The grapevine miR827a regulates the synthesis of stilbenes by targeting VqMYB14 and gives rise to susceptibility in plant immunity.

Grapevine (Vitis vinifera L.) is an economically important fruit crop cultivated worldwide. In China, grapevine cultivation is very extensive, and a few Vitis grapes have excellent pathogen and stress resistance, but the molecular mechanisms underlying the grapevine response to stress remain unclear. In this study, a microRNA (miRNA; miR827a), which negatively regulates its target gene VqMYB14, a key regulatory role in the synthesis of stilbenes, was identified in Vitis quinquangularis (V. quinquangularis) using transcriptome sequencing. Using overexpression and silencing approaches, we found that miR827a regulates the synthesis of stilbenes by targeting VqMYB14. We used flagellin N-terminal 22-amino-acid peptide (flg22), the representative elicitor in plant basal immunity, as the elicitor to verify whether miR827a is involved in the basal immunity of V. quinquangularis. Furthermore, the promoter activity of miR827a was alleviated in transgenic grape protoplasts and Arabidopsis thaliana following treatment with flg22 and Pseudomonas syringae pv. Tomato DC3000 (Pst DC3000), respectively. In addition, yeast one-hybrid and dual luciferase reporter assay revealed that the ethylene transcription factor VqERF057 acted as a key regulator in the inhibition of miR827a transcription. These results will contribute to the understanding of the biological functions of miR827a in grapevine and clarify the molecular mechanism of the interaction between miR827a and VqMYB14.

CRIF1 deficiency induces FOXP3LOW inflammatory non-suppressive regulatory T cells, thereby promoting antitumor immunity.

Recently identified human FOXP3lowCD45RA- inflammatory non-suppressive (INS) cells produce proinflammatory cytokines, exhibit reduced suppressiveness, and promote antitumor immunity unlike conventional regulatory T cells (Tregs). In spite of their implication in tumors, the mechanism for generation of FOXP3lowCD45RA- INS cells in vivo is unclear. We showed that the FOXP3lowCD45RA- cells in human tumors demonstrate attenuated expression of CRIF1, a vital mitochondrial regulator. Mice with CRIF1 deficiency in Tregs bore Foxp3lowINS-Tregs with mitochondrial dysfunction and metabolic reprograming. The enhanced glutaminolysis activated α-ketoglutarate-mTORC1 axis, which promoted proinflammatory cytokine expression by inducing EOMES and SATB1 expression. Moreover, chromatin openness of the regulatory regions of the Ifng and Il4 genes was increased, which facilitated EOMES/SATB1 binding. The increased α-ketoglutarate-derived 2-hydroxyglutarate down-regulated Foxp3 expression by methylating the Foxp3 gene regulatory regions. Furthermore, CRIF1 deficiency-induced Foxp3lowINS-Tregs suppressed tumor growth in an IFN-γ-dependent manner. Thus, CRIF1 deficiency-mediated mitochondrial dysfunction results in the induction of Foxp3lowINS-Tregs including FOXP3lowCD45RA- cells that promote antitumor immunity.

Hepatic T-cell senescence and exhaustion are implicated in the progression of fatty liver disease in patients with type 2 diabetes and mouse model with nonalcoholic steatohepatitis.

Immunosenescence and exhaustion are involved in the development and progression of type 2 diabetes (T2D) and metabolic liver diseases, including fatty liver, fibrosis, and cirrhosis, in humans. However, the relationships of the senescence and exhaustion of T cells with insulin resistance-associated liver diseases remain incompletely understood. To better define the relationship of T2D with nonalcoholic fatty liver disease, 59 patients (mean age 58.7 ± 11.0 years; 47.5% male) with T2D were studied. To characterize their systemic immunophenotypes, peripheral blood mononuclear cells were analyzed using flow cytometry. Magnetic resonance imaging (MRI)-based proton density fat fraction and MRI-based elastography were performed using an open-bore, vertical-field 3.0 T scanner to quantify liver fat and fibrosis, respectively. The participants with insulin resistance had a significantly larger population of CD28 - CD57+ senescent T cells among the CD4+ and CD8 + T cells than those with lower Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) values. The abundances of senescent CD4+ and CD8 + T cells and the HOMA-IR positively correlated with the severity of liver fibrosis, assessed using MRI-based elastography. Interleukin 15 from hepatic monocytes was found to be an inducer of bystander activation of T cells, which is associated with progression of liver disease in the participants with T2D. Furthermore, high expression of genes related to senescence and exhaustion was identified in CD4+ and CD8 + T cells from the participants with nonalcoholic steatohepatitis or liver cirrhosis. Finally, we have also demonstrated that hepatic T-cell senescence and exhaustion are induced in a diet or chemical-induced mouse model with nonalcoholic steatohepatitis. In conclusion, we have shown that T-cell senescence is associated with insulin resistance and metabolic liver disease in patients with T2D.

Exploring perceived restoration, landscape perception, and place attachment in historical districts: insights from diverse visitors.

Improving the quality of the built environment to enhance people's mental health is gaining traction across various fields, precipitating valuable actions on the wave of "Healthy China 2030" initiative. While ample studies have confirmed the benefits of interaction with natural or green spaces, the investigation into the restorative potential in urban built settings remains notably underexplored. In this study, we focused on historical districts, conducting a questionnaire survey to evaluate the restorative experiences of individuals visiting these sites. We used Partial Least Square-Structural Equation Modelling (PLS-SEM) to analyze a conceptual model that encompasses landscape perception, place attachment, and perceived restoration, with a specific focus on detecting the mediating role of place attachment and the moderating influence of visitor groups. The results showed that landscape perception significantly influenced the perceived restoration, which contained the indirect effect pathway through place dependence and place identity, as well as the potent direct impact of landscape perception. Moreover, employing a multi-group analysis (MGA), we discerned that different visitor groups partially moderate the relationship between landscape perception, place attachment, and perceived restoration. This study validates the restorative features in historic districts and highlights the importance of cognitive-emotional bond in promoting psychological restoration.

Leucine-enriched amino acid supplementation and exercise to prevent sarcopenia in patients on hemodialysis: a single-arm pilot study.

Background: Sarcopenia, which is strongly associated with mortality and quality of life, occurs in up to 40% of hemodialysis patients. Here, we investigated the preventive effects of leucine-enriched amino acid supplementation and resistance exercise in non-sarcopenic hemodialysis patients, and characterized the biochemical and immunophenotypic profiles of those who benefited from the intervention. Methods: Twenty-two patients on maintenance hemodialysis at our hospital were enrolled in this single center, prospective, single-arm pilot trial. For the first 12 weeks, the subjects were administered a total of 6 g of leucine per day. Three grams were supplied via capsules, and the remaining three grams were provided via beverages containing macro- and micro- nutrients, such as 10 µg of vitamin D and 290 mg of calcium. The supplements were not provided for the next 12 weeks. Muscle mass, grip strength, and physical performance were measured using the bioimpedance analyzer (BIA), handgrip strength (HGS), and short physical performance battery (SPPB) protocols, respectively, at baseline, 12 weeks, and 24 weeks. In addition, serum biochemistry, immunophenotype of peripheral blood mononuclear cells, and nutritional status was assessed at the three time points. Those who showed 5% or more improvement in parameters were defined as responders, otherwise, as non-responders (ClinicalTrials.gov identification number: NCT04927208). Results: Twenty-one out of twenty-two patients (95.4%) showed improvement in at least one or more parameters among muscle mass, grip strength, and physical performance. After 12 weeks of intervention, skeletal muscle index was increased in 14 patients (63.6%), and grip strength was improved in 7 patients (31.8%). Baseline grip strength lower than 35.0 kg was the strongest predictor of improvement in grip strength (AUC 0.933 from ROC curve). Grip strength showed a significant increase in females than males (7.6 ± 8.2 vs. -1.6 ± 7.2%, p = 0.03), in age over 60 than under 60 (5.3 ± 6.2 vs. -1.4 ± 9.1%, p = 0.04), and in higher (≥95%) than lower (<95%) exercise compliance (6.8 ± 7.7 vs. -3.2 ± 6.4%, p = 0.004). In SPPB study, gait speed and sit-to-stand time was improved in 13 patients (59.1%) and 14 patients (63.6%), respectively. Baseline hemoglobin lower than 10.5 g/dl and hematocrit lower than 30.8% were predictor of improvement in the sit-to-stand time (AUC 0.862 and 0.848, respectively). Serum biochemistry results showed that, compared to non-responders, responders in muscle mass had lower baseline monocyte fraction (8.4 ± 1.9 vs. 6.9 ± 1.1%, p = 0.03), and responders in grip strength had lower baseline total protein (6.7 ± 0.4 vs. 6.4 ± 0.3 g/dL, p = 0.04). Immunophenotypic analysis found that the intervention tended to increase the naïve/memory CD8+ T cell ratio (from 1.2 ± 0.8 to 1.4 ± 1.1, p = 0.07). Conclusion: Leucine-enriched amino acid supplementation and resistance exercise induced significant improvement in muscle mass, strength, and physical function in subpopulation of the non-sarcopenic hemodialysis patients. Those who benefited from the intervention were old-age females with lower baseline grip strength or lower hemoglobin or hematocrit, and who have good exercise compliance. Therefore, we propose that the intervention will help to prevent sarcopenia in selected patients on maintenance hemodialysis.

Effects of Different Dietary Protein Levels on the Growth Performance, Physicochemical Indexes, Quality, and Molecular Expression of Yellow River Carp (Cyprinus carpio haematopterus).

A 12-week rearing trial was carried out to estimate effects on the growth performance, physicochemical indexes, quality, and the molecular expression of Yellow River Carp (Cyprinus carpio haematopterus) using five practical diets, including dietary protein levels of 220, 250, 280, 310, and 340 g/kg. The results illustrated that the fish's weight gain (WG) and specific growth rate (SGR) were significantly influenced, with an ascending dietary protein level of up to 250 g/kg (p < 0.05). The carp muscle contents of total saturated fatty acids (∑SFA), monounsaturated fatty acids (∑MUFA), polyunsaturated fatty acids (∑PUFA), and fatty acids (∑FA) decreased significantly with the ascending dietary protein levels, except for the 250 g/kg protein diet (p < 0.05). Only the glutamic acid and total essential amino acid (∑EAA) contents were significantly influenced by the ascending dietary protein levels (p < 0.05). The relative GH expression of the carp muscle significantly decreased with the increase in the dietary protein level up to 310 g/kg, and then it significantly increased (p < 0.05). In the intestines, the peak relative TOR expression was observed on the 220 g/kg protein diet, while the relative 4EBP1 expression was significantly influenced by the dietary protein level up to 250 g/kg (p < 0.05). In the muscle, the peak relative TOR and 4EBP1 expression levels were observed on the 250 g/kg protein diet. In gills, the lowest relative Rhag, Rhbg, and Rhcg1 expression levels were observed on the 250 g/kg protein diet. Based on all of the aforementioned results, the optimal dietary protein level for Cyprinus carpio haematopterus (160.24 ± 15.56 g) is 250-280 g/kg.

Identification of ferroptosis-related signature with potential implications in prognosis and immunotherapy of renal cell carcinoma.

Developing individualized therapies for different renal cell carcinoma patients is pivotal for improving the efficacy of immunotherapy. It has been reported that ferroptosis is involved in T cell-mediated anti-tumor immunity, and that therapeutic approaches targeting tumor ferroptosis pathway in combination with immune checkpoint blockade drugs improve the efficacy of cancer immunotherapy. This study focused specifically on ferroptosis genes to identify novel biomarkers that reflect prognosis in different renal cell carcinoma subtypes. LASSO algorithm and multivariate Cox regression were initiated for identifying ferroptosis-related multigene risk signature (FRGsig) and established a FRGsig score model. We used multiple tumor microenvironment gene signatures and methods to infer tumor microenvironment status and immune cell invasion levels. Our study found that high FRGsig score was associated with poor prognosis in patients with predominant histologic subtypes of renal cell carcinoma. And high FRGsig score samples had higher levels of anti-tumor immunity cells infiltration, and there was a feedback mechanism whereby anti-tumor inflammation promoted the recruitment or differentiation of immunosuppressive cells. FRGsig was a potential biomarker for predicting the response to immune checkpoint blockade therapy in kidney clear cell carcinoma and kidney papillary cell carcinoma, and the kidney papillary cell carcinoma patients with high FRGsig was associated with better response to anti-VEGF therapy. Our findings provided further insights into assessing immunotherapy sensitivity of predominant histologic subtypes of renal cell carcinoma. FRGsig might be a potential biomarker for predicting the efficacy of angiogenic blocking drugs or immune checkpoint inhibitors in different renal cell carcinoma subtypes, enabling more precise patient selection.

Mitoribosomal defects aggravate liver cancer via aberrant glycolytic flux and T cell exhaustion.

BACKGROUND: Mitochondria are involved in cancer energy metabolism, although the mechanisms underlying the involvement of mitoribosomal dysfunction in hepatocellular carcinoma (HCC) remain poorly understood. Here, we investigated the effects of mitoribosomal impairment-mediated alterations on the immunometabolic characteristics of liver cancer. METHODS: We used a mouse model of HCC, liver tissues from patients with HCC, and datasets from The Cancer Genome Atlas (TCGA) to elucidate the relationship between mitoribosomal proteins (MRPs) and HCC. In a mouse model, we selectively disrupted expression of the mitochondrial ribosomal protein CR6-interacting factor 1 (CRIF1) in hepatocytes to determine the impact of hepatocyte-specific impairment of mitoribosomal function on liver cancer progression. The metabolism and immunophenotype of liver cancer was assessed by glucose flux assays and flow cytometry, respectively. RESULTS: Single-cell RNA-seq analysis of tumor tissue and TCGA HCC transcriptome analysis identified mitochondrial defects associated with high-MRP expression and poor survival outcomes. In the mouse model, hepatocyte-specific disruption of the mitochondrial ribosomal protein CRIF1 revealed the impact of mitoribosomal dysfunction on liver cancer progression. Crif1 deficiency promoted programmed cell death protein 1 expression by immune cells in the hepatic tumor microenvironment. A [U-13C6]-glucose tracer demonstrated enhanced glucose entry into the tricarboxylic acid cycle and lactate production in mice with mitoribosomal defects during cancer progression. Mice with hepatic mitoribosomal defects also exhibited enhanced progression of liver cancer accompanied by highly exhausted tumor-infiltrating T cells. Crif1 deficiency induced an environment unfavorable to T cells, leading to exhaustion of T cells via elevation of reactive oxygen species and lactate production. CONCLUSIONS: Hepatic mitoribosomal defects promote glucose partitioning toward glycolytic flux and lactate synthesis, leading to T cell exhaustion and cancer progression. Overall, the results suggest a distinct role for mitoribosomes in regulating the immunometabolic microenvironment during HCC progression.

Skeletal muscle mitoribosomal defects are linked to low bone mass caused by bone marrow inflammation in male mice.

BACKGROUND: Mitochondrial oxidative phosphorylation (OxPhos) is a critical regulator of skeletal muscle mass and function. Although muscle atrophy due to mitochondrial dysfunction is closely associated with bone loss, the biological characteristics of the relationship between muscle and bone remain obscure. We showed that muscle atrophy caused by skeletal muscle-specific CR6-interacting factor 1 knockout (MKO) modulates the bone marrow (BM) inflammatory response, leading to low bone mass. METHODS: MKO mice with lower muscle OxPhos were fed a normal chow or high-fat diet and then evaluated for muscle mass and function, and bone mineral density. Immunophenotyping of BM immune cells was also performed. BM transcriptomic analysis was used to identify key factors regulating bone mass in MKO mice. To determine the effects of BM-derived CXCL12 (C-X-C motif chemokine ligand 12) on regulation of bone homeostasis, a variety of BM niche-resident cells were treated with recombinant CXCL12. Vastus lateralis muscle and BM immune cell samples from 14 patients with hip fracture were investigated to examine the association between muscle function and BM inflammation. RESULTS: MKO mice exhibited significant reductions in both muscle mass and expression of OxPhos subunits but increased transcription of mitochondrial stress response-related genes in the extensor digitorum longus (P < 0.01). MKO mice showed a decline in grip strength and a higher drop rate in the wire hanging test (P < 0.01). Micro-computed tomography and von Kossa staining revealed that MKO mice developed a low mass phenotype in cortical and trabecular bone (P < 0.01). Transcriptomic analysis of the BM revealed that mitochondrial stress responses in skeletal muscles induce an inflammatory response and adipogenesis in the BM and that the CXCL12-CXCR4 (C-X-C chemokine receptor 4) axis is important for T-cell homing to the BM. Antagonism of CXCR4 attenuated BM inflammation and increased bone mass in MKO mice. In humans, patients with low body mass index (BMI = 17.2 ± 0.42 kg/m2 ) harboured a larger population of proinflammatory and cytotoxic senescent T-cells in the BMI (P < 0.05) and showed reduced expression of OxPhos subunits in the vastus lateralis, compared with controls with a normal BMI (23.7 ± 0.88 kg/m2 ) (P < 0.01). CONCLUSIONS: Defects in muscle mitochondrial OxPhos promote BM inflammation in mice, leading to decreased bone mass. Muscle mitochondrial dysfunction is linked to BM inflammatory cytokine secretion via the CXCL12-CXCR4 signalling axis, which is critical for inducing low bone mass.

Metabolite Changes during the Transition from Hyperthyroidism to Euthyroidism in Patients with Graves' Disease.

BACKGRUOUND: An excess of thyroid hormones in Graves' disease (GD) has profound effects on systemic energy metabolism that are currently partially understood. In this study, we aimed to provide a comprehensive understanding of the metabolite changes that occur when patients with GD transition from hyperthyroidism to euthyroidism with methimazole treatment. METHODS: Eighteen patients (mean age, 38.6±14.7 years; 66.7% female) with newly diagnosed or relapsed GD attending the endocrinology outpatient clinics in a single institution were recruited between January 2019 and July 2020. All subjects were treated with methimazole to achieve euthyroidism. We explored metabolomics by performing liquid chromatography-mass spectrometry analysis of plasma samples of these patients and then performed multivariate statistical analysis of the metabolomics data. RESULTS: Two hundred metabolites were measured before and after 12 weeks of methimazole treatment in patients with GD. The levels of 61 metabolites, including palmitic acid (C16:0) and oleic acid (C18:1), were elevated in methimazole-naïve patients with GD, and these levels were decreased by methimazole treatment. The levels of another 15 metabolites, including glycine and creatinine, were increased after recovery of euthyroidism upon methimazole treatment in patients with GD. Pathway analysis of metabolomics data showed that hyperthyroidism was closely related to aminoacyl-transfer ribonucleic acid biosynthesis and branched-chain amino acid biosynthesis pathways. CONCLUSION: In this study, significant variations of plasma metabolomic patterns that occur during the transition from hyperthyroidism to euthyroidism were detected in patients with GD via untargeted metabolomics analysis.

Immunometabolic signatures predict recovery from thyrotoxic myopathy in patients with Graves' disease.

BACKGROUND: Thyroid hormone excess induces protein energy wasting, which in turn promotes muscle weakness and bone loss in patients with Graves' disease. Although most studies have confirmed a relationship between thyrotoxicosis and muscle dysfunction, few have measured changes in plasma metabolites and immune cells during the development and recovery from thyrotoxic myopathy. The aim of this study was to identify specific plasma metabolites and T-cell subsets that predict thyrotoxic myopathy recovery in patients with Graves' disease. METHODS: One hundred patients (mean age, 40.0 ± 14.2 years; 67.0% female), with newly diagnosed or relapsed Graves' disease were enrolled at the start of methimazole treatment. Handgrip strength and Five Times Sit to Stand Test performance time were measured at Weeks 0, 12, and 24. In an additional 35 patients (mean age, 38.9 ± 13.5 years; 65.7% female), plasma metabolites and immunophenotypes of peripheral blood were evaluated at Weeks 0 and 12, and the results of a short physical performance battery assessment were recorded at the same time. RESULTS: In both patient groups, methimazole-induced euthyroidism was associated with improved handgrip strength and lower limb muscle function at 12 weeks. Elevated plasma metabolites including acylcarnitines were restored to normal levels at Week 12 regardless of gender, body mass index, or age (P trend <0.01). Senescent CD8+ CD28- CD57+ T-cell levels in peripheral blood were positively correlated with acylcarnitine levels (P < 0.05) and decreased during thyrotoxicosis recovery (P < 0.05). High levels of senescent CD8+ T cells at Week 0 were significantly associated with small increases in handgrip strength after 12 weeks of methimazole treatment (P < 0.05), but not statistically associated with Five Times Sit to Stand Test performance. CONCLUSIONS: Restoring euthyroidism in Graves' disease patients was associated with improved skeletal muscle function and performance, while thyroid hormone-associated changes in plasma acylcarnitines levels correlated with muscle dysfunction recovery. T-cell senescence-related systemic inflammation correlated with plasma acylcarnitine levels and was also associated with small increases in handgrip strength.

Mitochondrial Metabolic Signatures in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide. HCC progression and metastasis are closely related to altered mitochondrial metabolism, including mitochondrial stress responses, metabolic reprogramming, and mitoribosomal defects. Mitochondrial oxidative phosphorylation (OXPHOS) defects and reactive oxygen species (ROS) production are attributed to mitochondrial dysfunction. In response to oxidative stress caused by increased ROS production, misfolded or unfolded proteins can accumulate in the mitochondrial matrix, leading to initiation of the mitochondrial unfolded protein response (UPRmt). The mitokines FGF21 and GDF15 are upregulated during UPRmt and their levels are positively correlated with liver cancer development, progression, and metastasis. In addition, mitoribosome biogenesis is important for the regulation of mitochondrial respiration, cell viability, and differentiation. Mitoribosomal defects cause OXPHOS impairment, mitochondrial dysfunction, and increased production of ROS, which are associated with HCC progression in mouse models and human HCC patients. In this paper, we focus on the role of mitochondrial metabolic signatures in the development and progression of HCC. Furthermore, we provide a comprehensive review of cell autonomous and cell non-autonomous mitochondrial stress responses during HCC progression and metastasis.

Interleukin-10 Attenuates Liver Fibrosis Exacerbated by Thermoneutrality.

Background: Crosstalk between brown adipose tissue (BAT) and the liver is receiving increasing attention. This study investigated the effect of BAT dysfunction by thermoneutral (TN) housing on liver fibrosis in mice and examined the effect of secreted factors from brown adipocytes on the activation of hepatic stellate cells (HSCs). Methods: The carbon tetrachloride (CCl4)-induced liver fibrosis mouse model was used to evaluate fibrotic changes in the livers of mice housed under standard and TN conditions. The effect of BAT on the activation of HSCs was examined using cultured cells treated with conditioned media from brown adipocytes. Results: Under TN conditions, mice with CCl4-induced liver fibrosis exhibited increased liver injury, collagen deposition, and alpha smooth muscle actin (α-SMA) expression in the liver compared with mice maintained at room temperature. The numbers of liver-infiltrating immune cells and T cells producing IL-17A and IFN-γ were also significantly increased in the livers of mice housed under TN conditions. Treatment of HSCs with conditioned media from brown adipocytes markedly attenuated HSC activation, as shown by down-regulated α-SMA expression at day 4, day 7 and day 10 of culture. At thermoneutrality, with CCl4 administration, IL-10-deficient mice exhibited more severe liver fibrosis than wild-type mice. Interestingly, conditioned media from IL-10-deficient brown adipocytes could up-regulate the expression of α-SMA and induce HSCs activation. Conclusions: BAT inactivation by thermoneutrality contributes to the activation of pro-inflammatory and pro-fibrotic pathways in mice with CCl4-induced liver fibrosis. Normal brown adipocytes secreted factors that impair the activation of HSCs, while this protective effect was lost in IL-10-deficient brown adipocytes. Thus, the BAT-liver axis may serve as a potential therapeutic target for liver fibrosis, and IL-10 may be a key factor regulating the activation of HSCs by BAT.

A universal managing circuit with stabilized voltage for maintaining safe operation of self-powered electronics system.

Harvesting mechanical energy via a triboelectric nanogenerator (TENG) is a promising strategy for solving energy problems. However, it is necessary to develop an effective and safe energy managing circuit for preventing high voltage breaking electronic devices. Here, a universal managing circuit is developed to optimize TENG's output performance, which for the first time allows the TENG to safely power various sensor systems with a safe and stable voltage. Based on the circuit, TENG's output can be transformed into a stable voltage with tunable amplitude, while an enhanced short-circuit current of 94 mA with an energy loss lower than 5% is achieved. For demonstrations, three different types of TENGs, respectively, targeting at ocean energy, wind energy, and walking energy have been prepared to reveal the capability of the circuit. This study offers a strategy to greatly enhance the output performance of TENGs to provide useful guidance for constructing self-powered and distributed sensor systems.

Self-Powered Room-Temperature Ethanol Sensor Based on Brush-Shaped Triboelectric Nanogenerator.

Highly sensitive ethanol sensors have been widely utilized in environmental protection, industrial monitoring, and drink-driving tests. In this work, a fully self-powered ethanol detector operating at room temperature has been developed based on a triboelectric nanogenerator (TENG). The gas-sensitive oxide semiconductor is selected as the sensory component for the ethanol detection, while the resistance change of the oxide semiconductor can well match the "linear" region of the load characteristic curve of TENG. Hence, the output signal of TENG can directly reveal the concentration change of ethanol gas. An accelerator gearbox is applied to support the operation of the TENG, and the concentration change of ethanol gas can be visualized on the Liquid Crystal Display. This fully self-powered ethanol detector has excellent durability, low fabrication cost, and high selectivity of 5 ppm. Therefore, the ethanol detector based on TENG not only provides a different approach for the gas detection but also further demonstrates the application potential of TENG for various sensory devices.

Self-powered electro-tactile system for virtual tactile experiences.

Tactile sensation plays important roles in virtual reality and augmented reality systems. Here, a self-powered, painless, and highly sensitive electro-tactile (ET) system for achieving virtual tactile experiences is proposed on the basis of triboelectric nanogenerator (TENG) and ET interface formed of ball-shaped electrode array. Electrostatic discharge triggered by TENG can induce notable ET stimulation, while controlled distance between the ET electrodes and human skin can regulate the induced discharge current. The ion bombardment technique has been used to enhance the electrification capability of triboelectric polymer. Accordingly, TENG with a contact area of 4 cm2 is capable of triggering discharge, leading to a compact system. In this skin-integrated ET interface, touching position and motion trace on the TENG surface can be precisely reproduced on skin. This TENG-based ET system can work for many fields, including virtual tactile displays, Braille instruction, intelligent protective suits, or even nerve stimulation.

Effect of Salivary Exosomal miR-25-3p on Periodontitis With Insulin Resistance.

Periodontitis is caused by an oral microbial dysbiosis-mediated imbalance of the local immune microenvironment, which is promoted by insulin resistance and obesity. The prevalence and severity of periodontitis is higher in patients with type 2 diabetes than in healthy individuals, possibly because of differences in immune responses. The level of glycemic control also affects the saliva profile, which may further promote periodontal disease in diabetes patients. Therefore, we compared the salivary exosomal miRNA profiles of patients with type 2 diabetes with those of healthy individuals, and we found that exosomal miR-25-3p in saliva is significantly enriched (by approximately 2-fold, p < 0.01) in obese patients with type 2 diabetes. We also identified CD69 mRNA as a miR-25-3p target that regulates both activation of γδ T cells and the inflammatory response. Knockdown of CD69 increased (by approximately 2-fold) interleukin-17A production of γδ T cells in vitro. To evaluate the role of exosomal miRNA on progression of periodontitis, we analyzed regional immune cells in both periodontal tissues and lymph nodes from mice with periodontitis. We found that diet-induced obesity increased the population of infiltrating pro-inflammatory immune cells in the gingiva and regional lymph nodes of these mice. Treatment with miR-25-3p inhibitors prevented the local in vivo inflammatory response in mice with periodontitis and diet-induced obesity. Finally, we showed that suppression of interleukin 17-mediated local inflammation by a miR-25-3p inhibitor alleviated (by approximately 34%) ligature-induced periodontal alveolar bone loss in mice. Taken together, these data suggest that exosomal miR-25-3p in saliva contributes to development and progression of diabetes-associated periodontitis. Discovery of additional miR-25-3p targets may provide critical insights into developing drugs to treat periodontitis by regulating γδ T cell-mediated local inflammation.

Contributions of Different Functional Groups to Contact Electrification of Polymers.

Polymers are commonly used to fabricate triboelectric nanogenerators (TENGs). Here, several polymer films with similar main chains but different functional groups on the side chain are employed to clarify the contributions of each functional group to contact electrification (CE). The results show that the electron-withdrawing (EW) ability and density of these functional groups on the main chain can determine both the polarity and density of CE-induced surface charges. Similar results are obtained for CE in both the polymer-polymer and polymer-liquid modes. A theoretical mechanism involving electron cloud overlap is proposed to explain all of these results. More importantly, the unsaturated groups on poly(tetrafluoroethylene) molecular chain are proved to have a much stronger EW ability than the saturated groups. The density of these unsaturated groups can be increased using a sputtering technique, suggesting that this is a facile and effective method of enhancing the performance of TENGs. These results clarify the correlation between the molecular structure and macroscopic electrification behavior of polymers.

Environmental energy harvesting based on triboelectric nanogenerators.

With the fast development of the Internet of Things, the energy supply for electronics and sensors has become a critical challenge. The triboelectric nanogenerator (TENG), which can transfer mechanical energy from the surrounding environment into electricity, has been recognized as the most promising alternative technology to remedy the shortcomings of traditional battery technology. Environmental mechanical energy widely exists in activities in nature and these environmental energy sources can enable TENGs to achieve a clean and distributed energy network, which can finally benefit the innovation of various wireless devices. In this review, TENGs targeting different environmental energy sources have been systematically summarized and analyzed. Firstly, we give a brief introduction to the basic principle and working modes of the TENG. Then, TENGs targeting different energy sources, from blowing wind and raindrops to pounding waves, noise signalling, and so on, are summarized based on their design concept and output performance. In addition, combined with other energy technologies such as solar cells, electromagnetic generators, and piezoelectric nanogenerators, the application of hybrid nanogenerators is elaborated under different scenarios. Finally, the challenges, limitations, and future research trends of environmental energy collection are outlined.

A BMSCs-laden quercetin/duck's feet collagen/hydroxyapatite sponge for enhanced bone regeneration.

Treating critical-sized bone defects is an important issue in the field of tissue engineering and bone regeneration. From the various biomaterials for bone regeneration, collagen is an important and widely used biomaterial in biomedical applications, hence, it has numerous attractive properties including biocompatibility, hyper elastic behavior, prominent mechanical properties, support cell adhesion, proliferation, and biodegradability. In the present study, collagen was extracted from duck's feet (DC) as a new collagen source and combined with quercetin (Qtn), a type of flavonoids found in apple and onions and has been reported to affect the bone metabolism, for increasing osteogenic differentiation. Further, improving osteoconductive properties of the scaffold hydroxyapatite (HAp) a biodegradable material was used. We prepared 0, 25, 50, and 100 µM Qtn/DC/HAp sponges using Qtn, DC, and HAp. Their physiochemical characteristics were evaluated using scanning electron microscopy, compressive strength, porosity, and Fourier transform infrared spectroscopy. To assess the effect of Qtn on osteogenic differentiation, we cultured bone marrow mesenchymal stem cells on the sponges and evaluated by alkaline phosphatase, 3-4-2, 5-diphenyl tetrazolium bromide assay, and real-time polymerase chain reaction. Additionally, they were studied implanting in rat, analyzed through Micro-CT and histological staining. From our in vitro and in vivo results, we found that Qtn has an effect on bone regeneration. Among the different experimental groups, 25 µM Qtn/DC/HAp sponge was found to be highly increased in cell proliferation and osteogenic differentiation compared with other groups. Therefore, 25 µM Qtn/DC/HAp sponge can be used as an alternative biomaterial for bone regeneration in critical situations.