BioKA: a curated and integrated biomarker knowledgebase for animals.

Biomarkers play an important role in various area such as personalized medicine, drug development, clinical care, and molecule breeding. However, existing animals' biomarker resources predominantly focus on human diseases, leaving a significant gap in non-human animal disease understanding and breeding research. To address this limitation, we present BioKA (Biomarker Knowledgebase for Animals, https://ngdc.cncb.ac.cn/bioka), a curated and integrated knowledgebase encompassing multiple animal species, diseases/traits, and annotated resources. Currently, BioKA houses 16 296 biomarkers associated with 951 mapped diseases/traits across 31 species from 4747 references, including 11 925 gene/protein biomarkers, 1784 miRNA biomarkers, 1043 mutation biomarkers, 773 metabolic biomarkers, 357 circRNA biomarkers and 127 lncRNA biomarkers. Furthermore, BioKA integrates various annotations such as GOs, protein structures, protein-protein interaction networks, miRNA targets and so on, and constructs an interactive knowledge network of biomarkers including circRNA-miRNA-mRNA associations, lncRNA-miRNA associations and protein-protein associations, which is convenient for efficient data exploration. Moreover, BioKA provides detailed information on 308 breeds/strains of 13 species, and homologous annotations for 8784 biomarkers across 16 species, and offers three online application tools. The comprehensive knowledge provided by BioKA not only advances human disease research but also contributes to a deeper understanding of animal diseases and supports livestock breeding.

EXPERT: transfer learning-enabled context-aware microbial community classification.

Microbial community classification enables identification of putative type and source of the microbial community, thus facilitating a better understanding of how the taxonomic and functional structure were developed and maintained. However, previous classification models required a trade-off between speed and accuracy, and faced difficulties to be customized for a variety of contexts, especially less studied contexts. Here, we introduced EXPERT based on transfer learning that enabled the classification model to be adaptable in multiple contexts, with both high efficiency and accuracy. More importantly, we demonstrated that transfer learning can facilitate microbial community classification in diverse contexts, such as classification of microbial communities for multiple diseases with limited number of samples, as well as prediction of the changes in gut microbiome across successive stages of colorectal cancer. Broadly, EXPERT enables accurate and context-aware customized microbial community classification, and potentiates novel microbial knowledge discovery.

GMrepo v2: a curated human gut microbiome database with special focus on disease markers and cross-dataset comparison.

GMrepo (data repository for Gut Microbiota) is a database of curated and consistently annotated human gut metagenomes. Its main purposes are to increase the reusability and accessibility of human gut metagenomic data, and enable cross-project and phenotype comparisons. To achieve these goals, we performed manual curation on the meta-data and organized the datasets in a phenotype-centric manner. GMrepo v2 contains 353 projects and 71,642 runs/samples, which are significantly increased from the previous version. Among these runs/samples, 45,111 and 26,531 were obtained by 16S rRNA amplicon and whole-genome metagenomics sequencing, respectively. We also increased the number of phenotypes from 92 to 133. In addition, we introduced disease-marker identification and cross-project/phenotype comparison. We first identified disease markers between two phenotypes (e.g. health versus diseases) on a per-project basis for selected projects. We then compared the identified markers for each phenotype pair across datasets to facilitate the identification of consistent microbial markers across datasets. Finally, we provided a marker-centric view to allow users to check if a marker has different trends in different diseases. So far, GMrepo includes 592 marker taxa (350 species and 242 genera) for 47 phenotype pairs, identified from 83 selected projects. GMrepo v2 is freely available at: https://gmrepo.humangut.info.

HemI 2.0: an online service for heatmap illustration.

Recent high-throughput omics techniques have produced a large amount of biological data. Visualization of big omics data is essential to answer a wide range of biological problems. As a concise but comprehensive strategy, a heatmap can analyze and visualize high-dimensional and heterogeneous biomolecular expression data in an attractive artwork. In 2014, we developed a stand-alone software package, Heat map Illustrator (HemI 1.0), which implemented three clustering methods and seven distance metrics for heatmap illustration. Here, we significantly improved 1.0 and released the online service of HemI 2.0, in which 7 clustering methods and 22 types of distance metrics were implemented. In HemI 2.0, the clustering results and publication-quality heatmaps can be exported directly. For an in-depth analysis of the data, we further added an option of enrichment analysis for 12 model organisms, with 15 types of functional annotations. The enrichment results can be visualized in five idioms, including bubble chart, bar graph, coxcomb chart, pie chart and word cloud. We anticipate that HemI 2.0 can be a helpful web server for visualization of biomolecular expression data, as well as the additional enrichment analysis. HemI 2.0 is freely available for all users at: https://hemi.biocuckoo.org/.

Preparation, purification, and biochemical of fat-degrading bacterial enzymes from pig carcass compost and its application.

BACKGROUND: A lot of kitchen waste oil is produced every day worldwide, leading to serious environmental pollution. As one of the environmental protection methods, microorganisms are widely used treating of various wastes. Lipase, as one of the cleaning agents can effectively degrade kitchen waste oil. The composting process of pig carcasses produces many lipase producing microorganisms, rendering compost products an excellent source for isolating lipase producing microorganisms. To our knowledge, there are no reports isolating of lipase producing strains from the high temperature phase of pig carcass compost. METHODOLOGY: Lipase producing strains were isolated using a triglyceride medium and identified by 16S rRNA gene sequencing. The optimal fermentation conditions for maximum lipase yield were gradually optimized by single-factor tests. The extracellular lipase was purified by ammonium sulfate precipitation and Sephadex G-75 gel isolation chromatography. Amino acid sequence analysis, structure prediction, and molecular docking of the purified protein were performed. The pure lipase's enzymatic properties and application potential were evaluated by characterizing its biochemical properties. RESULTS: In this study, a lipase producing strain of Bacillus sp. ZF2 was isolated from pig carcass compost products, the optimal fermentation conditions of lipase: sucrose 3 g/L, ammonium sulfate 7 g/L, Mn2+ 1.0 mmol/L, initial pH 6, inoculum 5%, temperature 25 ℃, and fermentation time 48 h. After purification, the specific activity of the purified lipase reached 317.59 U/mg, a 9.78-fold improvement. Lipase had the highest similarity to the GH family 46 chitosanase and molecular docking showed that lipase binds to fat via two hydrogen bonds at Gln146 (A) and Glu203 (A). Under different conditions (temperature, metal ions, organic solvents, and surfactants), lipase can maintain enzymatic activity. Under different types of kitchen oils, lipase has low activity only for 'chicken oil', in treating other substrates, the enzyme activity can exceed 50%. CONCLUSIONS: This study reveals the potential of lipase for waste oil removal, and future research will be devoted to the application of lipase.

Transcriptome profiling of Microbacterium resistens MZT7 reveals mechanisms of 17ß-estradiol response and biotransformation.

17ß-estradiol (E2) pollution has attracted much attention, and the existence of E2 poses certain risks to the environment and human health. However, the mechanism of microbial degradation of E2 remains unclear. In this study, the location of E2-degrading enzymes was investigated, and transcriptome analysis of Microbacterium resistens MZT7 (M. resistens MZT7) exposed to E2. The degradation of E2 by M. resistens MZT7 was via the biological action of E2-induced intracellular enzymes. With the RNA sequencing, we found 1109 differentially expressed genes (DEGs). Among them, 773 genes were up-regulated and 336 genes were down-regulated. The results of the RNA sequencing indicated the DEGs were related to transport, metabolism, and stress response. Genes for transport, transmembrane transport, oxidoreductase activity, ATPase activity, transporter activity and quorum sensing were up-regulated. Genes for the tricarboxylic acid cycle, ribosome, oxidative phosphorylation and carbon metabolism were down-regulated. In addition, heterologous expression of one enzymes efficiently degraded E2. These findings provide some new insights into the molecular mechanism of biotransformation of E2 by M. resistens MZT7.

Development of the Emoji Faces Pain Scale and Its Validation on Mobile Devices in Adult Surgery Patients: Longitudinal Observational Study.

BACKGROUND: Measuring pain on digital devices using classic unidimensional pain scales such as the visual analog scale (VAS), numerical rating scale (NRS), and faces pain scale (FPS) has been proven to be reliable and valid. Emoji are pictographs designed in colorful form following the Unicode standard. It could be more beneficial to use emoji as faces of FPS on digital devices because emoji can easily fit on most devices and emoji are open-source so no approval would be needed before use. With a concise and user-friendly design, the emoji faces pain scale (Emoji-FPS) might be more generalizable to a wider population and more preferred by digital device users. OBJECTIVE: This study was designed to develop an Emoji-FPS as well as to evaluate its reliability, validity, and preference on mobile devices in adult patients who underwent surgery. METHODS: A modified Delphi technique with 2 rounds of web-based surveys was applied to obtain panelists' consensus on the sequence of emoji that can best represent 6 levels of pain. The initial candidate sequences of emoji for the Delphi process were constructed referring to 2 well-validated FPSs (Wong-Baker FACES pain rating scale [Wong-Baker FACES] and faces pain scale-revised [FPS-R]). Then, a prospective cohort of patients scheduled to receive perianal surgery was recruited and asked to complete a web-based questionnaire on a mobile device at 5 time points (before surgery [T1], wake up after surgery [T2], 4 hours after surgery [T3], the second day after surgery [T4], and 15 minutes after T4 [T5]). The 4 well-validated pain scales (NRS, VAS, Wong-Baker FACES, and FPS-R) were used as reference scales. RESULTS: After 2 rounds of surveys on 40 Delphi panelists, an Emoji-FPS was finally determined to represent 6 pain levels (0, 2, 4, 6, 8, and 10) from "no hurt" to "hurts worst." For validation, 300 patients were recruited and 299 were analyzed, the mean age of whom was 38.5 (SD 10.5) years, and 106 (35.5%) were women. For concurrent validity, the Emoji-FPS was highly correlated with 4 reference scales with Spearman correlation coefficient ρ ranging from 0.91 to 0.95. Excellent agreements were observed between 4 versions of Emoji-FPS (iOS, Android, Microsoft, and OpenMoji), with weighted κ coefficients ranging from 0.96 to 0.97. For discriminant validity, patients' mean preoperative Emoji-FPS score (T1) was significantly higher than their postoperative Emoji-FPS score (T4) with a difference of 1.4 (95% CI 1.3-1.6; P<.001). For test-retest reliability, Emoji-FPS scores measured at T4 and T5 were highly correlated with a ρ of 0.91. The Emoji-FPS was mostly preferred, followed by the Wong-Baker FACES, FPS-R, NRS, and VAS. CONCLUSIONS: The Emoji-FPS is reliable and valid compared with traditional pain scales in adult surgery patients.

Teaching of silver diamine fluoride for the management of dental caries and hypersensitivity - situation in the Southeast Asia dental schools.

BACKGROUND: Using silver diamine fluoride (SDF) for caries management has raised dentists' interests in Southeast Asia (SEA). However, information about the teaching of SDF in dental schools in SEA is limited. Therefore, this survey aimed to describe the extent to which SDF had been introduced into the education of undergraduate students in the dental schools in SEA. METHODS: An online questionnaire survey was conducted on the duration, method, contents, and barriers regarding the teaching of SDF. Teachers in charge of undergraduate program in pediatric dentistry and those in community dentistry in all the 90 dental schools in SEA were approached and we required each department to reply once only. Descriptive statistics and Chi-square test were used to describe and assess the differences between the two departments in the teaching of SDF. RESULTS: A total of 81 responses from the departments of 49 schools were received, giving a school-level response rate of 54% (49/90). SDF was taught in the undergraduate program in 86% (42/49) of the respondent schools, and 50% (21/42) of these schools had included SDF in the teaching for five or more years. Almost all (98%) of the departments taught SDF through lectures. Furthermore, 55% of them adopted SDF in clinical practice. Regarding the teaching content, the use of SDF for arresting cavitated caries lesion was the most commonly covered (82-97%), followed by for arresting early noncavitated lesions (69-82%), for preventing new caries development (66-79%) and for treating dental hypersensitivity (77%). There were variations in the post-treatment instruction taught. For the departments not teaching SDF, the most common reason (10/19, 53%) was that SDF was not available. CONCLUSION: SDF is covered in the undergraduate program in most of the dental schools in SEA. The use of SDF to arrest cavitated caries lesions in primary teeth is usually taught. However, other applications of SDF, such as for prevention of caries and treatment of dental hypersensitivity, are less commonly mentioned in the teaching.

Molecular Crowding Electrolytes for Stable Proton Batteries.

Proton electrochemistry is promising for developing post-lithium energy storage devices with high capacity and rate capability. However, some electrode materials are vulnerable because of the co-intercalation of free water molecules in traditional acid electrolytes, resulting in rapid capacity fading. Here, the authors report a molecular crowding electrolyte with the usage of poly(ethylene glycol) (PEG) as a crowding agent, achieving fast and stable electrochemical proton storage and expanded working potential window (3.2 V). Spectroscopic characterisations reveal the formation of hydrogen bonds between water and PEG molecules, which is beneficial for confining the activity of water molecules. Molecular dynamics simulations confirm a significant decrease of free water fraction in the molecular crowding electrolyte. Dynamic structural evolution of the MoO3 anode is studied by in-situ synchrotron X-ray diffraction (XRD), revealing a reversible multi-step naked proton (de)intercalation mechanism. Surficial adsorption of PEG molecules on MoO3 anode works in synergy to alleviate the destructive effect of concurrent water desolvation, thereby achieving enhanced cycling stability. This strategy offers possibilities of practical applications of proton electrochemistry thanks to the low-cost and eco-friendly nature of PEG additives.

Cerium oxide-based nanozyme suppresses kidney calcium oxalate crystal depositions via reversing hyperoxaluria-induced oxidative stress damage.

Oxidative stress damage to renal epithelial cells is the main pathological factor of calcium oxalate calculi formation. The development of medicine that could alleviate oxidative damage has become the key to the prevention and treatment of urolithiasis. Herein, porous nanorods CeO2 nanoparticles (CNPs) were selected from CeO2 with different morphologies as an antioxidant reagent to suppress kidney calcium oxalate crystal depositions with excellent oxidation resistance due to its larger specific surface area. The reversible transformation from Ce3+ to Ce4+ could catalyze the decomposition of excess free radicals and act as a biological antioxidant enzyme basing on its strong ability to scavenge free radicals. The protection capability of CNPS against oxalate-induced damage and the effect of CNPS on calcium oxalate crystallization were studied. CNPS could effectively reduce reactive oxygen species production, restore mitochondrial membrane potential polarity, recover cell cycle progression, reduce cell death, and inhibit the formation of calcium oxalate crystals on the cell surface in vitro. The results of high-throughput sequencing of mRNA showed that CNPs could protect renal epithelial cells from oxidative stress damage caused by high oxalate by suppressing the expression gene of cell surface adhesion proteins. In addition, CNPS can significantly reduce the pathological damage of renal tubules and inhibit the deposition of calcium oxalate crystals in rat kidneys while having no significant side effect on other organs and physiological indicators in vivo. Our results provide a new strategy for CNPS as a potential for clinical prevention of crystalline kidney injury and crystal deposition.

GMrepo: a database of curated and consistently annotated human gut metagenomes.

GMrepo (data repository for Gut Microbiota) is a database of curated and consistently annotated human gut metagenomes. Its main purpose is to facilitate the reusability and accessibility of the rapidly growing human metagenomic data. This is achieved by consistently annotating the microbial contents of collected samples using state-of-art toolsets and by manual curation of the meta-data of the corresponding human hosts. GMrepo organizes the collected samples according to their associated phenotypes and includes all possible related meta-data such as age, sex, country, body-mass-index (BMI) and recent antibiotics usage. To make relevant information easier to access, GMrepo is equipped with a graphical query builder, enabling users to make customized, complex and biologically relevant queries. For example, to find (1) samples from healthy individuals of 18 to 25 years old with BMIs between 18.5 and 24.9, or (2) projects that are related to colorectal neoplasms, with each containing >100 samples and both patients and healthy controls. Precomputed species/genus relative abundances, prevalence within and across phenotypes, and pairwise co-occurrence information are all available at the website and accessible through programmable interfaces. So far, GMrepo contains 58 903 human gut samples/runs (including 17 618 metagenomes and 41 285 amplicons) from 253 projects concerning 92 phenotypes. GMrepo is freely available at: https://gmrepo.humangut.info.

Construction of Magnetic Composite Bacterial Carrier and Application in 17ß-Estradiol Degradation.

Estrogen contamination is widespread and microbial degradation is a promising removal method; however, unfavorable environments can hinder microbial function. In this study, a natural estrogen 17ß-estradiol (E2) was introduced as a degradation target, and a new combination of bacterial carrier was investigated. We found the best combination of polyvinyl alcohol (PVA) and sodium alginate (SA) was 4% total concentration, PVA:SA = 5:5, with nano-Fe3O4 at 2%, and maltose and glycine added to promote degradation, for which the optimal concentrations were 5 g·L-1 and 10 g·L-1, respectively. Based on the above exploration, the bacterial carrier was made, and the degradation efficiency of the immobilized bacteria reached 92.3% in 5 days. The immobilized bacteria were reused for three cycles, and the degradation efficiency of each round could exceed 94%. Immobilization showed advantages at pH 5, pH 11, 10 °C, 40 °C, and 40 g·L-1 NaCl, and the degradation efficiency of the immobilized bacteria was higher than 90%. In the wastewater, the immobilized bacteria could degrade E2 to about 1 mg·L-1 on the 5th day. This study constructed a bacterial immobilization carrier using a new combination, explored the application potential of the carrier, and provided a new choice of bacterial immobilization carrier.

Trend on dental caries status and its risk indicators in children aged 12 years in China: a multilevel analysis based on the repeated national cross-sectional surveys in 2005 and 2015.

BACKGROUND: This study aimed to explore the trend and risk indicators for dental caries of children aged 12 years in China based on national oral health survey data in 2005 and 2015. METHODS: Research data were from the two latest national oral health surveys conducted in mainland China, including 30 and 31 provinces, autonomous regions, and municipalities in 2005 and 2015, respectively. Children aged 12 years were clinically examined for dental caries and dental fluorosis according to the World Health Organization criteria. Sociodemographic characteristics and oral health-related behaviours were collected using questionnaires. Multilevel zero-inflated negative binomial regression model was used to investigate the association between dental caries severity and dental fluorosis, sociodemographic characteristics, and oral health-related behaviours. RESULTS: The final analyses included 12,350 and 27,818 children surveyed in 2005 and 2015, respectively. The standardized prevalence of dental caries increased from 27.05% (95% confidence interval [CI], 24.25-28.85) in 2005 to 37.92% (95% CI, 34.94-40.90) in 2015, and the respective standardized mean decayed, missing, filled teeth (DMFT) index scores increased from 0.50 (standard deviation [SD], 1.04) to 0.83 (SD, 1.45) (P < 0.001). Fujian province had the highest increase in dental caries, followed by Liaoning, Heilongjiang, Hainan, and Yunnan. Results revealed that children who were girls, more frequently experienced dental pain, and had more recent dental visits, had significantly higher DMFT scores after adjusting for the survey year and other variables (all P < 0.05). CONCLUSIONS: Dental caries of 12-year-old children in China deteriorated from 2005 to 2015, particularly in the northeast and southwest regions. Dental caries was associated with sex, dental pain, and dental service utilization.

Host DNA contents in fecal metagenomics as a biomarker for intestinal diseases and effective treatment.

BACKGROUND: Compromised intestinal barrier (CIB) has been associated with many enteropathies, including colorectal cancer (CRC) and inflammatory bowel disease (IBD). We hypothesized that CIB could lead to increased host-derived contents including epithelial cells into the gut, change its physio-metabolic properties, and globally alter microbial community and metabolic capacities. RESULTS: Consistently, we found host DNA contents (HDCs), calculated as the percentage of metagenomic sequencing reads mapped to the host genome, were significantly elevated in patients of CRC and Crohn's disease (CD). Consistent with our hypothesis, we found that HDC correlated with microbial- and metabolic-biomarkers of these diseases, contributed significantly to machine-learning models for patient stratification and was consequently ranked as a top contributor. CD patients with treatment could partially reverse the changes of many CD-signature species over time, with reduced HDC and fecal calprotectin (FCP) levels. Strikingly, HDC showed stronger correlations with the reversing changes of the CD-related species than FCP, and contributed greatly in classifying treatment responses, suggesting that it was also a biomarker for effective treatment. CONCLUSIONS: Together, we revealed that association between HDCs and gut dysbiosis, and identified HDC as a novel biomarker from fecal metagenomics for diagnosis and effective treatment of intestinal diseases; our results also suggested that host-derived contents may have greater impact on gut microbiota than previously anticipated.

Shock Exfoliation of Graphene Fluoride in Microwave.

An unprecedented microwave-based strategy is developed to facilitate solid-phase, instantaneous delamination and decomposition of graphite fluoride (GF) into few-layer, partially fluorinated graphene. The shock reaction occurs (and completes in few seconds) under microwave irradiation upon exposing GF to either "microwave-induced plasma" generated in vacuum or "catalyst effect" caused by intense sparking of graphite at ambient conditions. A detailed analysis of the structural and compositional transformations in these processes indicates that the GF experiences considerable exfoliation and defluorination, during which sp2 -bonded carbon is partially recovered despite significant structural defects being introduced. The exfoliated fluorinated graphene shows excellent electrochemical performance as anode materials in potassium ion batteries and as catalysts for the conversion of O2 to H2 O2 . This simple and scalable method requires minimal energy input and does not involve the use of other chemicals, which is attractive for extensive research in fluorine-containing graphene and its derivatives in laboratories and industrial applications.

Backbone Structure Effect on the Thermoelectric Properties of IDT-Based p-Type Conjugated Polymers.

Four conjugated polymers are synthesized through indacenodithiohene (IDT) unit copolymerized with thiophene and thiophene derivatives. Indacenodithiohene-co-thieno[3,2-b]thiophene (IDT-TT) and indacenodithiohene-co-trans-1,2-di(2-thienyl)ethylene (IDT-TVT) exhibit better charge transport mobilities than indacenodithiohene-co-thiophene (IDT-T) and indacenodithiohene-co-3,4-ethoxylene dioxythiophene (IDT-EDOT), and also display superior thermoelectric properties after doping. Theoretical calculations suggest that IDT-EDOT and IDT-TVT have better coplanarities; the inferior performance for IDT-EDOT might be due to its low molecular weight. Meanwhile, it is worth mentioning that via the synergistic effect of two dopants (CN6CP, CuTFSI), the electrical conductivities of the polymers are further improved. The XPS data shows that the coordination interaction between copper ion and the cyano groups of CN6CP introduces cupric ions into the polymer films, which leads to the increase of the doping ratio.

Assessing the Influence of Chin Asymmetry on Perceived Facial Esthetics With 3-Dimensional Images.

PURPOSE: We used 3-dimensinonal (3D) images to assess the influence of chin asymmetry on perceived facial esthetics, investigate the cognitive boundaries of chin asymmetry among orthodontists, general dentists, and laypersons, and provide quantitative reference for clinical treatment. MATERIALS AND METHODS: A 3D facial image was obtained using the 3dMD imaging system (3dMD, Atlanta, GA). The chin was altered in 2-mm increments from 0 to 12 mm and to the left and right using the software program. These images were rated by 66 orthodontists, 89 general dentists, and 66 laypersons as 1) chin symmetry; 2) slight chin asymmetry but acceptable; and 3) serious asymmetry and treatment needed. Multivariate mixed linear regression and multivariate mixed logistic regression analyses were used for statistical data analysis. Descriptive and bivariate statistics were calculated, and statistical significance was considered present at P = .05. RESULTS: The observers progressively increased the grade ratings and the desire for surgery for greater asymmetries (P < .001). Orthodontists and general dentists could perceive a chin deviation of 4 mm to the right and 2 mm to the left, with 8-mm deviation considered to require treatment. Laypersons had a clear perception of a 4-mm chin deviation, with 8 mm to the right and 10 mm to the left considered to require treatment. The right chin deflection was more easily perceived than was the left (P < .05). CONCLUSIONS: Chin asymmetry has a great influence on facial esthetics. We found a statistically significant difference between clinicians (orthodontists and general dentists) and laypersons in the cognition of chin asymmetry and the recommendations for treatment.

Regional consistency and sample size considerations in a multiregional equivalence trial.

The main objective of a confirmatory multiregional clinical trial (MRCT) is to demonstrate the overall efficacy of test drugs in all participating regions as well as to evaluate the possibility of extrapolating the overall results to each region. With the emergence of the demands of biosimilar drugs development, some guidelines recommended using equivalence design to demonstrate the comparability of efficacy between biosimilar and reference drugs. Previous discussions about assessing regional consistency in MRCT are mainly focused on superiority or non-inferiority designs, while the extensions to equivalence designs were limited. In this work, we proposed a flexible regional consistency criterion for the MRCT with equivalence design. Based on this criterion, sample size determination and sample allocation were also discussed.

Narrow Bandgap Schottky Heterojunction Sonosensitizer with High Electron-Hole Separation Boosted Sonodynamic Therapy in Bladder Cancer.

Sonodynamic therapy (SDT) is applied to bladder cancer (BC) given its advantages of high depth of tissue penetration and nontoxicity due to the unique anatomical location of the bladder near the abdominal surface. However, low electron-hole separation efficiency and wide bandgap of sonosensitizers limit the effectiveness of SDT. This study aims to develop a TiO2-Ru-PEG Schottky heterojunction sonosensitizer with high electron-hole separation and narrow bandgap for SDT in BC. Density functional theory (DFT) calculations and experiments collectively demonstrate that the bandgap of TiO2-Ru-PEG is reduced due to the Schottky heterojunction with the characteristic of crystalline-amorphous interface formed by the deposition of ruthenium (Ru) within the shell layer of TiO2. Thanks to the enhancement of oxygen adsorption and the efficient separation of electron-hole pairs, TiO2-Ru-PEG promotes the generation of reactive oxygen species (ROS) under ultrasound (US) irradiation, resulting in cell cycle arrest and apoptosis of bladder tumor cells. The in vivo results prove that TiO2-Ru-PEG boosted the subcutaneous and orthotopic bladder tumor models while exhibiting good safety. This study adopts the ruthenium complex for optimizing sonosensitizers, contributing to the progress of SDT improvement strategies and presenting a paradigm for BC therapy.

Light-Triggered Nanozymes Remodel the Tumor Hypoxic and Immunosuppressive Microenvironment for Ferroptosis-Enhanced Antitumor Immunity.

Cancer immunotherapy holds significant promise for addressing diverse malignancies. Nevertheless, its efficacy remains constrained by the intricate tumor immunosuppressive microenvironment. Herein, a light-triggered nanozyme Fe-TCPP-R848-PEG (Fe-MOF-RP) was designed for remodeling the immunosuppressive microenvironment. The Fe-TCPP-MOFs were utilized not only as a core catalysis component against tumor destruction but also as a biocompatible delivery vector of an immunologic agonist, improving its long circulation and tumor enrichment. Concurrently, it catalyzes the decomposition of H2O2 within the tumor, yielding oxygen to augment photodynamic therapy. The induced ferroptosis, in synergy with photodynamic therapy, prompts the liberation of tumor-associated antigens from tumor cells inducing immunogenic cell death. Phototriggered on-demand release of R848 agonists stimulated the maturation of dendritic cells and reverted the tumor-promoting M2 phenotypes into adoptive M1 macrophages, which further reshaped the tumor immunosuppressive microenvironment. Notably, the nanozyme effectively restrains well-established tumors, such as B16F10 melanoma. Moreover, it demonstrates a distal tumor-inhibiting effect upon in situ light treatment. What is more, in a lung metastasis model, it elicits robust immune memory, conferring enduring protection against tumor rechallenge. Our study presents a straightforward and broadly applicable strategy for crafting nanozymes with the potential to effectively thwart cancer recurrence and metastasis.