Saliva and tongue microbiota in burning mouth syndrome: An exploratory study of potential roles.

OBJECTIVES: Burning mouth syndrome (BMS) is a chronic orofacial pain disorder with unclear etiology, in which the tongue is most commonly affected. This study aims to provide implication of the possible relationship between oral microbiota and the pathogenesis of BMS. MATERIALS AND METHODS: Saliva and tongue swabs of 15 primary BMS patients and 10 healthy controls were collected and assessed by 16S rRNA gene amplicon sequencing. The microbiota compositions were compared and bioinformatic analysis was conducted. RESULTS: Differences in microbiota compositions between BMS patients and healthy controls were revealed in both saliva and tongue samples. In saliva, Streptococcus, Rothia, and Neisseria were the predominant genus at the taxonomic level in BMS patients. In tongue samples, Prevotella, Streptococcus, and Neisseria were the dominant genus at the taxonomic level in BMS patients. LEfSe analysis and linear discriminant analysis score showed that Actinobacteria were the predominant phylum in saliva, and Selenomonas were enriched in the dorsum of the tongue of BMS patients. CONCLUSIONS: This study for the first-time reported saliva and tongue microbiota profiles were distinguished from that of healthy controls, indicating a necessity for further research on the possible relationship between oral microbes and the pathogenesis of BMS.

Atomic-scale observation of non-classical nucleation-mediated phase transformation in a titanium alloy.

Two-phase titanium-based alloys are widely used in aerospace and biomedical applications, and they are obtained through phase transformations between a low-temperature hexagonal closed-packed α-phase and a high-temperature body-centred cubic ß-phase. Understanding how a new phase evolves from its parent phase is critical to controlling the transforming microstructures and thus material properties. Here, we report time-resolved experimental evidence, at sub-ångström resolution, of a non-classically nucleated metastable phase that bridges the α-phase and the ß-phase, in a technologically important titanium-molybdenum alloy. We observed a nanosized and chemically ordered superstructure in the α-phase matrix; its composition, chemical order and crystal structure are all found to be different from both the parent and the product phases, but instigating a vanishingly low energy barrier for the transformation into the ß-phase. This latter phase transition can proceed instantly via vibrational switching when the molybdenum concentration in the superstructure exceeds a critical value. We expect that such a non-classical phase evolution mechanism is much more common than previously believed for solid-state transformations.

Simply and Cheaply Prepared Liposomal Membrane for Nanocarriers: High Encapsulation Efficiency Based on Broad Regulation of Surface Charges and pH-Switchable Performance.

The zeta potential of nanoparticles impacts their distribution and metabolism in the body as well as their interaction with medications of varying charges, hence altering therapeutic efficacy and safety. In this paper, the external charges of liposomes were regulated by utilizing a simple and economical method based on competition for protons of cationic chitosan (CS) and anion hyaluronic acid (HA). The charge regulation of a liposomal membrane is generally accomplished by adjusting the ratio of charged lipids within a liposome (e.g., cationic DOTAP or anionic DOPS), the stability of which was maintained by the coating materials of cationic chitosan (CS) or anion hyaluronic acid (HA). A series of nanoparticles could respond to pH-stimulation with adjustable surface charge. Moreover, the sizes of liposomes coated with CS and HA remain within a narrow range. In vitro cytotoxicity tests revealed that the nanocarriers were safe, and the nanoparticles containing antitumor medicines were efficient in tumor therapy. Considering liposomes with different external surface charges could be aimed at diverse therapy purposes. The strategies for regulating liposomal surface charges with high encapsulation rates and certain release cycles reported here could provide a versatile platform as carriers for the delivery of drugs and other macromolecules into human bodies.

Electroacupuncture regulates macrophage, neutrophil, and oral microbiota to alleviate alveolar bone loss and inflammation in experimental ligature-induced periodontitis.

AIM: Electroacupuncture (EA) regulates distant body physiology through somatic sensory autonomic reflexes, balances the microbiome, and can promote the release of immune cells into bloodstream, thereby inhibiting severe systemic inflammation. This makes it possible to use EA as an integrated treatment for periodontitis. MATERIALS AND METHODS: In this study, EA was applied to the ST36 acupoints in a ligature-induced periodontitis (LIP) mouse model. Then the effects of EA on periodontal myeloid cells, cytokines, and the microbiome were comprehensively analysed using flow cytometry, quantitative Polymerase Chain Reaction (PCR), and 16 S sequencing. RESULTS: Results demonstrated that EA could significantly relieve periodontal bone resorption. EA also suppressed the infiltration of macrophages and neutrophils, reduced gene expression of the pro-inflammatory cytokines IL-1ß, IL-6, IL-17 and TNF-α, and increased expression of the anti-inflammatory factors IL-4 and IL-10 in periodontal tissues. Moreover, composition of the periodontal microbiome was regulated by EA, finding that complex of microbiota, including supragingival Veillonella, subgingival Streptococcus, and subgingival Erysipelatoclostridium, were significantly reduced. Meanwhile, nitrate and nitrate-related activities of subgingival microbiota were reversed. Network analysis revealed close relationships among Veillonella, Streptococcus, and Bacteroides. CONCLUSIONS: Our study indicates that EA can effectively alleviate inflammation and bone resorption in LIP mice, potentially via the regulation of myeloid cells, cytokines, and periodontal microbiome.

Relationship between burning mouth disorder and gastroesophageal reflux disease: A scoping review.

OBJECTIVE: This study aims to provide a scoping review and attempts to uncover the possible association between burning mouth disorder and gastroesophageal reflux disease. METHODS: PubMed, EMBASE, Web of Science, the Cochrane Library, Ovid, Scopus, and a search platform (EBSCOhost) were searched from their inception to August 22, 2023. RESULTS: After screening 2795 records, 18 articles were included in the final review, comprising cross-sectional studies (n = 9), case-control studies (n = 5), case reports (n = 2), case series (n = 1), and experimental study (n = 1). The prevalence of gastroesophageal reflux disease and its extraesophageal manifestations of laryngopharyngeal reflux in burning mouth patients was reported 3.39%-23.4% and 50%-93.8%, respectively, while oral burning was reported in 9%-45% of patients with gastroesophageal reflux disease. In case-control studies, gastroesophageal reflux disease was more prevalent in patients with burning mouth disorder compared with controls. Burning mouth would be resolved after antireflux therapy in laryngopharyngeal reflux patients in case series. PH value and saliva alternation might be the possible mechanisms. CONCLUSION: The possibility of the correlation between burning mouth disorder and gastroesophageal reflux disease still needs to be clearly demonstrated through better-conducted studies. The link between them is worth to be explored in future research.

Study on the life maintenance mechanism of Eisenia fetida under low-density polyethylene stress: Based on path analysis and canonical correlation analysis.

The widespread use but low recovery rate of agricultural films has led to microplastic accumulation in farmlands, which poses a serious threat to the health of the soil ecosystem. There is an urgent need for early warning and monitoring of soil microplastics pollution, as well as the performance of bioremediation research. In this study, earthworms were used as test organisms to carry out toxicological tests under low-density polyethylene (LDPE) stress. A canonical correlation analysis model (CCA) was established to analyze the relationship between oxidative stress and microbial community. A path analysis model (PA) was also constructed to examine the detoxification mechanism of earthworms under LDPE stress. The results showed that low concentrations (100 and 500 mg/kg) of LDPE did not cause oxidative damage to earthworms but stimulated their physiological metabolism. Meanwhile, 1000 mg/kg LDPE concentrations caused oxidative damage to earthworms and altered their internal microbial community structure. Furthermore, at 1500 mg/kg LDPE concentrations, the oxidative stress to the earthworms is aggravated, and their physiological responses work in conjunction with the microbial community to cope with the adverse condition. Lastly, treatment with 2000 mg/kg LDPE induced the appearance of LDPE tolerant populations in the microbial community in vivo. Taken together, our results provide a theoretical basis for revealing the physiological response of earthworms when challenged in a polluted environment and provide a model for pollution remediation and ecological security monitoring of soil ecosystems.

Biological interactions of polystyrene nanoplastics: Their cytotoxic and immunotoxic effects on the hepatic and enteric systems.

As emerging pollutants in the environment, nanoplastics (NPs) can cross biological barriers and be enriched in organisms, posing a greatest threat to the health of livestock and humans. However, the size-dependent toxic effects of NPs in higher mammals remain largely unknown. To determine the size-dependent potential toxicities of NPs, we exposed mouse (AML-12) and human (L02) liver cell lines in vitro, and 6-week-old C57BL/6 mice (well-known preclinical model) in vivo to five different sizes of polystyrene NPs (PS-NPs) (20, 50, 100, 200 and 500 nm). We found that ultra-small NPs (20 nm) induced the highest cytotoxicity in mouse and human liver cell lines, causing oxidative stress and mitochondrial membrane potential loss on AML-12 cells. Unexpectedly in vivo, after long-term oral exposure to PS-NPs (75 mg/kg), medium NPs (200 nm) and large NPs (500 nm) induced significant hepatotoxicity, evidenced by increased oxidative stress, liver dysfunction, and lipid metabolism disorders. Most importantly, medium or large NPs generated local immunotoxic effects via recruiting and activating more numbers of neutrophils and monocytes in the liver or intestine, which potentially resulted in increased proinflammatory cytokine secretion and the tissue damage. The discrepancy in in vitro-in vivo toxic results might be attributed to the different properties of biodistribution and tissue accumulation of different sized NPs in vivo. Our study provides new insights regarding the hepatotoxicity and immunotoxicity of NPs on human and livestock health, warranting us to take immense measures to prevent these NPs-associated health damage.

Graphene Coated Ti-6Al-4V Exhibits Antibacterial and Antifungal Properties Against Oral Pathogens.

PURPOSE: This study aimed to explore the antimicrobial properties of graphene coated Ti-6Al-4V to oral pathogens. MATERIALS AND METHODS: Graphene directly synthesized on Ti-6Al-4V alloy was characterized by scanning electron microscopy (SEM) and Raman spectroscopy. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, live/dead fluorescent staining and SEM were used to analyze the antimicrobial properties of graphene coated Ti-6Al-4V alloy to Porphyromonas gingivalis (P. gingivalis), Fusobacterium nucleatum (F. nucleatum), and Candida albicans (C. albicans). Reactive oxygen species (ROS) generation was monitored to reveal the antimicrobial mechanism. RESULTS: Graphene coated Ti-6Al-4V alloy caused a significant reduction in the presence of both bacterial and fungal pathogens as compared to uncoated Ti-6Al-4V alloy. P. gingivalis, F. nucleatum, and C. albicans on graphene coated Ti-6Al-4V alloy were less active than on uncoated Ti-6Al-4V alloy, and tended to become shrunk and deformed. Meanwhile, graphene coated Ti-6Al-4V alloy induced more generation of ROS in the pathogens than uncoated Ti-6Al-4V alloy. CONCLUSIONS: Graphene coated Ti-6Al-4V alloy exhibited antimicrobial properties against oral pathogens, the induction of oxidative stress might be involved in its antimicrobial mechanisms.

Temporary Actuation of Bilayer Polymer Hydrogels Mediated by the Enzymatic Reaction.

Most soft actuators have the ability of monotonic responsiveness. That is, there is only one response action after being stimulated once. In this work, a temporarily responsive bilayer hydrogel actuator is designed and fabricated by combining a tertiary amine-containing pH-responsive layer and a urease-containing non-responsive layer. The hydrogel actuator can achieve programed deformation and recovery driven by chemical fuels (i.e., acidic urea solutions), which is essentially regulated by rapid acidification and slow enzymatic production of ammonia for recovering the pH of the system. The actuation extent and duration can be simply controlled by the fuel levels, and the repeated actuations are also possible via refueling. Furthermore, we fabricate several hydrogel devices that can display specific patterns or lift an item. This enzymatic method shows new possibilities to control the temporary actuation of polymer hydrogels potentially useful in many fields such as soft robotics, biomimetic devices, and environmental sensing.

Hot Melt Super Glue: Multi-Recyclable Polyphenol-Based Supramolecular Adhesives.

The rapid and facile synthesis of hot melt super glue (HMSG) via the formation of adhesive supramolecular networks between catechol or pyrogallol hydroxyl groups (-OH) of polyphenols and repeat units (-CH2 CH2 O-) of poly(ethylene glycol) (PEG) based on hydrogen bonds is reported. The adhesion strength of HMSG, processed by heating-cooling of polyphenols and PEG without additional solvents, can be tuned up to 8.8 MPa via changing the molecular weight of PEG and the ratio of hydrogen bonding donors and receptors. The advantages of the reported HMSG lie in the ease and scalability of the assembly process, rapid adhesion on various substrates with excellent processability, resistance of low temperature and organic solvents, and recyclable adhesion strength. The solvent-free HMSG represents a promising adhesive supramolecular network to expand the versatility and application of polyphenol-based materials.

Polystyrene microplastics induce apoptosis and necroptosis in swine testis cells via ROS/MAPK/HIF1α pathway.

Microplastics (MPs) generally refer to the plastic fragments or particles smaller than 5 mm in diameter, which are closely concerned due to their widespread presence in the environment. Recent studies have shown that MPs have a serious threat on the reproductive health of organisms. Pigs are often selected as the model animals because of their high similarity to human tissues and organs. However, there are no reports on the effects and mechanisms of MPs exposure on swine germ cells. In the present study, we established swine testis (ST) cell models exposed to 250, 500, and 1000 µg/ml polystyrene microplastics (PS-MPs, 1-10 µm), respectively. The findings revealed that PS-MPs reduced cell viability dose-dependently. Acridine orange/ethidium bromide staining and flow cytometry results indicated the occurrence of apoptosis and necrosis in ST cells under PS-MPs exposure, and the expression changes of relevant marker genes (B-cell lymphoma-2, Bcl-2 Associated X, Caspase-3, Caspase-9, Receptor-interacting protein kinase 1, Receptor-interacting protein kinase 3, Mixed lineage kinase domain-like, and Caspase-8) were clarified via quantitative real-time PCR and western blot. Further mechanistic studies found that PS-MPs treatment induced excessive intracellular reactive oxygen species (ROS) production, which promoted the phosphorylation of mitogen-activated protein kinase (MAPK) pathway-related genes (P38, c-Jun N-terminal kinase, extracellular regulated protein kinases) and activated the downstream gene hypoxia-inducible factor (HIF1α). In conclusion, our study suggests that PS-MPs treatment causes apoptosis and necroptosis in ST cells via ROS/MAPK/HIF1α signaling pathway.

Carbon Black/PDMS Based Flexible Capacitive Tactile Sensor for Multi-Directional Force Sensing.

Flexible sensing tends to be widely exploited in the process of human-computer interactions of intelligent robots for its contact compliance and environmental adaptability. A novel flexible capacitive tactile sensor was proposed for multi-directional force sensing, which is based on carbon black/polydimethylsiloxane (PDMS) composite dielectric layer and upper and lower electrodes of carbon nanotubes/polydimethylsiloxane (CNTs/PDMS) composite layer. By changing the ratio of carbon black, the resolution of carbon black/PDMS composite layer increases at 4 wt%, and then decreases, which was explained according to the percolation theory of the conductive particles in the polymer matrix. Mathematical model of force and capacitance variance was established, which can be used to predict the value of the applied force. Then, the prototype with carbon black/PDMS composite dielectric layer was fabricated and characterized. SEM observation was conducted and a ratio was introduced in the composites material design. It was concluded that the resolution of carbon sensor can reach 0.1 N within 50 N in normal direction and 0.2 N in 0-10 N in tangential direction with good stability. Finally, the multi-directional force results were obtained. Compared with the individual directional force results, the output capacitance value of multi-directional force was lower, which indicated the amplitude decrease in capacity change in the normal and tangential direction. This might be caused by the deformation distribution in the normal and tangential direction under multi-directional force.

A Two-Dimensional Metallacycle Cross-Linked Switchable Polymer for Fast and Highly Efficient Phosphorylated Peptide Enrichment.

The selective and efficient capture of phosphopeptides is critical for comprehensive and in-depth phosphoproteome analysis. Here we report a new switchable two-dimensional (2D) supramolecular polymer that serves as an ideal platform for the enrichment of phosphopeptides. A well-defined, positively charged metallacycle incorporated into the polymer endows the resultant polymer with a high affinity for phosphopeptides. Importantly, the stimuli-responsive nature of the polymer facilitates switchable binding affinity of phosphopeptides, thus resulting in an excellent performance in phosphopeptide enrichment and separation from model proteins. The polymer has a high enrichment capacity (165 mg/g) and detection sensitivity (2 fmol), high enrichment recovery (88%), excellent specificity, and rapid enrichment and separation properties. Additionally, we have demonstrated the capture of phosphopeptides from the tryptic digest of real biosamples, thus illustrating the potential of this polymeric material in phosphoproteomic studies.

Zwitterionic Phospholipidation of Cationic Polymers Facilitates Systemic mRNA Delivery to Spleen and Lymph Nodes.

Polymers represent a promising therapeutic platform for extrahepatic messenger RNA (mRNA) delivery but are hampered by low in vivo efficacy due to polyplex serum instability and inadequate endosomal escape following systemic administration. Here, we report the rational design and combinatorial synthesis of zwitterionic phospholipidated polymers (ZPPs) via cationic polymer postmodification by alkylated dioxaphospholane oxides to deliver mRNA to spleen and lymph nodes in vivo. This modular postmodification approach readily produces tunable zwitterionic species for serum resistance and introduces alkyl chains simultaneously to enhance endosomal escape, thereby transforming deficient cationic polymers to efficacious zwitterionic mRNA carriers without the need to elaborately synthesize functional monomers. ZPPs mediated up to 39 500-fold higher protein expression than their parent cationic counterparts in vitro and enabled efficacious mRNA delivery selectively in spleen and lymph nodes following intravenous administration in vivo. This zwitterionic phospholipidation methodology provides a versatile and generalizable postmodification strategy to introduce zwitterions into the side chains of cationic polymers, extending the utility of cationic polymer families for precise mRNA delivery and demonstrating substantial potential for immunotherapeutic applications.

Active-Targeting Polymeric Dual Nanosensor for Ratiometrically Measuring Proton and Oxygen Concentrations in Mitochondria.

Dysfunction of mitochondria is closely related to neurodegenerative diseases, heart diseases, cancers, and so on. Because both proton and oxygen participate in vital biochemical reactions occurring in mitochondria such as adenosine triphosphate (ATP) generation, measuring proton and oxygen concentrations in mitochondria is therefore crucial for monitoring mitochondria activities and understanding cellular behavior. For this purpose, we developed a ratiometric fluorescent nanosensor for simultaneously sensing and imaging O2 and pH in mitochondria. The steps are as follows: (1) Styrene was copolymerized with 2-aminoethyl methacrylate hydrochloride to produce amino-functionalized polymer nanoparticles. (2) The reference dye rhodamine B isothiocyanate (RBITC) and oxygen-sensitive dye platinum(II) octaethylporphyrin (PtOEP) were encapsulated into a polymer sphere during polymerization, while the pH indicator fluorescein isothiocyanate (FITC) and mitochondrial-targeting molecule (3-carboxypropyl)triphenylphosphonium bromide (TPP) were further modified on the surface of the nanoparticles. The developed nanosensor shows a narrow distribution of particle size, high sensitivity toward O2 and pH, excellent stability, and low cytotoxicity. These remarkable features of the dual nanosensor render them capable of real-time sensing and imaging of O2 and pH in mitochondria with high spatial resolution. Applying the mitochondrial-targeted dual nanosensor in HeLa cells, we quantitatively measured and imaged mitochondrial proton and oxygen concentration variations after carbonyl cyanide m-chlorophenylhydrazone (CCCP) treatment.

Determination of lipid-water partition coefficient of neutral and ionic drugs by liposome electrokinetic chromatography.

Profiling of lipid-water partition coefficients (KL/W ) of drugs is an essential issue during the early stage of drug development. In this study, two liposomes, including 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) + cholesterol (Chol) (DSPC/Chol liposomes) and soybean lecithin (SPC) + Chol (SPC/Chol liposomes), were prepared for the liposome electrokinetic chromatography (LEKC) analysis, and the logarithm of lipid-water partition coefficients (log KL/W ) of neutral and ionic drugs were determined based on an iterative method. The log KL/W values determined by the SPC/Chol or DSPC/Chol liposomes LEKC were linearly fitted, which showed a good fitting coefficient (R2 = 0.89). Furthermore, the linear relationship between the data obtained from LEKC system and octanol-water system, immobilized artificial membrane, Caco-2 cell model, and software prediction was analyzed, respectively. Results illustrated that DSPC/Chol liposomes or SPC/Chol liposomes had a good linear relationship with Caco-2 cell model, and R2 was 0.81 and 0.72, respectively. Moreover, the linear free energy relationship analysis suggested that the solute volume, hydrogen bond basicity, and J- were the main descriptors that drove the partition process of solutes in the SPC/Chol or DSPC/Chol LEKC system. In addition, the normalized properties of the SPC/Chol and DSPC/Chol LEKC systems through linear free energy relationship analysis were very close. In short, DSPC/Chol liposomes are more suitable for simulating cell membranes than SPC/Chol liposomes, and the developed LEKC is an effective partitioning model for measuring the log KL/W of drugs.

Multifunctional nanoplatforms as cascade-responsive drug-delivery carriers for effective synergistic chemo-photodynamic cancer treatment.

Synergistic chemo-photodynamic therapy has garnered attention in the field of cancer treatment. Here, a pH cascade-responsive micellar nanoplatform with nucleus-targeted ability, for effective synergistic chemo-photodynamic cancer treatment, was fabricated. In this micellar nanoplatform, 5-(4-carboxyphenyl)-10,15,20-triphenylporphyrin (Por), a photodynamic therapy (PDT) agent was utilized for carrying the novel anticancer drug GNA002 to construct a hydrophobic core, and cyclic RGD peptide (cRGD)-modified polyethylene glycol (PEG) (cRGD-PEG) connected the cell-penetrating peptide hexaarginine (R6) through a pH-responsive hydrazone bond (cRGD-PEG-N = CH-R6) to serve as a hydrophilic shell for increasing blood circulation time. After passively accumulating in tumor sites, the self-assembled GNA002-loaded nanoparticles were actively internalized into cancer cells via the cRGD ligands. Once phagocytosed by lysosomes, the acidity-triggered detachment of the cRGD-PEG shell led to the formation of R6-coated secondary nanoparticles and subsequent R6-mediated nucleus-targeted drug delivery. Combined with GNA002-induced nucleus-specific chemotherapy, reactive oxygen species produced by Por under 532-nm laser irradiation achieved a potent synergistic chemo-photodynamic cancer treatment. Moreover, our in vitro and in vivo anticancer investigations revealed high cancer-suppression efficacy of this ideal multifunctional nanoplatform, indicating that it could be a promising candidate for synergistic anticancer therapy.

Neuroinflammation changes with periodontal inflammation status during periodontitis in wild-type mice.

OBJECTIVE: To investigate neuroinflammation under different periodontal status. MATERIALS AND METHODS: Experimental periodontitis was induced by molar ligation (Lig group) or periodontal injection of lipopolysaccharide (LPS, Lps group). Periodontal status was assessed by alveolar bone resorption and periodontal inflammation. Micro-computed tomography and haematoxylin-eosin staining were performed to assess alveolar bone resorption and periodontal inflammation, respectively. Neuroinflammation was assessed by glial cell proliferation and proinflammatory factor expression. Microgliosis was determined by immunofluorescence. Astrogliosis was determined by immunohistochemistry. Expressions of tumour necrosis factor-alpha (TNF-α) and interleukin (IL)-1ß were assessed by enzyme-linked immunosorbent assay. RESULTS: Microgliosis and astrogliosis in the Lig group were notable with molar ligation for 2 weeks and 4 weeks (p < .05), but were only slightly different similar from the control group by week 12. Microgliosis and astrogliosis in the Lps group were significant with LPS injection for 4 and 8 weeks (p < .05). The groups displayed a positive correlation between the degree of periodontal inflammation and the number of glial cells (p < .05). Expressions of IL-1ß and TNF-α in the Lps group were significantly increased with LPS injection for 8 weeks (p < .05). In the Lig group, only TNF-α was highly expressed with molar ligation for 12 weeks (p < .05). CONCLUSION: Both models demonstrated that the inflammatory response in the hippocampus of mice can change during periodontitis depending on the periodontal inflammation status.

Long-term clinical benefit of Peg-IFNα and NAs sequential anti-viral therapy on HBV related HCC.

Analysis of the value of long-term antiviral therapy using sequential Peg-IFN therapy and nucleos(t)ide analogues (NAs) improves the prognosis of HBV-related HCC. HBV-related HCC patients were classified into sequential therapy with Peg-IFNα-2a and NAs, and NAs therapy alone. All patients were followed up for 5 years. The survival rate, HCC recurrence rate, Child-Pugh score, and side effects of drugs were evaluated. Firstly, the early and late cumulative survival rate was higher in patients receiving antiviral therapy compared with the control patients (p<0.05). Patients receiving sequential therapy with Peg-IFNα-2a and NAs showed a higher late cumulative survival rate and significantly reduced early and late recurrence rate, compared to those in the NA-alone group (p<0.05). Single NAs therapy only reduced the late recurrence rate in HCC-patients. Secondly, NAs therapy significantly increased the Child-Pugh score after five years of therapy (five-year therapy 7.03±1.50 vs. initial score 6.63±0.85; p<0.05), whereas the sequential therapy with Peg-IFNα-2a and NAs did not greatly alter the Child-Pugh score (6.88±1.26; p>0.05). Compared to the control patients, patients receiving antiviral therapy (NAs alone or sequential therapy with Peg-IFNα-2a and NAs) exhibited a significantly decreased Child-Pugh score (p<0.05). Compared to NAs alone, sequential therapy with Peg-IFNα-2a and NAs provided a more efficient strategy for improving both the five-year survival rate and the two-year or five-year recurrence rate in patients.

Acid-Activated Motion Switching of DB24C8 between Two Discrete Platinum(II) Metallacycles.

The precise operation of molecular motion for constructing complicated mechanically interlocked molecules has received considerable attention and is still an energetic field of supramolecular chemistry. Herein, we reported the construction of two tris[2]pseudorotaxanes metallacycles with acid-base controllable molecular motion through self-sorting strategy and host-guest interaction. Firstly, two hexagonal Pt(II) metallacycles M1 and M2 decorated with different host-guest recognition sites have been constructed via coordination-driven self-assembly strategy. The binding of metallacycles M1 and M2 with dibenzo-24-crown-8 (DB24C8) to form tris[2]pseudorotaxanes complexes TPRM1 and TPRM2 have been investigated. Furthermore, by taking advantage of the strong binding affinity between the protonated metallacycle M2 and DB24C8, the addition of trifluoroacetic acid (TFA) as a stimulus successfully induces an acid-activated motion switching of DB24C8 between the discrete metallacycles M1 and M2. This research not only affords a highly efficient way to construct stimuli-responsive smart supramolecular systems but also offers prospects for precisely control multicomponent cooperative motion.