OralExplorer: a web server for exploring the mechanisms of oral inflammatory diseases.

BACKGROUND: Oral inflammatory diseases are localized infectious diseases primarily caused by oral pathogens with the potential for serious systemic complications. However, publicly available datasets for these diseases are underutilized. To address this issue, a web tool called OralExplorer was developed. This tool integrates the available data and provides comprehensive online bioinformatic analysis. METHODS: Human oral inflammatory disease-related datasets were obtained from the GEO database and normalized using a standardized process. Transcriptome data were then subjected to differential gene expression analysis, immune infiltration analysis, correlation analysis, pathway enrichment analysis, and visualization. The single-cell sequencing data was visualized as cluster plot, feature plot, and heatmaps. The web platform was primarily built using Shiny. The biomarkers identified in OralExplorer were validated using local clinical samples through qPCR and IHC. RESULTS: A total of 35 human oral inflammatory disease-related datasets, covering 6 main disease types and 901 samples, were included in the study to identify potential molecular signatures of the mechanisms of oral diseases. OralExplorer consists of 5 main analysis modules (differential gene expression analysis, immune infiltration analysis, correlation analysis, pathway enrichment analysis and single-cell analysis), with multiple visualization options. The platform offers a simple and intuitive interface, high-quality images for visualization, and detailed analysis results tables for easy access by users. Six markers (IL1ß, SRGN, CXCR1, FGR, ARHGEF2, and PTAFR) were identified by OralExplorer. qPCR- and IHC-based experimental validation showed significantly higher levels of these genes in the periodontitis group. CONCLUSIONS: OralExplorer is a comprehensive analytical platform for oral inflammatory diseases. It allows users to interactively explore the molecular mechanisms underlying the action and regression of these diseases. It also aids dental researchers in unlocking the potential value of transcriptomics data related to oral diseases. OralExplorer can be accessed at https://smuonco.shinyapps.io/OralExplorer/  (Alternate URL: http://robinl-lab.com/OralExplorer ).

Effectiveness of Glutamine Oral Care in Reducing Oral Mucositis and Improving Oral Health After Neurosurgery: A Randomized Controlled Trial with Microbiome Analysis.

BACKGROUND Hospital-acquired infections negatively impact the health of inpatients and are highly costly to treat. Oral care reduces the microorganism number in the mouth and lungs and is essential in preventing postoperative oral inflammation, lung infection, and other complications. This study was designed to determine the effects of oral care with glutamine on oral health, oral flora, and incidence of pneumonia in patients after neurosurgery. MATERIAL AND METHODS This was a parallel, double-blind, randomized trial. Patients admitted to the Neurosurgery Department of the hospital from July to October 2021 were selected. Three hundred patients who met the inclusion criteria were randomized into 3 groups. The control group (n=100) received oral care with routine oral nursing methods with saline, whereas the experimental group (n=100) received oral care with 5% glutamine. A compound chlorhexidine group (n=100) was set as a positive control. All patients, care providers, and investigators were blinded to the group assignment. The incidence of local debris, oral mucositis, halitosis, dryness, oral mucositis disorders, and oral flora types were collected and analyzed in all groups. RESULTS The incidence of local debris, oral mucositis, halitosis, dryness, and other oral mucositis disorders in the glutamine oral care group was significantly decreased, compared with that of the control group. Oral flora types in the glutamine and chlorhexidine groups were significantly reduced. CONCLUSIONS Oral care with 5% glutamine after neurosurgery is associated with a lower incidence of oral disorders and pneumonia, and a significant reduction in oral flora.

Empyema caused by Streptococcus constellatus in a patient infected with HIV: a case report and literature review.

BACKGROUND: Empyema caused by Streptococcus constellatus (S. constellatus) is rare in patients with HIV. To analyze the clinical data of a patient living with HIV (PLHIV), who got empyema caused by S. constellatus, investigating the diagnosis and treatment of this disease through literature review to improve the clinical understanding of this disease. CASE PRESENTATION: We have reported here a 58-year-old male PLHIV with cough, wheezing, and fever for 20 days. He has a history type 2 diabetes, alcohol abuse, and a teeth extracted. Chest computed tomography revealed multiple encapsulated pleural effusions, pneumatosis, and partial compressive atelectasis in the right lung. Submission of pleural efusions timely, and then cultures revealed S. constellatus. After comprehensive treatment, including antibiotics, closed pleural drainage, and intrapleural injection of urokinase, the pleural efusion was absorbed, and chest computed tomography also confirmed the improvement. CONCLUSIONS: S. constellatus should not be neglected as a pus pathogen in patients with HIV. comprehensive treatment is important for empyema of S. constellatus.

Structure-induced Intelligence of Liquid Crystal Elastomers.

Liquid crystal elastomers (LCEs) are active soft matter-based materials with strong stimulus responsiveness and reversible, large-shape morphing capabilities. LCEs have demonstrated broad and growing applications in soft robotics, wearable devices, artificial muscles, and optical machines. The actuation intelligence and advanced functionality of LCEs depend on the smartness and properties of structures. In this review, we discuss recent advances in structure-induced intelligence of LCEs, specifically the integration of structural properties with the alignment and processing of LCEs. The structural design principles for three categories consisting of common structures (film, fiber, and tubule), smart structures (origami, kirigami, mechanical metamaterial, topology, and topography), and complex structures (monolithic and integrated) are presented. Various alignment controls of LCEs, including mechanical, surface, field-assisted, and shear alignment, are capable of inducing structural properties. The coupling and collaboration mechanisms of the LCE structures and the generated functions are discussed. The review concludes with perspectives on current challenges and emerging opportunities.

Dual-targeting multifunctional hyaluronic acid ligand-capped gold nanorods with enhanced endo-lysosomal escape ability for synergetic photodynamic-photothermal therapy of cancer.

Au nanorods (AuNRs) have attracted considerable interest as drug delivery systems because of their enhanced cell internalization and stronger drug-loading ability. In addition, the incorporation of photodynamic therapy (PDT) and photothermal therapy (PTT) into one nanosystem presents great promise to defect multiple drawbacks in cancer therapy. Herein, we fabricated a multifunctional and dual-targeting nanoplatform based on hyaluronic acid-grafted-(mPEG/triethylenetetramine-conjugated-lipoic acid/tetra(4-carboxyphenyl)porphyrin/folic acid) polymer ligand capped AuNRs (AuNRs@HA-g-(mPEG/Teta-co-(LA/TCPP/FA)) for combined photodynamic-photothermal therapy of cancer. The prepared nanoparticles displayed high TCPP loading capacity and excellent stability in different biological media. Furthermore, AuNRs@HA-g-(mPEG/Teta-co-(LA/TCPP/FA)) not only could produce a localized hyperthermia to conduct PTT, but also generate cytotoxic singlet oxygen (1 O2 ) to perform PDT under laser irradiation. Confocal imaging results disclosed that this nanoparticle endowing the specific function of polymeric ligand could enhance cellular uptake, accelerate endo/lysosomal escape, as well as produce higher reactive oxygen species. Importantly, this combination therapy strategy could also induce higher anticancer potential than PDT or PTT only against MCF-7 tumor cells in vitro. Therefore, this work presented an AuNRs-based therapeutic nanoplatform with great potential in dual-targeting and photo-induced combination therapy of cancer.

Maternal periodontal diseases affect the leukocyte profiles of umbilical cord blood: A cohort study.

AIM: This study evaluated the connection of periodontal status with the leukocyte profiles of maternal peripheral blood (MPB) and umbilical cord blood (UCB). MATERIALS AND METHODS: Ninety-nine pregnant females were recruited, and their data were collected via questionnaire and from medical records, including demographics, systemic conditions, complete blood count (CBC) and C-reaction protein (CRP) level in MPB. Full-mouth periodontal assessment was performed. CBC and CRP levels in UCB were measured after parturition. RESULTS: All subjects and their neonates were generally healthy. 30.3% of the participants presented with periodontal health condition, whereas 69.7% had different severities of periodontal diseases. The counts/percentages of eosinophils and monocytes in UCB from the subjects with periodontal diseases elevated, and the percentage of neutrophils decreased referencing to that from the counterparts (p < 0.05). There were positive correlations for total leukocyte count, neutrophils and lymphocytes counts/percentages in MPB and UCB among the periodontally healthy subjects (r > 0.4, p < 0.05), but such findings did not exist in those with periodontal diseases. Moreover, periodontal diseases independently accounted for the counts/percentages of neutrophils and eosinophils in UCB after controlling confounders in four testing models (ANCOVA, p < 0.05). CONCLUSION: Maternal periodontal diseases could to some extent disturb the leukocyte profiles of umbilical cord blood.

Integrated fecal microbiome and metabolome analysis explore the link between polystyrene nanoplastics exposure and male reproductive toxicity in mice.

Microplastics (MPs) and nanoplastics (NPs) are novel environmental pollutants that are ubiquitous in the environment and everyday life. NPs can easily enter the tissues and have more significant potential health risks due to their smaller diameter. Previous studies have shown that NPs can induce male reproductive toxicity, but the detailed mechanisms remain uncertain. In this study, intragastric administration treated mice with polystyrene NPs (PS-NPs, 50, and 90 nm) at 3 and 15 mg/mL/day doses for 30 days. Then, the fresh fecal samples were collected from those mice that the exposure doses of 50 nm PS-NPs at 3 mg/mL/day and 90 nm at 15 mg/mL/day for subsequent investigations of 16S rRNA and metabolomics according to significant toxicological effects (Sperm number, viability, abnormality, and testosterone level). The conjoint analysis findings indicated that PS-NPs disrupted the homeostasis of the gut microbiota, metabolism, and male reproduction, suggesting that abnormal gut microbiota-metabolite pathways may be important in PS-NPs-induced male reproductive toxicity. Meanwhile, the common differential metabolites such as 4-deoxy-Erythronic acid, 8-iso-15-keto-PGE2, apo-10'-violaxanthin, beta-D-glucosamine, isokobusone, oleamide, oxoadipic acid, sphingosine induced by 50 and 90 nm PS-NPs might be used as biomarkers to explore PS-NPs-induced male reproductive toxicity. In addition, this study systematically demonstrated that nano-scale PS-NPs induced male reproductive toxicity via the crosstalk of gut microbiota and metabolites. It also provided valuable insights into the toxicity of PS-NPs, which was conducive to reproductive health risk assessment for public health prevention and treatment.

Brassinosteroids Regulate the Water Deficit and Latex Yield of Rubber Trees.

Brassinolide (BR) is an important plant hormone that regulates the growth and development of plants and the formation of yield. The yield and quality of latex from Hevea brasiliensis are regulated by phytohormones. The understanding of gene network regulation mechanism of latex formation in rubber trees is still very limited. In this research, the rubber tree variety CATAS73397 was selected to analyze the relationship between BR, water deficit resistance, and latex yield. The results showed that BR improves the vitality of rubber trees under water deficit by increasing the rate of photosynthesis, reducing the seepage of osmotic regulatory substances, increasing the synthesis of energy substances, and improving the antioxidant system. Furthermore, BR increased the yield and quality of latex by reducing the plugging index and elevating the lutoid bursting index without decreasing mercaptan, sucrose, and inorganic phosphorus. This was confirmed by an increased expression of genes related to latex flow. RNA-seq analysis further indicated that DEG encoded proteins were enriched in the MAPK signaling pathway, plant hormone signal transduction and sucrose metabolism. Phytohormone content displayed significant differences, in that trans-Zeatin, ethylene, salicylic acid, kinetin, and cytokinin were induced by BR, whereas auxin, abscisic acid, and gibberellin were not. In summary, the current research lays a foundation for comprehending the molecular mechanism of latex formation in rubber trees and explores the potential candidate genes involved in natural rubber biosynthesis to provide useful information for further research in relevant areas.

Comparison of maxillary anterior mathematical proportions among 3 dental arch forms.

STATEMENT OF PROBLEM: Race and sex differences in the mathematical proportions of maxillary anterior teeth have been evaluated. However, studies exploring the relationship between the mathematical proportion of maxillary anterior teeth and maxillary dental arch form are lacking. PURPOSE: The purpose of this clinical study was to determine if a correlation exists between the mathematical proportions of maxillary anterior teeth and 3 dental arch forms. MATERIAL AND METHODS: Three hundred young participants were recruited according to predefined criteria, and images and maxillary casts were obtained. The perceived width and length of the maxillary anterior teeth were measured on the images by using a software program, and mathematical proportions, including width ratios and width-to-length ratios, were calculated for each. The casts were used to categorize each specimen into tapered, ovoid, or square groups by using a specific classification method, and the width ratios and width-to-height ratios of the 3 dental arch forms were compared. Statistical analysis was performed by using analysis of variance (ANOVA) or the Kruskal-Wallis H test to compare the mathematical proportions of maxillary anterior teeth among the 3 dental arch forms (α=.05). The intraclass correlation coefficient (ICC) was used to test the reliability of the investigators. RESULTS: Except for the width-to-length ratios of the central incisor, mathematical proportions were affected by the dental arch form. The perceived width ratios of the maxillary lateral incisor-to-central incisor gradually increased from the tapered arch to the ovoid arch and from the ovoid arch to the square arch, with mean ±standard deviation values of 0.71 ±0.04, 0.73 ±0.05, and 0.79 ±0.06, respectively. For the maxillary perceived width ratios of canine-to-lateral incisor, the ovoid arch had the maximum perceived width ratios (0.86 ±0.10), followed by the tapered (0.82 ±0.10) and square arches (0.77 ±0.11). The width-to-length ratios of the central incisor were not affected by the arch form (P=.075), and the width-to-length ratios of the lateral incisor increased as the arch form became flat, with respective values of 0.70 ±0.10, 0.74 ±0.10, and 0.76 ±0.10. For the width-to-length ratios of the canine, the ovoid arch had the maximum perceived width ratios (0.58 ±0.10), followed by the tapered (0.53 ±0.10) and square arches (0.52 ±0.10). CONCLUSIONS: The mathematical proportions varied among the 3 dental arch forms, and the dental arch form should be considered during the prosthodontic design of maxillary anterior teeth.

Multimodal Self-sustainable Autonomous Locomotions of Light-driven Seifert Ribbon Actuators based on Liquid Crystal Elastomers.

Multimodal self-sustainable autonomous locomotions integrated into one individual system, are high-level intelligent behavioral characteristics of living organisms and are the scientific hotspot of bionic soft actuators. Here, we report a light-fueled soft actuator with multimodal self-sustainable movements based on a Seifert ribbon bounded by a Hopf link. The Seifert ribbon actuator can self-sense the illumination area adjustment, and the actuation component becomes either a discontinuous strip-like structure or a continuous toroidal structure, which can realize adaptive switches between self-sustained oscillatory and rotary motions. The two motion modes are applied to the self-oscillatory piezoelectric generation and self-rotational work multiplication of cargo transport, respectively. The unique smartness of Seifert surface topology advances the level of actuation intelligence with broad implications for the adaptability, multifunctionality, and autonomy of soft robots.

Synthesis of Photo, Oxidative, and Reductive Triple-Stimuli-Responsive Block Copolymer Micelles as Nanocarriers for Controlled Release.

With the rapid development of nanotechnology, stimuli-responsive nanomaterials have provided an alternative for designing controllable drug delivery systems due to their spatiotemporally controllable properties. The environment of the human body is complex and cancer cells proliferate rapidly; the traditional nanocarriers could not release the loaded drugs sufficiently, and the release level of the drug is not sufficient for the requirement of treatment. Herein, a photoresponsive, glutathione, and reactive oxygen species block copolymer mPEG2k-ONB-SS-PO-mPEG2k is prepared by Cu(I)-catalyzed azide-alkyne cycloaddition click polymerization. The ο-nitrobenzyl groups, peroxalate ester bonds, disulfide bonds, and triazole units are regularly and repeatedly arranged in hydrophobic blocks. The photo, oxidative, and reductive responsive characteristics of the copolymers in different conditions were investigated by ultraviolet and visible spectrophotometry, dynamic light scattering, and transmission electron microscopy. Nile Red is encapsulated into the core of micelles as a model drug and exhibits the drug release behaviors in various environments. This research provides a way to design potential drug carriers and a promising platform for efficient intracellular drug delivery in cancer therapy.

Diagnostic performance of the AAP/EFP classification and the CDC/AAP case definition among pregnant women and a practical screening tool for maternal periodontal diseases.

BACKGROUND AND OBJECTIVE: There is a limited number of studies on the performance assessment of the 2017 AAP/EFP classification and the CDC/AAP case definition among pregnant females. This study evaluated the agreement between these two systems and explored a practical tool for screening maternal periodontal diseases by general dentists. MATERIALS AND METHODS: Totally, 204 systemically healthy females at different phases of pregnancy underwent a full-mouth periodontal examination. Demographic characteristics, lifestyles, and systemic conditions were recorded. Referring to the CDC/AAP definition, the diagnostic performance of the AAP/EFP classification was evaluated by the area under the ROC curve (AUC) and statistical tests (e.g., Youden's index and kappa coefficient). Additionally, a modified scoring system of the FDI Periodontal Diseases Chairside Guide (FDI-CG) was formulated with the addition of pregnancy for testing accordingly. RESULTS: Overall, there were 22.1% of the participants in early phase of pregnancy (7-13 weeks) and 77.9% in late phase (34-36 weeks). The majority of them were below 35 years and non-smokers without gestational diabetes. Notably, 30.9% of subjects presented with Moderate/Severe periodontitis (CDC/AAP), and 35.8% with Stages II-IV periodontitis (AAP/EFP). Referring to the CDC/AAP definition, the AUC, Youden's index, and κ of the AAP/EFP classification were 0.979, 0.890, and 92.9%, respectively. The modified FDI-CG system improved the AUC (0.815), Youden's index (63.0%), and κ (0.544) with reference to the original one. CONCLUSIONS: This study shows that the AAP/EFP classification is in high agreement with the CDC/AAP definition among the pregnant women. The phases of pregnancy-integrated FDI scoring system may serve as a convenient screening tool for maternal periodontal diseases in general dental practice.

Periodontitis links to concurrent metabolic disorders and abnormal liver function in pregnant women.

OBJECTIVE: This cross-sectional study investigated the association of periodontitis with the metabolic status and hepatic function in pregnant women. MATERIALS AND METHODS: Full-mouth periodontal conditions, metabolic profiles, and hepatic function were assessed in 219 self-reported healthy pregnant females. The association of periodontal status with the systemic parameters was evaluated by parametric and non-parametric tests, and multivariate logistic regression analysis. RESULTS: Overall, periodontal status was positively associated with the metabolic profiles and hepatic function test results. The subjects with periodontitis exhibited higher levels of body mass index (BMI) (p < 0.01) and serum aspartate transaminase (AST) (p < 0.05), elevated diastolic blood pressure (DBP) (p < 0.05), and lower levels of high-density lipoprotein cholesterol (p < 0.05) than those of the counterparts. The periodontitis severity was strongly correlated with BMI and AST levels, and the extent of periodontal inflammation was related to DBP (p < 0.01). The periodontitis patients at 34-36 gestational weeks showed higher blood pressure and AST levels than those of non-periodontitis subjects (p < 0.05). CONCLUSION: Our findings on the notable links of periodontitis to concurrent metabolic disorders and abnormal liver function in pregnant women highlight the need of proactive integration of regular periodontal screening and healthcare in maternal programs for promoting optimal health and wellbeing of mothers-to-be and newborns.

CD44-Targeted and Enzyme-Responsive Photo-Cross-Linked Nanogels with Enhanced Stability for In Vivo Protein Delivery.

One of the biggest challenges of the protein delivery system is to realize stable and high protein encapsulation efficiency in blood circulation and rapid release of protein in the targeted tumor cells. To overcome these hurdles, we fabricated enzyme-responsive photo-cross-linked nanogels (EPNGs) through UV-triggered chemical cross-linking of cinnamyloxy groups in the side chain of PEGylation hyaluronic acid (HA) for CD44-targeted transport of cytochrome c (CC). The EPNGs showed high loading efficiency and excellent stability in different biological media. Notably, CC leakage effectively suppressed under physiological conditions but accelerated release in the presence of hyaluronidase, an overexpressed enzyme in tumor cells. Moreover, thiazolylblue tetrazolium bromide (MTT) results indicated that the vacant EPNGs showed excellent nontoxicity, while CC-loaded EPNGs exhibited higher killing efficiency to CD44-positive A549 cells than to CD44-negative HepG2 cells and free CC. Confocal images confirmed that CC-loaded EPNGs could effectively be internalized by CD44-mediated endocytosis pathway and rapidly escape from the endo/lysosomal compartment. Human lung tumor-bearing mice imaging assays further revealed that CC-loaded EPNGs actively target tumor locations. Remarkably, CC-loaded EPNGs also exhibited enhanced antitumor activity with negligible systemic toxicity. These results implied that these EPNGs have appeared as stable and promising nanocarriers for tumor-targeting protein delivery.

Placebo modulation in orthodontic pain: a single-blind functional magnetic resonance study.

OBJECTIVES: The mechanism of orthodontic pain modulation with a placebo remains largely unknown. This study aimed to investigate the placebo modulation of brain activity associated with orthodontic pain using functional magnetic resonance imaging (fMRI). METHODS: This longitudinal fMRI experiment recruited 23 volunteers and a self-contrast method was used. At first time, the participants were scanned without placebo (first period), followed by a 30-day washout, the participants were scanned again with placebo administration (second period). Orthodontic pain was caused by orthodontic separators placement between the lower right molars for both two periods. 24 h after placement, the MRI scans were taken, including a bite/non-bite task fMRI and a resting-state fMRI. A generalized linear model was used to identify pain-regulating network from task fMRI. Functional connectivity analysis of pain-related brain regions was performed to study the placebo effect on connectivity of pain-regulating networks using resting-state fMRI. RESULTS: The results of brain activation patterns were largely similar under placebo and non-placebo conditions. Under the non-placebo condition, the activities in multiple brain regions, including the pre-central gyrus, superior frontal gyrus, superior parietal lobule, and supramarginal gyrus, were significantly higher than that of the placebo condition. However, the anterior cingulate cortex (ACC) was activated under the non-placebo condition but not in the placebo one. The functional connectivities between ACC and orbitofrontal cortex, and the dorsolateral prefrontal cortex and orbitofrontal cortex were reduced under placebo condition. CONCLUSION: Participants demonstrated similar brain activation patterns for orthodontic pain with or without placebos. With placebo, reduced activation in primary sensory cortex and decreased activation in ACC indicated that ACC could be fundamental in analgesia.

Molecular epidemiology of enteroviruses associated with severe hand, foot and mouth disease in Shenzhen, China, 2014-2018.

In this study, we investigated the epidemiology and molecular characteristics of enteroviruses associated with severe hand, foot and mouth disease (HFMD) in Shenzhen, China, during 2014-2018. A total of 137 fecal specimens from patients with severe HFMD were collected. Enterovirus (EV) types were determined using real-time reverse transcription polymerase chain reaction (RT-PCR), RT nested PCR, and sequencing. Sequences were analyzed using bioinformatics programs. Of 137 specimens tested, 97 (70.8%), 12 (8.8%), and 10 (7.3%) were positive for EV-A71, coxsackievirus A6 (CVA6), and CVA16, respectively. Other pathogens detected included CVA2 (2.9%, 4/137), CVA10 (2.9%, 4/137), CVA5 (0.7%, 1/137), echovirus 6 (E6) (0.7%, 1/137) and E18 (0.7%, 1/137). The most frequent complication in patients with proven EV infections was myoclonic jerk, followed by aseptic encephalitis, tachypnea, and vomiting. The frequencies of vomiting and abnormal eye movements were higher in EV-A71-infected patients than that in CVA6-infected or CVA16-infected patients. Molecular phylogeny based on the complete VP1 gene revealed no association between the subgenotype of the virus and disease severity. Nevertheless, 12 significant mutations that were likely to be associated with virulence or the clinical phenotype were observed in the 5'UTR, 2Apro, 2C, 3A, 3Dpol and 3'UTR of CVA6. Eight significant mutations were observed in the 5'UTR, 2B, 3A, 3Dpol and 3'UTR of CVA16, and 10 significant mutations were observed in the 5'UTR, VP1, 3A and 3Cpro of CVA10. In conclusion, EV-A71 is still the main pathogen causing severe HFMD, although other EV types can also cause severe complications. Potential virulence or phenotype-associated sites were identified in the genomes of CVA6, CVA16, and CVA10.

Recent Advances of pH-Induced Charge-Convertible Polymer-Mediated Inorganic Nanoparticles for Biomedical Applications.

The incorporation of functional polymers and inorganic nanoparticles into nanoplatforms has the potential to produce personalized nanomedicine systems for further biomedical applications. Polymers that endow inorganic nanoparticles with unique surface properties for prolonged blood circulation and improved tumor targeting and cellular uptake are especially desired. pH-induced charge-switchable polymers are sensitive to the pH of the tumor environment and maintain a negative or neutral charge in blood circulation, increasing their circulation time and enhancing tumor accumulation via the enhanced permeability and retention effect. This type of polymer further transforms its charge to positive in acidic tumor locations to promote cellular uptake. Furthermore, the combination of pH-induced charge-switchable polymers with various inorganic nanoparticles (e.g., magnetic nanoparticles, gold nanoparticles, quantum dots, and upconversion materials) activates their intrinsic functions in in situ diagnosis and disease therapy. This review briefly overviews the recent progress in the development and application of various pH-induced charge-convertible polymers functionalized with different types of inorganic nanoparticles for different biomedical applications. More importantly, future developments in this field are also discussed.

Global cytokine/chemokine profile identifies potential progression prediction indicators in hand-foot-and-mouth disease patients with Enterovirus A71 infections.

OBJECTIVE: New clinical indicators are urgently needed for predicting the progression and complications of hand-foot-and-mouth disease (HFMD) caused by EV-A71 infections. MATERIALS AND METHODS: Serum specimens from 132 EV-A71 HFMD patients and 73 health children were collected during 2012-2014 in Shenzhen, China. The specific cytokines/chemokines were detected with a 274-human cytokine antibody array, followed by a 38-inflammation cytokine array, and further validated by ELISA. RESULTS: Cytokines varied in different severity of EV-A71 HFMD patients. The ROC curve analysis revealed 5 serum cytokines with high sensitivity and specificity in predicting the disease progression. Eotaxin, IL-8 and IP-10 have showed high AUC values (0.90-0.95) for discrimination between the health controls and the patient group. The three cytokines showed high sensitivity (80-91%) and specificity (88-95%). MMP-8 had a high sensitivity and specificity to predict mild HFMD (100%, 100%). IL-1b and leptin discriminated the severe/critical group from the mild group (79% and 69% in sensitivity, 73% and 63% in specificity). CONCLUSIONS: Eotaxin, IP-10 and IL-8 could be potential indicators for predicting HFMD progression with EV-A71 infection. MMP-8 is a specific indicator for mild infection, while IL-1b and leptin display potential for predicting the severity and criticality.

Exfoliation and Sensitization of 2D Carbon Nitride for Photoelectrochemical Biosensing under Red Light.

Two-dimensional carbon nitride (CN) has drawn increasing attention as a conjugated metal-free polymer for photoelectrochemical (PEC) biosensing. However, CN only absorbs ultraviolet and very limited visible light (λ<460 nm), which poses potential risks for biomolecules and also cannot pass through tissue for in vivo detection. Herein, simultaneous exfoliation and functionalization of CN nanosheets (CNNS) with copper phthalocyanine (TsCuPc) simply by mechanical milling, thanks to the delicate π-π interaction between them, is reported. Moreover, due to energy-level matching, an effective donor-acceptor (D-A) interaction with much-improved photocurrent under irradiation with red light (λ>630 nm) was observed for the as-prepared CNNS-TsCuPc. As an example, dopamine in blood was detected by using red light by a CNNS-TsCuPc photoelectrode with uncompromised linear range and detection limit, as well high selectivity. As one of the few successful demonstrations of red-light-responsive PEC sensing systems, this work takes a first step toward future in vivo applications by enriching the optoelectronic properties of CN with task-specific antenna molecules via D-A interaction.

Novel Class of Ultrasound-Triggerable Drug Delivery Systems for the Improved Treatment of Tumors.

The controlled release of anticancer drugs at the tumor site is a central challenge in treating cancer. To achieve this goal, our strategy was based on tumor-specific targeting and ultrasound-triggered release of an anticancer agent from liposomal nanocarriers. To enhance the ultrasound-triggered drug release, we incorporated a lipophilic sonosensitizer, chlorin e6 (Ce6) ester, into the lipid bilayer of liposomes. Additionally, asparagine-glycine-arginine (NGR) that binds to CD13, which is overexpressed in tumor cells, was introduced into these liposomes. Under the navigation effects of the NGR, the novel ultrasound-triggerable NGR-modified liposomal nanocarrier (NGR/UT-L) accumulates in tumor sites. Once irradiated by ultrasound in tumor tissues, the sonodynamic effect produced by Ce6 could create more efficient disruptions of the lipid bilayer of the liposomal nanocarriers. After encapsulating doxorubicin (DOX) as the model drug, the ultrasound triggered lipid bilayer breakdown can spring the immediate release of DOX, making it possible for ultrasound-responsive chemotherapy with great selectivity. By combining tumor-specific targeting and stimuli-responsive controlled release into one system, NGR/UT-L demonstrated a perfect antitumor effect. Moreover, this report provides an example of controlled-release by means of a novel class of ultrasound triggering systems.