Inducing trained immunity in pro-metastatic macrophages to control tumor metastasis.

Metastasis is the leading cause of cancer-related deaths and myeloid cells are critical in the metastatic microenvironment. Here, we explore the implications of reprogramming pre-metastatic niche myeloid cells by inducing trained immunity with whole beta-glucan particle (WGP). WGP-trained macrophages had increased responsiveness not only to lipopolysaccharide but also to tumor-derived factors. WGP in vivo treatment led to a trained immunity phenotype in lung interstitial macrophages, resulting in inhibition of tumor metastasis and survival prolongation in multiple mouse models of metastasis. WGP-induced trained immunity is mediated by the metabolite sphingosine-1-phosphate. Adoptive transfer of WGP-trained bone marrow-derived macrophages reduced tumor lung metastasis. Blockade of sphingosine-1-phosphate synthesis and mitochondrial fission abrogated WGP-induced trained immunity and its inhibition of lung metastases. WGP also induced trained immunity in human monocytes, resulting in antitumor activity. Our study identifies the metabolic sphingolipid-mitochondrial fission pathway for WGP-induced trained immunity and control over metastasis.

Outer Membrane Vesicles Released from Garlic Exosome-like Nanoparticles (GaELNs) Train Gut Bacteria that Reverses Type 2 Diabetes via the Gut-Brain Axis.

Gut microbiota function has numerous effects on humans and the diet humans consume has emerged as a pivotal determinant of gut microbiota function. Here, a new concept that gut microbiota can be trained by diet-derived exosome-like nanoparticles (ELNs) to release healthy outer membrane vesicles (OMVs) is introduced. Specifically, OMVs released from garlic ELN (GaELNs) trained human gut Akkermansia muciniphila (A. muciniphila) can reverse high-fat diet-induced type 2 diabetes (T2DM) in mice. Oral administration of OMVs released from GaELNs trained A. muciniphila can traffick to the brain where they are taken up by microglial cells, resulting in inhibition of high-fat diet-induced brain inflammation. GaELNs treatment increases the levels of OMV Amuc-1100, P9, and phosphatidylcholines. Increasing the levels of Amuc-1100 and P9 leads to increasing the GLP-1 plasma level. Increasing the levels of phosphatidylcholines is required for inhibition of cGas and STING-mediated inflammation and GLP-1R crosstalk with the insulin pathway that leads to increasing expression of Insulin Receptor Substrate (IRS1 and IRS2) on OMV targeted cells. These findings reveal a molecular mechanism whereby OMVs from plant nanoparticle-trained gut bacteria regulate genes expressed in the brain, and have implications for the treatment of brain dysfunction caused by a metabolic syndrome.

Probiotic-derived nanoparticles inhibit ALD through intestinal miR194 suppression and subsequent FXR activation.

BACKGROUND AND AIMS: Intestinal farnesoid X receptor (FXR) plays a critical role in alcohol-associated liver disease (ALD). We aimed to investigate whether alcohol-induced dysbiosis increased intestinal microRNA194 (miR194) that suppressed Fxr transcription and whether Lactobacillus rhamnosus GG-derived exosome-like nanoparticles (LDNPs) protected against ALD through regulation of intestinal miR194-FXR signaling in mice. APPROACH AND RESULTS: Binge-on-chronic alcohol exposure mouse model was utilized. In addition to the decreased ligand-mediated FXR activation, alcohol feeding repressed intestinal Fxr transcription and increased miR194 expression. This transcriptional suppression of Fxr by miR194 was confirmed in intestinal epithelial Caco-2 cells and mouse enteriods. The alcohol feeding-reduced intestinal FXR activation was further demonstrated by the reduced FXR reporter activity in fecal samples and by the decreased fibroblast growth factor 15 (Fgf15) messenger RNA (mRNA) in intestine and protein levels in the serum, which caused an increased hepatic bile acid synthesis and lipogeneses. We further demonstrated that alcohol feeding increased-miR194 expression was mediated by taurine-upregulated gene 1 (Tug1) through gut microbiota regulation of taurine metabolism. Importantly, 3-day oral administration of LDNPs increased bile salt hydrolase (BSH)-harboring bacteria that decreased conjugated bile acids and increased gut taurine concentration, which upregulated Tug1, leading to a suppression of intestinal miR194 expression and recovery of FXR activation. Activated FXR upregulated FGF15 signaling and subsequently reduced hepatic bile acid synthesis and lipogenesis and attenuated ALD. These protective effects of LDNPs were eliminated in intestinal FxrΔIEC and Fgf15-/- mice. We further showed that miR194 was upregulated, whereas BSH activity and taurine levels were decreased in fecal samples of patients with ALD. CONCLUSIONS: Our results demonstrated that gut microbiota-mediated miR194 regulation contributes to ALD pathogenesis and to the protective effects of LDNPs through modulating intestinal FXR signaling.

Exosome-like nanoparticles from Mulberry bark prevent DSS-induced colitis via the AhR/COPS8 pathway.

Bark protects the tree against environmental insults. Here, we analyzed whether this defensive strategy could be utilized to broadly enhance protection against colitis. As a proof of concept, we show that exosome-like nanoparticles (MBELNs) derived from edible mulberry bark confer protection against colitis in a mouse model by promoting heat shock protein family A (Hsp70) member 8 (HSPA8)-mediated activation of the AhR signaling pathway. Activation of this pathway in intestinal epithelial cells leads to the induction of COP9 Constitutive Photomorphogenic Homolog Subunit 8 (COPS8). Utilizing a gut epithelium-specific knockout of COPS8, we demonstrate that COPS8 acts downstream of the AhR pathway and is required for the protective effect of MBELNs by inducing an array of anti-microbial peptides. Our results indicate that MBELNs represent an undescribed mode of inter-kingdom communication in the mammalian intestine through an AhR-COPS8-mediated anti-inflammatory pathway. These data suggest that inflammatory pathways in a microbiota-enriched intestinal environment are regulated by COPS8 and that edible plant-derived ELNs may hold the potential as new agents for the prevention and treatment of gut-related inflammatory disease.

Association Between the Metabolic Score for Insulin Resistance and Hypertension in Adults: A Meta-Analysis.

The metabolic score for insulin resistance (METS-IR) is a recently developed parameter for screening of metabolic disorder. However, the association between METS-IR and risk of hypertension in general adult population remains not fully determined. A meta-analysis was therefore performed. Observational studies evaluating the association between METS-IR and hypertension in adults were retrieved by searching PubMed, Embase, and Web of Science databases from inception to October 10, 2022. A random-effects model, which incorporates the potential influence of heterogeneity, was used to pool the results. Eight studies with 305 341 adults were included in the meta-analysis, and 47 887 (15.7%) of them had hypertension. Pooled results showed that a higher METS-IR was associated with hypertension after adjusting for multiple conventional risk factors [relative risk (RR) for highest versus lowest category of METS-IR: 1.67, 95% confidence interval (CI): 1.53 to 1.83, p<0.001, I2=8%]. The results were consistent in subgroup analyses according to study design, source of the cohort, age, sex, body mass index of the participants, and quality scores of the study (p for subgroup difference all>0.05). Results of meta-analysis with METS-IR analyzed in continuous variables also showed that METS-IR was associated with the risk of hypertension (RR for 1-unit increment of METS-IR: 1.15, 95% CI: 1.08 to 1.23, p<0.001, I2=79%). In conclusion, a high METS-IR is associated with hypertension in general adult population. Measuring METS-IR may be useful for screening participants at high risk of hypertension.

The Prognostic Model Established by the Differential Expression Genes Based on CD8+ T Cells to Evaluate the Prognosis and the Response to Immunotherapy in Osteosarcoma.

Osteosarcoma (OS) is a malignant tumor with an extremely poor prognosis, especially in progressive patients. Immunotherapy based on immune checkpoint inhibitors (ICIs) is considered to be a promising treatment option for OS. Due to tumor heterogeneity, only a minority of patients benefit from immunotherapy. Therefore, it is urgent to explore a model that can accurately assess the response of OS to immunotherapy. In this study, we obtained the single-cell RNA sequencing datasets of OS patients from public databases and defined 34 cell clusters by dimensional reduction and clustering analysis. PTPRC was applied to identify immune cell clusters and nonimmune cell clusters. Next, we performed clustering analysis on the immune cell clusters and obtained 25 immune cell subclusters. Immune cells were labeled with CD8A and CD8B to obtain CD8+ T cell clusters. Meanwhile, we extracted the differentially expressed genes (DEGs) of CD8+ T cell clusters and other immune cell clusters. Furthermore, we constructed a prognostic model (CD8-DEG model) based on the obtained DEGs of CD8+ T cells, and verified the excellent predictive ability of this model for the prognosis of OS. Moreover, we further investigated the value of the CD8-DEG model. The results indicated that the risk score of the CD8-DEG model was an independent risk factor for OS patients. Finally, we revealed that the risk score of the CD8-DEG model correlates with the immune profile of OS and can be used to evaluate the response of OS to immunotherapy. In conclusion, our study revealed the critical role of CD8 cells in OS. The risk score model based on CD8-DEGs can provide guidance for prognosis and immunotherapy of OS.

Restoring Oat Nanoparticles Mediated Brain Memory Function of Mice Fed Alcohol by Sorting Inflammatory Dectin-1 Complex Into Microglial Exosomes.

Microglia modulate pro-inflammatory and neurotoxic activities. Edible plant-derived factors improve brain function. Current knowledge of the molecular interactions between edible plant-derived factors and the microglial cell is limited. Here an alcohol-induced chronic brain inflammation model is used to identify that the microglial cell is the novel target of oat nanoparticles (oatN). Oral administration of oatN inhibits brain inflammation and improves brain memory function of mice that are fed alcohol. Mechanistically, ethanol activates dectin-1 mediated inflammatory pathway. OatN is taken up by microglial cells via ß-glucan mediated binding to microglial hippocalcin (HPCA) whereas oatN digalactosyldiacylglycerol (DGDG) prevents assess of oatN ß-glucan to dectin-1. Subsequently endocytosed ß-glucan/HPCA is recruited in an endosomal recycling compartment (ERC) via interaction with Rab11a. This complex then sequesters the dectin-1 in the ERC in an oatN ß-glucan dependent manner and alters the location of dectin-1 from Golgi to early endosomes and lysosomes and increases exportation of dectin-1 into exosomes in an Rab11a dependent manner. Collectively, these cascading actions lead to preventing the activation of the alcoholic induced brain inflammation signing pathway(s). This coordinated assembling of the HPCA/Rab11a/dectin-1 complex by oral administration of oatN may contribute to the prevention of brain inflammation.

Plant-derived exosomal microRNAs inhibit lung inflammation induced by exosomes SARS-CoV-2 Nsp12.

Lung inflammation is a hallmark of coronavirus disease 2019 (COVID-19). In this study, we show that mice develop inflamed lung tissue after being administered exosomes released from the lung epithelial cells exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Nsp12 and Nsp13 (exosomesNsp12Nsp13). Mechanistically, we show that exosomesNsp12Nsp13 are taken up by lung macrophages, leading to activation of nuclear factor κB (NF-κB) and the subsequent induction of an array of inflammatory cytokines. Induction of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß from exosomesNsp12Nsp13-activated lung macrophages contributes to inducing apoptosis in lung epithelial cells. Induction of exosomesNsp12Nsp13-mediated lung inflammation was abolished with ginger exosome-like nanoparticle (GELN) microRNA (miRNA aly-miR396a-5p. The role of GELNs in inhibition of the SARS-CoV-2-induced cytopathic effect (CPE) was further demonstrated via GELN aly-miR396a-5p- and rlcv-miR-rL1-28-3p-mediated inhibition of expression of Nsp12 and spike genes, respectively. Taken together, our results reveal exosomesNsp12Nsp13 as potentially important contributors to the development of lung inflammation, and GELNs are a potential therapeutic agent to treat COVID-19.

microRNA-200c-3p suppresses proliferation and invasion of nephroblastoma cells by targeting EP300 and inactivating the AKT/FOXO1/p27 pathway.

miR-200c-3p is aberrantly expressed in numerous cancers, but its underlying mechanisms in nephroblastoma are unknown. In our study, the differentially regulated miRNAs between the nephroblastoma tissues and adjacent non-neoplastic renal tissues were screened based on microarray analysis. The miR-200c-3p expression in nephroblastoma tissues and cells was detected by qRT-PCR. Then, the effects of miR-200c-3p mimic or inhibitor on cell proliferation, invasion, and migration were evaluated by CCK-8 assay, plate colony formation assay, soft agar assay, Transwell, and wound-healing assay in SK-NEP-1 and G401 cells. Afterward, the target gene of miR-200c-3p was predicted by TarBase, miRTarBase, miRDB softwares, and then verified by dual-luciferase reporter gene assay. The in vivo effects of miR-200c-3p on pathological changes and tumor volume were investigated in tumor xenograft mice by H&E staining and in vivo fluorescence imaging. ChIP assay was used to evaluate the relationship between histone acetyltransferase E1A-binding protein p300 (EP300) and P27, and the relationship of the role of miR-200c-3p in nephroblastoma and the AKT/FOXO1/p27 signaling pathways was evaluated by western blotting. Our study shows that miR-200c-3p was downregulated in nephroblastoma tissues and cells, and EP300 was a target gene of miR-200c-3p. Furthermore, miR-200c-3p mimic decreased cell proliferation and inhibited cell migration and invasion in nephroblastoma. Mechanistically, miR-200c-3p could inhibit p-AKT activity and enhance p-FOXO1 and p27 expression. Notably, the transcription factor P27 could bind to the EP300 promoter. This study demonstrates a new approach to treat nephroblastoma.

The prevalence, antibiotic resistance and multilocus sequence typing of colistin-resistant bacteria isolated from Penaeus vannamei farms in earthen ponds and HDPE film-lined ponds in China.

The aquaculture environment, especially the culture ponds and aquaculture products, is considered to be an important reservoir of colistin resistance genes. However, systematic investigations of colistin resistance in Penaeus vannamei farming in different culture modes are scarce. In this study, a total of 93 non-duplicated samples were collected from P. vannamei farms in five cities in China from 2019 to 2021. The prevalence, antibiotic resistance and multilocus sequence typing (MLST) of colistin-resistant bacteria were measured and analysed. The results showed that among the 1601 isolates in P. vannamei and its environmental samples, the pollution of colistin-resistant bacteria was serious (the overall prevalence was 37.3% and 28.8%, respectively), regardless of the earthen pond or high-density polyethylene (HDPE) film-lined pond. Among 533 isolates, the prevalence of mobile colistin resistance (mcr) genes, mcr-1, was the highest (60%, 320/533), followed by mcr-4 (1.5%, 8/533), mcr-8 (0.9%, 5/533), mcr-10 (0.6%, 3/533) and mcr-7 (0.4%, 2/533). The prevalence of mcr-1 in earthen ponds was significantly higher than that in HDPE film-lined ponds (67.5% vs. 49.1%, p < .001). The dominant strain carrying mcr-1 was Bacillus spp. (54.1%, 173/320), followed by Enterobacter spp. (8.1%, 26/320), Staphylococcus spp. (6.3%, 20/320) and Aeromonas spp. (5.3%, 17/320). The antibiotic resistance profiles of 173 Bacillus spp. varied among different sampling locations and culture types. These isolates were highly resistant to cefepime, ceftriaxone, trimethoprim-sulfamethoxazole and ceftiofur (>45%), and multidrug-resistant isolates were common (62.4%, 108/173). Sequence type (ST) 26 (37/66, 56%) was found to be the most prevalent ST in mcr-1-positive Bacillus cereus isolated from the aquaculture environment. In summary, our study pointed out that it is necessary to continuously monitor antibiotic usage and its residues regardless of the pond types, especially with regard to critical drugs such as colistin.

Duplex droplet digital PCR method for the detection of Enterocytozoon hepatopenaei and Vibrio parahaemolyticus acute hepatopancreatic necrosis disease.

Enterocytozoon hepatopenaei (EHP) and Vibrio parahaemolyticus acute hepatopancreatic necrosis disease (VPAHPND) are two of the diseases that have frequently infected farmed shrimp in recent years, causing great economic losses to the shrimp industry worldwide. In this study, we established a sensitive and accurate duplex droplet digital PCR (ddPCR) method that can simultaneously detect and quantify the two pathogens simultaneously. The results showed that the ddPCR methods could detect EHP and VPAHPND specifically. The sensitivity levels of ddPCR for EHP and VPAHPND were 2.3 copies/µl and 4.6 copies/µl, respectively, which were 10-fold higher than the sensitivity of the qPCR assay and showed good reproducibility. Twenty-six suspected diseased shrimp samples were used for practical determination. For EHP, the detection rates of ddPCR and qPCR were 53.84% and 42.31%, respectively; for VPAHPND, the detection rates of ddPCR and qPCR were both 23.08%. The results indicated that the ddPCR method shows superiority for detection in samples with low viral loads, which will facilitate monitoring of the source and transmission of EHP and VPAHPND and will help control shrimp epidemic disease.

HSP90AA1 promotes the inflammation in human gingival fibroblasts induced by Porphyromonas gingivalis lipopolysaccharide via regulating of autophagy.

BACKGROUND: Peri-implantitis of tooth seriously affects the life quality of patients. This study aimed to investigate the role of HSP90AA1 in the inflammatory of human gingival fibroblasts (HGFs) induced by porphyromonas gingivalis lipopolysaccharide (Pg-LPS), and to provide a potential therapeutic target for clinical treatment of peri-implantitis. METHODS: Pg-LPS (0.1, 1, 10 µg/mL) was used to construct the inflammatory model of HGFs to evaluate the effect of Pg-LPS on HGFs. Then HSP90AA1-siRNA was transfected to construct HSP90AA1 low expression HGFs cell line, and 3-MA was also added. After that, cell viability, apoptosis, the contents of inflammatory cytokines were detected by CCK-8, flow cytometry and ELISA assay, respectively. Intracellular ROS, the expressions of HSP90α, HSP90ß were detected by immunofluorescence. The levels of HSP90AA1, p-NF-κB p65/NF-κB p65, LC3 II/I, ATG5, Beclin-1 and TLR protein were detected by western blot. RESULTS: Pg-LPS treatment didn't affect the viability of HGFs cells, but induced the cell apoptosis and ROS generation, increased the contents of IL-1ß, IL-6, TNF-α, and the protein expressions of HSP90AA1, p-NF-κBp65/NF-κBp65, LC3II/I, ATG5, and Beclin-1 in HGFs. While HSP90AA1-siRNA transfected into Pg-LPS induced HGFs significantly reduced the HSP90AA1, HSP90α, HSP90ß expression, decreased the inflammatory factors, ROS generation, cell apoptosis rate, and autophagy-related proteins and TLR2/4 protein levels. What's more, the addition of autophagy inhibitor 3-MA further promote the effect of HSP90AA1-siRNA on Pg-LPS treated HGFs. CONCLUSIONS: This study showed that HSP90AA1 promoted the inflammatory response of Pg-LPS induced HGFs by regulating autophagy. The addition of 3-MA further confirmed that autophagy may mediate siHSP90AA1 to enhance the inflammatory response.

Is Biportal Endoscopic Spine Surgery More Advantageous Than Uniportal for the Treatment of Lumbar Degenerative Disease? A Meta-Analysis.

Background and Objectives: To estimate the clinical outcomes of uniportal and biportal full-endoscopic spine surgery for the treatment of lumbar degenerative disease (LDD), and to provide the latest evidence for clinical selection. Materials and Methods: Relevant literatures published in PubMed, Web of Science, Embase, CNKI, and WanFang Database before 21 November 2021 were searched systematically. Two researchers independently screened the studies, extracted data, and evaluated the risk of bias of the included studies. The systematic review and meta-analysis were performed using the Review Manager software (version 5.4; The Cochrane Collaboration). Results: A total of seven studies were included in this meta-analysis, including 198 patients in a uniportal endoscopy group and 185 patients in a biportal endoscopy group. The results of this meta-analysis demonstrated that the biportal endoscopy group experienced less intraoperative estimated blood loss (WMD = -2.54, 95%CI [-4.48, -0.60], p = 0.01), while the uniportal endoscopy group displayed significantly better recovery results in Visual Analog Scale (VAS) assessments of the back within 3 days of surgery (WMD = 0.69, 95%CI [0.02, 1.37], p = 0.04). However, no significant differences in operation time, length of hospital stay, complication rates, Oswestry Disability Index (ODI) (within 3 months), ODI (last follow-up), VAS for back (within 3 months), VAS for back (last follow-up), and VAS for leg (within 3 days, within 3 months, last follow-up) were identified between the two groups. Conclusions: According to our meta-analysis, patients who underwent the uniportal endoscopic procedure had more significant early postoperative back pain relief than those who underwent the biportal endoscopic procedure. Nevertheless, both surgical techniques are safe and effective.

Tumor Microenvironment Modulates Immunological Outcomes of Myeloid Cells with mTORC1 Disruption.

The role of the mTOR signaling pathway in different myeloid cell subsets is poorly understood in the context of tumor development. In this study, myeloid cell-specific Raptor knockout (KO) mice were used to determine the roles of mechanistic target of rapamycin complex 1 (mTORC1) in regulating macrophage function from Lewis lung carcinoma (LLC) s.c. tumors and lung tumor metastasis. We found no difference in tumor growth between conditional Raptor KO and control mice in the s.c. tumor models, although depletion of mTORC1 decreased the immunosuppressive function of tumor-associated macrophages (TAM). Despite the decreased immunosuppressive activity of TAM, M1-like TAM differentiation was impaired in the s.c. tumor microenvironment of mTORC1 conditional Raptor KO mice due to downregulated CD115 expression on macrophages. In addition, TNF-α production by mTORC1-deficient myeloid cells was also decreased in the s.c. LLC tumors. On the contrary, disruption of mTORC1 in myeloid cells promoted lung cancer metastasis. Accordingly, immunosuppressive interstitial macrophages/metastasis-associated macrophages (CD11b+F4/80high) were accumulated in the lungs of Raptor KO mice in the LLC lung metastasis model, leading to decreased Th1 responses. Taken together, our results demonstrate that differential tumor microenvironment dictates the immunological outcomes of myeloid cells, with mTORC1 disruption leading to different tumor growth phenotypes.

Development and comparison of qPCR and qLAMP for rapid detection of the decapod iridescent virus 1 (DIV1).

Decapod iridescent virus 1 (DIV1) is a new virus discovered in recent years that infects farmed shrimp. DIV1 is highly infectious and causes substantial economic loss to the aquaculture industry of China. To prevent and control the spread and outbreak of DIV1 in a timely manner, it is necessary to establish an efficient method for DIV1 diagnosis. In this study, quantitative real-time polymerase chain reaction (qPCR) and quantitative real-time loop-mediated isothermal amplification (qLAMP) detection methods were established based on the specific sequence of the viral ATPase gene. The results indicated that the minimum detection limits of qPCR and qLAMP were 1.9 × 101 copies/µL and 1.9 × 102 copies/µL, respectively; the designed primer had good specificity for DIV1 and did not react with 13 other viruses, including white spot syndrome virus (WSSV), Enterocytozoon hepatopenaei (EHP), acute hepatopancreatic necrosis disease (AHPND), infectious hypodermal and haematopoietic necrosis virus (IHHNV), etc. A total of 43 clinical samples suspected of DIV1 infection were diagnosed by qPCR and qLAMP. Our qPCR demonstrated results consistent with a qPCR assay published previously, and the diagnostic sensitivity (DSe) and diagnostic specificity (DSp) of qLAMP were 85.71% and 100%, respectively. This result indicates that qPCR and qLAMP have good accuracy in the detection of DIVI in clinical samples. As established in this study, qPCR and qLAMP combined with a comprehensive comparative analysis can provide effective new solutions for the detection of DIV1.

Effects of milling methods on the properties of glutinous rice flour and sweet dumplings.

Glutinous rice flour (GRF) was prepared using three milling process (wet milling, low temperature impact milling (dry milling), and roller milling (dry milling)) to investigate their effects on the physicochemical properties of glutinous rice flour and sweet dumplings prepared with that flour. Results revealed that a method of grinding used in the milling process had a significant (P < 0.05) effect on the properties of GRF and the resulting sweet dumplings. Dry milling (low temperature impact milling and roller milling) resulted in higher damaged starch content and coarser particle size than wet milling. Dry-milled flour exhibited a significantly lower hunter whiter value, apparent viscosity, pasting temperature, enthalpy value, and degree of crystalline compared to the wet-milling method. Dry milling significantly decreased the smoothness of the surface, whiteness value, transmittance of soup, resilience of dumplings, as well as increased the cracking rate and water loss during the fast-freeze. The obtained results could be used as reference for improving sweet dumpling made from dry-milled GRF.

Challenges and Strategies for High-Energy Aqueous Electrolyte Rechargeable Batteries.

Aqueous rechargeable batteries are becoming increasingly important to the development of renewable energy sources, because they promise to meet cost-efficiency, energy and power demands for stationary applications. Over the past decade, efforts have been devoted to the improvement of electrode materials and their use in combination with highly concentrated aqueous electrolytes. Here the latest ground-breaking advances in using such electrolytes to construct aqueous battery systems efficiently storing electrical energy, i.e., offering improved energy density, cyclability and safety, are highlighted. This Review aims to timely provide a summary of the strategies proposed so far to overcome the still existing hurdles limiting the present aqueous batteries technologies employing concentrated electrolytes. Emphasis is placed on aqueous batteries for lithium and post-lithium chemistries, with potentially improved energy density, resulting from the unique advantages of concentrated electrolytes.

Universal and Naked-Eye Gene Detection Platform Based on the Clustered Regularly Interspaced Short Palindromic Repeats/Cas12a/13a System.

Gold-nanoparticles-based colorimetric assay is an attractive detection format, but is limited by the tedious and ineffective posthybridization manipulations for genomic analysis. Here, we present a new design for a colorimetric gene-sensing platform based on the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system. In this strategy, programmable recognition of DNA by Cas12a/crRNA and RNA by Cas13a/crRNA with a complementary target activates the trans-ssDNA or -ssRNA cleavage. Target-induced trans-ssDNA or ssRNA cleavage triggers an aggregation behavior change for the designed AuNPs-DNA probes pair, enabling the completion of naked-eye gene detection (transgenic rice, African swine fever virus, and miRNAs as the models) within 1 h. This platform is also showing promise as a fast and inexpensive tool for bacteria identification using 16S rDNA or 16S rRNA. A CRISPR/Cas-based colorimetric platform shows superior characteristics, such as probe universality, compatibility with isothermal reaction conditions, on-site detection capability, and high sensitivity, thus, demonstrating its use as a robust next-generation gene detection platform.

Pivotal role of dermal IL-17-producing γδ T cells in skin inflammation.

Interleukin-23 (IL-23) and CD4(+) T helper 17 (Th17) cells are thought to be critical in psoriasis pathogenesis. Here, we report that IL-23 predominantly stimulated dermal γδ T cells to produce IL-17 that led to disease progression. Dermal γδ T cells constitutively expressed the IL-23 receptor (IL-23R) and transcriptional factor RORγt. IL-17 production from dermal γδ T cells was independent of αß T cells. The epidermal hyperplasia and inflammation induced by IL-23 were significantly decreased in T cell receptor δ-deficient (Tcrd(-/-)) and IL-17 receptor-deficient (Il17ra(-/-)) mice but occurred normally in Tcra(-/-) mice. Imiquimod-induced skin pathology was also significantly decreased in Tcrd(-/-) mice. Perhaps further promoting disease progression, IL-23 stimulated dermal γδ T cell expansion. In psoriasis patients, γδ T cells were greatly increased in affected skin and produced large amounts of IL-17. Thus, IL-23-responsive dermal γδ T cells are the major IL-17 producers in the skin and may represent a novel target for the treatment of psoriasis.

Determination of bioactive compounds in the nonmedicinal parts of Scrophularia ningpoensis using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry and chemometric analysis.

Although Scrophulariae Radix (root of Scrophularia ningpoensis) has received much attention, little is known about the nonmedicinal parts of S. ningpoensis. A comprehensive evaluation of the multibioactive constituents in the flowers, rhizomes, leaves, and stems of S. ningpoensis during different growth stages would be of value to fully understand the potential medicinal properties of all parts of the plant. Ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry was performed for accurately determining nine compounds in S. ningpoensis. The results indicated the content of total analytes in S. ningpoensis was in the order of flowers (81.82 mg/g) > roots (31.95 mg/g) > rhizomes (26.68 mg/g) > leaves (16.86 mg/g) > stems (14.35 mg/g). The chemometric analysis showed that these plant parts were rich in iridoids and should not be discarded during the processing of medicinal materials. Dynamic accumulation analysis suggested that the early flowering stage was the optimum time for harvesting flowers and appropriate amounts of stems and leaves. Moreover, considering the accumulation of constituents and biomass of medicinal materials, the medicinal parts should be harvested around December with the rhizomes attached. This research provides a theoretical basis and scientific evidence for comprehensive development and utilization of S. ningpoensis resources.