Reniformin A suppresses non-small cell lung cancer progression by inducing TLR4/NLRP3/caspase-1/GSDMD-dependent pyroptosis.

Pyroptosis is an inflammatory form of programmed cell death that plays an important role in regulating tumor progression. Reniformin A (RA) is a natural compound isolated from the medicinal herb Isodon excisoides that has been applied as folk medicine in the treatment of esophageal cancer. However, whether RA has an individual function in cancer and the molecular mechanisms remain unclear. Here, we show that in non-small-cell lung cancer (NSCLC), RA inhibits tumor growth by functioning as a pyroptosis inducer to promote TLR4/NLRP3/caspase-1/GSDMD axis. Specially, RA treatment increased Toll-like receptor 4 (TLR4) protein expression level by enhancing the TLR4 stability. Based on the molecular docking, we identified that RA directly bound to TLR4 to activate the NLRP3 inflammasome and promote pyroptosis in A549 cells. Moreover, TLR4 is essential for RA-induced pyroptosis, and loss of TLR4 abolished RA-induced pyroptosis and further reduced the inhibitory effect of RA on NSCLC. In vivo experiments confirmed that RA inhibited the growth of lung tumors in mice by affecting pyroptosis in a dose-dependent manner. Furthermore, TLR4 knockdown abolished RA-induced pyroptosis and inhibited the effect of RA chemotherapy in vivo. In conclusion, we propose that RA has a significant anticancer effect in NSCLC by inducing TLR4/NLRP3/caspase-1/GSDMD-mediated pyroptosis, which may provide a potential strategy for the treatment of NSCLC.

Multi-modal molecular determinants of clinically relevant osteoporosis subtypes.

Due to a rapidly aging global population, osteoporosis and the associated risk of bone fractures have become a wide-spread public health problem. However, osteoporosis is very heterogeneous, and the existing standard diagnostic measure is not sufficient to accurately identify all patients at risk of osteoporotic fractures and to guide therapy. Here, we constructed the first prospective multi-omics atlas of the largest osteoporosis cohort to date (longitudinal data from 366 participants at three time points), and also implemented an explainable data-intensive analysis framework (DLSF: Deep Latent Space Fusion) for an omnigenic model based on a multi-modal approach that can capture the multi-modal molecular signatures (M3S) as explicit functional representations of hidden genotypes. Accordingly, through DLSF, we identified two subtypes of the osteoporosis population in Chinese individuals with corresponding molecular phenotypes, i.e., clinical intervention relevant subtypes (CISs), in which bone mineral density benefits response to calcium supplements in 2-year follow-up samples. Many snpGenes associated with these molecular phenotypes reveal diverse candidate biological mechanisms underlying osteoporosis, with xQTL preferences of osteoporosis and its subtypes indicating an omnigenic effect on different biological domains. Finally, these two subtypes were found to have different relevance to prior fracture and different fracture risk according to 4-year follow-up data. Thus, in clinical application, M3S could help us further develop improved diagnostic and treatment strategies for osteoporosis and identify a new composite index for fracture prediction, which were remarkably validated in an independent cohort (166 participants).

Deciphering the Mechanism of Siwu Decoction Inhibiting Liver Metastasis by Integrating Network Pharmacology and In Vivo Experimental Validation.

BACKGROUND: Siwu Decoction (SWD) is a well-known classical TCM formula that has been shown to be effective as a basis for preventing and reducing liver metastases (LM). However, the active ingredients and potential molecular mechanisms remain unclear. OBJECTIVE: This study aimed to systematically analyze the active ingredients and potential molecular mechanisms of SWD on LM and validate mechanisms involved. MATERIALS AND METHODS: The active ingredients in SWD were extracted by UHPLC-MS/MS in a latest study. Protox II was retrieved to obtain toxicological parameters to detect safety. Swiss Target Prediction database was exploited to harvest SWD targets. Five databases, Gene Cards, DisGeNET, Drugbank, OMIM, and TTD, were employed to filter pathogenic targets of LM. STRING database was utilized to construct the protein-protein interaction network for therapeutic targets, followed by Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. GEPIA database and the Human Protein Atlas were taken to observe the expression of core genes and proteins. ImmuCellAI algorithm was applied to analyze the immune microenvironment and survival relevant to core genes. Molecular docking was performed to verify the affinity of SWD effective ingredients to core targets. In vivo experiments were carried out to validate the anti-LM efficacy of SWD and verify the pivotal mechanisms of action. RESULTS: Eighteen main bioactive phytochemicals identified were all non-hepatotoxic. PPI network acquired 118 therapeutic targets, of which VEGFA, CASP3, STAT3, etc. were identified as core targets. KEGG analysis revealed that HIF-1 pathway and others were critical. After tandem targets and pathways, HIF-1/VEGF was regarded as the greatest potential pathway. VEGFA and HIF-1 were expressed differently in various stages of cancer and normal tissues. There was a negative regulation of immunoreactive cells by VEGFA, which was influential for prognosis. Molecular docking confirmed the tight binding to VEGFA. This study revealed the exact effect of SWD against LM, and identified significant inhibition the expression of HIF-1α, VEGF, and CD31 in the liver microenvironment. CONCLUSION: This study clarified the active ingredients of SWD, the therapeutic targets of LM and potential molecular mechanisms. SWD may protect against LM through suppressing HIF-1/VEGF pathway.

Synergistic mechanism and environmental behavior of tank-mix adjuvants to topramezone and atrazine.

An effective way to reduce herbicide quantity is to use adjuvants in order to optimize the amount of herbicide and improve its control efficiency. In order to screen for efficient herbicide tank-mix adjuvants, improve the control of weeds in maize fields, reduce the amount of effective ingredients, and improve the adsorption and digestion behavior of herbicides in soil, this study evaluated the synergistic effects and soil behavior of four types of tank-mix adjuvants combined with herbicides. Different types of adjuvants can enhance herbicide production. Surface tension was significantly reduced by 13% after the pesticide solution was applied with AgroSpred™ Prime. The contact angle with the foliar surface was significantly reduced and solution wettability improved using Atp Lus 245-LQ-(TH). The permeability of topramezone and atrazine in leaves of Amaranthus retroflexus L. and Digitaria sanguinalis (L.) Scop. was increased by 22-96% after adding either tank-mix adjuvant. The solution drying time and maximum retention on leaves were not affected by the tank-mix adjuvants. Ethyl and methylated vegetable oils can reduce the adsorption of topramezone in the soil, thus reducing its half-life in soil. The tank-mix adjuvants had no significant effect on soil dissipation or adsorption of atrazine. AgroSpred™ Prime and Atp Lus 245-LQ-(TH) have the best synergistic effect on topramezone and atrazine in the control of A. retroflexus L. and D. sanguinalis (L.) Scop. in maize fields.

Tandem mass tag-based quantitative proteomics analyses of the spermatogenesis-ameliorating effect of Youjing granule on rats.

RATIONALE: Male infertility is a common reproductive system disease manifested as aberrant spermatogenesis and identified as "kidney deficiency and dampness" in Chinese traditional medicine. Youjing granule (YG) is a Chinese material medica based on tonifying kidneys and removing dampness. It has proven to be able to regulate semen quality in clinical application, but the underlying mechanism has not been clarified. METHODS: Using serum containing YG to treat primarily cultured spermatogonial stem cells (SSCs), the apoptotic rate and mitosis phase ratio of SSCs were measured. The liquid chromatography-tandem mass spectrometry with tandem mass tags method was applied for analyzing the serum of rats treated with YG/distilled water, and proteomic analyses were performed to clarify the mechanisms of YG. RESULTS: Totally, 111 proteins in YG-treated serum samples were differentially expressed compared with control groups, and 43 of them were identified as potential target proteins, which were further annotated based on their enrichment in Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways. Proteomic analyses showed that the mechanisms of YG may involve regulation of glycolysis, gluconeogenesis and nucleotide-binding and oligomerization domain-like receptor signaling pathway. In addition, RhoA and Lamp2 were found to be possible responders of YG through reviewing the literature. CONCLUSIONS: The results demonstrate that our serum proteomics platform is clinically useful in understanding the mechanisms of YG.

Synergistic neuroprotective effects of two natural medicinal plants against CORT-induced nerve cell injury by correcting neurotransmitter deficits and inflammation imbalance.

BACKGROUND: Lilium henryi Baker (Liliaceae) and Rehmannia glutinosa (Gaertn.) DC. (Plantaginaceae) were the traditional natural medicinal plants for the treatment of depression, but the antidepression mechanism of two plants co-decoction (Also known as Lily bulb and Rehmannia decoction (LBRD) drug-containing serum (LBRDDS) has not been elucidated in the in vitro model of depression. MATERIAL AND METHODS: Here, UHPLC-Q-TOF/MS was used to identify the active components of LBRDDS and the potential effector substance was identified by bioinformatics analysis. CORT-induced nerve cells cytotoxicity was used to investigate the neuroprotection effect of LBRDDS and the underlying pharmacological mechanisms were explored by multiple experimental methods such as molecular docking, immunofluorescence, gain- or loss-of function experiments. RESULTS: Bioactive compounds in LBRDDS absorbed from intestinal tract were transformed or metabolized by the gut microbiota including palmitic acid, adrenic acid, linoleic acid, arachidonic acid and docosapentaenoic acid. Network pharmacology analysis and molecular docking of showed fatty acid metabolism, neurotransmitter synthesis and neuroinflammation may be potential therapeutic targets of LBRDDS. LBRDDS can improve the activity of model cells, reduce cytotoxicity of lactate dehydrogenase, recover neurotransmitter imbalance, relieve inflammatory damage, down-regulate the expression of miRNA-144-3p, increase the mRNAs and protein expression level of Gad-67 and VGAT, and promote the synthesis and transport of GABA. CONCLUSION: Therefore, LBRDDS exerts neuroprotective effects by correcting neurotransmitter deficits and inflammation imbalance in the CORT-induced nerve cell injury model.

Verbascoside: A neuroprotective phenylethanoid glycosides with anti-depressive properties.

BACKGROUND: Verbascoside is a natural and water-soluble phenylethanoid glycoside found in several medicinal plants. It has extensive pharmacological effects, including antioxidative and antineoplastic actions, and a wide range of therapeutic effects against depression. PURPOSE: In this review, we appraised preclinical and limited clinical evidence to fully discuss the anti-depression capacity of verbascoside and its holistic characteristics that can contribute to better management of depression in vivo and in vitro models, as well as, its toxicities and medicinal value. METHODS: This review was prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A systematic review of 32 preclinical trials published up to April 2023, combined with a comprehensive bioinformatics analysis of network pharmacology and molecular docking, was conducted to elucidate the antidepressant mechanism of action of verbascoside. Studies included in the systematic review were obtained from 7 electronic databases: PubMed, Scopus, Web of Science, Cochrane, ResearchGate, ScienceDirect, and Google Scholar. RESULTS: Studies on the antidepressant effects of verbascoside showed that various pharmacological mechanisms and pathways, such as modulating the levels of monoamine neurotransmitters, inhibiting hypothalamic-pituitary-adrenal (HPA) axis hyperfunction and promoting neuroprotection may be involved in the process of its action against depression. Verbascoside promotes dopamine (DA) biosynthesis by promoting the expression of tyrosine hydroxylase mRNA and protein, upregulates the expression of 5-hydroxytryptamine receptor 1B (5-HT1B), prominence protein, microtubule-associated protein 2 (MAP2), hemeoxygenase-1 (HO-1), SQSTM1, Recombinant Autophagy Related Protein 5 (ATG5) and Beclin-1, and decreases the expression of caspase-3 and a-synuclein, thus exerting antidepressant effects. We identified seven targets (CCL2, FOS, GABARAPL1, CA9, TYR, CA12, and SQSTM1) and three signaling pathways (glutathione metabolism, metabolism of xenobiotics by cytochrome P450, fluid shear stress and atherosclerosis) as potential molecular biological sites for verbascoside. CONCLUSIONS: These findings provide strong evidence that verbascoside exerts its antidepressant effects through various pharmacological mechanisms. However, further multicentre clinical case-control and molecularly targeted fishing studies are required to confirm the clinical efficacy of verbascoside and its underlying direct targets.

The complete chloroplast genome of Aegle marmelos and its phylogenetic analysis.

Aegle marmelos (L.) Correa 1800, a plant belonging to the Rutaceae family, is extensively used in Tibetan medicine. We employed Illumina HiSeq reads to assemble the complete chloroplast (cp) genome of A. marmelos, which spans 144,538 bp. The genome comprises 114 genes, including 75 protein-coding genes, 31 tRNA genes, and 8 rRNA genes. It is characterized by four regions: The large single-copy (LSC) region (74,253 bp), the inverted repeat A (IRa) region (26,015 bp), the small single-copy (SSC) region (18,255 bp), and the inverted repeat B (IRb) region (26,015 bp). Phylogenomic analysis demonstrated a close relationship between A. marmelos and Citrus. The assembly of The cp genome in this study serves as a foundation for conservation efforts and phylogenetic investigations of A. marmelos, paving the way for future experimentation.

The complete chloroplast genome of Holarrhena pubescens and its phylogenetic analysis.

Holarrhena pubescens Wall. ex G. Don, 1837 is an important medicinal plant belonging to the Holarrhena genus in the Apocynaceae family. In this study, the complete chloroplast (cp) genome sequence of H. pubescens was sequenced using the Illumina NovaSeq platform. The cp genome of H. pubescens was 160,108 bp in length with 37.21% overall GC content. The cp genome of H. pubescens containing a large single-copy region (LSC, 88,685 bp), a small single-copy region (SSC, 18,671 bp), and a pair of inverted repeat regions (SSC, 26,376 bp). The cp genome encoded 129 genes, including 84 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Phylogenetic analysis based on complete protein coding genes sequences revealed that H. pubescens was closest to Beaumontia murtonii.

Safety and efficacy of acupuncture for varicocele-induced male infertility: a systematic review protocol.

INTRODUCTION: Varicocele (VC) is a common clinical disease in andrology. Among a number of ways for VC treatment, surgery is the most common one, but the measurable benefit of surgical repair was slight. A growing exploration of complementary therapies has been conducted in clinical research on acupuncture for VC, but there is no relevant systematic review and meta-analysis to assess the efficacy and safety of acupuncture for VC. METHODS AND ANALYSIS: All relevant publications published from database inception through August 2022 will be searched in three English-language databases (Embase, CENTRAL, MEDLINE) and four Chinese-language databases (China National Knowledge Infrastructure, China Science and Technology Journal Database, Chinese Biomedical Literature Database and Wanfang Data). Randomised controlled trials in English and Chinese concerned with acupuncture for patients with VC will be included. The input clinical data will be processed by the Review Manager software (RevMan). The literature will be appraised with the Cochrane Collaboration risk of bias tool. The Grading of Recommendations Assessment, Development and Evaluation system (GRADE system) will be used to evaluate the quality of evidence. ETHICS AND DISSEMINATION: This study is a secondary study based on clinical studies so it does not relate to any individual patient information or infringe the rights of participants. Hence no ethical approval is required. The results will be reported in peer-reviewed journals or disseminated at relevant conferences. PROSPERO REGISTRATION NUMBER: CRD42022316005.

Multiple PHT1 family phosphate transporters are recruited for mycorrhizal symbiosis in Eucalyptus grandis and conserved PHT1;4 is a requirement for the arbuscular mycorrhizal symbiosis.

Eucalypts engage in a mutualistic endosymbiosis with arbuscular mycorrhizal (AM) fungi to acquire mineral nutrients from soils, particularly inorganic phosphate (Pi). In return, the host plant provides organic carbons to its fungal partners. However, the mechanism by which the Eucalyptus plants acquire Pi released from the AM fungi has remained elusive. In this study, we investigated the characterization of potential PHOSPHATE TRANSPORTER1 (PHT1) family Pi transporters in AM symbiosis in Eucalyptus grandis W. Hill ex Maiden. We show that multiple PHT1 family Pi transporters were recruited for AM symbiosis in E. grandis. We further report that EgPT4, an E. grandis member of the PHT1 family, is conserved across angiosperms and is exclusively expressed in AM roots with arbuscule-containing cells and localizes to the periarbuscular membrane (PAM). EgPT4 was able to complement a yeast mutant strain defective in all inorganic Pi transporters and mediate Pi uptake. Importantly, EgPT4 is essential for improved E. grandis growth, total phosphorus concentration and arbuscule development during symbiosis. Moreover, silencing of EgPT4 led to the induction of polyphosphate accumulation relevant genes of Rhizophagus irregularis DAOM 197198. Collectively, our results unravel a pivotal role for EgPT4 in symbiotic Pi transport across the PAM required for arbuscule development in E. grandis.

Influence of Parameters on the Death Pathway of Gastric Cells Induced by Gold Nanosphere Mediated Phototherapy.

Gold nanosphere (AuS) is a nanosized particle with inert, biocompatible, easily modified surface functionalization and adequate cell penetration ability. Photothermal, photochemical, and vapor effects of AuS could be activated by irradiating with nanosecond laser to cause cell death. Hence, AuS-mediated phototherapy irradiated with nanosecond laser is a promising and minimally-invasive treatment method for cancer therapy. However, various effects require different parameters to be activated. At present, few studies have reported on the influence of parameters of AuS inducing cell death under nanosecond laser irradiation. This makes it very challenging to optimize gold-nanoparticle-mediated specific or synergistic anti-cancer therapy. In this study, we revealed the main parameters and threshold values for AuS-mediated gastric cancer phototherapy with nanosecond pulsed laser irradiation, evaluated the pathway of induced cell death, and discussed the roles of photothermal, photochemical and vapor effects which can induce the cell death. The results showed that AuS-mediated phototherapy activated with nanosecond pulsed laser is an effective method for gastric therapy, mainly based on the photochemical effect. Prolonging the incubation time could decrease the irradiation dose, increase ROS-mediated photothermal effect and vapor effect, and then quickly induce cell death to improve security.

Pomegranate Extract Improves Colitis in IL-10 Knockout Mice Fed a High Fat High Sucrose Diet.

SCOPE: The study tests the hypothesis that dietary pomegranate extract (PomX) supplementation attenuates colitis in a Western diet feed IL-10 deficient (IL-10-/-) murine model. METHODS AND RESULTS: Four-week-old male IL-10-/- mice are randomly assigned to a high fat high sucrose (HFHS) diet or a HFHS diet supplement with 0.25% PomX for 8 weeks. PomX supplementation lead to significantly lower histological score for colitis (2.6 ± 0.5 vs 3.9 ± 1.0), lower spleen weight (0.11 ± 0.01 vs 0.15 ± 0.02), and lower circulating Interleukin 6(IL-6) levels (15.8±2.2 vs 29.5±5.5) compared with HFHS fed controls. RNAseq analysis of colonic tissues showed 483 downregulated and 263 upregulated genes with PomX supplementation, which are mainly associated with inflammatory responses, defenses, and neutrophil degranulation. In addition, PomX treatment affects the cecal microbiome with increased alpha diversity, altered microbial composition, and increased levels of the tryptophan-related microbial metabolite indole propionate. CONCLUSION: The data demonstrate that dietary PomX supplementation ameliorated colitis and lowered inflammatory markers in HFHS fed IL-10-/- mice. These data support the anti-inflammatory effects of dietary PomX supplementation for IBD and a potential mediating role of gut microbiome, suggesting the need for future clinical studies to explore the use of PomX dietary supplementation in IBD patients.

Comparative Study of Sargassum fusiforme Polysaccharides in Regulating Cecal and Fecal Microbiota of High-Fat Diet-Fed Mice.

Seaweed polysaccharides represent a kind of novel gut microbiota regulator. The advantages and disadvantages of using cecal and fecal microbiota to represent gut microbiota have been discussed, but the regulatory effects of seaweed polysaccharides on cecal and fecal microbiota, which would benefit the study of seaweed polysaccharide-based gut microbiota regulator, have not been compared. Here, the effects of two Sargassum fusiforme polysaccharides prepared by water extraction (SfW) and acid extraction (SfA) on the cecal and fecal microbiota of high-fat diet (HFD) fed mice were investigated by 16S rRNA gene sequencing. The results indicated that 16 weeks of HFD dramatically impaired the homeostasis of both the cecal and fecal microbiota, including the dominant phyla Bacteroidetes and Actinobacteria, and genera Coriobacteriaceae, S24-7, and Ruminococcus, but did not affect the relative abundance of Firmicutes, Clostridiales, Oscillospira, and Ruminococcaceae in cecal microbiota and the Simpson's index of fecal microbiota. Co-treatments with SfW and SfA exacerbated body weight gain and partially reversed HFD-induced alterations of Clostridiales and Ruminococcaceae. Moreover, the administration of SfW and SfA also altered the abundance of genes encoding monosaccharide-transporting ATPase, α-galactosidase, ß-fructofuranosidase, and ß-glucosidase with the latter showing more significant potency. Our findings revealed the difference of cecal and fecal microbiota in HFD-fed mice and demonstrated that SfW and SfA could more significantly regulate the cecal microbiota and lay important foundations for the study of seaweed polysaccharide-based gut microbiota regulators.

Designed CXCR4 mimic acts as a soluble chemokine receptor that blocks atherogenic inflammation by agonist-specific targeting.

Targeting a specific chemokine/receptor axis in atherosclerosis remains challenging. Soluble receptor-based strategies are not established for chemokine receptors due to their discontinuous architecture. Macrophage migration-inhibitory factor (MIF) is an atypical chemokine that promotes atherosclerosis through CXC-motif chemokine receptor-4 (CXCR4). However, CXCR4/CXCL12 interactions also mediate atheroprotection. Here, we show that constrained 31-residue-peptides ('msR4Ms') designed to mimic the CXCR4-binding site to MIF, selectively bind MIF with nanomolar affinity and block MIF/CXCR4 without affecting CXCL12/CXCR4. We identify msR4M-L1, which blocks MIF- but not CXCL12-elicited CXCR4 vascular cell activities. Its potency compares well with established MIF inhibitors, whereas msR4M-L1 does not interfere with cardioprotective MIF/CD74 signaling. In vivo-administered msR4M-L1 enriches in atherosclerotic plaques, blocks arterial leukocyte adhesion, and inhibits atherosclerosis and inflammation in hyperlipidemic Apoe-/- mice in vivo. Finally, msR4M-L1 binds to MIF in plaques from human carotid-endarterectomy specimens. Together, we establish an engineered GPCR-ectodomain-based mimicry principle that differentiates between disease-exacerbating and -protective pathways and chemokine-selectively interferes with atherosclerosis.

The auxin-inducible phosphate transporter AsPT5 mediates phosphate transport and is indispensable for arbuscule formation in Chinese milk vetch at moderately high phosphate supply.

Phosphorus is a macronutrient that is essential for plant survival. Most land plants have evolved the ability to form a mutualistic symbiosis with arbuscular mycorrhizal (AM) fungi, which enhances phosphate (Pi) acquisition. Modulation of Pi transporter systems is the master strategy used by mycorrhizal plants to adapt to ambient Pi concentrations. However, the specific functions of PHOSPHATE TRANSPORTER 1 (PHT1) genes, which are Pi transporters that are responsive to high Pi availability, are largely unknown. Here, we report that AsPT5, an Astragalus sinicus (Chinese milk vetch) member of the PHT1 gene family, is conserved across dicotyledons and is constitutively expressed in a broad range of tissues independently of Pi supply, but is remarkably induced by indole-3-acetic acid (auxin) treatment under moderately high Pi conditions. Subcellular localization experiments indicated that AsPT5 localizes to the plasma membrane of plant cells. Using reverse genetics, we showed that AsPT5 not only mediates Pi transport and remodels root system architecture but is also essential for arbuscule formation in A. sinicus under moderately high Pi concentrations. Overall, our study provides insight into the function of AsPT5 in Pi transport, AM development and the cross-talk between Pi nutrition and auxin signalling in mycorrhizal plants.

Discovery and mechanism of intestinal bacteria in enzymatic cleavage of C-C glycosidic bonds.

C-Glycosides, a special type of glycoside, are frequently distributed in many kinds of medicinal plants, such as puerarin and mangiferin, showing various and significant bioactivities. C-Glycosides are usually characterized by the C-C bond that forms between the anomeric carbon of sugar moieties and the carbon atom of aglycon, which is usually resistant against acidic hydrolysis and enzymatic treatments. Interestingly, C-glycosides could be cleaved by several intestinal bacteria, but whether the enzymatic cleavage of C-C glycosidic bond is reduction or hydrolysis has been controversial; furthermore, whether existence of a "C-glycosidase" directly catalyzing the cleavage is not clear. Here we review research advances about the discovery and mechanism of intestinal bacteria in enzymatic cleavage of C-C glycosidic bond with an emphasis on the identification of enzymes manipulation the deglycosylation. Finally, we give a brief conclusion about the mechanism of C-glycoside deglycosylation and perspectives for future study in this field.

Chlorin-Based Photoactivable Galectin-3-Inhibitor Nanoliposome for Enhanced Photodynamic Therapy and NK Cell-Related Immunity in Melanoma.

Photodynamic therapy (PDT) is an encouraging alternative therapy for melanoma treatment and Ce6-mediated PDT has shown some exciting results in clinical trials. However, PDT in melanoma treatment is still hampered by some melanoma's protective mechanisms like antiapoptosis mechanisms and treatment escape pathways. Combined therapy and enhancing immune stimulation were proposed as effective strategies to overcome this resistance. In this paper, a Chlorin-based photoactivable Galectin-3-inhibitor nanoliposome (PGIL) was designed for enhanced Melanoma PDT and immune activation of Natural Killer (NK) cells. PGIL were synthesized by encapsulating the photosensitizer chlorin e6 and low molecular citrus pectin in the nanoliposome to realize NIR-triggered PDT and low molecular citrus pectin (LCP) release into the cytoplasm. The intracellular release of LCP inhibits the activity of galectin-3, which increases the apoptosis, inhibits the invade ability, and enhances the recognition ability of Natural Killer (NK) cells to tumor cells in melanoma cells after PDT. These effects of PGIL were tested in cells and nude mice, and the mechanisms during the in vivo treatment were preliminarily studied. The results showed that PGIL can be an effective prodrug for melanoma therapy.

Cantharidin-encapsulated thermal-sensitive liposomes coated with gold nanoparticles for enhanced photothermal therapy on A431 cells.

PURPOSE: Plasmonic nanostructure-mediated photothermal therapy (PTT) is a promising alternative therapy for the treatment of skin cancer and other diseases. However, the insufficient efficiency of PTT at irradiation levels tolerable to tissues and the limited biodegradability of nanomaterials are still crucial challenges. In this study, a novel nanosystem for PTT based on liposome-nanoparticle assemblies (LNAs) was established. MATERIALS AND METHODS: Thermal-sensitive liposomes (TSLs) encapsulating cantharidin (CTD) were coated with gold nanoparticles (GNPs) and used in near-infrared (NIR) illumination-triggered PTT and thermally induced disruption on A431 cells. RESULTS: The coated GNPs disintegrated into small particles of 5-6 nm after disruption of TSLs, allowing their clearance by the liver and kidneys. CTD encapsulated in the TSLs was released into cytoplasm after PTT. The released CTD increased the apoptosis of PTT-treated tumor cells by blocking the heat shock response (HSR) and inhibiting the expression of HSP70 and BAG3 inhibiting the expression of HSP70 and BAG3 with the synergistic enhancement of CTD, the new nanosystem CTD-encapsulated TSLs coated with GNPs (CTD-TSL@GNPs) had an efficient PTT effect using clinically acceptable irradiation power (200 mW//cm2) on A431 cells. CONCLUSION: The developed CTD-TSL@GNPs may be a promising PTT agent for clinical skin cancer therapy.

Multifunctional effect of Al2O3, SiO2 and CaO on the volatilization of PbO and PbCl2 during waste thermal treatment.

Minerals including Al2O3, SiO2 and CaO are predominant matrixes in waste, and are thought to facilitate lead (Pb) emission control. This study distinguished the inhibition of each mineral on common stable Pb-containing compounds, including highly volatile PbCl2 and less volatile PbO. Al2O3 can lower the volatilization temperature of Pb by 29 °C due to the generation of a eutectic compound and play a minor but non-negligible role in reducing Pb volatilization. The most conspicuous inhibition effect was exerted by SiO2 and a mixture of Al2O3 and SiO2, which completely integrated PbO into the glass phase at 690 °C and prohibited its migration. In contrast, SiO2 had no significant inhibition on volatile PbCl2. CaO inhibited PbO volatilization in the absence of oxygen by controlling its diffusion, while it converted PbO to Ca2PbO4 in the presence of oxygen, thus controlling Pb diffusion and decreasing the Pb volatilization ratio and rate. The influence of CaO on PbCl2 was complex because CaO can convert PbCl2 to PbO with formation of CaCl2, and CaCl2 can also be a Cl-donor for PbO. The roles of mineral matrixes in Pb conversion were shown to be important for Pb emission control.