Long-term combined blockade of CXCR4 and PD-L1 with in vivo reassembly for intensive tumor interference.

Negative immunoregulatory signal (PD-L1, CXCR4, et al.) and weak immunogenicity elicited immune system failing to detect and destroy cancerous cells. CXCR4 blockade promoted T cell tumor infiltration and increased tumor sensitivity to anti-PD-L1 therapy. Here, pH-responsive reassembled nanomaterials were constructed with anti-PD-L1 peptide and CXCR4 antagonists grafting (APAB), synergized with photothermal therapy for melanoma and breast tumor interference. The self-assembled APAB nanoparticles accumulated in the tumor and rapidly transformed into nanofibers in response to the acidic tumor microenvironment, leading to the exposure of grafted therapeutic agents. APAB enabling to reassemble around tumor cells and remained stable for over 96 h due to the aggregation induced retention (AIR) effect, led to long-term efficiently combined PD-L1 and CXCR4 blockade. Photothermal efficiency (ICG) induced immunogenic cell death (ICD) of tumor cells so as to effectively improve the immunogenicity. The combined therapy (ICG@APAB) could effectively inhibit the growth of primary tumor (∼83.52%) and distant tumor (∼76.24%) in melanoma-bearing mice, and significantly (p < 0.05) prolong the survival time over 42 days. The inhibition assay on tumor metastasis in 4 T1 model mice exhibited ICG@APAB almostly suppressed the occurrence of lung metastases and the expression levels of CD31, MMP-9 and VEGF in tumor decreased by 82.26%, 90.45% and 41.54%, respectively. The in vivo reassembly strategy will offer novel perspectives benefical future immunotherapies and push development of combined therapeutics into clinical settings.

Intraspecific and Intrageneric Genomic Variation across Three Sedum Species (Crassulaceae): A Plastomic Perspective.

Sedum is the largest succulent genus in Crassulaceae. Because of predominant maternal inheritance, little recombination, and slow evolution, plastomes can serve as powerful super barcodes for inter- or intra-species phylogenetic analyses. While previous research has focused on plastomes between Sedum species, intra-species studies are scarce. Here, we sequenced plastomes from three Sedum species (Sedum alfredii, Sedum plumbizincicola, and Sedum japonicum) to understand their evolutionary relationships and plastome structural evolution. Our analyses revealed minimal size and GC content variation across species. However, gene distribution at IR boundaries, repeat structures, and codon usage patterns showed diversity at both inter-specific and intra-specific levels. Notably, an rps19 gene expansion and a bias toward A/T-ending codons were observed. Codon aversion motifs also varied, potentially serving as markers for future studies. Phylogenetic analyses confirmed the non-monophyly of Sedum and divided the Acre clade into two groups. Individuals from the same species clustered together, with strong support for the relationships between S. alfredii, S. tricarpum, and S. plumbizincicola. Additionally, S. japonicum clearly affiliates with the Acre clade. This study provides valuable insights into both intra-specific and intra-generic plastome variation in Sedum, as well as overall plastome evolution within the genus.

Phylogenomics and plastomics offer new evolutionary perspectives on Kalanchoideae (Crassulaceae).

BACKGROUND AND AIMS: Kalanchoideae is one of three subfamilies within Crassulaceae and contains four genera. Despite previous efforts, the phylogeny of Kalanchoideae remains inadequately resolved with persistent issues including low support, unstructured topologies and polytomies. This study aimed to address two central objectives: (1) resolving the pending phylogenetic questions within Kalanchoideae by using organelle-scale 'barcodes' (plastomes) and nuclear data; and (2) investigating interspecific diversity patterns among Kalanchoideae plastomes. METHODS: To explore the plastome evolution in Kalanchoideae, we newly sequenced 38 plastomes representing all four constituent genera (Adromischus, Cotyledon, Kalanchoe and Tylecodon). We performed comparative analyses of plastomic features, including GC and gene contents, gene distributions at the IR (inverted repeat) boundaries, nucleotide divergence, plastomic tRNA (pttRNA) structures and codon aversions. Additionally, phylogenetic inferences were inferred using both the plastomic dataset (79 genes) and nuclear dataset (1054 genes). KEY RESULTS: Significant heterogeneities were observed in plastome lengths among Kalanchoideae, strongly correlated with LSC (large single copy) lengths. Informative diversities existed in the gene content at SSC/IRa (small single copy/inverted repeat a), with unique patterns individually identified in Adromischus leucophyllus and one major Kalanchoe clade. The ycf1 gene was assessed as a shared hypervariable region among all four genera, containing nine lineage-specific indels. Three pttRNAs exhibited unique structures specific to Kalanchoideae and the genera Adromischus and Kalanchoe. Moreover, 24 coding sequences revealed a total of 41 lineage-specific unused codons across all four constituent genera. The phyloplastomic inferences clearly depicted internal branching patterns in Kalanchoideae. Most notably, by both plastid- and nuclear-based phylogenies, our research offers the first evidence that Kalanchoe section Eukalanchoe is not monophyletic. CONCLUSIONS: This study conducted comprehensive analyses on 38 newly reported Kalanchoideae plastomes. Importantly, our results not only reconstructed well-resolved phylogenies within Kalanchoideae, but also identified highly informative unique markers at the subfamily, genus and species levels. These findings significantly enhance our understanding of the evolutionary history of Kalanchoideae.

Intranasal Morphology Transformation Nanomedicines for Long-Term Intervention of Allergic Rhinitis.

Intranasal administration has been widely explored as a potential treatment for allergic rhinitis, and improving intranasal penetration and retention of drugs is a challenging requirement to further improve efficacy. Delivery strategies of nanocarriers that enhance mucosal adhesion or mucus penetration have been proposed to improve nasal drug delivery; however, delivery efficiency remains limited by excessive pulmonary deposition and nonspecific cell phagocytosis. In this work, a "nasal in situ assembly" strategy was presented to construct intranasal morphology transformation nanomedicines with enhanced effective drug concentration for long-term intervention of allergic rhinitis. The polymer-polypeptide nanomedicine (PHCK) with a CCR3 antagonistic peptide (C) and a pH-responsive polyethylene glycol (H) was developed, encapsulating ketotifen (KT). PHCK nanoparticles displayed nasal mucosa permeability and transformed to nanofibers in the acidic environment of the nasal cavity, realizing responsive burst release of KT simultaneously. The fibrotic reassembly reduced the cellular internalization of nanomedicine and increased the CCR3 blockade on the eosinophil (EOS) membranes. Both in vitro and in vivo data indicated that PHCK achieved improved drug accumulation and retention in the nasal cavity and decreased pulmonary deposition, then effectively inhibited mast cell degranulation and EOS chemotaxis. This study demonstrates that the "nasal in situ assembly" strategy can improve drug delivery efficiency upon nasal responsive morphologic transformation, providing exploratory perspectives for nasal delivery platforms establishment and boosting therapeutic effect of allergic rhinitis.

Genome evolution of Buchnera aphidicola (Gammaproteobacteria): Insights into strand compositional asymmetry, codon usage bias, and phylogenetic implications.

Taxa of Buchnera aphidicola (hereafter "Buchnera") are mutualistic intracellular symbionts of aphids, known for their remarkable biological traits such as genome reduction, strand compositional asymmetry, and symbiont-host coevolution. With the growing availability of genomic data, we performed a comprehensive analysis of 103 genomes of Buchnera strains from 12 host subfamilies, focusing on the genomic characterizations, codon usage patterns, and phylogenetic implications. Our findings revealed consistent features among all genomes, including small genome sizes, low GC contents, and gene losses. We also identified strong strand compositional asymmetries in all strains at the genome level. Further investigation suggested that mutation pressure may have played a crucial role in shaping codon usage of Buchnera. Moreover, the genomic asymmetries were reflected in asymmetric codon usage preferences within chromosomal genes. Notably, the levels of these asymmetries were varied among strains and were significantly influenced by the degrees of genome shrinkages. Lastly, our phylogenetic analyses presented an alternative topology of Aphididae, based on the Buchnera symbionts, providing robust confirmation of the paraphylies of Eriosomatinae, and Macrosiphini. Our objectives are to further understand the strand compositional asymmetry and codon usage bias of Buchnera taxa, and provide new perspectives for phylogenetic studies of Aphididae.

The impact of internet use on health status among older adults in China: The mediating role of social support.

Background: With the popularization of the Internet, the use of the Internet is becoming more and more important in the daily life of older adults. However, previous research mainly focuses on Internet use and health in general, and the mechanism of this effect remains to be studied. To bridge this gap, this study aims to explore the mediational effects of social support between Internet use and health among older adults in China. Methods: The data used in this article are from the 2021 Chinese General Social Survey (CGSS). Social support is divided into two aspects and four dimensions: informal social support (relatives support, friends support, neighbors support) and formal social support (social insurance). This article uses the nested multivariate OLS regression models to analyze the impact of Internet use on health. Furthermore, Finally, SPSS macro PROCESS is applied to test their mediation effects. Results: Informal social support positively influenced the health status among older adults, while formal social support did not. Among the three types of informal social support, relatives support and friends support significantly affected health status among Chinese older adults. Regarding social support differences between urban and rural areas, it was found that relatives support is a positively significant factor for rural older adults, while friends support is significant for urban older adults. Conclusions: Since Internet use has many ways of impacting health status, social support only plays a partial mediating role in this study. It recommends that the government should take compelling measures to encourage and promote the use of the Internet among older adults and obtain various social support to improve their health status.

Physical Activity, Screen Time, and Academic Burden: A Cross-Sectional Analysis of Health among Chinese Adolescents.

This paper aims to analyze the effects of physical activity, screen time, and academic burden on adolescent health in China and compare their effects by using the nationally representative sample data from the CEPS (China Educational Panel Survey) cross-section data. This paper first uses regression analysis to examine the relationship between physical activity, screen time, academic burden and health among Chinese adolescents. Then, this paper uses the clustering analysis the influence of physical activity, screen time, and academic burden on the health of Chinese adolescents. The empirical results show that: (1) along with exercise, helping with the housework also has a clear health-promoting effect on adolescents; (2) the time spent surfing the Internet or playing video games, and heavy studying or homework off campus have a negative effect on adolescents' self-rated health and mental health; (3) physical activity has the greatest impact on self-rated health, while screen time has the greatest impact on mental health, and academic burden is not the most important factor affecting adolescent health in China.

Ten Plastomes of Crassula (Crassulaceae) and Phylogenetic Implications.

The genus Crassula is the second-largest genus in the family Crassulaceae, with about 200 species. As an acknowledged super-barcode, plastomes have been extensively utilized for plant evolutionary studies. Here, we first report 10 new plastomes of Crassula. We further focused on the structural characterizations, codon usage, aversion patterns, and evolutionary rates of plastomes. The IR junction patterns-IRb had 110 bp expansion to rps19-were conservative among Crassula species. Interestingly, we found the codon usage patterns of matK gene in Crassula species are unique among Crassulaceae species with elevated ENC values. Furthermore, subgenus Crassula species have specific GC-biases in the matK gene. In addition, the codon aversion motifs from matK, pafI, and rpl22 contained phylogenetic implications within Crassula. The evolutionary rates analyses indicated all plastid genes of Crassulaceae were under the purifying selection. Among plastid genes, ycf1 and ycf2 were the most rapidly evolving genes, whereas psaC was the most conserved gene. Additionally, our phylogenetic analyses strongly supported that Crassula is sister to all other Crassulaceae species. Our findings will be useful for further evolutionary studies within the Crassula and Crassulaceae.

Structural Diversities and Phylogenetic Signals in Plastomes of the Early-Divergent Angiosperms: A Case Study in Saxifragales.

As representative of the early-divergent groups of angiosperms, Saxifragales is extremely divergent in morphology, comprising 15 families. Within this order, our previous case studies observed significant structural diversities among the plastomes of several lineages, suggesting a possible role in elucidating their deep phylogenetic relationships. Here, we collected 208 available plastomes from 11 constituent families to explore the evolutionary patterns among Saxifragales. With thorough comparisons, the losses of two genes and three introns were found in several groups. Notably, 432 indel events have been observed from the introns of all 17 plastomic intron-containing genes, which could well play an important role in family barcoding. Moreover, numerous heterogeneities and strong intrafamilial phylogenetic implications were revealed in pttRNA (plastomic tRNA) structures, and the unique structural patterns were also determined for five families. Most importantly, based on the well-supported phylogenetic trees, evident phylogenetic signals were detected in combinations with the identified pttRNAs features and intron indels, demonstrating abundant lineage-specific characteristics for Saxifragales. Collectively, the results reported here could not only provide a deeper understanding into the evolutionary patterns of Saxifragales, but also provide a case study for exploring the plastome evolution at a high taxonomic level of angiosperms.

The prognostic value of NLRP1/NLRP3 and its relationship with immune infiltration in human gastric cancer.

BACKGROUND: Inflammasomes are related to tumorigenesis and immune-regulation. Here, we investigated the prognostic value of the NLR family pyrin domain containing (NLRP) 1/NLRP3 inflammasome and its potential mechanisms in immune-regulation in gastric cancer (GC). METHODS: We analyzed the differential expression of NLRP1/NLRP3 between tumor and normal tissues using the Oncomine and Tumor Immune Estimate Resource (TIMER) databases. Immunohistochemistry and western blotting were used to detect NLRP1/NLRP3 protein expression in GC tissues. Correlations between NLRP1/NLRP3 expression levels and patient survival were analyzed using Kaplan-Meier survival curves. The relationships of NLRP1/NLRP3 expression and tumor-infiltrating immune cells/marker genes were assessed using the TIMER database. NLRP1/NLRP3 and immune checkpoint gene correlations were verified by single-gene co-expression analyses, and tumor immune-related pathways involving NLRP1/NLRP3 were analyzed using gene set enrichment analysis (GSEA). RESULTS: Elevated NLRP1/NLRP3 expression was significantly correlated with lymph node metastasis, poor survival, immune-infiltrating cell abundances, and immune cell markers. NLRP3 showed stronger correlations with immune infiltration and the prognosis of gastric cancer. NLRP1 and NLRP3 might be involved in the same tumor immune-related pathways. Thus, high NLRP1/NLRP3 expression promotes immune cell infiltration and poor prognosis in GC. NLRP1/NLRP3, particularly NLRP3, may have important roles in immune infiltration and may serve as a prognostic biomarker for GC. CONCLUSIONS: NLRP1/NLRP3, particularly NLRP3, may have important roles in immune infiltration and may serve as a prognostic biomarker for GC.

The Mitogenome of Sedum plumbizincicola (Crassulaceae): Insights into RNA Editing, Lateral Gene Transfer, and Phylogenetic Implications.

As the largest family within the order Saxifragales, Crassulaceae contains about 34 genera with 1400 species. Mitochondria play a critical role in cellular energy production. Since the first land plant mitogenome was reported in Arabidopsis, more than 400 mitogenomic sequences have been deposited in a public database. However, no entire mitogenome data have been available for species of Crassulaceae to date. To better understand the evolutionary history of the organelles of Crassulaceae, we sequenced and performed comprehensive analyses on the mitogenome of Sedum plumbizincicola. The master mitogenomic circle is 212,159 bp in length, including 31 protein-coding genes (PCGs), 14 tRNA genes, and 3 rRNA genes. We further identified totally 508 RNA editing sites in PCGs, and demonstrated that the second codon positions of mitochondrial genes are most prone to RNA editing events. Notably, by neutrality plot analyses, we observed that the mitochondrial RNA editing events have large effects on the driving forces of plant evolution. Additionally, 4 MTPTs and 686 NUMTs were detected in the mitochondrial and nuclear genomes of S. plumbizincicola, respectively. Additionally, we conducted further analyses on gene transfer, secondary structures of mitochondrial RNAs, and phylogenetic implications. Therefore, the findings presented here will be helpful for future investigations on plant mitogenomes.

Bridging nanoplatform and vaccine delivery, a landscape of strategy to enhance nasal immunity.

Vaccination is an urgently needed and effective option to address epidemic, cancers, allergies, and other diseases. Nasal administration of vaccines offers many benefits over needle-based injection including high compliance and less risk of infection. Inactivated or attenuated vaccines as convention vaccine present potential risks of pathogenic virulence reversal, the focus of nasal vaccine development has shifted to the use of next-generation (subunit and nucleic acid) vaccines. However, subunit and nucleic acid vaccine intranasally have numerous challenges in development and utilization due to mucociliary clearance, mucosal epithelial tight junction, and enzyme/pH degradation. Nanoplatforms as ideal delivery systems, with the ability to enhance the retention, penetration, and uptake of nasal mucosa, shows great potential in improving immunogenic efficacy of nasal vaccine. This review provides an overview of delivery strategies for overcoming nasal barrier, including mucosal adhesion, mucus penetration, targeting of antigen presenting cells (APCs), enhancement of paracellular transportation. We discuss methods of enhancing antigen immunogenicity by nanoplatforms as immune-modulators or multi-antigen co-delivery. Meanwhile, we describe the application status and development prospect of nanoplatforms for nasal vaccine administration. Development of nanoplatforms for vaccine delivery via nasal route will facilitate large-scale and faster global vaccination, helping to address the threat of epidemics.

Machine learning for the micropeptide encoded by LINC02381 regulates ferroptosis through the glucose transporter SLC2A10 in glioblastoma.

Glioblastoma (GBM) is the most common primary intracranial tumor in the central nervous system, and resistance to temozolomide is an important reason for the failure of GBM treatment. We screened out that Solute Carrier Family 2 Member 10 (SLC2A10) is significantly highly expressed in GBM with a poor prognosis, which is also enriched in the NF-E2 p45-related factor 2 (NRF2) signalling pathway. The NRF2 signalling pathway is an important defence mechanism against ferroptosis. SLC2A10 related LINC02381 is highly expressed in GBM, which is localized in the cytoplasm/exosomes, and LINC02381 encoded micropeptides are localized in the exosomes. The micropeptide encoded by LINC02381 may be a potential treatment strategy for GBM, but the underlying mechanism of its function is not precise yet. We put forward the hypothesis: "The micropeptide encoded by LINC02381 regulates ferroptosis through the glucose transporter SLC2A10 in GBM." This study innovatively used machine learning for micropeptide to provide personalized diagnosis and treatment plans for precise treatment of GBM, thereby promoting the development of translational medicine. The study aimed to help find new disease diagnoses and prognostic biomarkers and provide a new strategy for experimental scientists to design the downstream validation experiments.

Damage Identification Method for Medium- and Small-Span Bridges Based on Macro-Strain Data under Vehicle-Bridge Coupling.

The damage identification method based on macro-strain modality has shown good results for large-span flexible bridges. However, medium- and small-span bridges have a high stiffness, and the axle system is embodied. The strong time-varying vibration characteristics, coupled with the non-stationary characteristics of vehicle loads, make it difficult to accurately determine the stable strain modes of such bridges. To solve this problem, a damage localization index in the form of an amplitude vector matrix of the mutual energy density spectrum based on macro-strain was constructed using wavelet transform de-noising and reconstruction technology and cross-correlation function. The macro-static strain and macro-dynamic strain data obtained from a vehicle-bridge coupling experiment were reconstructed through wavelet transform, and the factors influencing the damage indices were analyzed. The results showed that the proposed indicators could help realize an accurate damage localization for medium- and small-span bridge systems with different damage degrees under the action of vehicle-bridge coupling.

Mitogenomic Codon Usage Patterns of Superfamily Certhioidea (Aves, Passeriformes): Insights into Asymmetrical Bias and Phylogenetic Implications.

The superfamily Certhioidea currently comprises five families. Due to the rapid diversification, the phylogeny of Certhioidea is still controversial. The advent of next generation sequencing provides a unique opportunity for a mitogenome-wide study. Here, we first provided six new complete mitogenomes of Certhioidea (Certhia americana, C. familiaris, Salpornis spilonota, Cantorchilus leucotis, Pheugopedius coraya, and Pheugopedius genibarbis). We further paid attention to the genomic characteristics, codon usages, evolutionary rates, and phylogeny of the Certhioidea mitogenomes. All mitogenomes we analyzed displayed typical ancestral avian gene order with 13 protein-coding genes (PCGs), 22 tRNAs, 2 rRNAs, and one control region (CR). Our study indicated the strand-biased compositional asymmetry might shape codon usage preferences in mitochondrial genes. In addition, natural selection might be the main factor in shaping the codon usages of genes. Additionally, evolutionary rate analyses indicated all mitochondrial genes were under purifying selection. Moreover, MT-ATP8 and MT-CO1 were the most rapidly evolving gene and conserved genes, respectively. According to our mitophylogenetic analyses, the monophylies of Troglodytidae and Sittidae were strongly supported. Importantly, we suggest that Salpornis should be separated from Certhiidae and put into Salpornithidae to maintain the monophyly of Certhiidae. Our findings are useful for further evolutionary studies within Certhioidea.

Acrylamide impairs the developmental potential of germinal vesicle oocytes by inducing mitochondrial dysfunction and autophagy/apoptosis in mice.

Background: Acrylamide (ACR), an important endogenous contaminant in carbohydrate-rich foods, has been involved in various negative effects on multiple organ networks, including the reproductive system. Previous studies have reported that ACR affects oocyte quality and fertility. Purpose: This study aimed to explore the toxic effects and regulatory mechanisms of ACR on mouse germinal vesicle (GV) oocytes. Research Design: In this study, adult female mice were exposed to ACR at 10 mg/kg/day/body weight through their drinking water continuously for 4 weeks. Study Sample and Data Analysis: The mitochondrial function, autophagy/apoptosis, and development potential of GV oocytes were investigated. Results: The results showed that ACR reduced the oocyte diameter, sperm-binding ability, parthenogenetic activation and in vitro fertilization (IVF) rate, and development potential of pre-implantation embryos. We also found that ACR exposure disrupted chromatin configuration, mitochondrial distribution, and membrane potential (Δφm) of oocytes. Actin filament expression was significantly reduced in both the membrane and cytoplasm of mouse oocytes. Moreover, ACR exposure increased LC3-positive signals, early apoptosis rate, aberrant ATG3, ATG5, LC3, Beclin1, and mTOR mRNA expression. Conclusions: These results suggest that ACR exposure can affect the developmental potential of GV oocytes by inducing mitochondrial dysfunction, actin filament assembly, and autophagy/apoptosis.

Codon usage patterns and evolution of HSP60 in birds.

Heat shock protein 60 (HSP60) is highly conserved from prokaryotic to eukaryotic organisms, acting as molecular chaperone and other vital biological functions. In spite of increasing knowledge of HSP60, its evolutionary mechanism on functional adaption is still far from completely understood. Moreover, analysis of codon usage bias (CUB) is a powerful tool to understand evolutionary association studies. However, so far, as we know, no scientific work on CUB of HSP60 in birds has been reported. In this study, we provide a comprehensive analysis on the codon usage and molecular evolution of HSP60 across birds. The results indicated that HSP60 had a weak codon usage bias with high ENC values (range from 52.66 to 61), low RSCU, and A/T-ending codons were mostly preferred. Meanwhile, it was considered that mutation, natural selection, and genetic drift combined to shape codon usage patterns with different strength proportions among various birds for HSP60. Then, the LRT tests suggested that different lineages of birds might be under similar selective pressures. Besides, the two positive selection sites (151 and 131) were detected and might undergo radical changes. These findings would contribute to understand function diversity and molecular evolution of HSP60 in birds.

Mitochondrial genome characterization of Gryllodes sigillatus (Orthoptera: Gryllidae) and its phylogenetic implications.

Gryllodes sigillatus is a cricket widely distributed throughout the world. In this study, we reported the first complete mitogenome sequence of Genus Gryllodes and inferred its phylogeny. The mitogenome of G. sigillatus was 16,369 bp and consisted of a control region and a typical set of 37 genes. It was AT-rich with strong codon usage bias and possessed a gene arrangement of trnE-trnS1-trnN. Phylogenetic analysis indicated G. sigillatus was sister species to Velarifictorus hemelytrus, together belonging to the Family Gryllidae. Our findings would contribute to understanding mitogenomic evolution and phylogeny of Ensifera.

SWEET Transporters and the Potential Functions of These Sequences in Tea (Camellia sinensis).

Tea (Camellia sinensis) is an important economic beverage crop. Its flowers and leaves could be used as healthcare tea for its medicinal value. SWEET proteins were recently identified in plants as sugar transporters, which participate in diverse physiological processes, including pathogen nutrition, seed filling, nectar secretion, and phloem loading. Although SWEET genes have been characterized and identified in model plants, such as Arabidopsis thaliana and Oryza sativa, there is very little knowledge of these genes in C. sinensis. In this study, 28 CsSWEETs were identified in C. sinensis and further phylogenetically divided into four subfamilies with A. thaliana. These identified CsSWEETs contained seven transmembrane helixes (TMHs) which were generated by an ancestral three-TMH unit with an internal duplication experience. Microsynteny analysis revealed that the large-scale duplication events were the main driving forces for members from CsSWEET family expansion in C. sinensis. The expression profiles of the 28 CsSWEETs revealed that some genes were highly expressed in reproductive tissues. Among them, CsSWEET1a might play crucial roles in the efflux of sucrose, and CsSWEET17b could control fructose content as a hexose transporter in C. sinensis. Remarkably, CsSWEET12 and CsSWEET17c were specifically expressed in flowers, indicating that these two genes might be involved in sugar transport during flower development. The expression patterns of all CsSWEETs were differentially regulated under cold and drought treatments. This work provided a systematic understanding of the members from the CsSWEET gene family, which would be helpful for further functional studies of CsSWEETs in C. sinensis.

Resveratrol induces PD-L1 expression through snail-driven activation of Wnt pathway in lung cancer cells.

PURPOSE: Recent clinical trials with agents targeting immune checkpoint pathway have emerged as an important therapeutic approach for a broad range of cancer types. Resveratrol has been shown to possess cancer preventive and therapeutic effects and has potential to be chemotherapeutic agent/adjuvant. Here, we assessed the effect of resveratrol on immune checkpoint pathways. METHODS: The expression patterns of Wnt components and PD-L1 were examined by Western blot, Chromatin immunoprecipitation (ChIP) was used for analysis of DNA-protein interaction, the promoter activity was determined by luciferase reporter assay, apoptosis was analyzed by flow cytometry and the ability of the resveratrol to modulate T cell function was assessed in a co-culture system. RESULTS: Although the dose-, and cell-type dependent effects of resveratrol on PD-L1 expression have been reported, we show here that resveratrol dose-dependently upregulates PD-L1 expression at the range of pharmacologic-achievable concentrations in lung cancer cells and that is essential for suppression of T-cell-mediated immune response. We also found that Wnt pathway is critical for mediating resveratrol-induced PD-L1 upregulation. Mechanistically, resveratrol activates SirT1 deacetylase to deacetylate and stabilize transcriptional factor Snail. Snail in turn inhibits transcription of Axin2, which leads in disassembly of destruction complex and enhanced binding of ß-catenin/TCF to PD-L1 promoter. CONCLUSION: We conclude that resveratrol is capable to suppress anti-tumor immunity by controlling mainly PD-L1 expression. This finding will extend the understanding of resveratrol in regulation of tumor immunity and is relevant to the debate on resveratrol supplements for lung cancer patients.