Novel ferroptosis signature for improving prediction of prognosis and indicating gene targets from single-cell level in oral squamous cell carcinoma.

Background: Oral squamous cell carcinoma (OSCC) is one of the most prevalent kinds of cancers. Therefore, there is a pressing need to create a new risk scoring model to personalize the prognosis of OSCC patients and screen for patient-specific therapeutic agents and molecular targets. Methods: Firstly, A series of bioinformatics was performed to construct a novel ferroptosis-related prognostic model; Further, drug sensitivity analysis was used to screen for specific therapeutic agents for OSCC; Single-cell analysis was employed to investigate the enrichment of FRDEGs (ferroptosis-related differentially expressed genes) in the OSCC microenvironment; Finally, various experiments were conducted to screen and validate molecular therapeutic targets for OSCC. Results: In this study, we constructed a novel 10-FRDEGs risk scoring model. Base on the risk scoring model, we founded three potential chemotherapeutic agents for OSCC: 5Z)-7-Oxozeaenol, AT-7519, KIN001-266; In addition, FRDEGs were enriched in the epithelial cells of OSCC. Finally, we found that CA9 and CAV1 could regulate OSCC proliferation, migration and ferroptosis in vitro. Conclusion: A novel 10-FRDEGs risk scoring model can predict the prognosis of patients with OSCC.Further,5Z)-7-Oxozeaenol, AT-7519, KIN001-266 are potential chemotherapeutic agents for OSCC.Moreover, we identified CA9、CAV1 as potential molecular target for the treatment of OSCC.Our findings provide new directions for prognostic assessment and precise treatment of oral cell squamous carcinoma.

Immunomodulatory functions of microorganisms in tissue regenerative healing.

External pathogenic microorganisms and commensal microorganisms in the body have either harmful or beneficial impacts on the regenerative repair of tissues, and the immune system plays a crucial regulatory role in this process. This review summarises our current understanding of microorganism-immune system interactions, with a focus on how these interactions impact the renewal and repair ability of tissues, including skin, bone, gut, liver, and nerves. This review concludes with a discussion of the mechanisms by which microbes act on various types of immune cells to affect tissue regeneration, offers potential strategies for using microbial therapies to enhance the regenerative repair function of tissues, and suggest novel therapeutic approaches for regenerative medicine. STATEMENT OF SIGNIFICANCE: Microbiological communities have crucial impacts on human health and illness by participating in energy collection and storage and performing various metabolic processes. External pathogenic microorganisms and commensal microorganisms in the body have either harmful or beneficial impacts on the regenerative repair of tissues, and the immune system plays a critical regulatory role in this process. This study reviews the important correlation between microorganisms and the immune system and investigates the mechanism of various microorganism that participate in the regeneration and repair of tissues and organs by modulating immune system.

From nitrate to NO: potential effects of nitrate-reducing bacteria on systemic health and disease.

Current research has described improving multisystem disease and organ function through dietary nitrate (DN) supplementation. They have provided some evidence that these floras with nitrate (NO3-) reductase are mediators of the underlying mechanism. Symbiotic bacteria with nitrate reductase activity (NRA) are found in the human digestive tract, including the mouth, esophagus and gastrointestinal tract (GT). Nitrate in food can be converted to nitrite under the tongue or in the stomach by these symbiotic bacteria. Then, nitrite is transformed to nitric oxide (NO) by non-enzymatic synthesis. NO is currently recognized as a potent bioactive agent with biological activities, such as vasodilation, regulation of cardiomyocyte function, neurotransmission, suppression of platelet agglutination, and prevention of vascular smooth muscle cell proliferation. NO also can be produced through the conventional L-arginine-NO synthase (L-NOS) pathway, whereas endogenous NO production by L-arginine is inhibited under hypoxia-ischemia or disease conditions. In contrast, exogenous NO3-/NO2-/NO activity is enhanced and becomes a practical supplemental pathway for NO in the body, playing an essential role in various physiological activities. Moreover, many diseases (such as metabolic or geriatric diseases) are primarily associated with disorders of endogenous NO synthesis, and NO generation from the exogenous NO3-/NO2-/NO route can partially alleviate the disease progression. The imbalance of NO in the body may be one of the potential mechanisms of disease development. Therefore, the impact of these floras with nitrate reductase on host systemic health through exogenous NO3-/NO2-/NO pathway production of NO or direct regulation of floras ecological balance is essential (e.g., regulation of body homeostasis, amelioration of diseases, etc.). This review summarizes the bacteria with nitrate reductase in humans, emphasizing the relationship between the metabolic processes of this microflora and host systemic health and disease. The potential effects of nitrate reduction bacteria on human health and disease were also highlighted in disease models from different human systems, including digestive, cardiovascular, endocrine, nervous, respiratory, and urinary systems, providing innovative ideas for future disease diagnosis and treatment based on nitrate reduction bacteria.

Advanced Delivery Strategies for Immunotherapy in Type I Diabetes Mellitus.

Type 1 diabetes mellitus (T1DM) has been defined as an autoimmune disease characterised by immune-mediated destruction of the pancreatic ß cells, leading to absolute insulin deficiency and hyperglycaemia. Current research has increasingly focused on immunotherapy based on immunosuppression and regulation to rescue T-cell-mediated ß-cell destruction. Although T1DM immunotherapeutic drugs are constantly under clinical and preclinical development, several key challenges remain, including low response rates and difficulty in maintaining therapeutic effects. Advanced drug delivery strategies can effectively harness immunotherapies and improve their potency while reducing their adverse effects. In this review, we briefly introduce the mechanisms of T1DM immunotherapy and focus on the current research status of the integration of the delivery techniques in T1DM immunotherapy. Furthermore, we critically analyse the challenges and future directions of T1DM immunotherapy.

Family with Sequence Similarity 72 (FAM72) - A prospective biomarker for poor prognosis in patients with oral squamous cell carcinoma.

OBJECTIVE: To study the effect of FAM72 on the prognosis of patients with oral squamous cell carcinoma (OSCC) and to explore the relationship between FAM72 and OSCC. DESIGN: We used a vast array of databases and analytical vehicles to assess the relation between FAM72 and OSCC, including The Cancer Genome Atlas (TCGA), Metascape, and MethSurv. We made a preliminary verification of OSCC lines and tissues by real time quantitative polymerase chain reaction (RT-qPCR). RESULTS: FAM72 was higher in OSCC than in normal tissues. Analysis of univariate COX data indicated that elevated expression of FAM72A, FAM72B, and FAM72C in OSCC was related to poor overall survival. Moreover, FAM72B and FAM72C were independent of overall survival in multiple COX regression. FAM72A-D and its coexpressed genes in Metascape were analyzed by Gene Ontology (GO), they were enriched in cellular cycle, mitotic and DNA metabolism. Gene set enrichment analysis (GSEA) demonstrated an enrichment in pathways related to cell metabolism. Additionally, high FAM72 expression related to a worse prognosis in OSCC patients. FAM72A-D linked to the infiltration of tumor immune cell in OSCC patients. We found that methylation levels are likely linked to prognosis in OSCC patients. We used RT-qPCR to ascertain the differential FAM72B and FAM72C expression levels in cancer and paracancerous tissues of OSCC, human normal oral keratinocytes (HOK), and human tongue squamous cell carcinoma (Cal-33). CONCLUSION: Our findings indicate that FAM72B and FAM72C are potential molecular markers of poor prognosis in OSCC and may act as novel targets for OSCC treatment strategies.

Saliva - a new opportunity for fluid biopsy.

Saliva is a complex biological fluid with a variety of biomolecules, such as DNA, RNA, proteins, metabolites and microbiota, which can be used for the screening and diagnosis of many diseases. In addition, saliva has the characteristics of simple collection, non-invasive and convenient storage, which gives it the potential to replace blood as a new main body of fluid biopsy, and it is an excellent biological diagnostic fluid. This review integrates recent studies and summarizes the research contents of salivaomics and the research progress of saliva in early diagnosis of oral and systemic diseases. This review aims to explore the value and prospect of saliva diagnosis in clinical application.

The role and therapeutic potential of gut microbiome in severe burn.

Severe burn is a serious acute trauma that can lead to significant complications such as sepsis, multiple organ failure, and high mortality worldwide. The gut microbiome, the largest microbial reservoir in the human body, plays a significant role in this pathogenic process. Intestinal dysbiosis and disruption of the intestinal mucosal barrier are common after severe burn, leading to bacterial translocation to the bloodstream and other organs of the body, which is associated with many subsequent severe complications. The progression of some intestinal diseases can be improved by modulating the composition of gut microbiota and the levels of its metabolites, which also provides a promising direction for post-burn treatment. In this article, we summarised the studies describing changes in the gut microbiome after severe burn, as well as changes in the function of the intestinal mucosal barrier. Additionally, we presented the potential and challenges of microbial therapy, which may provide microbial therapy strategies for severe burn.

Hydrogels for the treatment of oral and maxillofacial diseases: current research, challenges, and future directions.

Oral and maxillofacial diseases such as infection and trauma often involve various organs and tissues, resulting in structural defects, dysfunctions and/or adverse effects on facial appearance. Hydrogels have been applied in the treatment of oral diseases and defect repair due to their three-dimensional network structure. With their biocompatible structure and unique stimulus-responsive property, hydrogels have been applied as an excellent drug-delivery system for treatments that mainly include oral mucosal diseases, wounds, periodontitis and cancer therapy. Hydrogels are also ideal scaffolds in regenerative engineering of dentin-pulp complex, periodontal tissue, bone and cartilage. This review discusses the fundamental structure of hydrogels in brief and then focuses on the characteristics and limitations in current research and applications of hydrogels. Finally, potential future directions are proposed.

More Than Just a Periodontal Pathogen -the Research Progress on Fusobacterium nucleatum.

Fusobacterium nucleatum is a common oral opportunistic bacterium that can cause different infections. In recent years, studies have shown that F. nucleatum is enriched in lesions in periodontal diseases, halitosis, dental pulp infection, oral cancer, and systemic diseases. Hence, it can promote the development and/or progression of these conditions. The current study aimed to assess research progress in the epidemiological evidence, possible pathogenic mechanisms, and treatment methods of F. nucleatum in oral and systemic diseases. Novel viewpoints obtained in recent studies can provide knowledge about the role of F. nucleatum in hosts and a basis for identifying new methods for the diagnosis and treatment of F. nucleatum-related diseases.

Research Progress, Challenges, and Breakthroughs of Organoids as Disease Models.

Traditional cell lines and xenograft models have been widely recognized and used in research. As a new research model, organoids have made significant progress and development in the past 10 years. Compared with traditional models, organoids have more advantages and have been applied in cancer research, genetic diseases, infectious diseases, and regenerative medicine. This review presented the advantages and disadvantages of organoids in physiological development, pathological mechanism, drug screening, and organ transplantation. Further, this review summarized the current situation of vascularization, immune microenvironment, and hydrogel, which are the main influencing factors of organoids, and pointed out the future directions of development.

Ferroptosis: The Silver Lining of Cancer Therapy.

Regulatory cell death has been a major focus area of cancer therapy research to improve conventional clinical cancer treatment (e.g. chemotherapy and radiotherapy). Ferroptosis, a novel form of regulated cell death mediated by iron-dependent lipid peroxidation, has been receiving increasing attention since its discovery in 2012. Owing to the highly iron-dependent physiological properties of cancer cells, targeting ferroptosis is a promising approach in cancer therapy. In this review, we summarised the characteristics of ferroptotic cells, associated mechanisms of ferroptosis occurrence and regulation and application of the ferroptotic pathway in cancer therapy, including the use of ferroptosis in combination with other therapeutic modalities. In addition, we presented the challenges of using ferroptosis in cancer therapy and future perspectives that may provide a basis for further research.

Dynamic Model for a Uniform Microwave-Assisted Continuous Flow Process of Ethyl Acetate Production.

The aim of this work is to present a model of a reaction tube with cross structures in order to improve ethyl acetate production and microwave heating uniformity. A commercial finite element software, COMSOL Multiphysics 4.3a (Newton, MA, USA), is used to build the proposed model for a BJ-22 rectangular waveguide system. Maxwell's equations, the heat conduction equation, reaction kinetics equation and Navier-Stokes equation are combined to describe the continuous flow process. The electric field intensity, the temperature, the concentration of water, the coefficient of variation (COV) and the mean temperature at different initial velocities are compared to obtain the best flow rate. Four different initial velocities are employed to discuss the effect of flow velocity on the heating uniformity and heating efficiency. The point temperatures are measured by optical fibers to verify the simulated results. The results show the electric field intensity distributions at different initial velocities have little difference, which means the initial velocity will have the decisive influence on the heating process. At lower velocity, the COV will be smaller, which means better heating uniformity. Meanwhile, the distance between each cross structure has great influence on the heating uniformity and heating efficiency, while the angle has little. The proposed model can be applied to large-scale production of microwave-assisted ethyl acetate production.

Anomalous dielectric relaxation with linear reaction dynamics in space-dependent force fields.

The anomalous dielectric relaxation of disordered reaction with linear reaction dynamics is studied via the continuous time random walk model in the presence of space-dependent electric field. Two kinds of modified reaction-subdiffusion equations are derived for different linear reaction processes by the master equation, including the instantaneous annihilation reaction and the noninstantaneous annihilation reaction. If a constant proportion of walkers is added or removed instantaneously at the end of each step, there will be a modified reaction-subdiffusion equation with a fractional order temporal derivative operating on both the standard diffusion term and a linear reaction kinetics term. If the walkers are added or removed at a constant per capita rate during the waiting time between steps, there will be a standard linear reaction kinetics term but a fractional order temporal derivative operating on an anomalous diffusion term. The dielectric polarization is analyzed based on the Legendre polynomials and the dielectric properties of both reactions can be expressed by the effective rotational diffusion function and component concentration function, which is similar to the standard reaction-diffusion process. The results show that the effective permittivity can be used to describe the dielectric properties in these reactions if the chemical reaction time is much longer than the relaxation time.

Multilevel conductance switching of memory device through photoelectric effect.

A photoelectronic switch of a multilevel memory device has been achieved using a meta-conjugated donor-bridge-acceptor (DBA) molecule. Such a DBA optoelectronic molecule responds to both the optical and electrical stimuli. The device exhibits good electrical bistable switching behaviors under dark, with a large ON/OFF ratio more than 10(6). In cooperation with the UV light, photoelectronic ternary states are addressable in a bistable switching system. On the basis of the CV measurement, charge carriers transport modeling, quantum chemical calculation, and absorption spectra analysis, the mechanism of the DBA memory is suggested to be attributed to the substep charge transfer transition process. The capability of tailoring photoelectrical properties is a very promising strategy to explore the multilevel storage, and it will give a new opportunity for designing multifunctional devices.

A novel bulk heterojunction solar cell based on a donor-acceptor conjugated triphenylamine dye.

In this communication, a novel bulk heterojunction solar cell based on an electron donor-acceptor conjugated triphenylamine dye was fabricated, and a high conversion efficiency of 1.23% was achieved under AM 1.5 illumination (100 mW cm(-2)).

Benzothiadiazole containing D-pi-A conjugated compounds for dye-sensitized solar cells: synthesis, properties, and photovoltaic performances.

Two D-pi-A conjugated molecules, BzTCA and BzTMCA, were developed through facile synthetic approaches for dye-sensitized solar cells. The investigation of the photophysical properties of BzTCA and BzTMCA both in dilute solutions and in thin films indicates that their absorption exhibits a wide coverage of the solar spectrum. The absorption features for BzTCA and BzTMCA commence at about 710 nm in solution, and at about 800 nm in the solid state. The absorption maxima (lambda(max)) for both BzTCA and BzTMCA on TiO(2) film are almost the same as those in dilute solution. Their HOMOs and LUMOs were found to partly overlap at the center of these dyes, which guarantees appreciable interactions between the donors and acceptors. The investigation of the performance of dye-sensitized solar cells fabricated from BzTCA and BzTMCA indicated that the power-conversion efficiencies are 6.04 % and 4.68 %, respectively, which could be comparable with the normal sensitizer N3. BzTMCA showed lower incident photon-to-electron conversion efficiency (IPCE) and J(sc) values relative to BzTCA, which is probably because of the weaker driving force of dye regeneration and electron injection process of BzTMCA. The IPCE responsive area reached nearly 800 nm, which provides great potential for further improvement of the photocurrent density and power-conversion efficiency. Our investigations demonstrate that both dyes BzTCA and BzTMCA could be promising candidates for dye-sensitized solar cells.

Star-shaped donor-pi-acceptor conjugated molecules: synthesis, properties, and modification of their absorptions features.

Well-defined star-shaped donor-pi-acceptor meta-conjugated systems with broad absorption features were constructed through facilely synthetic routes, in which triphenylamine (TPA) moiety as an electron donor and 2-dicyanomethylen-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran (TCF) unit as an electron acceptor were introduced in various ratios. The investigation of the photophysical properties indicated that the absorption bands of these compounds covered the whole visible range from 300 to 800 nm. For instance, the absorption onset of D1A2T2 was located at about 780 nm and peaked at 606 nm in thin film. The steady and transient emission spectra showed that these compounds possess an intramolecular energy transfer in such a meta-conjugation system, which was further supported by our computational investigation. Our systematic structural variation provides us insight into the tuning strategy of optical properties in D-pi-A systems and offered us a series of broad absorption molecules.

Solution-processed bulk heterojunction photovoltaic cells from gradient pi-conjugated thienylene vinylene dendrimers.

A series of gradient pi-conjugated dendrimers and their corresponding models based on 5,5,10,10,15,15-hexahexyltruxene moieties as nodes and oligo(thienylene vinylene) (OTVs) units with different lengths as branching arms are synthesized in good yields through Wittig-Horner reactions. All new compounds are fully characterized by (1)H and (13)C NMR spectroscopy, elemental analysis, and MALDI-TOF MS or ESI-MS. Investigation of their photophysical properties reveals that the gradient dendritic scaffold not only results in a higher molar absorption coefficient and broader absorption region than those of their corresponding model compounds, but also improves the PL quantum yields relative to the corresponding OTVs. The suitable HOMO and LUMO levels as well as excellent film forming properties make these molecules potential candidates for organic solar cells. Solution-processed bulk heterojunction solar cells using these dendrimers as donor and [6,6]-phenyl-C(61) butyric acid methyl ester as acceptor are prepared and tested. The power conversion efficiency of the devices based on G0-4-2 is 0.40 % under illumination of air mass 1.5 and 100 mW cm(-2). This is the highest record value for OTV-based materials to date. Although the absorption band of dendrimer G0-4-2 is much narrower than that of poly(3-hexylthienylene vinylene) (P3HTV), the efficiency of its solar cell device is almost twice that of the device based on P3HTV. This result shows clearly the advantage of gradient dendritic structures as active materials for photovoltaic cells.

Star-shaped D-pi-A conjugated molecules: synthesis and broad absorption bands.

Two donor-acceptor hybrid star-shaped D-pi-A molecules were facilely developed. The absorption spectra of TrTD2A and TrT2DA, which almost covered the whole visible range, were tuned by changing the ratio of donor and acceptor groups. However, the PL quantum efficiencies of TrTD2A and TrT2DA in solutions were dramatically reduced after the introduction of benzothiadiazole unit as acceptor chromophore.

Energy transfer in new D-pi-A conjugated dendrimers: their synthesis and photophysical properties.

A series of new D-pi-A conjugated dendrimers based on benzothiadiazole and triphenylamine were developed via facile synthetic approaches. By changing the types of bridges between the different functional moieties of these dendrimers, their photophysical properties, especially the intramolecular energy transfer process, were effectively modulated.