption spectra, synchronous fluorescence spectra and circular dichroism spectra. These results offer important insights into the essence of the interaction between flavonol-MUTAB-AuNPs and γ-globulin/fibrinogen/trypsin/pepsin. They will contribute to the development of safe and effective flavonol-MUTAB-AuNPs in biomedical fields. • The cationic AuNPs coated with flavonols (flavonol-MUTAB-AuNPs) were designed. • Flavonol-MUTAB-AuNPs have stronger antioxidant activity compared with flavonols. • Flavonol-MUTAB-AuNPs have stronger antibacterial activity compared with flavonols. • The interaction mechanism of flavonol-MUTAB-AuNPs with proteins was investigated. • The effect of flavonol-MUTAB-AuNPs on the conformation of proteins was studied. [ABSTRACT FROM AUTHOR]

• Effects of B-ring structures on flavonol-protein interaction are elucidated. • The quenching of the four proteins by flavonols is static quenching. • The non-covalent forces are mainly hydrophobic and hydrogen bonds. • Flavonols have different effects on the secondary conformation of proteins. • Flavonols bind to the active center of proteins and affect their activity. Flavonols are studied extensively because of their interesting biological activities. Galangin, kaempferol, quercetin, and myricetin are structurally related flavonols that differ only in the number of B-ring hydroxyl substituents. In this work, we have carried out a detailed study on the interaction of these structurally related flavonols and γ-globulin/fibrinogen/trypsin/pepsin by using experimental as well as molecular docking approaches. Studies show that the flavonol-protein complex is formed after the interaction of flavonols with the four proteins, which has moderate quenching and binding ability. The effects of the number and position of the hydroxyl groups in flavonols B-ring on the quenching constant, binding constant, number of binding sites, thermodynamic parameters as well as the changes of the secondary structure of proteins are elucidated. The interaction between flavonols and γ-globulin/fibrinogen/trypsin/pepsin is a spontaneous exothermic process driven by enthalpy and entropy, and the main force types are hydrophobic and hydrogen bonds. For some systems, electrostatic forces are also involved. The interaction of flavonols with the four proteins results in loosening and unfolding of backbone of proteins. Moreover, galangin and quercetin also reduce the hydrophobicity of the tryptophan (Trp) microenvironment. The secondary structure of γ-globulin/fibrinogen/trypsin is affected by the number of hydroxyl groups on the B-ring. Except that myricetin does not bind to the catalytic active center of pepsin and seems to have no inhibitory effect on the activity of pepsin, for other flavonol-fibrinogen/trypsin/pepsin systems, flavonols are bound to the active center of the three proteins, and have certain influence on the activity of them. [Display omitted] [ABSTRACT FROM AUTHOR]

Controlling parasitic interface reactions and the Li dendrite growth remains challenging for all-solid-state (ASS) Li batteries, though the progress in Li-ion transport of solid electrolytes (SEs). Herein, ZnO and ZrO 2 oxides are used as dopants to synthesize Li 7 P 3 S 11 (LPS) glass SEs through mechanochemical synthesis. The oxide doping not only improves the ionic conductivity and air stability of LPS SEs, but more importantly also enhances the chemical stability in the interface of Li|SE as well as the Li dendrite suppression capability. Combining FIB milling with SEM-EDS detection, transversal Li dendrite deposition and growth are disclosed to occur inside the interface layer. The ASS battery using the oxide-doped LPS SE and metallic Li anode significantly outperforms that with the O-free LPS, demonstrating the merits of oxide doping toward advancing sulfide SEs. [Display omitted] • Oxide-doped Li 7 P 3 S 11 glass solid electrolytes are synthesized. • Metal-O co-doping improves the ionic conductivity and air stability. • Doping mitigates the interfacial reaction of sulfide/Li and dendrite growth. • Transversal Li dendrite deposition and growth occur inside the Li|SE interface. • Oxide-doped solid electrolyte is promising to use Li metal anode. [ABSTRACT FROM AUTHOR]

Summary Background Sepsis encompasses two phases, the ‘hyper’-reactive phase and the ‘hypo’-reactive phase. The initial inflammatory stage is quickly counterbalanced by an anti-inflammatory response, which compromises the immune system, leading to immune suppression. Regulatory T cells (Tregs) have been implicated in the pathogenesis of sepsis by inducing immunosuppression; however, the role of CD39 + Tregs in the process of sepsis is uncertain. This study investigated the dynamic levels of CD39 + Tregs and their phenotypic change in sepsis. Methods Fourteen patients with systemic inflammatory response syndrome (SIRS), 42 patients with sepsis, and 14 healthy controls were enrolled. Sequential blood samples were used to analyze the numbers of CD39 + Tregs and their phenotypic changes. Survival at 28 days was used to evaluate the capacity of CD39 + Treg levels to predict mortality in sepsis patients. Results Sepsis patients displayed a high percentage (3.13%, 1.46%, and 0.35%, respectively) and mean fluorescence intensity (MFI) (59.65, 29.7, and 24.3, respectively) of CD39 + Tregs compared with SIRS patients and healthy subjects. High-level expression of CD39 + Tregs was correlated with the severity of sepsis, which was reflected by the sepsis-related organ failure assessment score ( r = 0.322 and r = 0.31, respectively). In addition, the expression of CD39 + Tregs was associated with survival of sepsis patients ( p < 0.01). By receiver-operating characteristic (ROC) curve analysis, the percentage and MFI of CD39 + Tregs showed similar sensitivities and specificities to predict mortality (74.2% and 85.1%, and 73.9% and 84.1%, respectively). Using Kaplan–Meier curves to assess the impact of CD39 + Tregs percentage and MFI on overall survival, we found that a high CD39 + Tregs percentage ( p < 0.001; >4.1%) and MFI ( p < 0.001; >49.2) were significantly associated with mortality. Phenotypically, CD39 + Tregs from sepsis patients showed high expression of CD38 and PD-1 ( p < 0.01 and p < 0.01 respectively). Conclusions Increased expression of CD39 + Tregs was associated with a poor prognosis for sepsis patients, which suggests that CD39 + Treg levels could be used as a biomarker to predict the outcome of sepsis patients. [ABSTRACT FROM AUTHOR]

Complement 5a (C5a) is a critical modulator of liver immunity. In this study, we investigated the role of C5a and its receptor in liver fibrosis in patients with hepatitis B virus infection. We found that plasma C5a concentration was significantly increased in patients with chronic hepatitis B, particularly in those patients with higher grade and stage scores. Further analysis indicated that the increased C5a concentration was positively correlated with clinical parameters reflecting liver fibrosis severity, including type IV collagen and procollagen type III N-terminal peptide. Our in vitro data indicated that the C5a receptor is highly expressed in hepatic stellate cells ( HSCs). Addition of C5a significantly activated HSCs and up-regulated α-smooth muscle actin, hyaluronic acid and type IV collagen expression. Also, addition of C5a could inhibit the spontaneous and soluble tumour necrosis factor-related apoptosis-inducing ligand-induced apoptosis of HSCs. These findings highlight the potential role of C5a in the regulation of liver fibrosis. [ABSTRACT FROM AUTHOR]

In this work, spherical silver nanoparticles (AgNPs) with a mean diameter of 50.4 nm were prepared by sodium citrate reduction. The interaction mechanism of AgNPs with γ-globulin fibrinogen and hyaluronidase (HAase) was studied using multispectral methods. The results presented clearly indicate that the intrinsic fluorescence of γ-globulin, fibrinogen and HAase is effectively quenched by AgNPs through a static quenching mechanism, which is further confirmed by UV-vis analysis. The order of the binding constant and Hill coefficient is the same, fibrinogen–AgNPs > γ-globulin–AgNPs > HAase–AgNPs. The interaction between γ-globulin/fibrinogen and AgNPs is an endothermic and entropy-driven process, and the main non-covalent force is hydrophobic interaction. The interaction between HAase and AgNPs is an exothermic, enthalpy-driven process, and van der Waals force and hydrogen bonding are the main non-covalent forces. The interaction of γ-globulin/fibrinogen with AgNPs reduces the hydrophobicity of the tryptophan (Trp) microenvironment, but has no effect on the tyrosine (Tyr) microenvironment. The interaction between HAase and AgNPs has no obvious effect on the microenvironment of Trp and Tyr. CD spectra indicate that the secondary structure of γ-globulin/fibrinogen/HAase changes with the increase of AgNP concentration, and the content of α-helix (fibrinogen and HAase) or β-sheet (γ-globulin) decreases, inducing partial unfolding of the three proteins. [ABSTRACT FROM AUTHOR]

A stable interface and preventing dendrite‐growth are two crucial factors to realize long‐life all‐solid‐state Li batteries (ASSLBs) using sulfide‐based solid electrolytes (SEs) and Li metal anodes. But it remains a challenge to accomplish the two factors simultaneously. Here, an effective strategy is reported to realize this goal in Li‐argyrodites via self‐engineered metastable decomposition that is enabled by Si doping in Cl‐rich argyrodites. It is shown that Cl atoms in the lattice become metastable and are highly reactive with Li atoms. The locally deposited/grown Li crystal nuclei are thus depleted by the metastable Cl during electrochemical cycling, in situ generating electrically insulated LiCl shells concentrated at the argyrodite grain boundaries. The shells in turn prevent the autochthonous Li redeposition and act as self‐protective layers to restrain the continuous decomposition in the interior argyrodite, that is, self‐assembly of reactive‐cores‐stable‐shells to Li metal, thereby enabling an ultra‐long life ASSLB using Li metal anodes at room temperature under relatively high current densities. [ABSTRACT FROM AUTHOR]

[Display omitted] • Quenching mechanism of HAase by flavonoids is static quenching. • Among the six flavonoids, rutin has the strongest binding affinity with HAase. • Hydrophobic, electrostatic interactions and hydrogen bonding are the main forces. • The same core structure has similar effects on the structure of HAase. • Flavonoids binding at the HAase active site may inhibit the activity of HAase. Hyaluronidase (HAase) is an important enzyme involved in a promoting inflammation pathway. Flavonoids are a group of major polyphenols including flavonols (such as myricetin and rutin), dihydroflavones (such as naringin and hesperidin), and isoflavones (such as genistein and puerarin), which have been proved to possess anti-inflammatory effects. In this study, the binding of the six flavonoids to HAase was investigated by steady state and time-resolved fluorescence, circular dichroism (CD) spectroscopy and molecular docking methods. Fluorescence data reveal that the fluorescence quenching mechanism of HAase by flavonoids is all static quenching procedure regardless of their core structure. The binding affinity is strongest for rutin and ranks in the order rutin > hesperidin > myricetin > puerarin > genistein > naringin. The thermodynamic analysis implies that hydrophobic interaction, electrostatic force and hydrogen bonding are the main interaction forces. Synchronous fluorescence spectroscopy and CD spectroscopy indicate that flavonoids have the same core structure and have similar effects on the microenvironment around Trp and Tyr residues and the secondary structure of HAase. The results of molecular docking show that the binding of flavonoids with the catalytic amino acid residues of HAase may lead to the decrease of enzyme activity. [ABSTRACT FROM AUTHOR]

Purple-colored leaves in plants attain much interest for their important biological functions and could be a potential source of phenotypic marker in selecting individuals in breeding. The transcriptional profiling helps to precisely identify mechanisms of leaf pigmentation in crop plants. In this study, two genetically unlike rice genotypes, the mutant purple leaf (pl) and wild (WT) were selected for RNA-sequencing and identifying the differentially expressed genes (DEGs) that are regulating purple leaf color. In total, 609 DEGs were identified, of which 513 and 96 genes were up- and down-regulated, respectively. The identified DEGs are categorized into metabolic process, carboxylic acid biosynthesis, phenylpropanoids, and phenylpropanoid biosynthesis process enrichment by GO analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) confirmed their association with phenylpropanoid synthesis, flavonoid synthesis, and phenylalanine metabolism. To explore molecular mechanism of purple leaf color, a set of anthocyanin biosynthetic and regulatory gene expression patterns were checked by qPCR. We found that OsPAL (Os02g0626100, Os02g0626400, Os04g0518400, Os05g0427400 and Os02g0627100), OsF3H (Os03g0122300), OsC4HL (Os05g0320700), and Os4CL5 (Os08g0448000) are associated with anthocyanin biosynthesis, and they were up-regulated in pl leaves. Two members of regulatory MYB genes (OsMYB55; Os05g0553400 and Os08g0428200), two bHLH genes (Os01g0196300 and Os04g0300600), and two WD40 genes (Os11g0132700 and Os11g0610700) also showed up-regulation in pl mutant. These genes might have significant and vital roles in pl leaf coloration and could provide reference materials for further experimentation to confirm the molecular mechanisms of anthocyanin biosynthesis in rice. [ABSTRACT FROM AUTHOR]

To investigate the impact of exosomes released by Porphyromonas gingivalis -Lipopolysaccharide activated THP-1 macrophages and human periodontal ligament fibroblasts on hepatocyte fat metabolism. The liver of rats with experimental periodontitis showed obvious steatosis and inflammation compared with control rats. The culture supernatant of macrophages and human periodontal ligament fibroblasts (hPDLFs), when stimulated with Pg-LPS, induced lipogenesis in HepG2 cells. Furthermore, the lipid-promoting effect was effectively inhibited by the addition of the exosome inhibitor GW4869. Subsequently, we isolated exosomes from cells associated with periodontitis. Exosomes released by Pg-LPS-stimulated macrophages and hPDLFs are taken up by hepatocytes, causing mRNA expression related to fat synthesis, promoting triglyceride synthesis, and aggravating NAFLD progression. Finally, two sets of exosomes were injected into mice through the tail vein. In vivo experiments have also demonstrated that periodontitis-associated exosomes promote the development of hepatic injury and steatosis, upregulate SCD-1 expression and inhibit the AMPK signaling pathway. In conclusion, we found that exosomes associated with periodontitis promote hepatocyte adipogenesis by increasing the expression of SCD-1 and suppressing the AMPK pathway, which indicates that close monitoring of the progression of stomatopathy associated extra-oral disorders is important and establishes a theoretical foundation for the prevention and management of fatty liver disease linked to periodontitis. [Display omitted] • Periodontitis can promote liver fat deformation in rats. • Periodontitis can promote hepatocyte fat deformation through exosomes. • Periodontitis-associated exosomes promote steatosis by regulating SCD-1/AMPK signaling pathway in hepatocytes. [ABSTRACT FROM AUTHOR]

This paper presents the manipulability analysis of free-floating multi-arm space robots. Evaluation of manipulator capability is useful both in the design and in the operation phase. After capturing a target, closed kinematic chains are formed with multi-arm cooperative manipulating a common object. Owing to the dynamic coupling effect, the manipulability analysis of free-floating systems is more complex than that of ground-fixed closed chain systems. To analyze the cooperative manipulability, kinematic and dynamic formulations for the free-floating closed chain systems are firstly derived. The formulations describe the mapping of joint velocities and torques, respectively, to task velocities and forces, as well as joint torques to task accelerations and forces, by using the generalized Jacobian matrices. Next, the well-known concepts of manipulability ellipsoid, manipulability measure and task compatibility of the free-floating closed chain system are formally extended. Besides, a new approach called scaling factor method is used in the analysis of the task compatibility, which is more accurate compared with the manipulability ellipsoid method. Three applications of the performance indices are considered: (1) the feasibility analysis for a given task, (2) the trajectory planing giving a desired task path, and (3) configuration optimization with different task requirements. The proposed index is proved a very efficient tool that can be utilized in the cooperative manipulation tasks for free-floating space robotic systems. • Kinematic and dynamic formulations for free-floating multi-arm space robots with closed chain constraints are derived, which describe the mapping relationship of joint space to task space. • The concepts of manipulability ellipsoid, manipulability measure and task compatibility are extended to the free-floating closed chain system. And a new approach called scaling factor method is used to calculate the task compatibility. • Three applications of the proposed performance indices are given to prove the effectiveness of the proposed method in cooperative manipulation tasks. [ABSTRACT FROM AUTHOR]

To evaluate independent factors that affect the chance of live birth (LB) after hysteroscopic adhesiolysis in patients with intrauterine adhesions. Retrospective cohort study. Hysteroscopic center of Fuxing Hospital in Beijing, China. Patients diagnosed with Asherman syndrome between June 2020, and February 2022. Hysteroscopic adhesiolysis is followed by a second look hysteroscopy to assess the outcome and follow-up for a year. Live birth rate (LBR) without the use of assisted reproductive technologies at 12-month follow-up. Of the 544 women included in the cohort, the pregnancy rate at the end of 1 year of follow-up was 47.6% (95% confidence interval [CI] 45.5%–49.7%), and the LBR was 41.0% (95% CI 38.9%–43.1%). Stepwise multiple logistic regression analysis identified three independent predictors of LB in decreasing order of significance: increase in menstrual flow after surgery (odds ratio [OR] 3.69, 95% CI 1.77–8.21), postoperative endometrial thickness in the midluteal phase (OR 1.53, 95% CI 1.31–1.80), and the severity of recurred adhesion at second-look hysteroscopy (OR 0.62, 95% CI 0.50–0.76). Among subjects with good independent prognostic factors, namely, increased menstrual flow after surgery, postoperative endometrial thickness in the midluteal phase >6 mm, and no or minimal recurrence of adhesions at second-look hysteroscopy, the LBR was 69.0% (95% CI 65.4%–72.6%). On the other hand, in women (n = 26) without any of the three good prognostic factors, none had a successful LB (0). Overall, the LBR after treatment for Asherman syndrome was 41.0%. The prognosis is dependent on three outcome measures after surgery, namely, improvement in menstrual flow, postoperative endometrial thickness, and the minimal degree of recurrent adhesions at second-look hysteroscopy. [ABSTRACT FROM AUTHOR]

Background: The gut is an important site for human immunodeficiency virus (HIV) infection and immune responses. The role of gut mucosal immune cells in immune restoration in patients infected with HIV undergoing antiretroviral therapy remains unclear. Methods: Ileocytes, including 54 475 immune cells, were obtained from colonoscopic biopsies of five HIV‐negative controls, nine immunological responders (IRs), and three immunological non‐responders (INRs) and were analyzed using single‐cell RNA sequencing. Immunohistochemical assays were performed for validation. The 16S rRNA gene was amplified using PCR in faecal samples to analyze faecal microbiota. Flow cytometry was used to analyze CD4+ T‐cell counts and the activation of T cells. Results: This study presents a global transcriptomic profile of the gut mucosal immune cells in patients infected with HIV. Compared with the IRs, the INRs exhibited a lower proportion of gut plasma cells, especially the IGKC+IgA+ plasma cell subpopulation. IGKC+IgA+ plasma cells were negatively associated with enriched f. Prevotellaceae the INRs and negatively correlated with the overactivation of T cells, but they were positively correlated with CD4+ T‐cell counts. The INRs exhibited a higher proportion of B cells than the IRs. Follicular and memory B cells were significantly higher in the INRs. Reduced potential was observed in the differentiation of follicular or memory B cells into gut plasma cells in INRs. In addition, the receptor‐ligand pairs CD74_MIF and CD74_COPA of memory B/ follicular helper T cells were significantly reduced in the INRs, which may hinder the differentiation of memory and follicular B cells into plasma cells. Conclusions: Our study shows that plasma cells are dysregulated in INRs and provides an extensive resource for deciphering the immune pathogenesis of HIV in INRs. Key points: An investigation was carried out at the single‐cell‐level to analyze gut mucosal immune cells alterations in PLWH after ART.B cells were significantly increased and plasma cells were significantly decreased in the INRs compared to the IRs and NCs.There are gaps in the transition from gut follicular or memory B cellsinto plasma cells in INRs. [ABSTRACT FROM AUTHOR]

Background: Multiple myeloma (MM), characterized by cancerous proliferation of plasmablasts (PB) and plasma cells (PC), remains incurable in many patients. Differentially expressed molecules between MM PCs and healthy PCs have been explored in order to identify novel targets for treating MM. In the present study, we searched for novel MM therapeutic targets by comparing mRNA expression patterns between the Mus musculus myeloma plasmablast-like SP 2/0 cell line and LPS-induced PB/PC.Methods: Gene expression profiles of LPS-induced PB/PC and SP 2/0 cells were determined using RNA-sequencing. A predicted gene (Gm40600) was found to be expressed at a low level in SP 2/0 cells. To study the role of Gm40600 in malignant PC, Gm40600 cDNA was cloned into a lentiviral vector (LV201) containing a puromycin selectable marker that was then transfected into SP 2/0 cells. Stable Gm40600-expressing SP 2/0 cells were selected using puromycin. The effect of Gm40600 on SP 2/0 cell proliferation, cell cycle/apoptosis, and tumor progression was assessed by cell counting kit-8 (CCK8), flow cytometry (FACS), and the SP 2/0 isograft mouse model, respectively. The effect of Gm40600 on mRNA and protein expression was evaluated by RNA-sequencing and western blotting, respectively.Results: We found that SP 2/0 cells expressed lower level of Gm40600 mRNA as compared to LPS-induced PB/PC. Overexpression of Gm40600 significantly suppressed SP 2/0 cell proliferation and isograft tumor progression in an isograft mouse model by promoting apoptosis. In addition, Gm40600 overexpression suppressed transcription of the gene encoding Bcl2. Gm40600 overexpression also reduced the expression of PC-associated transcription factors Blimp1 and Xbp1, which promote transcription of the gene that encodes Bcl2.Conclusions: Gm40600 reduced SP 2/0 cell proliferation and isograft tumor growth and progression by suppressing Blimp1 and Xbp1-mediated Bcl2 transcription to induce apoptosis. Thus, regulation of a human homolog of Gm40600, or associated factors, may be a potential therapeutic approach for treating MM. [ABSTRACT FROM AUTHOR]

Background: Both multiple myeloma (MM) and systemic lupus erythematosus (SLE) are associated with abnormal production of plasma cells, although their pathological mechanism of each disease is different. The main characteristic of both diseases is uncontrolled differentiation of B cells into plasmablast/plasma cells. Despite continuous research on prognostic factors and the introduction of new agents for MM and SLE, treatments still do not exist for controlling plasmablast/plasma cells. Thus, it is necessary to identify novel therapeutic targets of plasmablast/plasma cells. Because of its plasmablast-like characteristics, the mus musculus myeloma SP 2/0 cell line was used in this study to test the effect of a novel therapeutic agent (BC094916 overexpression) on plasmablast/plasma cells. Methods: We first determined gene expression profiles of plasma cells using Affymetrix microarrays and RNA-sequencing. The effect of BC094916 on SP 2/0 cell proliferation, cell cycle, and apoptosis was determined by CCK8 and fluorescence-activated cell sorting. The SP 2/0 xenograft mouse model was used to assess the impact of BC094916 on tumor progression. The luciferase reporter system was used to evaluate the effect of BC094916 on Creb1 and Bcl2 transcription. Results: We found that BC094916 mRNA was decreased in plasma cells. The mouse myeloma cell line SP 2/0 expressed low levels of BC094916 mRNA, whereas BC094916 overexpression suppressed SP 2/0 cell proliferation by inducing apoptosis. BC094916 overexpression suppressed tumor progression in the SP 2/0 xenograft mouse model. We also found that BC094916 mediate apoptosis by suppressing transcription of the Creb1 and Bcl2 genes, which promote the transcription of eukaryotic translation initiation and elongation factor genes. Conclusions: BC094916 overexpression suppressed Creb1 and Bcl2 transcription to induce cell apoptosis, which suppressed SP 2/0 proliferation and xenograft tumor progression. Thus, BC094916 overexpression may be a potential therapeutic agent for treatment of MM and autoimmune diseases such as SLE. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) results from biased proliferation of cancerous plasma cells (PC). Therapeutic strategies that target MM PC will provide immense value to the treatment of MM. For this, it is necessary to identify novel molecules that differ between MM PC and healthy PC. RNA sequencing was used to determine differences in gene expression profiles between LPS-induced plasmablasts (PB)/PC and the PB-like myeloma SP 2/0 cell line. Compared to LPS-induced PB/PC, SP 2/0 cells expressed significantly lower levels of Loc108167440 mRNA. Loc108167440 overexpression reduced the number of SP 2/0 cells by stimulating apoptotic cell death. In addition, Loc108167440 overexpression suppressed tumor progression in the SP 2/0 xenograft mouse model. Finally, we demonstrated that Loc108167440 overexpression up-regulated expression of p53 in SP 2/0 cells. These results suggest that Loc108167440 overexpression suppressed SP 2/0 cell growth by inducing p53-mediated apoptosis. Thus, Loc108167440 overexpression may be a potential therapy for treating MM. [ABSTRACT FROM AUTHOR]

• The novel flavonol-AuNPs antioxidants have stronger antioxidant capacity. • The larger the size of the novel antioxidants, the stronger the antioxidant capacity. • The quenching of proteins by the novel antioxidants is the protein corona formation. • The main noncovalent force in protein corona formation is hydrophobic interaction. • The novel antioxidants do not affect the structure of the four proteins very much. In this work, we reported the methodology involved in the binding of galangin/kaempferol/quercetin/myricetin onto the surface of 10.3 nm and 31.3 nm citrate-capped gold nanoparticles (AuNPs) by a simple in situ method to prepare the eight novel flavonol-AuNPs antioxidants. We systematically performed UV–vis spectroscopy, the hydrodynamic diameter, and zeta potential to characterize the novel flavonol-AuNPs antioxidants. The antioxidative effect of the novel flavonol-AuNPs antioxidants was determined using DPPH radical, hydroxyl radical and superoxide anion radical scavenging assays. The results indicate that the novel flavonol-AuNPs antioxidants scavenging ability of these three free radicals is significantly enhanced compared with flavonols or AuNPs. The scavenging capacity of 31.3 nm flavonol-AuNPs antioxidants is greater than that of 13.3 nm flavonol-AuNPs antioxidants. The free radical scavenging ability of quercetin/myricetin-AuNPs antioxidants is higher than that of galangin/kaempferol-AuNPs antioxidants. And then, the mechanism of protein corona formation between the eight novel AuNPs-flavonol antioxidants and γ-globulin/fibrinogen/trypsin/pepsin and the conformational changes of the four proteins caused by the protein corona formation were systematically and quantitatively investigated by various spectral techniques. Overall, we ascertain the fact that this kind of novel flavonol-AuNPs antioxidants will contribute to the development of safe and effective AuNPs antioxidants in biological systems. [Display omitted] The study prepares novel flavonol-gold nanoparticles antioxidants and provides an accurate and full basic data for clarifying the mechanism of protein corona formation. [ABSTRACT FROM AUTHOR]

Cl-rich Li-argyrodites are promising solid electrolytes (SEs) used in all-solid-state Li batteries (ASSLBs) owing to the fast ion transport. However, they are unstable in the air and their compatibility to metallic Li still needs to be strengthened. Here, we improve these properties through O doping with a relatively high concentration. The high O solid solution in the argyrodite lattice is verified. The optimized Li 5.7 PS 4.5 O 0.2 Cl 1.3 SE possesses an enhanced room temperature ionic conductivity. In parallel, in the sample with a relatively high oxygen dose, a Cl-O coexistence interface layer is revealed at the Li|SE interface region, associated with the formation of LiCl and Li 3 OCl interphases. The highest amount of Li 3 OCl appears also in the interface of Li 5.7 PS 4.5 O 0.2 Cl 1.3 SE. Along with a more stable PS 4- x O x unit, a proper O doing concentration is beneficial to mitigate the decomposition rate of SEs and to improve the compatibility of SE against Li metal. Moreover, Li 5.7 PS 4.5 O 0.2 Cl 1.3 gains significantly enhanced air stability in contrast to the O-free sample. Consequently, the ASSLBs using both pristine and air-exposed Li 5.7 PS 4.5 O 0.2 Cl 1.3 SE demonstrate decent electrochemical performance. In sharp contrast, the ASSLBs using the O-free argyrodite SE after air exposure cannot work for even one cycle. A high amount of O incorporation in Cl-rich Li-argyrodite SEs is thus a facile and effective route for achieving good overall performance including a high ionic conductivity, Li|SE interface stability, Li dendrite suppression capability, and notably, air stability. • The Cl-rich argyrodite lattice can accommodate high O dose. • A Cl-O coexistence interface layer associated with LiCl and Li3OCl interphases is revealed. • O doping improves the interface stability of Li/SE and Li dendrite suppression capability. • O doping dramatically enhances the moisture resistance of Cl-rich argyrodites. • O-doped SEs enable a decent battery performance even air-exposed in high humidity. [ABSTRACT FROM AUTHOR]

Background: Antiretroviral therapy (ART) can reduce viral load in individuals infected with human immunodeficiency virus (HIV); however, some HIV-infected individuals still cannot achieve optimal immune recovery even after ART. Hence, we described the profile of peripheral immune cells and explored the association with disease progression in patients infected with HIV-1. Methods: Mass cytometry analysis was used to characterize the circulating immune cells of 20 treatment-naïve (TNs), 20 immunological non-responders (INRs), 20 immunological responders (IRs), and 10 healthy controls (HCs). Correlation analysis was conducted between cell subpopulation percentages and indicators including HIV-1 cell-associated (CA)-RNA, DNA, CD4+ T cell count, and CD4/CD8 ratio. Results: Global activation, immunosenescence, and exhaustion phenotypes were observed in myeloid cells and T cells from individuals with HIV-1 infection. We also found that specific subsets or clusters of myeloid, CD4+ T, and CD8+ T cells were significantly lost or increased in TN individuals, which could be partially restored after receiving ART. The percentages of several subpopulations correlated with HIV-1 CA-RNA, DNA, CD4+ T cell count, and CD4/CD8 ratio, suggesting that changes in immune cell composition were associated with therapeutic efficacy. Conclusion: These data provide a complete profile of immune cell subpopulations or clusters that are associated with disease progression during chronic HIV-1 infection, which will improve understanding regarding the mechanism of incomplete immune recovery in INRs. [ABSTRACT FROM AUTHOR]

People living with human immunodeficiency virus (PLWH) are a vulnerable population with a higher risk of severe coronavirus disease 2019 (COVID-19); therefore, vaccination is recommended as a priority. Data on viral reservoirs and immunologic outcomes for PLWH breakthrough infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are currently limited. In this study, we investigated the effects of SARS-CoV-2 breakthrough infection on hematological parameters, human immunodeficiency virus (HIV) reservoir size, and T-cell recovery in PLWH receiving antiretroviral therapy (ART) after SARS-CoV-2 booster vaccination. The results indicated that during breakthrough infection, booster vaccination with homologous and heterologous vaccines was safe in PLWH after receiving two doses of inactivated vaccination. The absolute CD4 counts decreased in the heterologous group, whereas the CD8 counts decreased in the homologous booster group after breakthrough infection in PLWH. Breakthrough infection increased HIV reservoirs and was associated with increased T-cell activation in PLWH who received virally suppressed ART and a 3-dose vaccination. According to our data, the breakthrough infection of SARS-CoV-2 may put PLWH at a greater risk for increased HIV reservoirs, even if these individuals were virally suppressed with ART after 3-dose SARS-CoV-2 vaccination. [ABSTRACT FROM AUTHOR]

Polymorphonuclear neutrophils (PMNs) and proinflammatory cytokines have been implicated in the pathogenesis of acute-on-chronic liver failure (ACLF). But the utility of CXC chemokine receptor expression on PMNs as a biomarker for prediction of disease severity is still uncertain. In this study, we investigated the dynamic expression of CXCR1 and CXCR2 on neutrophils, and found that patients with hepatitis B virus-related ACLF displayed low expression of CXCR1 and CXCR2 on peripheral neutrophils compared with healthy subjects and patients with chronic hepatitis B. This expression pattern was correlated with disease severity. Additionally, increased production of IL-8 in peripheral blood was significantly associated with reduced CXCR1 and CXCR2 expression, as shown by the decreased CXCR1 and CXCR2 expression on neutrophils after treating neutrophils with plasma from ACLF patients. This effect could be overcomed through IL-8 blockage with an anti-IL-8 antibody. We also found that IL-8 production and neutrophil infiltration were coordinately increased in the liver tissue of HBV-ACLF patients, and this increase was associated with liver inflammation. Overall, increased production of IL-8 associated with neutrophils infiltration into the liver and decreased CXCR1/2 expression on peripheral neutrophils. CXCR1 and CXCR2 expression levels could be served as early markers to predict the severity of ACLF. [ABSTRACT FROM AUTHOR]

Highlights • Ebi3 promotes T-activation and Th1, Th17 and Treg cell differentiation. • Anti-Ebi3 antibody suppresses T-cell division and differentiation. • Ebi3 expresses in activated B cells and plasma cells. • Ebi3 promotes B-cell division and differentiation. • Ebi3 induced STAT3 signaling via gp130. Abstract Although sharing the same subunit Ebi3, IL-27 (p28/Ebi3) and IL-35 (p35/Ebi3) have different biological functions, suggesting that Ebi3 subunit may functions as a carrier. Our data demonstrated that activated T cells and B cells effectively up-regulated Ebi3 expression. In addition, Ebi3 effectively promoted T-cell activation and the differentiation of helper T 1 (Th1), Th17, and Foxp3+ regulatory T (Treg) cells induced by Th1, Th17, and Treg polarizing condition, respectively. Naturally, Ebi3 could promote B-cell activation and the production of CD138+ plasma cells (PC) induced by LPS. Conversely, neutralizing anti-Ebi3 antibody could significantly suppress T/B-cell activation and production of Th1, Th17, Tregs, and PC induced by Th1, Th17, Treg polarizing condition, and LPS, respectively. Furthermore, we found that Ebi3 time-dependently induced STAT3 activation in CD4+T cells and B cells. Conversely, STAT3−/− effectively reduced Ebi3 expression and the production of Th1, Th17, Tregs, and plasma cells. Finally, we showed that gp130 but not IL-27Rα mediates Ebi3-induced STAT3 activation. These results suggest that Ebi3 promotes Th- and B-cell differentiation via gp130-STAT3 signaling pathway. Thus, autocrine Ebi3 may play an important role in the differentiation of Th and B cells and thus in infection, inflammation, and autoimmune disorders. [ABSTRACT FROM AUTHOR]

CD8 + T cells are essential for long-lasting HIV-1 control and have been harnessed to develop therapeutic and preventive approaches for people living with HIV-1 (PLWH). HIV-1 infection induces marked metabolic alterations. However, it is unclear whether these changes affect the anti-HIV function of CD8 + T cells. Here, we show that PLWH exhibit higher levels of plasma glutamate than healthy controls. In PLWH, glutamate levels positively correlate with HIV-1 reservoir and negatively correlate with the anti-HIV function of CD8 + T cells. Single-cell metabolic modeling reveals glutamate metabolism is surprisingly robust in virtual memory CD8 + T cells (TVM). We further confirmed that glutamate inhibits TVM cells function via the mTORC1 pathway in vitro. Our findings reveal an association between metabolic plasticity and CD8 + T cell-mediated HIV control, suggesting that glutamate metabolism can be exploited as a therapeutic target for the reversion of anti-HIV CD8 + T cell function in PLWH. Analysis of plasma metabolites in virologically suppressed individuals infected with HIV-1 and controls, reveals an association between metabolic plasticity and CD8 + T cell-mediated HIV infection control. [ABSTRACT FROM AUTHOR]

Studies assessing the gut mucosal immune balance in HIV-infected patients using intestinal samples are scarce. In this study, we used intestinal mucosal specimens from the ileocecal region of seven immunological nonresponders (INRs), nine immunological responders (IRs), and six HIV-negative controls. We investigated T helper 17 (Th17) and T regulatory (Treg) cell counts and their ratio, zonula occludens-1 (ZO-1), intestinal fatty acid-binding protein (I-FABP), tumor necrosis factor-α, CD4+ T cell counts, HIV DNA, and cell-associated HIV RNA. The results showed that INRs had lower Th17 and higher Treg cell counts than IR, resulting in a significant difference in the Th17/Treg ratio between IRs and INRs. In addition, INRs had lower ZO-1 and higher I-FABP levels than IRs. The Th17/Treg ratio was positively associated with ZO-1 and negatively associated with I-FABP levels. There was a positive correlation between Th17/Treg ratio and CD4+ T cell counts and a negative correlation between the Th17/Treg ratio and HIV DNA in the intestine. Our study suggests that the imbalance of Th17/Treg in the intestine is a characteristic of incomplete immune reconstitution to antiretroviral therapy and is associated with intestinal damage. [ABSTRACT FROM AUTHOR]

Humoral immunity confers protection against COVID-19. The longevity of antibody responses after receiving an inactivated vaccine in individuals with previous SARS-CoV-2 infection is unclear. Plasma samples were collected from 58 individuals with previous SARS-CoV-2 infection and 25 healthy donors (HDs) who had been vaccinated with an inactivated vaccine. The neutralizing antibodies (NAbs) and S1 domain-specific antibodies against the SARS-CoV-2 wild-type and Omicron strains and nucleoside protein (NP)-specific antibodies were measured using a chemiluminescent immunoassay. Statistical analysis was performed using clinical variables and antibodies at different timepoints after SARS-CoV-2 vaccination. NAbs targeting the wild-type or Omicron strain were detected in individuals with previous SARS-CoV-2 infection at 12 months after infection (wild-type: 81%, geometric mean (GM): 20.3 AU/mL; Omicron: 44%, GM: 9.4 AU/mL), and vaccination provided further enhancement of these antibody levels (wild-type: 98%, GM: 53.3 AU/mL; Omicron: 75%, GM: 27.8 AU/mL, at 3 months after vaccination), which were significantly higher than those in HDs receiving a third dose of inactivated vaccine (wild-type: 85%, GM: 33.6 AU/mL; Omicron: 45%, GM: 11.5 AU/mL). The level of NAbs in individuals with previous infection plateaued 6 months after vaccination, but the NAb levels in HDs declined continuously. NAb levels in individuals with previous infection at 3 months post-vaccination were strongly correlated with those at 6 months post-vaccination, and weakly correlated with those before vaccination. NAb levels declined substantially in most individuals, and the rate of antibody decay was negatively correlated with the neutrophil-to-lymphocyte ratio in the blood at discharge. These results suggest that the inactivated vaccine induced robust and durable NAb responses in individuals with previous infection up to 9 months after vaccination. [ABSTRACT FROM AUTHOR]

Gold nanoparticles (AuNPs), as a type of biocompatible nanomaterial, possess many characteristics and show great potential in the biomedical field. Trypsin and pepsin are the main proteolytic enzymes in the digestive system. A comprehensive elucidation of the interaction between AuNPs and trypsin/pepsin is essential, mainly because AuNPs are likely to interact with trypsin and pepsin when they enter the organism through the digestive system. In this study, AuNPs with different particle sizes were prepared by reduction of HAuCl4 with sodium citrate. The synthesized AuNPs were characterized using UV-vis spectroscopy, TEM and DLS. The interaction of 17 nm and 30 nm AuNPs with trypsin and pepsin was comprehensively investigated from the perspective of thermodynamics. AuNPs can act as a quencher to quench the fluorescence intensity of trypsin or pepsin, and the quenching mechanism mainly comes from static quenching, which is further confirmed by UV-vis analysis. The binding constant Ka and the Hill coefficient n of the interaction between AuNPs and trypsin/pepsin were calculated. The results show that AuNPs have a high affinity with trypsin or pepsin. The binding ability of trypsin to AuNPs is stronger than that of pepsin, and the binding ability of 17 nm AuNPs is stronger than that of 30 nm AuNPs. In addition, the positive cooperative effect of 17 nm AuNPs is more significant than that of 30 nm AuNPs. By evaluating the thermodynamic parameters, it is found that the interaction between AuNPs and trypsin/pepsin is a spontaneous, endothermic and entropy-driven process, and the main non-covalent force is the hydrophobic interaction. For the AuNP (17 nm)–trypsin system and the AuNP (30 nm)–pepsin system, the hydrophobicity of the Trp microenvironment of the two proteases decreases due to the interaction of AuNPs. AuNPs have different effects on the secondary structure of trypsin and pepsin, but AuNPs have more obvious effects on the secondary structure of pepsin than trypsin. The activity of trypsin/pepsin decreases with the addition of AuNPs. [ABSTRACT FROM AUTHOR]

Background/Aims: The bradykinin B2 receptor (BDKRB2) +9/-9 gene polymorphisms have been shown to be associated with the susceptibility and severity of osteoarthritis (OA); however, the underlying mechanisms are unclear. In this study, we investigated the correlation between the BDKRB2 +9/-9 polymorphisms and pro-inflammatory cytokine levels in OA and the molecular mechanisms involved. Methods: A total of 156 patients with primary knee OA and 121 healthy controls were enrolled. The BDKRB2 +9/-9 polymorphisms were genotyped. The tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8 levels were determined using Enzyme-linked immunosorbent assay (ELISA). The toll-like receptor (TLR)-2 and TLR-4 mRNA levels were determined by quantitative real-time PCR. The basal and bradykinin-stimulated pro-inflammatory cytokine secretion in human OA synoviocytes and the involvement of TLR-2 and mitogen-activated protein kinases (MAPKs) were investigated. Results: The presence of -9 bp genotype is associated with higher TNF-α, IL-6, and IL-8 levels and higher TLR-2 expression in OA patients. The basal and bradykinin-induced TLR-2 expressions in human OA synoviocytes were significantly reduced by specific inhibitors of p38, JNK1/2, and ERK1/2. Both the B2 receptor antagonist MEN16132 and TLR-2 silencing inhibited IL-6 and IL-8 secretion in human OA synoviocytes. Conclusion: The data suggested that the BDKRB2 +9/-9 polymorphisms influence pro-inflammatory cytokine levels in knee osteoarthritis by altering TLR-2 expression. [ABSTRACT FROM AUTHOR]

SUMMARY: Peroxisomes are universal eukaryotic organelles essential to plants and animals. Most peroxisomal matrix proteins carry peroxisome targeting signal type 1 (PTS1), a C‐terminal tripeptide. Studies from various kingdoms have revealed influences from sequence upstream of the tripeptide on peroxisome targeting, supporting the view that positive charges in the upstream region are the major enhancing elements. However, a systematic approach to better define the upstream elements influencing PTS1 targeting capability is needed. Here, we used protein sequences from 177 plant genomes to perform large‐scale and in‐depth analysis of the PTS1 domain, which includes the PTS1 tripeptide and upstream sequence elements. We identified and verified 12 low‐frequency PTS1 tripeptides and revealed upstream enhancing and inhibiting sequence patterns for peroxisome targeting, which were subsequently validated in vivo. Follow‐up analysis revealed that nonpolar and acidic residues have relatively strong enhancing and inhibiting effects, respectively, on peroxisome targeting. However, in contrast to the previous understanding, positive charges alone do not show the anticipated enhancing effect and that both the position and property of the residues within these patterns are important for peroxisome targeting. We further demonstrated that the three residues immediately upstream of the tripeptide are the core influencers, with a 'basic‐nonpolar‐basic' pattern serving as a strong and universal enhancing pattern for peroxisome targeting. These findings have significantly advanced our knowledge of the PTS1 domain in plants and likely other eukaryotic species as well. The principles and strategies employed in the present study may also be applied to deciphering auxiliary targeting signals for other organelles. Significance Statement: Large‐scale in silico and in vivo studies identified and validated low‐frequency peroxisome targeting signal type 1 tripeptides in plants and revealed enhancing and inhibiting sequence patterns upstream of the tripeptide for peroxisome targeting. The findings from the present study significantly advance our understanding of peroxisome targeting and similar strategies may be applied to elucidate auxiliary targeting signals for other organelles. [ABSTRACT FROM AUTHOR]

Large-scale applications of Li 6 PS 5 I electrolytes have been limited due to their low ionic conductivities. This work demonstrated the conductivity enhancement of Li 6 PS 5 I via introducing more iodine in the structure. Li 5.5 PS 4.5 I 1.5 electrolyte synthesized by the mechanical milling route exhibits high ionic conductivity of 0.31 mS/cm at room temperature, which is double times higher than the pristine material. Symmetric cell and half-cell tests confirm that Li 5.5 PS 4.5 I 1.5 suffers from poor chemical/electrochemical stability towards the high-voltage cathode and high activation energy for lithium-ions transport in cathode/electrolyte interface. The introduction of Li 3 InCl 6 ionic additive in the cathode can improve compatibility with LiNi 0.7 Co 0.1 Mn 0.2 O 2 cathode, yielding better electrochemical performances. Li 5.5 PS 4.5 I 1.5 -based solid-state battery using Se 0.05 S 0.95 @pPAN displays a high initial discharge capacity and a capacity of 728 mAh/g after 30 cycles. This work provides a new route to explore iodine-based solid electrolytes with higher ionic conductivity for solid-state batteries. [Display omitted] [ABSTRACT FROM AUTHOR]

IL-1α in vitro promotes immunoglobulin secretion by inducing proliferation of mature B cells, whereas IL-1α deficiency has no effect on in vivo antibody production. However, the reason IL-1α deficiency does not reduce in vivo antibody production is still unclear. In this study, we found that similar as in vivo data, IL-1α deficiency did not affect antibody production in in vitro LPS-stimulated B cells. Surprisingly, LPS-stimulated IL-1α −/− B cells reduced a key antibody production-related transcription factor X-box binding protein 1 (Xbp-1) expression. Furthermore, we found that IL-1α deficiency up-regulated mTOR expression, which bypassed Xbp-1 for immunoglobulin secretion. Finally, we showed that Xbp-1 suppressed mTOR expression, whereas mTOR suppressed the activation of Xbp-1 promoter via JunB. Together, these data suggest that IL-1a deficiency reduced Xbp-1 and up-regulated mTOR. This may explain why IL-1α deficiency has no effect on antibody production. [ABSTRACT FROM AUTHOR]

Notch1 signaling regulates B and T lymphocyte development and also in vitro promotes antibody secretion upon B cell activation. However, it is still unclear about the role of Notch1 in antibody production upon in vitro and in vivo mixture lymphocytes activation. We first showed that Notch1 expressed in LPS-activated CD19 hi B cells and CD19 cre mediated Notch1 knock-down in LPS-activated B cells. Furthermore, we demonstrated that Notch1 knock-down in B cells reduced antibody production in LPS-stimulated B cells but did not affect antibody production in LPS-stimulated splenocytes and in experimental allergic encephalomyelitis (EAE) mice. Importantly, Notch1 ligands Dll1 and Jag1 expressed in B cells and pre-coated Notch1 protein promotes Notch1-knocked down B cells to produce antibody in LPS-stimulated B cells suggesting that Notch1 in other cells may promote antibody production by binding its ligands Dll1 and Jag1 in B cells. Together, our results suggest that both Notch1 and its ligands in B cells play an important role in antibody production. [ABSTRACT FROM AUTHOR]

[Display omitted] • The quenching mechanism of transferrin by flavonols is static quenching. • Flavonols have a moderate affinity with transferrin. • Myricetin may be a superior ligand for transferrin. • The main forces are hydrophobic interaction, electrostatic force and hydrogen bonds. • Flavonols decrease α-helix and β-turn, while increase β-sheet of transferrin. Transferrin is the indispensable component in the body fluids and has been explored as a potential drug carrier for target drugs to cancer cells. Flavonols are widely distributed in plants and shown a wide range of biological activities. In the present study, the interaction between flavonols (including galangin, kaempferol, quercetin, and myricetin) and transferrin under physiological conditions was investigated by using experimental as well as computational approaches. Fluorescence data reveal that the fluorescence quenching mechanism of transferrin by flavonols is static quenching. Transferrin has moderate affinity with flavonols, and the binding constants (K a) are 103-104 L/mol. In addition, there are two different binding sites for the interaction between kaempferol and transferrin. Thermodynamic parameter analysis shows that the interaction of flavonols and transferrin is synergistically driven by enthalpy and entropy. Hydrophobic interaction, electrostatic force and hydrogen bonds are the main force types. Synchronous fluorescence spectroscopy shows that flavonols decrease the hydrophobicity of the microenvironment around tryptophan (Trp) and have no effect on the microenvironment around tyrosine (Tyr). UV–vis and CD spectra show that the interaction between transferrin and flavonols leads to the loosening and unfolding of transferrin backbone. The increase of β-sheet is accompanied by the decrease of α-helix and β-turn. The specific binding sites of flavonols to transferrin are confirmed by molecular docking. Molecular dynamic simulation suggests that the transferrin-flavonols docked complex is stable throughout the simulation trajectory. [ABSTRACT FROM AUTHOR]

• The quenching mechanism of fibrinogen by flavonoids is static quenching. • The binding constants between flavonoids and fibrinogen are all moderate. • Rutin or genistein has two different binding sites on fibrinogen. • Hydrophobic, electrostatic forces and hydrogen bonds are the main force types. • α-helix structure of fibrinogen decreases with the addition of flavonoids. Fibrinogen is a key component of the inflammation and clotting pathways and an established risk factor for cardiovascular disease. Flavonoids have been shown to be pharmacologically active and for many years they have been used in the treatment of many types of diseases. In this study, the interaction between flavonoids (including myricetin, rutin, naringin, hesperidin, genistein and puerarin) and fibrinogen under physiological conditions was investigated by using multiple spectroscopic and molecular docking methods. Fluorescence data reveal that the fluorescence quenching mechanism of fibrinogen by flavonoids is static quenching in the linear range. Fibrinogen has moderate affinity with flavonoids, and the binding constants (K a) are 103–104 L mol−1. In addition, there are two different binding sites for the interaction between rutin/genistein and fibrinogen. Thermodynamic parameter analysis shows that the interaction of flavonoids and fibrinogen is synergistically driven by enthalpy and entropy, and hydrophobic interaction, electrostatic force and hydrogen bonds are the main force types. Synchronous fluorescence spectroscopy shows that rutin increases the hydrophobicity of the microenvironment around tryptophan (Trp), while the other five flavonoids have the opposite effect. Myricetin and naringin decrease the hydrophobicity of the microenvironment around tyrosine (Tyr), while the other four flavonoids have no effect on the microenvironment around Tyr. UV-vis and CD spectra show that the interaction between flavonoids and fibrinogen leads to the loosening and unfolding of fibrinogen backbone and the α-helix structure of fibrinogen decreases with the addition of flavonoids. The specific binding sites of flavonoids to fibrinogen are confirmed by molecular docking. [Display omitted] [ABSTRACT FROM AUTHOR]

Background and Aim [ABSTRACT FROM AUTHOR]

Decompensated liver cirrhosis (LC), a life-threatening complication of chronic liver disease, is one of the major indications for liver transplantation. Recently, mesenchymal stem cell (MSC) transfusion has been shown to lead to the regression of liver fibrosis in mice and humans. This study examined the safety and efficacy of umbilical cord-derived MSC (UC-MSC) in patients with decompensated LC. A total of 45 chronic hepatitis B patients with decompensated LC, including 30 patients receiving UC-MSC transfusion, and 15 patients receiving saline as the control, were recruited; clinical parameters were detected during a 1-year follow-up period. No significant side-effects and complications were observed in either group. There was a significant reduction in the volume of ascites in patients treated with UC-MSC transfusion compared with controls ( P < 0.05). UC-MSC therapy also significantly improved liver function, as indicated by the increase of serum albumin levels, decrease in total serum bilirubin levels, and decrease in the sodium model for end-stage liver disease scores. UC-MSC transfusion is clinically safe and could improve liver function and reduce ascites in patients with decompensated LC. UC-MSC transfusion, therefore, might present a novel therapeutic approach for patients with decompensated LC. [ABSTRACT FROM AUTHOR]

Abstract: Excessive complement-activated product complement 5a (C5a) has been implicated in the pathogenesis of sepsis development. Herein, we employed in vitro and in vivo models of sepsis to investigate the functional relationship between overtly produced C5a and IL-8. Our data revealed that C5a could strongly amplify IL-8 expression from human whole blood cells induced by LPS and other types of TLR agonists. ERK1/2 and p38, but not JNK, were mainly participated in signaling pathways for IL-8 production. In the whole blood stimulated by E scherichia coli, C5a levels were quickly elevated and blockage of C5a significantly decreased E. coli-elicited IL-8 production. In the mouse model of sepsis induced by cecal ligation and puncture (CLP), the markedly increased keratinocyte-derived cytokine (KC) could be strongly suppressed by blockage of C5a. These data suggest that excessive C5a functions as a critical inflammatory mediator to enhance IL-8 production mainly through MAPK signaling pathways. [ABSTRACT FROM AUTHOR]

Abstract: Our previous studies have shown that Foxp3 under the control of IFN-γ promoter (IγP-Foxp3) converts pathogenic CD4+Th1 cells into regulatory T cells (Tregs), which control diabetes in non-obese diabetic (NOD) mice. Here, we tested the other hypothesis that transient expression of Foxp3 as controlled by the transient expression of IL-12Rβ2 during Th1 cell derivation is sufficient to convert cells to Tregs. Foxp3, under the control of IL-12Rβ2 promoter (Iβ2P), was lentivirally transduced into naïve CD4+T cells from NOD mice. Iβ2P-Foxp3-transduced CD4+T cells could not effectively suppress the incidence of diabetes when transferred into NOD mice. Furthermore, we found that Iβ2P-Foxp3-transduced CD4+T cells, stimulated by a high dose of autoantigen, did not suppress CD4+T cell activation, produce CD4+Foxp3+Tregs, and up-regulate CTLA4 expression. These results suggest that Iβ2P cannot mediate Foxp3 to convert pathogenic CD4+Th1 cells into Tregs which control diabetes in NOD mice. [Copyright &y& Elsevier]

Background: Our previous studies have demonstrated that GAD-IgG-transduced splenocytes protect non-obese diabetic (NOD) mice from diabetes by in vitro-inducing CD4+Foxp3+Treg cells. However, the underlying mechanisms by which CD4+Foxp3+Treg cells suppress diabetes remain unclear. Methods: Seven-week-old female NOD mice were intravenously injected with GAD-IgG-transduced splenocytes. The ratio of CD80+:CD86+ cells in splenocytes was analyzed by flow cytometry. The effect of the ratio of CD80+:CD86+ cells on tolerance, diabetes prevention, and Foxp3 expression in GAD-IgG-treated NOD mice was tested by in vitro proliferation, in vivo antibody block, and semi-quantified RT-PCR, respectively. Results: We found that the ratio of CD80+:CD86+ cells increased in GAD-IgG-treated NOD mice. After CD4+Treg cells were depleted from GAD-IgG-transduced splenocytes before transfer, the ratio of CD80+:CD86+ cells decreased in NOD mice recipients. The increasing ratio of CD80+:CD86+ cells was positively associated with tolerance, diabetes prevention, and the high level of Foxp3 in GAD-IgG-treated NOD mice. Conclusions: These findings suggest that the high ratio of CD80+:CD86+ cells is required for the suppressive function of GAD-IgG-inducing CD4+Foxp3+Treg cells in NOD mice. [Copyright &y& Elsevier]

Abstract: We previously found that adeno-associated viral vector serotype 2 (AAV-2) muscle gene delivery of GAD500–585 autoantigen efficiently prevented autoimmune diabetes in NOD mice. Recent reports suggest that AAV vectors based on serotype 1 (AAV-1) transduce murine skeletal muscle much more efficiently than AAV-2, with reported increases in expression ranging from 2 to 1000-fold. To determine whether this increased efficacy of AAV-1 could result in increased therapeutic effects in mice, we constructed rAAV1/GAD500–585 vectors and compared their effects in preventing autoimmune diabetes in NOD mice with those of rAAV2/GAD500–585 after muscle injection. rAAV1/GAD500–585 gene therapy prevented diabetes in NOD mice. However, although much higher level of GAD500–585 expression was found in mice using AAV-1 as gene delivery vector than those using AAV-2, no increased efficiency of AAV-1 vectors were found in their capability to prevent autoimmune diabetes, as higher titers of rAAV1/GAD500–585 virus (3×1011 v.g./mouse) were needed to obtain therapeutic effects in NOD mice, a titer not different from that of AAV-2. Protection resulted from rAAV1/GAD500–585 gene therapy were marked by enhanced Th2 immune response and up-regulated CD4+Foxp3+T regulatory cells, which might actively suppress effector T cells in NOD mice. As here we found that the therapeutic effects of AAV1 were not positively correlated to it''s transduction efficiency, our data suggested that the safety and other factors besides efficiency should be considered when use different AAV serotype to treat autoimmune disease. [Copyright &y& Elsevier]

Abstract: The extracellular cysteine-rich domains of ErbB2 receptors play important roles in ligand binding and receptor dimerization. The aim of the present study was to design a novel peptide exerting cytostatic effect toward ErbB2-overexpessing tumors based on one of the cysteine-rich domain (S1) of ErbB2. In order to create a stable molecule with unique structural and binding property, a chimeric molecule PL45 composed of ErbB2 S1 domain targeting peptide and the five stranded coiled coil domain from cartilage oligomeric matrix protein (COMP) was generated. PL45 was efficiently expressed in Escherichia coli and exhibited remarkable thermal and pH stability. It was capable of interfering with dimerization of ErbB2 and inhibiting the growth of ErbB2-overexpessing tumor cells in vitro and in vivo. The results provide evidence that the coiled coil structure can be used as a new scaffold to stabilize short peptides with potential application for anti-cancer immunotherapy and S1 domain of ErbB2 is a promising target for drug design. [Copyright &y& Elsevier]

Abstract: Unraveling the events that control the suppressive function of regulatory T (Treg) cells is extremely important because it will enable investigators to manipulate these cells to inhibit or enhance their functions as necessary. One of the members of the Signal Transducer and Activators of Transcription (STATs) family, STAT3, has emerged as a negative regulator of inflammatory responses. Here, we study the role of STAT3 in Treg cell induction. We found that GAD–IgG-transduced splenocytes induce a CD4+Foxp3+Treg cell increase in NOD mice. In parallel with the Treg cell increase, an IL-6-STAT3 signal pathway is activated. When STAT3 activation is blocked, GAD-specific tolerance disappears, the percentage of Treg cells decreases and IL-10 secretion is reduced in the splenocytes of NOD mice recipients of GAD–IgG-transduced splenocytes. Our findings indicate that transcription factor STAT3 plays an important role in immune tolerance. [Copyright &y& Elsevier]

[Display omitted] • Quenching mechanisms of trypsin/pepsin by naringenin/naringin are static quenching. • Naringin binds trypsin/pepsin in a more firmly way than naringenin. • Hydrophobic, electrostatic interactions and hydrogen bonding are the main forces. • The interactions of these systems are synergistically driven by enthalpy and entropy. • Naringenin and naringin respective bind near the active sites of trypsin and pepsin. Naringenin and naringin are two natural compounds with important health benefits, whether as food or drug. It is necessary to study the interactions between naringenin/naringin and digestive proteases, such as trypsin and pepsin. In this study, the bindings of naringenin and naringin to trypsin and pepsin were investigated using multi-spectroscopy analysis and computational modeling approaches. Fluorescence experiments indicate that both naringenin and naringin can quench the intrinsic fluorescence of trypsin/pepsin via static quenching mechanism. Naringin binds trypsin/pepsin in a more firmly way than naringenin. Thermodynamic analysis reveals that the interactions of naringenin/naringin and trypsin/pepsin are synergistically driven by enthalpy and entropy, and the major driving forces are hydrophobic, electrostatic interactions and hydrogen bonding. Synchronous fluorescence spectroscopy, circular dichroism spectroscopy and FT-IR show that naringenin/naringin may induce microenvironmental and conformational changes of trypsin and pepsin. Molecular docking reveals that naringenin binds in the close vicinity of the active site (Ser-195) of trypsin and Asp-32 (the catalytic activity of pepsin) appears in naringin-pepsin system. The direct interactions between naringenin or naringin and catalytic amino acid residues will inhibit the catalytic activity of trypsin and pepsin, respectively. The results of molecular dynamic simulation validate the reliability of the docking results. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) modulate endometriosis. The current study investigated the mechanisms and effects of SNHG4 on endometriosis. The qRT-PCR was conducted to examine the miR-148a-3p and SNHG4 expressions in endometriosis tissues. The 5-ethynyl-2′-deoxyuridine incorporation assay and 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide assay were used to measure the rate of cell proliferation. The association between miR-148a-3p, SNHG4 and c-Met was confirmed via bioinformatical approach and luciferase reporter gene assay. Also, the function of SNHG4 on the growth of endometriotic lesions was investigated in vivo. The SNHG4 expression was considerably upregulated in endometriosis tissues, whereas the level of miR-148a-3p expression was reduced. In addition, SNHG4 can be considered as ceRNAs that bind miR-148a-3p and rise the proliferation activity of HESCs by downregulating miR-148a-3p. Furthermore, silencing SNHG4 could downregulate the c-Met level by enhancing miR-148a-3p expression, and finally inhibiting endometriosis development in vivo. LncRNA SNHG4 promotes the increased growth of endometrial tissue outside the uterine cavity via regulating c-Met mediated by miR-148a-3p, which may be used as diagnostic biomarker as well as molecular target in the treatment of endometriosis. • SNHG4 was upregulated in ectopic endometrium, while miR-148a-3p was decreased. • MiR-148a-3p was the direct target of SNHG4. • Silencing SNHG4 could downregulate the c-Met level by enhancing miR-148a-3p expression. • Silencing SNHG4 suppressed endometriotic lesions growth in vivo. [ABSTRACT FROM AUTHOR]

The E3 ubiquitin ligase Itch interacts with Foxo1 and targets it for ubiquitination and degradation during follicular helper T-cell differentiation, whereas the transcription factor Foxo1 plays a critical role in B-cell development. Thus, we proposed that Itch mediates B-cell differentiation. Unexpectedly, we found that Itch deficiency downregulated Foxo1 expression in B cells. Itch cKO (conditional knock out in B cells) mice had fewer pro-B cells in the bone marrow, more small resting IgM−IgD−B cells in the periphery, and lower B-cell numbers in the lymph nodes through decreased Foxo1-mediated IL-7Rα, RAG, and CD62L expression, respectively. Importantly, Itch deficiency reduced Foxo1 mRNA expression by up-regulating JunB-mediated miR-182. Finally, Foxo1 negatively regulated JunB expression by up-regulating Itch. Thus, we have identified a novel regulatory axis between Itch and Foxo1 in B cells, suggesting that Itch is essential for B-cell development. [ABSTRACT FROM AUTHOR]