Gold core@CeO2 halfshell Janus nanocomposites catalyze targeted sulfate radical for periodontitis therapy.

The sulfate radical (SO4•-), known for its high reactivity and long lifespan, has emerged as a potent antimicrobial agent. Its exceptional energy allows for the disruption of vital structures and metabolic pathways in bacteria that are usually inaccessible to common radicals. Despite its promising potential, the efficient generation of this radical, particularly through methods involving enzymes and photocatalysis, remains a substantial challenge. Here, we capitalized on the peroxidase (POD)-mimicking activity and photocatalytic properties of cerium oxide (CeO2) nanozymes, integrating these properties with the enhanced concept of plasma gold nanorod (GNR) to develop a half-encapsulated core@shell GNRs@CeO2 Janus heterostructure impregnated with persulfate. Under near-infrared irradiation, the GNRs generate hot electrons, thereby boosting the CeO2's enzyme-like activity and initiating a potent reactive oxygen species (ROS) storm. This distinct nanoarchitecture facilitates functional specialization, wherein the heterostructure and efficient light absorption ensured continuous hot electron flow, not only enhancing the POD-like activity of CeO2 for the production of SO4•- effectively, but also contributing a significant photothermal effect, disrupting periodontal plaque biofilm and effectively eradicating pathogens. Furthermore, the local temperature elevation synergistically enhances the POD-like activity of CeO2. Transcriptomics analysis, as well as animal experiments of the periodontitis model, have revealed that pathogens undergo genetic information destruction, metabolic disorders, and pathogenicity changes in the powerful ROS system, and profound therapeutic outcomes in vivo, including anti-inflammation and bone preservation. This study demonstrated that energy transfer to augment nanozyme activity, specifically targeting ROS generation, constitutes a significant advancement in antibacterial treatment.

Near-infrared light-triggered nitric oxide nanocomposites for photodynamic/photothermal complementary therapy against periodontal biofilm in an animal model.

Background: Periodontal disease, an oral disease that initiates with plaque biofilm infection, affects 10% of the global population. Due to the complexity of tooth root anatomy, biofilm resistance and antibiotic resistance, traditional mechanical debridement and antibiotic removal of biofilms are not ideal. Nitric oxide (NO) gas therapy and its multifunctional therapy are effective methods to clear biofilms. However, large and controlled delivery of NO gas molecules is currently a great challenge. Methods: The core-shell structure of Ag2S@ZIF-90/Arg/ICG was developed and characterized in detail. The ability of Ag2S@ZIF-90/Arg/ICG to produce heat, ROS and NO under 808 nm NIR excitation was detected by an infrared thermal camera, probes and Griess assay. In vitro anti-biofilm effects were evaluated by CFU, Dead/Live staining and MTT assays. Hematoxylin-eosin staining, Masson staining and immunofluorescence staining were used to analyze the therapeutic effects in vivo. Results: Antibacterial photothermal therapy (aPTT) and antibacterial photodynamic therapy (aPDT) could be excited by 808 nm NIR light, and the produced heat and ROS further triggered the release of NO gas molecules simultaneously. The antibiofilm effect had a 4-log reduction in vitro. The produced NO caused biofilm dispersion through the degradation of the c-di-AMP pathway and improved biofilm eradication performance. In addition, Ag2S@ZIF-90/Arg/ICG had the best therapeutic effect on periodontitis and NIR II imaging ability in vivo. Conclusions: We successfully prepared a novel nanocomposite with NO synergistic aPTT and aPDT. It had an outstanding therapeutic effect in treating deep tissue biofilm infection. This study not only enriches the research on compound therapy with NO gas therapy but also provides a new solution for other biofilm infection diseases.

Novel Twin-Crystal Nanosheets with MnO2 Modification to Combat Bacterial Biofilm against Periodontal Infections via Multipattern Strategies.

Nowadays the multifunctional approaches to kill oral bacteria based on various nanocomposites have made great progress against periodontal infections, while the material structure and its functional integration are still insufficient. Herein, this work proposes a therapeutic strategy of chemodynamical therapy (CDT) and photothermal therapy (PTT) in monocrystals to effectively enhance the synergistic treatment. The CuS/MnS@MnO2 consisting of hexagonal CuS/MnS nano-twin-crystal with a shell layer of MnO2 is developed. In this nanosystem, the purpose of synergistic treatment of periodontitis by combining PTT/CDT is achieved within a CuS/MnS monocrystal, where CuS serves to achieve photothermal conversion, dissipate the biofilm and transfer the heat in situ to the integrated MnS, thus promoting the Mn2+ -mediated CDT process. Meanwhile, the CDT process can generate the highly toxic hydroxyl radical to destroy extracellular DNA by utilization of endogenous H2 O2 produced by Streptococci in the oral biofilm, cooperating with PTT to dissipate the bacterial biofilm. With the design of the outer shell of MnO2 , the selective bacteria-killing can be realized by producing oxygen which can protect the periodontal non-pathogenic aerobic bacteria and threaten the survival of anaerobic pathogens. Therefore, such design via multipattern strategies to combat microorganisms would provide a bright prospect for the clinical treatment of bacterial infections.

State-of-the-Art on the Sulfate Radical-Advanced Oxidation Coupled with Nanomaterials: Biological and Environmental Applications.

Sulfate radicals (SO4-·) play important biological roles in biomedical and environmental engineering, such as antimicrobial, antitumor, and disinfection. Compared with other common free radicals, it has the advantages of a longer half-life and higher oxidation potential, which could bring unexpected effects. These properties have prompted researchers to make great contributions to biology and environmental engineering by exploiting their properties. Peroxymonosulfate (PMS) and peroxydisulfate (PDS) are the main raw materials for SO4-· formation. Due to the remarkable progress in nanotechnology, a large number of nanomaterials have been explored that can efficiently activate PMS/PDS, which have been used to generate SO4-· for biological applications. Based on the superior properties and application potential of SO4-·, it is of great significance to review its chemical mechanism, biological effect, and application field. Therefore, in this review, we summarize the latest design of nanomaterials that can effectually activate PMS/PDS to create SO4-·, including metal-based nanomaterials, metal-free nanomaterials, and nanocomposites. Furthermore, we discuss the underlying mechanism of the activation of PMS/PDS using these nanomaterials and the application of SO4-· in the fields of environmental remediation and biomedicine, liberating the application potential of SO4-·. Finally, this review provides the existing problems and prospects of nanomaterials being used to generate SO4-· in the future, providing new ideas and possibilities for the development of biomedicine and environmental remediation.

Nanometric Surface-Selective Regulation of Au/In2O3 Nanofibers as an Exhaled H2S Chemiresistor for Periodontitis Diagnosis.

As one of the most prevalent diseases in the world, timely early intervention for periodontitis is a great challenge because the indicator is imperceptible. The exhaled H2S is considered to be a promising biomarker for fast and invasive periodontitis screening; however, the high-performance H2S gas sensor with excellent selectivity and sensitivity which is applicable to the oral cavity remains technically challenging. Herein, a self-assembled monolayer (SAM)-functionalized Au/In2O3 nanofiber (NF) sensor for H2S exhalation analysis was developed to flexibly and effectively modulate the selectivity of the sensor. Through optimizing the specific binding capacity to H2S by systematic adjustment with terminal groups and alkyl chains of SAMs, the sensing performance of the SAM-functionalized Au/In2O3 NF sensor is greatly enhanced. In the optimal (Au/In2O3-MPTES) sensor, the functionalization of the MPTES molecule could achieve significant response enhancement because of the stronger interaction between the sulfhydryl group at the end of the MPTES and H2S. Density functional theory simulation supports the proposed selective sensing mechanism via the analysis of adsorption energy and charge density distribution. The sensor exhibited a high response to H2S (1505.3-10 ppm) at an operating temperature of 100 °C with a low practical detection limit of 10 ppb and 13-145 fold enhanced selectivity. Furthermore, the Au/In2O3-MPTES sensor was successfully applied to distinguish the breath of healthy individuals and patients with severe periodontitis. This study provides novel design insights for the development of highly selective gas sensors for clinical aids in the diagnosis and detection of oral diseases such as periodontitis.

Tuberculosis-specific antigen stimulated and unstimulated interferon-γ for tuberculous meningitis diagnosis: A systematic review and meta-analysis.

OBJECTIVE: Tuberculous meningitis (TBM) is one of the most devastating TB. Accurate identification of TBM is helpful to eliminate TB. Therefore, we assessed the performance of TBAg stimulated IFN-γ (IGRA) and unstimulated IFN-γ in blood and cerebrospinal fluid (CSF) for diagnosing TBM. METHODS: We searched Web of Science, PubMed, Embase and the Cochrane Library databases until March 2022. Bivariate and hierarchical summary receiver operating characteristic models were employed to compute summary estimates for diagnostic accuracy parameters of IGRA and unstimulated IFN-γ in blood and CSF for diagnosing TBM. RESULTS: 28 studies including 1,978 participants and 2,641 samples met the inclusion criteria. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the curve (AUROC) of blood IGRA were separately as 0.73, 0.83, 4.32, 0.33, 13.22 and 0.86, indicating a good diagnostic accuracy of blood IGRA for detecting TBM. The summary sensitivity, specificity, PLR, NLR, DOR and AUROC of CSF IGRA were separately as 0.77, 0.91, 8.82, 0.25, 34.59 and 0.93, indicating good diagnostic accuracy of CSF IGRA for detecting TBM. The summary sensitivity, specificity, PLR, NLR, DOR and AUROC of CSF IFN-γ were separately as 0.86, 0.92, 10.27, 0.16, 65.26 and 0.95, suggesting CSF IFN-γ provided excellent accuracy for diagnosing TBM. CONCLUSIONS: For differentiating TBM from non-TBM individuals, blood and CSF IGRA are good assays and unstimulated CSF IFN-γ is an auxiliary excellent marker.

Active Learning Plus Deep Learning Can Establish Cost-Effective and Robust Model for Multichannel Image: A Case on Hyperspectral Image Classification.

Relying on large scale labeled datasets, deep learning has achieved good performance in image classification tasks. In agricultural and biological engineering, image annotation is time-consuming and expensive. It also requires annotators to have technical skills in specific areas. Obtaining the ground truth is difficult because natural images are expensive. In addition, images in these areas are usually stored as multichannel images, such as computed tomography (CT) images, magnetic resonance images (MRI), and hyperspectral images (HSI). In this paper, we present a framework using active learning and deep learning for multichannel image classification. We use three active learning algorithms, including least confidence, margin sampling, and entropy, as the selection criteria. Based on this framework, we further introduce an "image pool" to make full advantage of images generated by data augmentation. To prove the availability of the proposed framework, we present a case study on agricultural hyperspectral image classification. The results show that the proposed framework achieves better performance compared with the deep learning model. Manual annotation of all the training sets achieves an encouraging accuracy. In comparison, using active learning algorithm of entropy and image pool achieves a similar accuracy with only part of the whole training set manually annotated. In practical application, the proposed framework can remarkably reduce labeling effort during the model development and upadting processes, and can be applied to multichannel image classification in agricultural and biological engineering.

Can haloperidol prophylaxis reduce the incidence of delirium in critically ill patients in intensive care units? A systematic review and meta-analysis.

INTRODUCTION: The purpose of this study was to evaluate the efficacy and safety of haloperidol in the prevention of delirium in intensive care unit (ICU) patients. METHODS: We systematically searched PubMed, Embase, and the Cochrane Library for eligible randomized controlled trials up to July 2019. No publication type or language restrictions were applied. RESULTS: Compared to the placebo, haloperidol did not significantly reduce the incidence of delirium in all ICU patients (relative risk (RR), 0.83; 95% confidence interval (CI), 0.62-1.10, p = 0.20). However, haloperidol prophylaxis could reduce the incidence of delirium exclusively in postoperative patients admitted to an ICU (RR, 0.63; 95% CI, 0.47-0.86, p = 0.004). We observed no significant differences between the haloperidol and placebo groups in terms of length of ICU stay, all-cause mortality, and adverse events. CONCLUSIONS: The use of prophylactic haloperidol might reduce the incidence of delirium in postoperative patients admitted to an ICU, but not in all ICU patients.

Chronic paradoxical sleep deprivation-induced depression-like behavior, energy metabolism and microbial changes in rats.

AIMS: Given the lasting impact of chronic paradoxical sleep deprivation (PSD) on behavior and organism metabolic alternations, along with the role of the microbiome in neurobehavioral development and metabolism, we sought to examine the relationship between the microbiota and chronic PSD-induced behavioral and metabolic changes. MATERIALS AND METHODS: Psychological status of 7-day PSD (7d-PSD) male rats was tested by behavioral method, serum inflammatory cytokines and hypothalamic-pituitary-adrenal (HPA) axis-related hormones. In addition, GC-MS based urine metabolomics and 16S rRNA gene sequencing approaches were applied to estimate the influences of chronic PSD on host metabolism and gut-microbiota. Furtherly, microbial functional prediction and Spearman's correlation analysis were implemented to manifest the relations between the differential urinary metabolites and gut microbiota. KEY FINDINGS: 7d-PSD rats displayed depression-like behavior, metabolic and microbial changes. By integrating differential gut bacteria with indicators of depression and differential metabolites, we found that the alterations of Akkermansia, Oscillospira, Ruminococcus, Parabacteroides, Aggregatibacter and Phascolarctobacterium were closely related to abnormalities of depression symptoms and inflammatory cytokines. These bacteria also had close connections with host energy metabolism concerning arginine and proline metabolism, glycine, serine and threonine metabolism, and glyoxylate and dicarboxylate metabolism, pyruvate metabolism, which overlapped with the results of 16S rRNA gene function annotation. SIGNIFICANCE: These data suggest that a specific situation of circadian disturbance, chronic PSD-induced alterations in gut microbiota and related host changes in metabolism may be the pathogenesis of depression.

Nighttime is associated with decreased survival for out of hospital cardiac arrests: A meta-analysis of observational studies.

INTRODUCTION: The relationship between time of day and the clinical outcomes of patients with out-of-hospital cardiac arrest (OHCA) remains inconclusive. We undertook a meta-analysis to assess the available evidence on the relationship between nighttime and prognosis for patients with OHCA. MATERIALS AND METHODS: PubMed and EMBASE were searched through June 20, 2018, to identify all studies assessing the relationship between nighttime and prognosis for patients with OHCA. Random effects modes were used to estimate odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Eight observational studies met the inclusion criteria. Meta-analysis of 8 studies showed that compared with nighttime, the daytime OHCA patients had higher 1-month/in-hospital survival (OR, 1.25; 95% CI, 1.15-1.37; P = 0.00), with high heterogeneity among the studies (I2 = 82.8%, P = 0.00). CONCLUSIONS: Patients who experienced OHCA during the nighttime had lower 1-month/in-hospital survival than those with daytime OHCA. In addition to arrest event and pre-hospital care factors, patients' comorbidity and hospital-based care may also be responsible for lower survival at night.

OCT4B regulates p53 and p16 pathway genes to prevent apoptosis of breast cancer cells.

Octamer-binding transcription factor 4 (OCT4) is a transcription factor with a well-defined role in stem cell pluripotency. Two OCT4 isoforms, OCT4A and OCT4B, tend to be downregulated as normal cells differentiate. However, OCT4, particularly OCT4B, may become reactivated in cancer cells. Despite this observation, the exact function of OCT4B re-expression in cancer is unclear. In the present study, the role of OCT4 in breast cancer cells was determined. In particular, the ability of OCT4 to regulate key genes involved in cellular proliferation and apoptosis, two pathways that are frequently deregulated in cancer, was examined. The cyclin-dependent kinase inhibitor 2A locus encodes p16INK4a and p14ARF, two important cell cycle inhibitors. The tumor suppressor p53 also has well characterized roles in suppressing proliferation and promoting apoptosis. The present study demonstrated, via overexpression and genetic knockdown techniques, that OCT4B regulates the expression of several of these genes and ultimately regulates the rate of apoptosis of MCF-7 breast cancer cells. It was also observed that, while OCT4B and OCT4A regulate one another, it is OCT4B that serves a more prominent role in regulating the transcription of downstream genes. Taken together, the present results suggest that OCT4B is re-expressed in a number of breast cancer cell lines, where it affects both the transcription of cell cycle genes and the rate of apoptosis. These properties of OCT4B may depend on, at least in part, the co-function of OCT4A.

[Network meta-analysis on selecting Chinese medical injections in radiotherapy for esophageal cancer].

To assess the clinical effect and safety of Chinese traditional medicine injection combined with radiotherapy for esophageal cancer. The relative randomized controlled trials (RCTs) of Chinese medical injections (CMI) combined with radiotherapy as well as simple radiotherapy for esophageal cancer were searched from PubMed, Cochrane Library, EMBASE, Chinese Biomedical Literature Database(CBM), China National Knowledge Infrastructure (CNKI), Wanfang Database and VIP Database as at September 2014. Two researchers completed the data extraction and quality evaluation independently. The data were analyzed by GeMTC 0.14.3 and Stata 12. 0 software. Finally, 43 RCTs involving 3 289 patients were finally included. The star network was constructed by different comparison groups. The results of network meta-analysis showed that the seven CMIs combined with radiotherapy was superior to simple radiotherapy in the treatment of esophageal cancer in efficacy, quality of life, and reduction in the incidence of nausea and leucopenia, but with no significant difference among the seven CMIs. Probability ranking result showed a great possibility for Shenqi Fuzheng and astragalus polysaccharide injections in improving the overall response rate and quality of life, which were followed by cinobufagin and kangai injections. However, only one study was included for Shenqi Fuzheng and astragalus polysaccharide injections. Therefore, cinobufagin or kangai injections were preferred in improving the overall response rate and quality of life. Aidi or compound sophora injections were better than other CMIs in reducing? the incidences of nausea (III-IV) and leukopenia. More RCTs of Shenqi Fuzheng and astragalus polysaccharide injections combined with radiotherapy for patients with esophageal cancer were expected in the future to confirm our results. Moreover, study findings will be reported, particularly for the adverse events in radiotherapy for esophageal cancer.

The expression of Pax6 variants is subject to posttranscriptional regulation in the developing mouse eyelid.

Pax6 is a pivotal transcription factor that plays a role during early eye morphogenesis, but its expression and function in eyelid development remain unknown. In this study, the expression patterns of Pax6 mRNA and protein were examined in the developing mouse eyelid at embryonic days 14.5, 15.5, and 16.5. The function of Pax6 in eyelid development was determined by comparing it to that in the eyes-open-at-birth mutant mouse. In the normally developing eyelid, Pax6 and Pax6(5a) mRNA levels were low at E14.5, increased at E15.5, and then declined at E16.5, accompanied by a change in the Pax6/Pax6(5a) ratio. Pax6 protein was mainly located in the mesenchyme and conjunctiva. It was expressed at low levels in the epidermis at E14.5, severely reduced at E15.5, but re-expressed in the keratinocyte cells of the periderm at E16.5. In contrast, Pax6 and the Pax6/Pax6(5a) ratio were considerably higher with strong nuclear expression in the mutant at E15.5. Next, we examined the relationship of Pax6 to epidermal cell proliferation, migration, and the associated signalling pathways. The Pax6 protein in the developing eyelid was negatively correlated with epidermal cell proliferation but not migration, and it is in contrast to the activation of the EGFR-ERK pathway. Our in vivo data suggest that Pax6 expression and the Pax6/Pax6(5a) ratio are at relatively low levels in the eyelid, and acting as a transcription factor, Pax6 is required for the initiation of eyelid formation and for differential development of the keratinised cells in the closed eyelid. The Pax6 protein is likely to be controlled by the EGFR-ERK pathways. An abnormal increase in Pax6 expression and the Pax6/Pax6(5a) ratio due to alteration of the pathway activity could suppress epidermal cell proliferation leading to the eyes-open-at-birth defect. This study offers insight into the function of the Pax6 protein in eyelid development.

Oct-4B isoform is differentially expressed in breast cancer cells: hypermethylation of regulatory elements of Oct-4A suggests an alternative promoter and transcriptional start site for Oct-4B transcription.

The human Oct-4 gene has three isoforms, Oct-4A, Oct-4B and Oct-4B1, which are thought to be derived from alternative splicing. It remains controversial whether the Oct-4 gene is expressed in cancer cells. Expression of Oct-4A is regulated by two elements, the PE (proximal enhancer) and DE (distal enhancer), but the expression and regulation of Oct-4B are not well known. Here, we firstly report that Oct-4B is expressed at low levels in MCF-7 cells, while the Oct-4A gene is inactivated. By analysing the function of different promoter constructs and the DNA methylation status of three regulatory regions, we demonstrate that the Oct-4A gene in MCF-7 cells is repressed by epigenetic control rather than transcriptional control. In addition, we speculate that the transcription of Oct-4B in MCF-7 cells is differentially regulated by additional regulatory elements. This work will enhance the understanding of Oct-4 gene in differential regulation.

Spontaneously immortalised bovine mammary epithelial cells exhibit a distinct gene expression pattern from the breast cancer cells.

BACKGROUND: Spontaneous immortalisation of cultured mammary epithelial cells (MECs) is an extremely rare event, and the molecular mechanism behind spontaneous immortalisation of MECs is unclear. Here, we report the establishment of a spontaneously immortalised bovine mammary epithelial cell line (BME65Cs) and the changes in gene expression associated with BME65Cs cells. RESULTS: BME65Cs cells maintain the general characteristics of normal mammary epithelial cells in morphology, karyotype and immunohistochemistry, and are accompanied by the activation of endogenous bTERT (bovine Telomerase Reverse Transcriptase) and stabilisation of the telomere. Currently, BME65Cs cells have been passed for more than 220 generations, and these cells exhibit non-malignant transformation. The expression of multiple genes was investigated in BME65Cs cells, senescent BMECs (bovine MECs) cells, early passage BMECs cells and MCF-7 cells (a human breast cancer cell line). In comparison with early passage BMECs cells, the expression of senescence-relevant apoptosis-related gene were significantly changed in BME65Cs cells. P16INK4a was downregulated, p53 was low expressed and Bax/Bcl-2 ratio was reversed. Moreover, a slight upregulation of the oncogene c-Myc, along with an undetectable level of breast tumor-related gene Bag-1 and TRPS-1, was observed in BME65Cs cells while these genes are all highly expressed in MCF-7. In addition, DNMT1 is upregulated in BME65Cs. These results suggest that the inhibition of both senescence and mitochondrial apoptosis signalling pathways contribute to the immortality of BME65Cs cells. The expression of p53 and p16INK4a in BME65Cs was altered in the pattern of down-regulation but not "loss", suggesting that this spontaneous immortalization is possibly initiated by other mechanism rather than gene mutation of p53 or p16INK4a. CONCLUSIONS: Spontaneously immortalised BME65Cs cells maintain many characteristics of normal BMEC cells and exhibit non-malignant transformation. Although this cell line displays altered patterns of gene expression, it is clearly distinct from malignant breast cancer cell line. It showed that co-inhibition of cellular senescence and mitochondrial apoptosis pathways coordinates BME65Cs cells immortalisation. Additionally, mechanisms other than gene mutation are likely to be involved in regulation of cellular functions. This study provides an insight into the relationship between cell senescence and immortalisation. BME65Cs cells will be useful in future studies of cellular senescence and tumorigenesis.