Neurotoxic ß-amyloid oligomers cause mitochondrial dysfunction-the trigger for PANoptosis in neurons.

As the global population ages, the incidence of elderly patients with dementia, represented by Alzheimer's disease (AD), will continue to increase. Previous studies have suggested that ß-amyloid protein (Aß) deposition is a key factor leading to AD. However, the clinical efficacy of treating AD with anti-Aß protein antibodies is not satisfactory, suggesting that Aß amyloidosis may be a pathological change rather than a key factor leading to AD. Identification of the causes of AD and development of corresponding prevention and treatment strategies is an important goal of current research. Following the discovery of soluble oligomeric forms of Aß (AßO) in 1998, scientists began to focus on the neurotoxicity of AßOs. As an endogenous neurotoxin, the active growth of AßOs can lead to neuronal death, which is believed to occur before plaque formation, suggesting that AßOs are the key factors leading to AD. PANoptosis, a newly proposed concept of cell death that includes known modes of pyroptosis, apoptosis, and necroptosis, is a form of cell death regulated by the PANoptosome complex. Neuronal survival depends on proper mitochondrial function. Under conditions of AßO interference, mitochondrial dysfunction occurs, releasing lethal contents as potential upstream effectors of the PANoptosome. Considering the critical role of neurons in cognitive function and the development of AD as well as the regulatory role of mitochondrial function in neuronal survival, investigation of the potential mechanisms leading to neuronal PANoptosis is crucial. This review describes the disruption of neuronal mitochondrial function by AßOs and elucidates how AßOs may activate neuronal PANoptosis by causing mitochondrial dysfunction during the development of AD, providing guidance for the development of targeted neuronal treatment strategies.

DesTrans: A medical image fusion method based on Transformer and improved DenseNet.

Medical image fusion can provide doctors with more detailed data and thus improve the accuracy of disease diagnosis. In recent years, deep learning has been widely used in the field of medical image fusion. The traditional method of medical image fusion is to operate by superimposing and other methods of pixels. The introduction of deep learning methods has improved the effectiveness of medical image fusion. However, these methods still have problems such as edge blurring and information redundancy. In this paper, we propose a deep learning network model based on Transformer and an improved DenseNet network module integration that can be applied to medical images and solve the above problems. At the same time, the method can be moved to natural images. The use of Transformer and dense concatenation enhances the feature extraction capability of the method by limiting the feature loss which reduces the risk of edge blurring. We compared several representative traditional methods and more advanced deep learning methods with this method. The experimental results show that the Transformer and the improved DenseNet network module have a strong capability of feature extraction. The method yields good results both in terms of visual quality and objective image evaluation metrics.

Antibiotics daptomycin interacts with S protein of SARS-CoV-2 to promote cell invasion of Omicron (B1.1.529) pseudovirus.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has posed enormous challenges to global public health. The use of antibiotics has greatly increased during the SARS-CoV-2 epidemic owing to the presence of bacterial co-infection and secondary bacterial infections. The antibiotics daptomycin (DAP) is widely used in the treatment of infectious diseases caused by gram-positive bacteria owing to its highly efficient antibacterial activity. It is pivotal to study the antibiotics usage options for patients of coronavirus infectious disease (COVID-19) with pneumonia those need admission to receive antibiotics treatment for bacterial co-infection in managing COVID-19 disease. Herein, we have revealed the interactions of DAP with the S protein of SARS-CoV-2 and the variant Omicron (B1.1.529) using the molecular docking approach and Omicron (B1.1.529) pseudovirus (PsV) mimic invasion. Molecular docking analysis shows that DAP has a certain degree of binding ability to the S protein of SARS-CoV-2 and several derived virus variants, and co-incubation of 1-100 µM DAP with cells promotes the entry of the PsV into human angiotensin-converting enzyme 2 (hACE2)-expressing HEK-293T cells (HEK-293T-hACE2), and this effect is related to the concentration of extracellular calcium ions (Ca2+). The PsV invasion rate in the HEK-293T-hACE2 cells concurrently with DAP incubation was 1.7 times of PsV infection alone. In general, our findings demonstrate that DAP promotes the infection of PsV into cells, which provides certain reference of antibiotics selection and usage optimization for clinicians to treat bacterial coinfection or secondary infection during SARS-CoV-2 infection.

Ozone degradation of tetracycline hydrochloride enhanced by magnetic nanofluid composed of Fe3O4 nanoparticles.

Magnetic Fe3O4 nanoparticles were added into the aqueous phase to form nanofluid systems, in which ozone was used for the oxidation of tetracycline hydrochloride (TC) in the solution. The nanomaterials were characterized using SEM, XRD, EDS, and FT-IR. The effects of nanoparticles size, addition ratio, and number of cycles on the process of ozone oxidation of TC were investigated. The results indicated that the addition ratio of nanoparticles have a certain impact on the performance of ozone oxidation. When the addition ratio increased from 0.02% to 0.4%, the removal rate of TC in the solution was improved significantly. Besides, the particle size of nanoparticles showed a greater impact on ozone oxidation. At the nanoscale, Fe3O4 nanoparticles exhibited significant strengthening properties, which is attributed to the construction of nanofluid systems. The removal rate of TC in solution decreased obviously with the increase of nanoparticles size. The Fe3O4 nanoparticles with particle size of 20 nm showed the most significant effect on TC degradation. The recycling experiment showed that magnetic Fe3O4 nanoparticles had stable regeneration performance. For three times of recycling treatment, with a Fe3O4 addition ratio of 0.4%, the removal rate of TC reached 98.7%, 97.21%, and 96%, respectively. Based on the characterization results, the strengthening mechanism was analyzed. The experimental results indicated that construction of nanofluids systems could improve the utilization rate of ozone, and Fe3O4 nanoparticles were reusable and easily recyclable.

Knocking out FAM20C in pre-osteoblasts leads to up-regulation of osteoclast differentiation to affect long bone development.

Family with sequence similarity 20 member C (FAM20C) is a Golgi casein kinase that phosphorylates extracellularly-secreted regulatory proteins involved in bone development and mineralization, but its specific role in bone development is still largely unknown. In this study, to examine the specific mechanisms that FAM20C influences bone development, we cross-bred Osx-Cre with FAM20Cflox/flox mice to establish a Osx-Cre; FAM20Cflox/flox knockout (oKO) mouse model; FAM20C was KO in pre-osteoblasts. oKO development was examined at 1-10 weeks, in which compared to control FAM20Cflox/flox, they had lower body weights and bone tissue mineralization. Furthermore, oKO had lower bone volume fractions, thickness, and trabecular numbers, along with higher degrees of trabecular separation. These mice also had decreased femoral metaphyseal cartilage proliferation layer, along with thickened hypertrophic layer and increased apoptotic cell counts. Transcriptomic analysis found that differentially-expressed genes in oKO were concentrated in the osteoclast differentiation pathway, in line with increased osteoclast presence. Additionally, up-regulation of osteoclast-related, and down-regulation of osteogenesis-related genes, were identified, in which the most up-regulated genes were signal regulatory protein ß-1 family (Sirpb1a-c) and mitogen-activated protein kinase 13. Overall, FAM20C KO in pre-osteoblasts leads to abnormal long bone development, likely due to subsequent up-regulation of osteoclast differentiation-associated genes.

Prokaryotic Expression and Affinity Purification of DDX3 Protein.

BACKGROUND: DDX3 is a protein with RNA helicase activity that is involved in a variety of biological processes, and it is an important protein target for the development of broad-spectrum antiviral drugs, multiple cancers and chronic inflammation. OBJECTIVE: The objective of this study is to establish a simple and efficient method to express and purify DDX3 protein in E. coli, and the recombinant DDX3 should maintain helicase activity for further tailor-made screening and biochemical function validation. METHODS: DDX3 cDNA was simultaneously cloned into pET28a-TEV and pNIC28-Bsa4 vectors and transfected into E. coli BL21 (DE3) to compare one suitable prokaryotic expression system. The 6×His-tag was fused to the C-terminus of DDX3 to form a His-tagging DDX3 fusion protein for subsequent purification. Protein dissolution buffer and purification washing conditions were optimized. The His-tagged DDX3 protein would bind with the Ni-NTA agarose by chelation and collected by affinity purification. The 6×His-tag fused with N-terminal DDX3 was eliminated from DDX3 by TEV digestion. A fine purification of DDX3 was performed by gel filtration chromatography. RESULTS: The recombinant plasmid pNIC28-DDX3, which contained a 6×His-tag and one TEV cleavage site at the N terminal of DDX3 sequence, was constructed for DDX3 prokaryotic expression and affinity purification based on considering the good solubility of the recombinant His-tagging DDX3, especially under 0.5 mM IPTG incubation at 18 °C for 18 h to obtain more soluble DDX3 protein. Finally, the exogenous recombinant DDX3 protein was obtained with more than 95% purity by affinity purification on the Ni-NTA column and removal of miscellaneous through gel filtration chromatography. The finely-purified DDX3 still retained its ATPase activity. CONCLUSION: A prokaryotic expression pNIC28-DDX3 system is constructed for efficient expression and affinity purification of bioactive DDX3 protein in E. coli BL21(DE3), which provides an important high-throughput screening and validation of drugs targeting DDX3.

A 36-nW Electrocardiogram Anomaly Detector Based on a 1.5-bit Non-Feedback Delta Quantizer for Always-on Cardiac Monitoring.

An always-on electrocardiogram (ECG) anomaly detector (EAD) with ultra-low power (ULP) consumption is proposed for continuous cardiac monitoring applications. The detector is featured with a 1.5-bit non-feedback delta quantizer (DQ) based feature extractor, followed by a multiplier-less convolutional neural network (CNN) engine, which eliminates the traditional high-resolution analog-to-digital converter (ADC) in conventional signal processing systems. The DQ uses a computing-in-capacitor (CIC) subtractor to quantize the sample-to-sample difference of ECG signal into 1.5-bit ternary codes, which is insensitive to low-frequency baseline wandering. The subsequent event-driven classifier is composed of a low-complexity coarse detector and a systolic-array-based CNN engine for ECG anomaly detection. The DQ and the digital CNN are fabricated in 65-nm and 180-nm CMOS technology, respectively, and the two chips are integrated on board through wire bonding. The measured detection accuracy is 90.6% ∼ 91.3% when tested on the MIT-BIH arrhythmia database, identifying three different ECG anomalies. Operating at 1 V and 1.4 V power supplies for the DQ and the digital CNN, respectively, the measured long-term average power consumption of the core circuits is 36 nW, which makes the detector among those state-of-the-art always-on cardiac anomaly detection devices with the lowest power consumption.

Tethered Small-Molecule Acceptor Refines Hierarchical Morphology in Ternary Polymer Solar Cells: Enhanced Stability and 19% Efficiency.

Polymer solar cells (PSCs) are promising for efficient solar energy conversion, but achieving high efficiency and device longevity within a bulk-heterojunction (BHJ) structure remains a challenge. Traditional small-molecule acceptors (SMAs) in the BHJ blend show thermodynamic instability affecting the morphology. In contrast, tethered SMAs exhibit higher glass transition temperatures, mitigating these concerns. Yet, they might not integrate well with polymer donors, causing pronounced phase separation and overpurification of mixed domains. Herein, a novel ternary device is introduced that uses DY-P2EH, a tethered dimeric SMA with conjugated side-chains as host acceptor, and BTP-ec9, a monomeric SMA as secondary acceptor, which respectively possess hypomiscibility and hypermiscibility with the polymer donor PM6. This unique combination affords a parallel-connected ternary BHJ blend, leading to a hierarchical and stable morphology. The ternary device achieves a remarkable fill factor of 80.61% and an impressive power conversion efficiency of 19.09%. Furthermore, the ternary device exhibits exceptional stability, retaining over 85% of its initial efficiency even after enduring 1100 h of thermal stress at 85 °C. These findings highlight the potential advantage of tethered SMAs in the design of ternary devices with a refined hierarchical structure for more efficient and durable solar energy conversion technologies.

Association of gut microbiome and oral cavity cancer: A two sample mendelian randomization and case-control study.

INTRODUCTION: Considering the interconnectedness of the oral cavity and gut tract and the presence of abundant natural microbiota in both. We utilized Mendelian Randomization (MR) in a two-sample study to unveil the genetic causal impact of gut microbiota on the development of oral cavity cancer. MATERIALS & METHODS: The instrumental variables employed in this study consisted of single nucleotide polymorphisms (SNPs) that demonstrated a robust association with 211 distinct gut microbiota taxa, encompassing a sample size of 18,340 individuals. Our investigation sought to explore the potential causal relationship between these genetic variants and the incidence of oral cavity cancer. To accomplish this, we adopted a random effect inverse variance-weighted approach to analyze the causal effect. Additionally, sensitivity analyses were performed utilizing Cochran's Q tests, funnel plots, leave-one-out analyses, and MR-Egger intercept tests, to assess the robustness and validity of our findings. RESULTS: Five gut microbiota taxa (the family Prevotellaceae, the genus Alloprevotella, the genus Erysipelatoclostridium, the genus Parabacteroides, the genus Ruminococcus gauvreauii group) are predicted to play a causal role in promoting the initiation of the risk of oral cavity cancer. While the genus Christensenellaceae R 7 group, the genus Intestinimonas, the genus Ruminococcaceae, and the order Bacillales causally reduce the risk of oral cavity cancer. Furthermore, no significant evidence suggesting heterogeneity or pleiotropy was observed. DISCUSSION: The novel genetic causal effects of 211 gut microbiota taxa on oral cavity cancer are elucidated in this investigation, thus offering valuable insights for clinical interventions targeting oral cavity cancer.

HAKE: A Knowledge Engine Foundation for Human Activity Understanding.

Human activity understanding is of widespread interest in artificial intelligence and spans diverse applications like health care and behavior analysis. Although there have been advances with deep learning, it remains challenging. The object recognition-like solutions usually try to map pixels to semantics directly, but activity patterns are much different from object patterns, thus hindering another success. In this article, we propose a novel paradigm to reformulate this task in two-stage: first mapping pixels to an intermediate space spanned by atomic activity primitives, then programming detected primitives with interpretable logic rules to infer semantics. To afford a representative primitive space, we build a knowledge base including 26+ M primitive labels and logic rules from human priors or automatic discovering. Our framework, Human Activity Knowledge Engine (HAKE), exhibits superior generalization ability and performance upon canonical methods on challenging benchmarks. Code and data are available at http://hake-mvig.cn/.

Development of a nomogram-based model combining intra- and peritumoral ultrasound radiomics with clinical features for differentiating benign from malignant in Breast Imaging Reporting and Data System category 3-5 nodules.

Background: The differences in benign and malignant breast tumors are not only within the nodules but also involve changes in the surrounding tissues. Radiomics can reveal many details that are not discernible to the naked eye. This study aimed to distinguish between benign and malignant breast nodules using an ultrasound-based intra- and peritumoral radiomics model. Methods: This study retrospectively collected the information from 379 patients with Breast Imaging Reporting and Data System (BI-RADS) category 3-5 nodules and clear pathological diagnosis of breast nodules screened by routine ultrasound examination in the Sixth People's Hospital Affiliated to Medical College of Shanghai Jiao Tong University from January 2017 to December 2022. The largest dimension of the lesion on the 2D ultrasound image was selected to outline the area of interest which was conformally and outwardly expanded automatically by 5 mm to extract intra- and peritumor radiomics features. The included cases were randomly divided into training sets and test sets in a ratio of 7:3. The optimal features of the included models were retained by statistical and machine learning methods of dimensionality reduction, and logistic regression was used as the classifier to build an intratumoral model and a combined intratumoral-peritumoral radiomics model, respectively; through single-factor and multifactor logistic regression, the optimal features that could predict benign and malignant breast tumors were screened. The clinical and imaging models were established by selecting independent risk factors as clinical and imaging features through univariate and multifactorial logistic regression. Results: Among 379 BI-RADS category 3-5 breast nodules, there were 124 malignant nodules and 255 benign nodules; patients were aged 14 to 88 (46.22±15.51) years, and the age differences, radiomics score, and mass diameter between the training and test sets were not statistically significant (P>0.05). The intra- and peritumor radiomics model had an area under the curve (AUC) of 0.840 [95% confidence interval (CI): 0.766-0.914] in the test set. The model with intra- and peritumoral ultrasound radiomics features combined with clinical features had an AUC value of 0.960 (95% CI: 0.920-0.999). Conclusions: The nomogram, developed using intratumoral and peritumoral radiomics features combined with clinical risk features, demonstrated superior performance in distinguishing between benign and malignant BI-RADS 3-5 lesions.

Association between gut microbiome and intracerebral hemorrhage based on genome-wide association study data. / 基于GWASæ•°æ®åˆ†æžè‚ é“èŒç¾¤ä¸Žè„‘å‡ºè¡€çš„å ³ç³».

OBJECTIVES: Intracerebral hemorrhage (ICH) has the highest mortality and disability rates among various subtypes of stroke. Previous studies have shown that the gut microbiome (GM) is closely related to the risk factors and pathological basis of ICH. This study aims to explore the causal effect of GM on ICH and the potential mechanisms. METHODS: Genome wide association study (GWAS) data on GM and ICH were obtained from Microbiome Genome and International Stroke Genetics Consortium. Based on the GWAS data, we first performed Mendelian randomization (MR) analysis to evaluate the causal association between GM and ICH. Then, a conditional false discovery rate (cFDR) method was conducted to identify the pleiotropic variants. RESULTS: MR analysis showed that Pasteurellales, Pasteurellaceae, and Haemophilus were negatively correlated with the risk of ICH, whileVerrucomicrobiae, Verrucomicrobiales, Verrucomicrobiaceae, Akkermansia, Holdemanella, and LachnospiraceaeUCG010 were positively correlated with ICH. By applying the cFDR method, 3 pleiotropic loci (rs331083, rs4315115, and rs12553325) were found to be associated with both GM and ICH. CONCLUSIONS: There is a causal association and pleiotropic variants between GM and ICH.

Epithelial-specific deletion of FAM20A leads to short root defects.

Short Root Defects defined by a reduced ratio of root to crown, may culminate in root resorption and subsequent tooth loss, in spite of the absence of apparent symptoms. Such defects present considerable impediments to orthodontic treatment and restoration. Recent identification of Fam20a, an emergent pseudokinase, has been associated with enamel development and tooth eruption, yet its definitive role in root formation and eruption remains ambiguous. In this research, we initially ascertained that the targeted knockout of Fam20a within the epithelium led to truncated tooth roots, irregular breaks in the epithelial root sheath initiation of the WNT signaling pathway, and decreased expression of the cell polarity-related transcription factor Cdc42 in murine models. This was concomitant with the participation of the associated epithelial root sheath developmental pathways BMP2, Gli1, and Nfic. Furthermore, we observed that Fam20a predominantly affects the intraosseous eruption phase of tooth emergence. During this phase, the osteoclast peak around the mandibular first molar in cKO mice is delayed, leading to a slower formation of the eruption pathway, ultimately resulting in delayed tooth eruption in mice. The findings of this study enrich the extant knowledge regarding the role of Fam20a, suggesting its potential regulatory function in tooth root development through the WNT/ß-catenin/Cdc42 pathway.

Insight into the enhancement effect of amino functionalized carbon nanotubes on the H2S removal performance of nanofluid system.

By constructing nanofluid system, trace functionalized nanoparticles can significantly enhance the absorption performance of basic liquid. In this work, amino functionalized carbon nanotubes (ACNTs) and carbon nanotubes (CNTs) were introduced into alkaline deep eutectic solvents to build nanofluid systems and used for the dynamic absorption of H2S. The experiment results showed that the introduction of nanoparticles can significantly enhance the H2S removal performance of original liquid. When performing H2S removal experiments, the optimal mass concentrations of ACNTs versus CNTs were 0.05 % and 0.01 %, respectively. The characterization showed that the surface morphology and structure of the nanoparticles unchanged significantly during the absorption-regeneration process. A double mixed gradientless gas-liquid reactor was used to explore the gas-liquid absorption kinetics characteristics of the nanofluid system. It was found that the gas-liquid mass transfer rate increased significantly after the addition of nanoparticles. The highest total mass transfer coefficient of the nanofluid system of ACNTs was increased to more than 400 % of the value before the addition of nanoparticles. The analysis showed that the shuttle effect and hydrodynamic effect of nanoparticles play important role in the process of enhancing gas-liquid absorption, and the amino functionalization enhanced the shuttle effect of nanoparticles significantly.

Fam20c regulates the calpain proteolysis system through phosphorylating Calpasatatin to maintain cell homeostasis.

BACKGROUND: The family with sequence similarity 20-member C (FAM20C) kinase, a Golgi casein kinase, which is responsible for phosphorylating the majority of the extracellular phosphoproteins within S-x-E/pS motifs, and is fundamentally associated with multiple biological processes to maintain cell proliferation, biomineralization, migration, adhesion, and phosphate homeostasis. In dissecting how FAM20C regulates downstream molecules and potential mechanisms, however, there are multiple target molecules of FAM20C, particularly many phenomena remain elusive, such as changes in cell-autonomous behaviors, incompatibility in genotypes and phenotypes, and others. METHODS: Here, assay for transposase-accessible chromatin using sequencing (ATAC-seq), RNA sequencing (RNA-seq), proteomics, and phosphoproteomics were performed in Fam20c-dificient osteoblasts and to facilitate an integrated analysis and determine the impact of chromatin accessibility, genomic expression, protein alterations, signaling pathway, and post translational modifcations. RESULTS: By combining ATAC-seq and RNA-seq, we identified TCF4 and Wnt signaling pathway as the key regulators in Fam20c-dificient cells. Further, we showed Calpastatin/Calpain proteolysis system as a novel target axis for FAM20C to regulate cell migration and F-actin cytoskeleton by integrated analysis of proteomics and phosphoproteomics. Furthermore, Calpastatin/Calpain proteolysis system could negatively regulate the Wnt signaling pathway. CONCLUSION: These observations implied that Fam20c knockout osteoblasts would cause cell homeostatic imbalance, involving changes in multiple signaling pathways in the conduction system.

L-Ascorbic Acid 2-Phosphate Attenuates Methylmercury-Induced Apoptosis by Inhibiting Reactive Oxygen Species Accumulation and DNA Damage in Human SH-SY5Y Cells.

Methylmercury (MeHg) is a toxin that causes severe neuronal oxidative damage. As vitamin C is an antioxidant well-known to protect neurons from oxidative damage, our goal was to elucidate its protective mechanism against MeHg-induced oxidative stress in human neuroblastomas (SHSY5Y). We treated cells with MeHg, L-ascorbic acid 2-phosphate (AA2P), or both, and used MTT, flow cytometry, and Western blot analyses to assess cell damage. We found that MeHg significantly decreased the survival rate of SH-SY5Y cells in a time- and dose-dependent manner, increased apoptosis, downregulated PAR and PARP1 expression, and upregulated AIF, Cyto C, and cleaved Caspase-3 expression. A time course study showed that MeHg increased reactive oxygen species (ROS) accumulation; enhanced apoptosis; increased DNA damage; upregulated expression ofγH2A.X, KU70, 67 and 57 kDa AIF, CytoC, and cleaved Caspase-3; and downregulated expression of 116 kDa PARP1, PAR, BRAC1, and Rad51. Supplementation with AA2P significantly increased cell viability and decreased intrinsic ROS accumulation. It also reduced ROS accumulation in cells treated with MeHg and decreased MeHg-induced apoptosis. Furthermore, AA2P conversely regulated gene expression compared to MeHg. Collectively, we demonstrate that AA2P attenuates MeHg-induced apoptosis by alleviating ROS-mediated DNA damage and is a potential treatment for MeHg neurotoxicity.

Functionalized Prussian Blue Nanozyme as Dual-Responsive Drug Therapeutic Nanoplatform Against Maxillofacial Infection via Macrophage Polarization.

Purpose: Maxillofacial infection is a common disease in stomatology and is difficult to treat owing to its high potential to spread to vital anatomical structures. Excessive levels of reactive oxygen species (ROS) in infected tissues lead to cellular damage and impede tissue regeneration. However, uncontrollable strategies to remove ROS have limited therapeutic efficacy. Nanoparticle systems for scavenging ROS and remodeling the inflammatory microenvironment offer much promise in the treatment of maxillofacial inflammation. Methods: Here, a novel microenvironment-stimuli-responsive drug delivery nanoplatform (HMPB@Cur@PDA) based on a polydopamine (PDA)-functionalized hollow mesoporous Prussian blue (HMPB) nanozyme was developed for the delivery of curcumin (Cur) in the treatment of maxillofacial infection. Low pH and excess ROS in the inflammatory microenvironment cause degradation of the outer PDA layer of the nanocomplex, exposing the HMPB nanozyme and loaded Cur, which synergistically act as a ROS scavenger and anti-inflammatory agent, respectively, and induce macrophage polarization from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype. Results: Experiments in vitro provided strong evidence for the application of novel nanocomplexes in scavenging multiple ROS and inhibiting lipopolysaccharide-induced inflammation. In addition, in vivo results obtained using a mouse maxillofacial infection model demonstrated that HMPB@Cur@PDA had excellent biocompatibility, significantly attenuated the inflammatory response in periodontal tissue, and improved the repair of damaged tissue. Conclusion: Our results indicate that HMPB@Cur@PDA nanocomposites have great potential for ROS regulation as well as having anti-inflammatory effects, providing new insights for the development of dual-response maxillofacial infection treatments.

Design of A-D-A-Type Organic Third-Order Nonlinear Optical Materials Based on Benzodithiophene: A DFT Study.

The acceptor-donor-acceptor (A-D-A) type conjugated organic molecule has been widely applied in the organic optoelectronics field. A total of Nine compounds (1-9) were designed under the A-D-A framework, with the electron donor benzodithiophene as the core and dicyanomethylene as the acceptor moiety, modifying the benzodithiophene with the phenyl, naphthyl, and difluorinated phenyl groups. The conjugation length can be changed by introducing a thiophene π-conjugated bridge. The geometric structures, electronic structure, excited state properties, aromaticity, and the static- and frequency-dependent second hyperpolarizabilities were investigated by employing high-precision density functional theory (DFT) calculations with an aug-cc-pVDZ basis set. As a result, the three compounds with the longest conjugation length exhibit a smaller energy gap (Egap), larger UV-vis absorption coefficient, and response range, which are the three strongest third-order nonlinear optical (NLO) response properties in this work. This work systematically explored the connection between molecular structure and NLO response, which provides a rational design strategy for high-performance organic NLO materials.

Role of ferroptosis-related genes in periodontitis based on integrated bioinformatics analysis.

BACKGROUND: Cell survival or death is one of the key scientific issues of inflammatory response. To regulate cell death during the occurrence and development of periodontitis, various forms of programmed cell death, such as pyroptosis, ferroptosis, necroptosis, and apoptosis, have been proposed. It has been found that ferroptosis characterized by iron-dependent lipid peroxidation is involved in cancer, degenerative brain diseases and inflammatory diseases. Furthermore, NCOA4 is considered one of ferroptosis-related genes (FRGs) contributing to butyrate-induced cell death in the periodontitis. This research aims to analyze the expression of FRGs in periodontitis tissues and to explore the relationship between ferroptosis and periodontitis. METHOD: Genes associated with periodontitis were retrieved from two Gene Expression Omnibus datasets. Then, we normalized microarray data and removed the batch effect using the R software. We used R to convert the mRNA expression data and collected the expression of FRGs. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), transcription factor (TF) and protein-protein interaction (PPI) network analyses were used. In addition, we constructed a receiver operating characteristic curve and obtained relative mRNA expression verified by quantitative reverse-transcription polymerase chain reaction (PCR). RESULTS: Eight and 10 FRGs related to periodontitis were upregulated and downregulated, respectively. GO analysis showed that FRGs were enriched in the regulation of glutathione biosynthetic, glutamate homeostasis, and endoplasmic reticulum-nucleus signaling pathway. The top TFs included CEBPB, JUND, ATF2. Based on the PPI network analysis, FRGs were mainly linked to the negative regulation of IRE1-mediated unfolded protein response, regulation of type IIa hypersensitivity, and regulation of apoptotic cell clearance. The expression levels of NCOA4, SLC1A5 and HSPB1 using PCR were significantly different between normal gingival samples and periodontitis samples. Furthermore, the diagnostic value of FRGs for periodontitis were "Good". CONCLUSIONS: We found significant associations between FRGs and periodontitis. The present study not only provides a new possible pathomechanism for the occurrence of periodontitis but also offers a new direction for the diagnosis and treatment of periodontitis.

Downregulated Expression of RIPOR3 Correlated with Immune Infiltrates Predicts Poor Prognosis in Oral Tongue Cancer.

BACKGROUND Tongue cancer is the most prevalent of head and neck squamous cell carcinomas, including base of tongue cancer (BOT) and oral squamous cell carcinoma of the mobile tongue (OTSCC). We aimed to investigate the role of RIPOR3 in tumorigenesis and its development as a potential prognostic biomarker for tongue cancer, especially OTSCC. MATERIAL AND METHODS Associations of expression, clinical pathologic features, and overall survival were analyzed by logistic regression, multivariate Cox analysis, and Kaplan-Meier methods. Gene set enrichment analysis (GSEA) and the CIBERSORT algorithm were performed to determine the correlation between RIPOR3 and tumor immune infiltration. cBioPortal was used for methylation and copy number variation (CNV) analysis. The Human Protein Atlas (HPA) and GSE31056 dataset were used for further external validation. RESULTS RIPOR3 expression in OTSCC was significantly associated with various clinicopathological parameters. Kaplan-Meier survival analysis showed that OTSCC with low RIPOR3 expression had a worse prognosis than that with high RIPOR3 expression. Multivariate analysis revealed that lower RIPOR3 expression was an independent prognostic factor for poor prognosis. GSEA and Neighbor Gene Network analysis showed RIPOR3 expression was related with the modulation and function of the immune-related pathway. Methylation level and CNV analysis showed that the downregulated expression of RIPOR3 was significantly related to hypermethylation but not to CNV. Finally, high RIPOR3 expression was validated at the protein level using the HPA database and GSE31056 dataset. CONCLUSIONS These findings suggested that RIPOR3 might serve as a promising prognostic biomarker and is related to the immune cell infiltration of OTSCC.