Cannabinoid receptor 2 selective agonist alleviates systemic sclerosis by inhibiting Th2 differentiation through JAK/SOCS3 signaling.

Systemic sclerosis (SSc) poses a significant challenge in autoimmunology, characterized by the development of debilitating fibrosis of skin and internal organs. The pivotal role of dysregulated T cells, notably the skewed polarization toward Th2 cells, has been implicated in the vascular damage and progressive fibrosis observed in SSc. In this study, we explored the underlying mechanisms by which cannabinoid receptor 2 (CB2) highly selective agonist HU-308 restores the imbalance of T cells to alleviate SSc. Using a bleomycin-induced SSc (BLM-SSc) mouse model, we demonstrated that HU-308 effectively attenuates skin and lung fibrosis by specifically activating CB2 on CD4+ T cells to inhibit the polarization of Th2 cells in BLM-SSc mice, which was validated by Cnr2-specific-deficient mice. Different from classical signaling downstream of G protein-coupled receptors (GPCRs), HU-308 facilitates the expression of SOCS3 protein and subsequently impedes the IL2/STAT5 signaling pathway during Th2 differentiation. The deficiency of SOCS3 partially mitigated the impact of HU-308. Analysis of a cohort comprising 80 SSc patients and 82 healthy controls revealed an abnormal elevation in the Th2/Th1 ratio in SSc patients. The proportion of Th2 cells showed a significant positive correlation with mRSS score and positivity of anti-Scl-70. Administration of HU-308 to PBMCs and peripheral CD4+ T cells from SSc patients led to the upregulation of SOCS3, which effectively suppressed the aberrantly activated STAT5 signaling pathway and the proportion of CD4+IL4+ T cells. In conclusion, our findings unveil a novel mechanism by which the CB2 agonist HU-308 ameliorates fibrosis in SSc by targeting and reducing Th2 responses. These insights provide a foundation for future therapeutic approaches in SSc by modulating Th2 responses.

FBXO38 mediates PD-1 ubiquitination and regulates anti-tumour immunity of T cells.

Dysfunctional T cells in the tumour microenvironment have abnormally high expression of PD-1 and antibody inhibitors against PD-1 or its ligand (PD-L1) have become commonly used drugs to treat various types of cancer1-4. The clinical success of these inhibitors highlights the need to study the mechanisms by which PD-1 is regulated. Here we report a mechanism of PD-1 degradation and the importance of this mechanism in anti-tumour immunity in preclinical models. We show that surface PD-1 undergoes internalization, subsequent ubiquitination and proteasome degradation in activated T cells. FBXO38 is an E3 ligase of PD-1 that mediates Lys48-linked poly-ubiquitination and subsequent proteasome degradation. Conditional knockout of Fbxo38 in T cells did not affect T cell receptor and CD28 signalling, but led to faster tumour progression in mice owing to higher levels of PD-1 in tumour-infiltrating T cells. Anti-PD-1 therapy normalized the effect of FBXO38 deficiency on tumour growth in mice, which suggests that PD-1 is the primary target of FBXO38 in T cells. In human tumour tissues and a mouse cancer model, transcriptional levels of FBXO38 and Fbxo38, respectively, were downregulated in tumour-infiltrating T cells. However, IL-2 therapy rescued Fbxo38 transcription and therefore downregulated PD-1 levels in PD-1+ T cells in mice. These data indicate that FBXO38 regulates PD-1 expression and highlight an alternative method to block the PD-1 pathway.

A comparative study to investigate the individual contribution of metabolic and physical interaction on volatiles formation in the mixed fermentation of Torulaspora delbrueckii and Saccharomyces cerevisiae.

It is well-known that the co-inoculation of Saccharomyces cerevisiae and non-Saccharomyces strains can modulate and improve the aromatic quality of wine through their multi-level interactions. However, the individual contribution of metabolic interaction (MI) and physical interaction (PI) on wine volatiles remains poorly understood. In this work, we utilized a double-compartment bioreactor to examine the aromatic effect of MI and PI by comparing the volatiles production in Torulaspora delbrueckii and Saccharomyces cerevisiae single fermentations to their mixed fermentations with or without physical separation. Results showed that the PI between T. delbrueckii and S. cerevisiae increased the production of most aroma compounds, especially for acetate esters and volatile fatty acids. In comparison, the MI only promoted a few volatile compounds, including ethyl decanoate, isoamyl acetate, and isobutanol. Noticeably, the MI significantly decreased the levels of ethyl dodecanoate, 2-phenylethyl alcohol, and decanoic acid, which exhibited opposite profiles in PI. Our results indicated that the PI was mainly responsible for the improved volatiles in T. delbrueckii/S. cerevisiae mixed fermentation, while the MI can be targeted to modulate the specific aroma compounds. A thorough understanding of the PI and MI aromatic effect will empower winemakers to accurately and directionally control the volatile profile of the wine, promoting the application of multi-starters to produce diverse styles of wines.

A mutant GH3 family ß-glucosidase from Oenococcus oeni exhibits superior adaptation to wine stresses and potential for improving wine aroma and phenolic profiles.

In this study, we conducted a comprehensive investigation into a GH3 family ß-glucosidase (BGL) from the wild-type strain of Oenococcus oeni and its mutated counterpart from the acid-tolerant mutant strain. Our analysis revealed the mutant BGL's remarkable capacity to adapt to wine-related stress conditions, including heightened tolerance to low pH, elevated ethanol concentrations, and metal ions. Additionally, the mutant BGL exhibited superior hydrolytic activity towards various substrates. Through de novo modeling, we identified specific amino acid mutations responsible for its resilience to low pH and high ethanol environments. In simulated wine conditions, the mutant BGL outperformed both wild-type and commercial BGLs, efficiently releasing terpene and phenolic aglycones from glycosides in wine grapes. These findings not only expand our understanding of O. oeni BGLs but also highlight their potential in enhancing wine production. The mutant BGL's enhanced adaptation to wine stress conditions opens promising avenue for improving wine quality and flavor.

Potentiating the antitumour response of CD8(+) T cells by modulating cholesterol metabolism.

CD8(+) T cells have a central role in antitumour immunity, but their activity is suppressed in the tumour microenvironment. Reactivating the cytotoxicity of CD8(+) T cells is of great clinical interest in cancer immunotherapy. Here we report a new mechanism by which the antitumour response of mouse CD8(+) T cells can be potentiated by modulating cholesterol metabolism. Inhibiting cholesterol esterification in T cells by genetic ablation or pharmacological inhibition of ACAT1, a key cholesterol esterification enzyme, led to potentiated effector function and enhanced proliferation of CD8(+) but not CD4(+) T cells. This is due to the increase in the plasma membrane cholesterol level of CD8(+) T cells, which causes enhanced T-cell receptor clustering and signalling as well as more efficient formation of the immunological synapse. ACAT1-deficient CD8(+) T cells were better than wild-type CD8(+) T cells at controlling melanoma growth and metastasis in mice. We used the ACAT inhibitor avasimibe, which was previously tested in clinical trials for treating atherosclerosis and showed a good human safety profile, to treat melanoma in mice and observed a good antitumour effect. A combined therapy of avasimibe plus an anti-PD-1 antibody showed better efficacy than monotherapies in controlling tumour progression. ACAT1, an established target for atherosclerosis, is therefore also a potential target for cancer immunotherapy.

Ultrasensitive and Specific Detection of Anticancer Drug 5-Fluorouracil in Blood Samples by a Surface-Enhanced Raman Scattering (SERS)-Based Lateral Flow Immunochromatographic Assay.

5-Fluorouracil (5-FU) is an effective anticancer drug widely used in the world. To improve therapy efficiency and reduce side effects, it is very important to frequently detect the concentration of 5-FU in blood samples of patients. In this work, a new type of lateral flow immunochromatographic assay (LFIA) based on surface-enhanced Raman scattering (SERS) for ultrasensitive and specific detection of 5-FU in blood samples was developed. Au@Ag/Au nanoparticles (NPs) employing Au particles as the core and Ag/Au alloy as the shell were synthesized, characterized and used as the substrate in SERS-LFIA due to their high SERS enhancement and biocompatibility. The immunoprobe was made in the form of AuMBA@Ag/Au-Ab in which mercaptobenzoic acid (MBA, a common Raman active reporter) was embedded in the core-shell layer and the monoclonal antibody (mAb) against 5-FU was immobilized on the surface. The performance of SERS-LFIA was similar to that in colloidal gold based-LFIA, and the entire assay time was within 20 min. According to the color intensity on the testing (T) lines of LFIA strips visualized by eyes, the contents of 5-FU in the samples could be qualitatively or semi-quantitatively identified. Furthermore, by measuring the characteristic Raman intensities of MBA on T lines, quantitative detection of 5-FU in the samples were achieved. The IC50 and limit of detection (LOD) of the LFIA for 5-FU were found to be 20.9 pg mL-1 and 4.4 pg mL-1, respectively. There was no cross-reactivity (CR) of the LFIA with nine relative compounds, and the CR with cytosine, tegafur and carmofur were less than 4.5%. The recoveries of 5-FU from spiked blood samples were in the range of 78.6~86.4% with the relative standard deviation (RSD) of 2.69~4.42%. Five blood samples containing 5-FU collected from the Cancer Hospital were measured by SERS-LFIA, and the results were confirmed by LC-MS/MS. It was proven that the proposed method was able to simply and rapidly detect 5-FU in blood samples with high sensitivity, specificity, accuracy and precision.

High-affinity neoantigens correlate with better prognosis and trigger potent antihepatocellular carcinoma (HCC) activity by activating CD39+CD8+ T cells.

OBJECTIVE: It remains controversial whether tumour mutational burden (TMB) or neoantigens are prognostic markers in hepatocellular carcinoma (HCC). This study aimed to define the function of TMB or neoantigens in antitumour immunotherapy. DESIGN: Neoantigens of patients (n=56) were analysed by pVAC tools with major histocompatibility complex-1 (MHC-I) algorithms based on whole exome sequencing and neoantigens with mutant type IC50 <50 nM were defined as high-affinity neoantigens (HANs). Patients were segregated into HAN-high/low groups by median of HAN value, and overall survival (OS) was analysed. Autologous organoid killing model was developed to clarify the antitumour activity of HANs. RESULTS: The value of HAN showed a better correlation with OS (p=0.0199) than TMB (p=0.7505) or neoantigens (p=0.2297) in patients with HCC and positively correlated with the frequency of CD39+CD8+ tumour infiltrating lymphocytes (TILs). Furthermore, HAN-specific CD8+ T cells were identified in CD39+CD8+ TILs, which showed better antitumour activity in HAN-high versus HAN-low group. In addition, more effective HAN peptides were identified in HAN-high versus HAN-low group. Besides, flow cytometry data showed that in fresh tumour, CD39+PD-1intCD8+ TILs displayed an effector phenotype and stronger antitumour activity in HAN-high versus HAN-low group. More importantly, patients in HAN-high versus HAN-low group showed a better prognosis after anti-PD-1 therapy. CONCLUSIONS: Our study first demonstrates that HAN value positively correlates with better OS in patients with HCC. HANs trigger antitumour activity by activating tumour-reactive CD39+CD8+ T cells, and patients in HAN-high group benefited more from anti-PD-1 therapy than HAN-low group. These findings may provide a novel strategy for personalised antitumour therapies for HCC.

Chimeric antigen receptor-modified T-cell therapy for platelet-derived growth factor receptor α-positive rhabdomyosarcoma.

BACKGROUND: New immunotherapeutic approaches are urgently needed for metastatic rhabdomyosarcoma, which is associated with poor survival and unsatisfactory treatment outcomes. Platelet-derived growth factor receptor α (PDGFRA) plays an essential role in the onset and development of rhabdomyosarcoma and is a new potential therapeutic target for rhabdomyosarcoma. The objective of this study was to generate humanized PDGFRA single-chain variable fragment-based chimeric antigen receptor (CAR)-modified T cells (CAR-T cells) against PDGFRA-positive rhabdomyosarcoma. METHODS: PDGFRA antigen expression was evaluated in specimens from patients with rhabdomyosarcoma. CAR-T cells containing a PDGFRA-specific single-chain variable fragment was developed in combination with a 4-1BB costimulatory domain and a CD3-ζ signaling domain. Specific cytotoxic effects of PDGFRA CAR-T cells, T-cell proliferation, and cytokine secretion were investigated in vitro and in vivo. RESULTS: PDGFRA CAR-T cells produced large amounts of immune-promoting cytokines, including interleukin 2, tumor necrosis factor α, and interferon γ, and exhibited efficient cytotoxic activity toward human PDGFRA-overexpressing rhabdomyosarcoma cells in vitro. In a subcutaneous xenograft model, CAR-T cells were more effective against PDGFRA-overexpressing rhabdomyosarcoma than against rhabdomyosarcoma with low PDGFRA expression in terms of tumor regression and patient survival. Expanded CAR-T cells also were detected in peripheral blood. CONCLUSIONS: The current study demonstrates for the first time that the PDGFRA antigen is a promising target for CAR-T-cell therapy in rhabdomyosarcoma and likely in a wide spectrum of other PDGFRA-expressing cancers.

In vivo discovery of immunotherapy targets in the tumour microenvironment.

Recent clinical trials showed that targeting of inhibitory receptors on T cells induces durable responses in a subset of cancer patients, despite advanced disease. However, the regulatory switches controlling T-cell function in immunosuppressive tumours are not well understood. Here we show that such inhibitory mechanisms can be systematically discovered in the tumour microenvironment. We devised an in vivo pooled short hairpin RNA (shRNA) screen in which shRNAs targeting negative regulators became highly enriched in murine tumours by releasing a block on T-cell proliferation upon tumour antigen recognition. Such shRNAs were identified by deep sequencing of the shRNA cassette from T cells infiltrating tumour or control tissues. One of the target genes was Ppp2r2d, a regulatory subunit of the PP2A phosphatase family. In tumours, Ppp2r2d knockdown inhibited T-cell apoptosis and enhanced T-cell proliferation as well as cytokine production. Key regulators of immune function can therefore be discovered in relevant tissue microenvironments.

Effects of oral selenium and magnesium co-supplementation on lipid metabolism, antioxidative status, histopathological lesions, and related gene expression in rats fed a high-fat diet.

BACKGROUND: Supplementation with Selenium (Se) has been shown to lower blood cholesterol and increase tissue concentrations of the antioxidant glutathione (GSH); however, the effects of Se supplementation, in combination with supplemental magnesium, on high fat-induced hyperlipidemia have not been studied. This study was designed to elucidate the effects of oral selenium and magnesium co-supplementation on antihyperlipidemic and hepatoprotective, antioxidative activities, and related gene expression in a hyperlipidemic rat model. METHODS: Forty male Sprague Dawley rats were divided into 4 groups: one group served as control group (CT), provided control diet; The other groups were made hyperlipidemic with high-fat diet; specifically, a high-fat diet group (HF); low-dose selenium (0.05 mg/kg·bw) + low-dose magnesium (5.83 mg/kg·bw) supplement high-fat diet group (HF + LSe + LMg) and high-dose selenium (0.10 mg/kg·bw) + high-dose magnesium (58.33 mg/kg·bw) supplement high-fat diet group (HF + HSe + HMg). The first 4 weeks of the experiment was a hyperlipidemia inducing period using high-fat diet and the following 8 weeks involved in selenium and magnesium co-supplementation. On day 0, 20, 40 and 60 of the intervention, lipid profile was measured. At the end of the 12-week experiments, final blood and liver samples were collected for the measurements of lipid profile, antioxidative indexes, pathological examination, and liver lipid metabolism related gene expression. RESULTS: The elevated levels of serum and liver total cholesterol (TC) and serum LDL-C induced by feeding high-fat diets were significantly reduced by low-dose Se and Mg co-supplementation. Both doses of selenium and magnesium co-supplementation notably decreased the blood and liver TG levels, liver function indexes ALT and AST and the ratio of TC/HDL-C and TG/HDL-C. In contrast, Se and Mg supplementation showed a substantial increase in Se-dependent glutathione peroxidase (GSH-Px) and SOD activities and an significant reduce of level of MDA of hyperlipidemic rats. Oil Red O staining showed that selenium and magnesium co-supplementation significantly reduced hepatic intracellular triacylglycerol accumulation. H&E staining also showed that selenium and magnesium co-supplementation can attenuate liver steatosis. Selenium and magnesium co-supplementation remarkably inhibited the mRNA expression level of hepatic lipogenesis genes liver X receptor alpha (LXRα),SREBP-1c and FASN (fatty acid synthase), regulated the mRNA expression levels of liver enzymes related to cholesterol metabolism, including the down regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) and the upregulation of cholesterol 7α-hydroxylase (CYP7A1) and lecithin cholesterol acyltransferase (LCAT) in the liver of hyperlipidemia rats. CONCLUSIONS: Oral selenium and magnesium co-supplementation inhibited an increase of lipid and liver profile and liver function index induced by a high-fat diet, and enhanced the activity of the antioxidant enzymes. Selenium combined with magnesium is a promising therapeutic strategy with lipid-lowering and antioxidative effects that protects the liver against hyperlipidemia.

Twin defects engineered Pd cocatalyst on C3N4 nanosheets for enhanced photocatalytic performance in CO2 reduction reaction.

Photocatalytic conversion of CO2 to value-added chemicals, a potential route to addressing the depletion of fossil fuels and anthropogenic climate change, is greatly limited by the low-efficient semiconductor photocatalyst. The integration of cocatalyst with light-harvesting semiconductor is a promising approach to enhancing the photocatalytic performance in CO2 reduction reaction. The enhancement is greatly determined by the catalytic active sites on the surface of cocatalyst. Herein, we demonstrate that the photocatalytic performance in the CO2 reduction reaction is greatly promoted by twin defects engineered Pd cocatalyst. In this work, Pd nanoicosahedrons with twin defects were in situ grown on C3N4 nanosheets, which effectively improve the photocatalytic performance in reduction of CO2 to CO and CH4 in comparison with Pd nanotetrahedrons without twin defects. It is proposed that the twin boundary (TB) terminations on the surface of Pd cocatalysts are highly catalytic active sites for CO2 reduction reaction. Based on the proposed mechanism, the photocatalytic activity and selectivity in CO2 reduction were further advanced through reducing the size of Pd icosahedral cocatalyst resulted from the increased surface density of TB terminations. The defect engineering on the surface of cocatalyst represents a novel route in realizing high-performance photocatalytic applications.

New Approaches in CAR-T Cell Immunotherapy for Breast Cancer.

Despite significant advances in surgery, chemotherapy, radiotherapy, endocrine therapy, and molecular-targeted therapy, breast cancer remains the leading cause of death from malignant tumors among women. Immunotherapy has recently become a critical component of breast cancer treatment with encouraging activity and mild safety profiles. CAR-T therapy using genetically modifying T cells with chimeric antigen receptors (CAR) is the most commonly used approach to generate tumor-specific T cells. It has shown good curative effect for a variety of malignant diseases, especially for hematological malignancies. In this review, we briefly introduce the history and the present state of CAR research. Then we discuss the barriers of solid tumors for CARs application and possible strategies to improve therapeutic response with a focus on breast cancer. At last, we outlook the future directions of CAR-T therapy including managing toxicities and developing universal CAR-T cells.

[Study on the correlation between serum lipid and serum carnitine palmitoyl transferase 1A in rural adults over 40 years in Tianjin].

OBJECTIVE: To explore the status of serum lipids and analyze its relationship with carnitine palmitoyl transferase 1A (CPT1 A) in rural people over 40 in Tianjin, China. METHODS: By cluster multi-stratified sample of 719 people over 40 was investigated with a questionnaire from rural areas in Tianjin. And finally draw a conclusion based on data analysis from fasting blood and measured total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and CPT1 A. RESULTS: In this research, the rate of dyslipidemia was 46.73%, in which 48.22 percent male and 45.41 percent female, a nonsignificant difference. CPT1 A correlated with TC, LDL-C were 0.123 and 0.130, with simple linear regression, and there was only significant difference between LDL-C and CPT1 A by multiple regression analysis. CONCLUSION: There is a high rate of dyslipidemia among the rural people over the age of 40 in Tianjin, and the CPT1 A is closely associated with serum lipid.

Fast and eco-friendly synthesis of carbon dots from pinecone for highly effective detection of 2,4,6-trinitrophenol in environmental samples.

2,4,6-Trinitrophenol (TNP) has high explosive risks and biological toxicity, and there has been considerable concern over the determination of TNP. In the present work, fluorescent carbon dots (CDs) stemmed from a green carbon source of pinecone by the facile hydrothermal approach. A novel environment- friendly fluorescent probe was developed to efficiently detect TNP by using the obtained CDs with remarkable fluorescence stability. The fluorescent CDs exhibited obvious excitation dependence with the highest peaks for excitation and emission occurring at 321 and 411 nm, respectively. The fluorescence intensity is significantly reduced by TNP owing to the inner filter effect with the CDs. The probe exhibited good linearity with TNP concentrations in the range of 0.025-20 µg mL-1, and the limit of detection was as low as 8.5 ng mL-1. Additionally, the probe proved successful in sensing TNP quantitatively in actual environmental samples with satisfied recoveries of 95.6-99.6%. The developed fluorescent probe offered an environment-friendly, efficient, rapid, and reliable platform for detecting trace TNP in the environmental field.HighlightsNovel carbon dots were synthesised from green precursors of pineal powder.The highly effective quenching process was put down to the inner filter effect.The as-constructed fluorescent probe was successfully utilised for sensing 2,4,6-trinitrophenol in environmental samples.The proposed method was simple, rapid, efficient, economical, and eco-friendly.

The hapten rigidity improves antibody performances in immunoassay for rifamycins: Immunovalidation and molecular mechanism.

The immunogenicity of haptens determines the performance of the resultant antibody for small molecules. Rigidity is one of the basic physicochemical properties of haptens. However, few studies have investigated the effect of hapten rigidity on the strength of an immune response and overall antibody performance. Herein, we introduce three molecular descriptors that quantify hapten rigidity. By using of these descriptors, four rifamycin haptens with varied rigidity were designed. The structural and physicochemical feasibility of the designed haptens was then assessed by computational chemistry. Immunization demonstrated that the strength of induced immune responses, i.e., the titer and affinity of antiserum, was significantly increased with increased rigidity of haptens. Furthermore, molecular dynamic simulations demonstrated conformation constraint of rigid haptens contributed to the initial binding and activation of naïve B cells. Finally, a highly sensitive indirect competitive enzyme-linked immunosorbent assay was developed for detection of rifaximin, with an IC50 of 1.1 µg/L in buffer and a limit of detection of 0.2-11.3 µg/L in raw milk, river water, and soil samples. This work provides new insights into the effect of hapten rigidity on immunogenicity and offers new hapten design strategies for antibody discovery and vaccine development of small molecules.

Preparation and structural characterization of epoxidized soybean oils-based pressure sensitive adhesive grafted with tea polyphenol palmitate.

Vegetable oils-based pressure sensitive adhesives (PSAs) are green and sustainable but face unsatisfactory adhesion strengths and are prone to aging during storage and application due to the existence of residual double bonds and massive ester bonds. Nine common antioxidants (tea polyphenol palmitate (TPP), caffeic acid, ferulic acid, gallic acid, butylated hydroxytoluene, tertiary butylhydroquinone, butylated hydroxyanisole, propyl gallate, and tea polyphenols) were grafted into epoxidized soybean oils-PSA (ESO-PSA) system to enhance antiaging properties and adhesion strengths. Results showed ESO-PSAs grafted with caffeic acid, tertiary butylhydroquinone, butylated hydroxyanisole, propyl gallate, tea polyphenols, or TPP didn't occur failure with TPP having best performance. The optimal conditions were ESO reacted with 0.9 % TPP, 70 % rosin ester, and 7.0 % phosphoric acid at 50 °C for 5 min, under which peel strength and loop tack increased to 2.460 N/cm and 1.66 N, respectively, but peel strength residue reduced to 138.09 %, compared with control (0.407 N/cm, 0.43 N, and 1669.99 %). Differential scanning calorimetry and thermogravimetric results showed TPP grafting increased the glass transition temperature of ESO-PSA slightly but improved its thermal stability significantly. Fourier transform infrared spectroscopy and 1H nuclear magnetic resonance results showed TPP, phosphoric acid, and rosin ester all partially participated in the covalently crosslinking polymerization of ESO-PSAs and the rest existed in the network structures in the free form.

Preharvest application of MeJA enhancing the quality of postharvest grape berries via regulating terpenes biosynthesis and phenylpropanoid metabolisms.

Methyl jasmonate (MeJA) is an important phytohormone that regulates the development of grape, but the effect and underpin mechanism of its preharvest application on secondary metabolites accumulation in postharvest grape berries are still unclear. In this study, the transcriptome profiles combined with metabolic components analysis were used to determine the effect of preharvest MeJA application on the quality formation of postharvest rose-flavor table grape Shine Muscat. The results indicated that preharvest MeJA treatment had no significant effect on TSS content, but had a down-regulation effect on the accumulation of reducing sugar and titratable acid in the berries. The content of chlorophylls and carotenoids in treated berries was significantly higher than that of the control. Many phenolic components, such as trans-ferulic acid, resveratrol, quercetin, and kaempferol, were sensitive to MeJA and their contents were also significantly higher than that of the control under MeJA treatments during the shelf life. Compared with other volatile aroma components, terpenoid components were more sensitive to preharvest MeJA signals, the content of which presented an overall upward trend with increasing MeJA concentration and prolonging storage time. Furthermore, most of the differentially expressed genes in the general phenylpropanoid pathway and terpenoid biosynthesis pathway were up-regulated responding to MeJA signals. The most upregulated regulatory factors, such as VvWRKY72, VvMYB24, and VvWRI1, may be involved in MeJA signal transduction and regulation. Preharvest MeJA may be an effective technique for enhancing the quality of postharvest Shine Muscat grape berries, with its positive effect on enhancing the characteristic aroma and nutritional components.

Constructing an eco-friendly and ratiometric fluorescent sensor for highly efficient detection of mercury ion in environmental samples.

Mercury ion (Hg2+) is a highly toxic and ubiquitous pollutant, whose effective detection has aroused widespread concern. A novel ratiometric fluorescent sensor has been designed to rapidly and efficiently detect Hg2+ based on blue/red carbon dots (CDs) with environmental friendliness. This sensor was well characterized via TEM, FTIR, XPS, UV-vis, and zeta potential analysis and displayed excellent fluorescence properties and stability. The fluorescence of blue CDs at 447 nm was significantly quenched with the addition of Hg2+ resulted from the static quenching, whereas that of red CDs at 650 nm remained invariable. A sensitive method for Hg2+ determination was constructed in the range of 0.05-7.0 nmol mL-1 with optimal conditions, and the detection limit was down to 0.028 nmol mL-1. Meanwhile, compared to other 17 metal ions, the ratiometric fluorescent sensor exhibited high selectivity for Hg2+. Furthermore, satisfied recoveries had also been obtained for measuring trace Hg2+ in practical environmental samples. This developed ratiometric fluorescent sensor provided a reliable, environmental-friendly, rapid, and efficient platform for the detection of Hg2+ in environmental applications.

Impact of indigenous Oenococcus oeni and Lactiplantibacillus plantarum species co-culture on Cabernet Sauvignon wine malolactic fermentation: Kinetic parameters, color and aroma.

Malolactic fermentation (MLF) is a crucial process to enhance wine quality, and the utilization of indigenous microorganisms has the potential to enhance wine characteristics distinct to a region. Here, the MLF performance of five indigenous Oenococcus oeni strains and six synthetic microbial communities (SynComs), were comparatively evaluated in Cabernet Sauvignon wine. In terms of malate metabolism rate and wine aroma diversity, the strain of O. oeni Oe114-46 demonstrated comparable MLF performance to the commercial strain of O. oeni Oe450 PreAc. Furthermore, the corresponding SynComs (Oe144-46/LpXJ25) exhibited improved fermentation properties, leading to increased viable cell counts of both species, more rapid and thorough MLF, and increased concentrations of important aroma compounds, such as linalool, 4-terpinenol, α-terpineol, diethyl succinate, and ethyl lactate. These findings highlight the remarkable MLF performance of indigenous O. oeni and O. oeni-L. plantarum microbial communities, emphasizing their immense potential in improving MLF efficiency and wine quality.

Activated STING-containing R-EVs from iPSC-derived MSCs promote antitumor immunity.

We recently revealed that activated STING is secreted into RAB22A-induced extracellular vesicles (R-EVs) and promotes antitumor immunity in cancer cells. Whether mesenchymal stem cell (MSC)-derived R-EVs containing activated STING can be used as a novel antitumor immunotherapy remains unclear, as MSC-derived EVs are promising cell-free therapeutics due to their superior biocompatibility and safety, as well as low immunogenicity. Here, we report that induced pluripotent stem cell (iPSC)-derived MSCs can generate R-EVs with a size and mechanism of formation that are similar to those of R-EVs produced from cancer cells. Furthermore, these MSC-derived R-EVs containing activated STING induced IFNß expression in recipient THP-1 monocytes and antitumor immunity in mice. Our findings reveal that the use of MSC-derived R-EVs containing activated STING is a promising cell-free strategy for antitumor immunity.