Drug-coated balloon angioplasty with provisional stenting versus primary stenting for the treatment of de novo coronary artery lesions: REC-CAGEFREE I trial rationale and design.

BACKGROUND: Percutaneous coronary intervention (PCI) with primary stenting, which stands for stent implantation regardless of obtaining satisfactory results with balloon angioplasty, has superseded conventional plain old balloon angioplasty with provisional stenting. With drug-coated balloon (DCB), primary DCB angioplasty with provisional stenting has shown non-inferiority to primary stenting for de novo coronary small vessel disease. However, the long-term efficacy and safety of such a strategy to the primary stenting on clinical endpoints in de novo lesions without vessel diameter restrictions remain uncertain. STUDY DESIGN: The REC-CAGEFREE I is an investigator-initiated, multicenter, randomized, open-label trial aimed to enroll 2270 patients with acute or chronic coronary syndrome from 43 interventional cardiology centers in China to evaluate the non-inferiority of primary paclitaxel-coated balloons angioplasty to primary stenting for the treatment of de novo, non-complex lesions without vessel diameter restrictions. Patients who fulfill all the inclusion and exclusion criteria and have achieved a successful lesion pre-dilatation will be randomly assigned to the two arms in a 1:1 ratio. Protocol-guided DCB angioplasty and bailout stenting after unsatisfactory angioplasty are mandatory in the primary DCB angioplasty group. The second-generation sirolimus-eluting stent will be used as a bailout stent in the primary DCB angioplasty group and the treatment device in the primary stenting group. The primary endpoint is the incidence of Device-oriented Composite Endpoint (DoCE) within 24 months after randomization, including cardiac death, target vessel myocardial infarction, and clinically and physiologically indicated target lesion revascularization. DISCUSSION: The ongoing REC-CAGEFREE I trial is the first randomized trial with a clinical endpoint to assess the efficacy and safety of primary DCB angioplasty for the treatment of de novo, non-complex lesions without vessel diameter restrictions. If non-inferiority is shown, PCI with primary DCB angioplasty could be an alternative treatment option to primary stenting. TRIAL REGISTRATION: Registered on clinicaltrial.gov (NCT04561739).

Boosting the Photocatalysis of Plasmonic Au-Cu Nanocatalyst by AuCu-TiO2 Interface Derived from O2 Plasma Treatment.

Plasmonic gold (Au) and Au-based nanocatalysts have received significant attention over the past few decades due to their unique visible light (VL) photocatalytic features for a wide variety of chemical reactions in the fields of environmental protection. However, improving their VL photocatalytic activity via a rational design is prevalently regarded as a grand challenge. Herein we boosted the VL photocatalysis of the TiO2-supported Au-Cu nanocatalyst by applying O2 plasma to treat this bimetallic plasmonic nanocatalyst. We found that O2 plasma treatment led to a strong interaction between the Au and Cu species compared with conventional calcination treatment. This interaction controlled the size of plasmonic metallic nanoparticles and also contributed to the construction of AuCu-TiO2 interfacial sites by forming AuCu alloy nanoparticles, which, thus, enabled the plasmonic Au-Cu nanocatalyst to reduce the Schottky barrier height and create numbers of highly active interfacial sites. The catalyst's characterizations and density functional theory (DFT) calculations demonstrated that boosted VL photocatalytic activity over O2 plasma treated Au-Cu/TiO2 nanocatalyst arose from the favorable transfer of hot electrons and a low barrier for the reaction between CO and O with the construction of large numbers of AuCu-TiO2 interfacial sites. This work provides an efficient approach for the rational design and development of highly active plasmonic Au and Au-based nanocatalysts and deepens our understanding of their role in VL photocatalytic reactions.

Treponema denticola Induces Interleukin-36γ Expression in Human Oral Gingival Keratinocytes via the Parallel Activation of NF-κB and Mitogen-Activated Protein Kinase Pathways.

The oral epithelial barrier acts as both a physical barrier to the abundant oral microbiome and a sentry for the immune system that, in health, constrains the accumulation of the polymicrobial plaque biofilm. The immune homeostasis during gingivitis that is largely protective becomes dysregulated, unproductive, and destructive to gingival tissue as periodontal disease progresses to periodontitis. The progression to periodontitis is associated with the dysbiosis of the oral microbiome, with increasing prevalences and abundances of periodontal pathogens such as Treponema denticola. Despite the association of T. denticola with a chronic inflammatory disease, relatively little is known about gingival epithelial cell responses to T. denticola infection. Here, we characterized the transcriptome of gingival keratinocytes following T. denticola challenge and identified interleukin-36γ (IL-36γ) as the most differentially expressed cytokine. IL-36γ expression is regulated by p65 NF-κB and the activation of both the Jun N-terminal protein kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) pathways downstream of Toll-like receptor 2 (TLR2). Finally, we demonstrate for the first time that mitogen- and stress-activated kinase 1 (MSK1) contributes to IL-36γ expression and may link the activation of MAPK and NF-κB signaling. These findings suggest that the interactions of T. denticola with the gingival epithelium lead to elevated IL-36γ expression, which may be a critical inducer and amplifier of gingival inflammation and subsequent alveolar bone loss.

Genome-wide identification of Streptococcus sanguinis fitness genes in human serum and discovery of potential selective drug targets.

Streptococcus sanguinis is a primary colonizer of teeth and is associated with oral health. When it enters the bloodstream, however, this bacterium may cause the serious illness infective endocarditis. The genes required for survival and proliferation in blood have not been identified. The products of these genes could provide a rich source of targets for endocarditis-specific antibiotics possessing greater efficacy for endocarditis, and also little or no activity against those bacteria that remain in the mouth. We previously created a comprehensive library of S. sanguinis mutants lacking every nonessential gene. We have now screened each member of this library for growth in human serum and discovered 178 mutants with significant abundance changes. The main biological functions disrupted in these mutants, including purine metabolism, were highlighted via network analysis. The components of an ECF-family transporter were required for growth in serum and were shown for the first time in any bacterium to be essential for endocarditis virulence. We also identified two mutants whose growth was reduced in serum but not in saliva. This strategy promises to enable selective targeting of bacteria based on their location in the body, in this instance, treating or preventing endocarditis while leaving the oral microbiome intact.

Platelet-rich fibrin accelerates skin wound healing in pressure injuries: a rat model.

OBJECTIVE: Platelet-rich fibrin (PRF) plays a role in promoting wound healing by releasing cytokines, chemokines and growth factors, and by inducing proliferation and activation of cells. A pressure injury (PI) is a treatable but serious and costly disease with adverse outcomes for the patient. However, traditional PI treatments are time-consuming, with limited effectiveness. Thus, we aimed to investigate the effects and mechanisms of PRF on skin wound healing in PIs in vivo in a rat model. METHOD: PRF was prepared from the blood of male Wistar rats. A rat model for PI ischaemia/reperfusion injury was established by placing a magnet onto the back skin, where a magnetic steel plate had been previously implanted. The rats were randomised into two groups: the control group was treated with sterile gauze dressings and the iPRF group received additional PRF. Skin wound healing rate was calculated and a CD31/Masson's trichrome stain performed. RESULTS: In this study, 16 rats were allocated to the two groups (n=8 in each group). PRF improved the skin wound healing rate of PIs in the rats; haematoxylin and eosin staining and CD31 staining showed that the number of capillaries increased significantly in the wound. However, Masson's trichrome staining showed no increase in fibrotic tissues after PRF treatment. CONCLUSION: In this in vivo rat model for PI, PRF accelerated skin wound healing by increasing angiogenesis in the wound.

The occurrence of peri-implant mucositis associated with the shift of submucosal microbiome in patients with a history of periodontitis during the first two years.

AIM: To investigate the dynamic changes of peri-implant microbiome in patients with a history of periodontitis and to construct a microbial prediction model. MATERIALS AND METHODS: The prospective study was performed at one month (T1), one year (T2) and two years (T3) after restoration. Clinical examinations [probing depth (PD), bleeding on probing (BOP), suppuration (SUP)], radiographic examinations and sample collection were conducted at three timepoints. Peri-implant sulcular fluid (PISF) was collected and analysed by 16S rRNA gene sequencing. Generalized linear mixed model (GLMM) was used to identify differences. RESULTS: Totally, 168 subjects were assessed for eligibility. Twenty-two patients were recruited in the longitudinal study. Eventually, 67 PISF samples from 24 implants of 12 patients were collected and analysed. Peri-implant microbiome showed increasing diversity and complexity over time. Disease-associated genera Porphyromonas, Tannerella, Treponema and Prevotella dramatically increased from T1 to T3. The prediction model for clinical suppuration at T1 showed a high accuracy of 90%. CONCLUSION: The dysbiosis of peri-implant microbiome increased with time during the two-year observation in patients with a history of periodontitis. Genera of Porphyromonas, Tannerella, Treponema and Prevotella were biomarkers of peri-implant mucositis. Microbiota at the early stage could predict subsequent microbial dysbiosis and clinical suppuration.

Spatiotemporal characteristics and meteorological determinants of hand, foot and mouth disease in Shaanxi Province, China: a county-level analysis.

BACKGROUND: Hand, foot and mouth disease (HFMD) is one of the common intestinal infectious diseases worldwide and has caused huge economic and disease burdens in many countries. The average annual incidence rate of HFMD was 11.66% in Shaanxi during the time span from 2009 to 2018. There are distinct differences within Shaanxi, as it is a special region that crosses three temperature zones. Hence, in this study, a spatiotemporal analysis of Shaanxi was performed to reveal the characteristics of the distribution of HFMD and to explore the meteorological determinants of HFMD. METHODS: The county-level and municipal data from Shaanxi Province from 2009 to 2018 were applied to research the spatiotemporal characteristics of HFMD and its meteorological determinants. Time series and spatial autocorrelation analyses were applied to assess the spatiotemporal characteristics of HFMD. This study used spatial econometric panel models to explore the relationship between HFMD and meteorological factors based on the data of 107 counties and 10 municipalities. RESULTS: The incidence rate of HFMD displayed no variable trend throughout the whole research period. A high incidence rate of HFMD was observed from June to September, corresponding to a time when the climate is characterized by heavy rain, high temperature, and high humidity. The high-incidence areas were mainly located in the central region in Shaanxi, whereas the low-incidence spots were mainly found in Northern Shaanxi. Regarding the meteorological factors analysed in this study, in general, the incidence rate of HFMD in specific regions was positively associated with the rainfall, temperature and humidity. CONCLUSION: These results could be applied by the government and the general public to take effective measures to prevent disease. Region-targeted policies could be enacted and implemented in the future according to specific situations in different areas and the relevant meteorological determinants. Additionally, meteorological conditions normally extend to a wide-ranging region; thus, cooperation among surrounding regions is necessary.

Research progress on the biological modifications of implant materials in 3D printed intervertebral fusion cages.

Anterior spine decompression and reconstruction with bone grafts and fusion is a routine spinal surgery. The intervertebral fusion cage can maintain intervertebral height and provide a bone graft window. Titanium fusion cages are the most widely used metal material in spinal clinical applications. However, there is a certain incidence of complications in clinical follow-ups, such as pseudoarticulation formation and implant displacement due to nonfusion of bone grafts in the cage. With the deepening research on metal materials, the properties of these materials have been developed from being biologically inert to having biological activity and biological functionalization, promoting adhesion, cell differentiation, and bone fusion. In addition, 3D printing, thin-film, active biological material, and 4D bioprinting technology are also being used in the biofunctionalization and intelligent advanced manufacturing processes of implant devices in the spine. This review focuses on the biofunctionalization of implant materials in 3D printed intervertebral fusion cages. The surface modifications of implant materials in metal endoscopy, material biocompatibility, and bioactive functionalizationare summarized. Furthermore, the prospects and challenges of the biofunctionalization of implant materials in spinal surgery are discussed. Fig.a.b.c.d.e.f.g As a pre-selected image for the cover, I really look forward to being selected. Special thanks to you for your comments.

Targeted Delivery of Drugs and Genes Using Polymer Nanocarriers for Cancer Therapy.

Cancer is one of the primary causes of worldwide human deaths. Most cancer patients receive chemotherapy and radiotherapy, but these treatments are usually only partially efficacious and lead to a variety of serious side effects. Therefore, it is necessary to develop new therapeutic strategies. The emergence of nanotechnology has had a profound impact on general clinical treatment. The application of nanotechnology has facilitated the development of nano-drug delivery systems (NDDSs) that are highly tumor selective and allow for the slow release of active anticancer drugs. In recent years, vehicles such as liposomes, dendrimers and polymer nanomaterials have been considered promising carriers for tumor-specific drug delivery, reducing toxicity and improving biocompatibility. Among them, polymer nanoparticles (NPs) are one of the most innovative methods of non-invasive drug delivery. Here, we review the application of polymer NPs in drug delivery, gene therapy, and early diagnostics for cancer therapy.

Inflammation has synergistic effect with nicotine in periodontitis by up-regulating the expression of α7 nAChR via phosphorylated GSK-3ß.

Periodontitis is the leading cause of adult tooth loss, and those who smoke are at an increased risk of developing periodontitis. α7 nicotinic acetylcholine receptor (α7 nAChR) is proposed to mediate the potential synergistic effect of nicotine and inflammation in smoking-related periodontitis. However, this has not been experimentally demonstrated. We isolated and cultured human periodontal ligament stem cells (PDLSCs) from healthy and inflamed tissues. PDLSCs were treated with either inflammatory factors or nicotine. We measured expression of genes that are associated with osteogenic differentiation and osteoclast formation using RT-qPCR and Western blot analyses. Besides, immunohistochemical staining, micro-CT analysis and tartaric acid phosphatase staining were used to measure α7 nAChR expression and function. Inflammation up-regulated α7 nAChR expression in both periodontal ligament tissues and PDLSCs. The up-regulated α7 nAChR contributed to the synergistic effect of nicotine and inflammation, leading to a decreased capability of osteogenic differentiation and increased capability of osteoclast formation-induction of PDLSCs. Moreover, the inflammation-induced up-regulation of α7 nAChR was partially dependent on the level of phosphorylated GSK-3ß. This study provides experimental evidence for the pathological development of smoking-related periodontitis and sheds new light on developing inflammation and α7 nAChR-targeted therapeutics to treat and prevent the disease.

Spatio-temporal variations of licensed doctor distribution in China: measuring and mapping disparities.

BACKGROUND: The licensed doctor misdistribution is one of the major challenges faced by China. However, this subject remains underexplored as spatial distribution characteristics (such as spatial clustering patterns) have not been fully mapped out by existing studies. To fill the void, this study aims to explore the spatio-temporal dynamics and spatial clustering patterns of different subtypes of licensed doctors (i.e., clinicians, traditional Chinese medicine doctors, dentists, public health doctors, general practitioners) in China. METHODS: Data on the licensed doctor quantity and population during 2012-2016 was obtained from the National Health (and Family Planning) Yearbook. Functional boxplots were used to visualize and compare the temporal trends of densities of different subtypes of licensed doctors. This study adopted two complementary spatial statistics (space-time scan statistics and Moran's I statistics) to explore the spatio-temporal dynamics and spatial clustering patterns of licensed doctor distribution in China. The former was used to explore the spatial variations in the temporal trends of licensed doctor density during 2012-2016, and the latter was adopted to explore the spatial changing patterns of licensed doctor distribution during the research period. RESULTS: The results show that the densities of almost all subtypes of licensed doctors displayed upward trends during 2012-2016, though some provincial units were left behind. Besides, spatial distribution characteristics varied across different subtypes of licensed doctors, with the low-low cluster area of general practitioners being the largest. CONCLUSIONS: The misdistribution of licensed doctors is a global problem and China is no exception. In order to achieve a balanced distribution of licensed doctors, the government is suggested to introduce a series of measures, such as deliberative policy design and effective human resource management initiatives to educate, recruit, and retain licensed doctors and prevent a brain drain of licensed doctors from disadvantaged units.

A descriptive analysis of the Spatio-temporal distribution of intestinal infectious diseases in China.

BACKGROUND: Intestinal infectious diseases (IIDs) have caused numerous deaths worldwide, particularly among children. In China, eight IIDs are listed as notifiable infectious diseases, including cholera, poliomyelitis, dysentery, typhoid and paratyphoid (TAP), viral Hepatitis A, viral Hepatitis E, hand-foot-mouth disease (HFMD) and other infectious diarrhoeal diseases (OIDDs). The aim of the study is to analyse the spatio-temporal distribution of IIDs from 2006 to 2016. METHODS: Data on the incidence of IIDs from 2006 to 2016 were collected from the public health science data centre issued by the Chinese Center for Disease Control and Prevention. This study applied seasonal decomposition analysis, spatial autocorrelation analysis and space-time scan analysis. Plots and maps were constructed to visualize the spatio-temporal distribution of IIDs. RESULTS: Regarding temporal analysis, the incidence of HFMD and Hepatitis E showed a distinct increasing trend, while the incidence of TAP, dysentery, and Hepatitis A presented decreasing trends over the last decade. The incidence of OIID remained steady. Summer is the season with the greatest number of cases of different IIDs. Regarding the spatial distribution, approximately all p values for the global Moran's I from 2006 to 2016 were less than 0.05, indicating that the incidences of the epidemics were unevenly distributed throughout the country. The high-risk areas for HFMD and OIDD were located in the Beijing-Tianjin-Tangshan (BTT) region and south China. The high-risk areas for TAP were located in some parts of southwest China. A higher incidence rates for dysentery and Hepatitis A were observed in the BTT region and some west provincial units. The high-risk areas for Hepatitis E were the BTT region and the Yangtze River Delta area. CONCLUSIONS: Based on our temporal and spatial analysis of IIDs, we identified the high-risk periods and clusters of regions for the diseases. HFMD and OIDD exhibited high incidence rates, which reflected the negligence of Class C diseases by the government. At the same time, the incidence rate of Hepatitis E gradually surpassed Hepatitis A. The authorities should pay more attention to Class C diseases and Hepatitis E. Regardless of the various distribution patterns of IIDs, disease-specific, location-specific, and disease-combined interventions should be established.

Analysis of essential gene dynamics under antibiotic stress in Streptococcus sanguinis.

The paradoxical response of Streptococcus sanguinis to drugs prescribed for dental and clinical practices has complicated treatment guidelines and raised the need for further investigation. We conducted a high throughput study on concomitant transcriptome and proteome dynamics in a time course to assess S. sanguinis behaviour under a sub-inhibitory concentration of ampicillin. Temporal changes at the transcriptome and proteome level were monitored to cover essential genes and proteins over a physiological map of intricate pathways. Our findings revealed that translation was the functional category in S. sanguinis that was most enriched in essential proteins. Moreover, essential proteins in this category demonstrated the greatest conservation across 2774 bacterial proteomes, in comparison to other essential functional categories like cell wall biosynthesis and energy production. In comparison to non-essential proteins, essential proteins were less likely to contain 'degradation-prone' amino acids at their N-terminal position, suggesting a longer half-life. Despite the ampicillin-induced stress, the transcriptional up-regulation of amino acid-tRNA synthetases and proteomic elevation of amino acid biosynthesis enzymes favoured the enriched components of essential proteins revealing 'proteomic signatures' that can be used to bridge the genotype-phenotype gap of S. sanguinis under ampicillin stress. Furthermore, we identified a significant correlation between the levels of mRNA and protein for essential genes and detected essential protein-enriched pathways differentially regulated through a persistent stress response pattern at late time points. We propose that the current findings will help characterize a bacterial model to study the dynamics of essential genes and proteins under clinically relevant stress conditions.

Novel in vitro dynamic metabolic system for predicting the human pharmacokinetics of tolbutamide.

Liver metabolism is commonly considered the major determinant in drug discovery and development. Many in vitro drug metabolic studies have been developed and applied to understand biotransformation. However, these methods have disadvantages, resulting in inconsistencies between in vivo and in vitro experiments. A major factor is that they are static systems that do not consider the transport process in the liver. Here we developed an in vitro dynamic metabolic system (Bio-PK metabolic system) to mimic the human pharmacokinetics of tolbutamide. Human liver microsomes (HLMs) encapsulated in a F127'-Acr-Bis hydrogel (FAB hydrogel) were placed in the incubation system. A microdialysis sampling technique was used to monitor the metabolic behavior of tolbutamide in hydrogels. The measured results in the system were used to fit the in vitro intrinsic clearance of tolbutamide with a mathematical model. Then, a PBPK model that integrated the corresponding in vitro intrinsic clearance was developed to verify the system. Compared to the traditional incubation method, reasonable PK profiles and the in vivo clearance of tolbutamide could be predicted by integrating the intrinsic clearance of tolbutamide obtained from the Bio-PK metabolic system into the PBPK model. The predicted maximum concentration (Cmax), area under the concentration-time curve (AUC), time to reach the maximum plasma concentration (Tmax) and in vivo clearance were consistent with the clinically observed data. This novel in vitro dynamic metabolic system can compensate for some limitations of traditional incubation methods; it may provide a new method for screening compounds and predicting pharmacokinetics in the early stages, supporting the development of compounds.

Highly selective capture of nucleosides with boronic acid functionalized polymer brushes prepared by atom transfer radical polymerization.

The nucleoside or modified nucleoside level in biological fluids reflects the pathological or physiological state of the body. Boronate affinity absorbents are widely used to selectively extract nucleosides from complex samples. In this work, a novel functionalized absorbent was synthesized by attaching 4-mercaptophenylboronic acid to gold nanoparticles on modified attapulgite. The surface of the attapulgite was modified by poly(acryloyloxyethyltrimethyl ammonium chloride) by atom transfer radical polymerization, creating many polymer brushes on the surface. The resultant material exhibited superior binding capacity (30.83 mg/g) for adenosine and was able to capture cis-diol nucleosides from 1000-fold interferences. Finally, to demonstrate its potential for biomolecule extraction, this boronate affinity material was used to preconcentrate nucleosides from human urine and plasma.

GSK3ß is a checkpoint for TNF-α-mediated impaired osteogenic differentiation of mesenchymal stem cells in inflammatory microenvironments.

BACKGROUND: The fate and differentiation of mesenchymal stem cells (MSCs) depend on various microenvironmental cues. In chronic inflammatory bone disease, bone regeneration is inhibited. The present study therefore sought to identify the underlying molecule mechanisms. METHODS: We isolated periodontal ligament stem cells (PDLSCs), a new population of MSCs, from the periodontal ligament tissues of periodontitis patients and healthy controls (p-PDLSCs and h-PDLSCs). The secretion of inflammatory cytokines, like TNF-α, IL-1ß, IL-6 and IL-8, after LPS stimulation was measured by ELISA. The expressions of p-GSK3ß and GSK3ß in two types of PDLSCs were detected by Western blot. TOPFlash was used to assay the Tcf/Lef transcriptional activity. Knockdown of GSK3ß by siRNA and over-expression of GSK3ß by adenoviruses were performed to confirm the role of GSK3ß in the impaired osteogenic differentiation of PDLSCs under inflammatory microenvironment. RESULTS: We demonstrated that p-PDLSCs displayed impaired osteogenic capacity than h-PDLSCs. Upon inflammatory stimulation, monocytes, but not PDLSCs, released inflammatory cytokines among which TNF-α directly act on PDLSCs and suppressed their osteogenic differentiation. TNF-α induced the phosphorylation of GSK3ß, the deactivated form of GSK3ß, which increased nuclear ß-catenin and Lef-1 accumulation, and eventually reduced the Runx2-associated osteogenesis in PDLSCs. Over-expression of GSK3ß rescued osteogenesis in TNF-α-stimulated PDLSCs, whereas inactivation of GSK3ß was sufficient to liberate the ß-catenin/Lef-1/Runx2 pathway. CONCLUSION: GSK3ß plays an obligatory role in the TNF-α-mediated inhibition of osteogenesis in MSCs. GENERAL SIGNIFICANCE: The strategy to target GSK3ß may provide a potential approach to bone regeneration in inflammatory microenvironments.

High-throughput characterization of the influence of Streptococcus sanguinis genes on the interaction between Streptococcus sanguinis and Porphyromonas gingivalis.

Porphyromonas gingivalis is a keystone pathogen in periodontitis, and Streptococcus sanguinis is an abundant oral commensal bacterium associated with periodontal health. However, the interaction between P. gingivalis and S. sanguinis remains obscure. Here, we established a strategy for high-throughput measurement of the cell number of P. gingivalis in the coculture with S. sanguinis by detecting the concentration of hydrogen sulfate. The interaction between P. gingivalis and over 2000 S. sanguinis single-gene mutants was characterized using this strategy, and several interaction-associated genes in S. sanguinis were determined by detecting more P. gingivalis cells in the coculture with matched S. sanguinis mutants. Three S. sanguinis interaction-associated genes were predicted to be responsible for cysteine metabolism, and the supplementation of exogenous L-cysteine promoted the cell number of P. gingivalis in the coculture with S. sanguinis. Thus, exogenous L-cysteine and the compromised cysteine metabolism in S. sanguinis enhanced the growth of P. gingivalis in the existence of S. sanguinis. Additionally, the interaction between P. gingivalis and other Streptococcus spp. was examined, and S. pneumoniae was the only streptococci that had no inhibition on the cell number of P. gingivalis. In total, this study established a new strategy for high-throughput screening of the interaction between Streptococcus and P. gingivalis and discovered a set of genes in S. sanguinis that impacted the interaction. The influence of exogenous L-cysteine on the interaction between P. gingivalis and S. sanguinis in the oral cavity needs further investigation.

Effect of α7 nAChR-autophagy axis of deciduous tooth pulp stem cells in regulating IL-1ß in the process of physiological root resorption of deciduous teeth.

Physiological root resorption of deciduous teeth is a normal phenomenon occurring during the developmental stages of children. Previous research has indicated the pivotal role of the inflammatory microenvironment in this process, although the specific mechanisms remain unclear. This study is aimed at elucidating the involvement of the alpha7 nicotinic acetylcholine receptors (α7 nAChR)-autophagy axis in the regulation of the inflammatory microenvironment during physiological root resorption in deciduous teeth. Samples were collected from deciduous teeth at various stages of physiological root resorption, and deciduous dental pulp stem cells (DDPSCs) were isolated and cultured during the mid-phase of root resorption. The findings revealed a substantial infiltration of the pulp of deciduous teeth at the mid-phase of root resorption, characterized by elevated expression levels of α7 nAChR and IL-1ß. Significantly increased IL-1ß and α7 nAChR expressions were observed in DDPSCs during the mid-phase of root resorption, with α7 nAChR demonstrating a regulatory effect on IL-1ß. Moreover, evidence suggested that mechanical stress may act as a trigger, regulating autophagy and IL-1 expression via α7 nAChR. In conclusion, mechanical stress was identified as a regulator of autophagy in DDPSCs through α7 nAChR, influencing the expression of IL-1ß and contributing to the formation of the inflammatory microenvironment. This mechanism plays a crucial role in the physiological root resorption of deciduous teeth. KEY MESSAGES: The pulp of deciduous teeth at mid-phase of root resorption was heavily infiltrated with high expression of α7nAChR and IL-1ß. α7 nAChR acts as an initiating factor to regulate IL-1ß through autophagy in DDPSCs. Mechanical stress can regulate autophagy of DDPSCs through α7 nAChR and thus affect IL-1ß expression and inflammatory microenvironment formation in physiological root resorption in deciduous teeth.

Organism-Inspired Antioxidant Bioadhesive with Strong Sealing Ability to Prevent Epidural Adhesion.

Epidural adhesion or epidural fibrosis is the major reason for postoperative pain, which remains a clinically challenging problem. Current physical barriers fail to provide a satisfactory therapeutic outcome mainly due to their lack of adhesion, inability to prevent fluid leakage, and exhibiting limited antioxidant properties. Herein, we fabricated a cysteine-modified bioadhesive (SECAgel) with improved sealing and antioxidant properties for epidural adhesion prevention, inspired by the organism's antioxidant systems. The resulting SECAgel showed good injectability and in situ adhesion ability, effectively covering every corner of the irregular wound. Besides, it possessed efficient sealing properties (395.2 mmHg), effectively stopping blood leakage in the rabbit carotid artery transection model. The antioxidant experiments demonstrated that the SECAgel effectively scavenged various radicals and saved the cells from oxidative stress. Two animal models were used to show that the SECAgel effectively inhibited adhesion in both situations with and without cerebrospinal fluid leakage. The RNA sequencing analysis showed that SECAgel treatment effectively inhibited the expression of key genes related to adhesion development, inflammatory response, and oxidative stress. The SECAgel, together with good biocompatibility, can be a good candidate for preventing epidural adhesion in the clinic.

Realizing a Gabor zone plate with quasi-random distributed hexagon dots.

We propose a quasi-random-dot-array binary Gabor zone plate (QBGZP) with focusing properties of single order foci only. These features are verified with simulations and experiments in the visible light region. Moreover, we find that the performance of QBGZP, which is composed of hexagon patterns, is determined by the ratio of hexagon circumcircle diameter to the outermost zone width. The QBGZP offers a potential alternative for focusing and imaging in the soft x-ray and extreme ultraviolet region.