Interpenetrating nanofibrillar membrane of self-assembled collagen and antimicrobial peptides for enhanced bone regeneration.

Bone regeneration remains a major clinical challenge, especially when infection necessitates prolonged antibiotic treatment. This study presents a membrane composed of self-assembled and interpenetrating GL13K, an antimicrobial peptide (AMP) derived from a salivary protein, in a collagen membrane for antimicrobial activity and enhanced bone regeneration. Commercially available collagen membranes were immersed in GL13K solution, and self-assembly was initiated by raising the solution pH to synthesize the multifunctional membrane called COL-GL. COL-GL was composed of interpenetrating large collagen fibers and short GL13K nanofibrils, which increased hydrophobicity, reduced biodegradation from collagenase, and stiffened the matrix compared to control collagen membranes. Incorporation of GL13K led to antimicrobial and anti-fouling activity against early oral surface colonizer Streptococcus gordonii while not affecting fibroblast cytocompatibility or pre-osteoblast osteogenic differentiation. GL13K in solution also reduced macrophage inflammatory cytokine expression and increased pro-healing cytokine expression. Bone formation in a rat calvarial model was accelerated at eight weeks with COL-GL compared to the gold-standard collagen membrane based on microcomputed tomography and histology. Interpenetration of GL13K within collagen sidesteps challenges with antimicrobial coatings on bone regeneration scaffolds while increasing bone regeneration. This strength makes COL-GL a promising approach to reduce post-surgical infections and aid bone regeneration in dental and orthopedic applications. STATEMENT OF SIGNIFICANCE: The COL-GL membrane, incorporating the antimicrobial peptide GL13K within a collagen membrane, signifies a noteworthy breakthrough in bone regeneration strategies for dental and orthopedic applications. By integrating self-assembled GL13K nanofibers into the membrane, this study successfully addresses the challenges associated with antimicrobial coatings, exhibiting improved antimicrobial and anti-fouling activity while preserving compatibility with fibroblasts and pre-osteoblasts. The accelerated bone formation observed in a rat calvarial model emphasizes the potential of this innovative approach to minimize post-surgical infections and enhance bone regeneration outcomes. As a promising alternative for future therapeutic interventions, this material tackles the clinical challenges of extended antibiotic treatments and antibiotic resistance in bone regeneration scenarios.

Unilateral or Bilateral Percutaneous Endoscopic Debridement and Drainage for Thoracolumbar Infections: A Systemic Review and Meta-analysis.

BACKGROUND: Unilateral percutaneous endoscopic debridement and drainage (UPEDD) and bilateral PEDD (BPEDD) are commonly implemented, and have consistently yielded favorable clinical outcomes. Nevertheless, there is a scarcity of literature contrasting the advantages and disadvantages between these 2 procedures. OBJECTIVE: The goal of this research was to conduct a meta-analysis to compare the clinical effects of UPEDD and BPEDD. STUDY DESIGN: A systematic review and meta-analysis. METHODS: A systematic review of studies reporting outcomes following UPEDD and/or BPEDD procedures was performed. The extracted data were used for meta-analysis. Pooled event rates for positive bacteria culture, pain control satisfaction, reoperation, and complications were estimated. The pooled operation time and blood loss were also calculated. RESULTS: Among 764 retrieved articles, 28 studies with 661 patients met the inclusion criteria and were used for our meta-analysis. A total of 21 studies (462 patients) investigated UPEDD outcomes and 7 studies (199 patients) investigated BPEDD outcomes. For the UPEDD group, the pooled event rates for positive bacteria culture, pain control satisfaction, reoperation, and complications were 72%, 91%, 9% and 4%, respectively; the pooled operation time and blood loss were 89.90 minutes and 59.77 mL. For the BPEDD group, these were 79%, 92%, 4%, 8%, 93.23 minutes and 64.93 mL, respectively. LIMITATIONS: First, all included studies were retrospective series, limiting our study design to a single-arm meta-analysis. Second, there was a limited amount of studies that were determined to be fitting, particularly on BPEDD; the sample size was also small. Third, the clinical effects of UPEDD and BPEDD needed to be compared in greater detail, such as the time it took for inflammatory markers to return to normal, the incidence of local kyphosis, and whether the duration of antibiotic use could be shortened after adequate debridement with BPEDD. Lastly, further studies are necessary to compare the clinical outcome of PEDD and percutaneous endoscopic interbody debridement and fusion. CONCLUSIONS: Both UPEDD and BPEDD can provide a relatively reliable causative-pathogen identification and satisfactory clinical outcome. The 2 techniques are not significantly different in terms of positive bacteria culture rate, pain control satisfaction rate, complication rate, and reoperation rate.

Harnessing antimicrobial peptides in endodontics.

Endodontic therapy includes various procedures such as vital pulp therapy, root canal treatment and retreatment, surgical endodontic treatment and regenerative endodontic procedures. Disinfection and tissue repair are crucial for the success of these therapies, necessitating the development of therapeutics that can effectively target microbiota, eliminate biofilms, modulate inflammation and promote tissue repair. However, no current endodontic agents can achieve these goals. Antimicrobial peptides (AMPs), which are sequences of amino acids, have gained attention due to their unique advantages, including reduced susceptibility to drug resistance, broad-spectrum antibacterial properties and the ability to modulate the immune response of the organism effectively. This review systematically discusses the structure, mechanisms of action, novel designs and limitations of AMPs. Additionally, it highlights the efforts made by researchers to overcome peptide shortcomings and emphasizes the potential applications of AMPs in endodontic treatments.

Novel PLCZ1 mutation caused polyspermy during in vitro fertilization.

ABSTRACT: Failure of oocyte activation, including polyspermy and defects in pronuclear (PN) formation, triggers early embryonic developmental arrest. Many studies have shown that phospholipase C zeta 1 (PLCZ1) mutations cause failure of PN formation following intracytoplasmic sperm injection (ICSI); however, whether PLCZ1 mutation is associated with polyspermy during in vitro fertilization (IVF) remains unknown. Whole-exome sequencing (WES) was performed to identify candidate mutations in couples with primary infertility. Sanger sequencing was used to validate the mutations. Multiple PLCZ1-mutated sperm were injected into human and mouse oocytes to explore whether PN formation was induced. Assisted oocyte activation (AOA) after ICSI was performed to overcome the failure of oocyte activation. We identified three PLCZ1 mutations in three patients who experienced polyspermy during IVF cycles, including a novel missense mutation c.1154C>T, p.R385Q. PN formation failure was observed during the ICSI cycle. However, injection of multiple PLCZ1-mutated sperm induced PN formation, suggesting that the Ca2+ oscillations induced by the sperm exceeded the necessary threshold for PN formation. AOA after ICSI enabled normal fertilization, and all patients achieved successful pregnancies. These findings expand the mutational spectrum of PLCZ1 and suggest an important role for PLCZ1 in terms of blocking polyspermy. Furthermore, this study may benefit genetic diagnoses in cases of abnormal fertilization and provide potential appropriate therapeutic measures for these patients with sperm-derived polyspermy.

Synthesis of a novel monomer "DDTU-IDI" for the development of low-shrinkage dental resin composites.

OBJECTIVE: The current dental resin composites often suffer from polymerization shrinkage, which can lead to microleakage and potentially result in recurring tooth decay. This study presents the synthesis of a novel monomer, (3,9-diethyl-1,5,7,11-tetraoxaspiro[5,5]undecane-3,9-diyl)bis(methylene) bis((2-(3-(prop-1-en-2-yl)phenyl)propan-2-yl)carbamate) (DDTU-IDI), and evaluates its effect in the formulation of low-shrinkage dental resin composites. METHODS: DDTU-IDI was synthesized through a two-step reaction route, with the initial synthesis of the required raw material monomer 3,9-diethyl-3,9-dihydroxymethyl-1,5,7,11-tetraoxaspiro-[5,5] undecane (DDTU). The structures were confirmed using Fourier-transform infrared (FT-IR) spectroscopy and hydrogen nuclear magnetic resonance (1HNMR) spectroscopy. Subsequently, DDTU-IDI was incorporated into Bis-GMA-based composites at varying weight percentages (5, 10, 15, and 20 wt%). The polymerization reaction, degree of conversion, polymerization shrinkage, mechanical properties, physicochemical properties and biocompatibility of the low-shrinkage composites were thoroughly evaluated. Furthermore, the mechanical properties were assessed after a thermal cycling test with 10,000 cycles to determine the stability. RESULTS: The addition of DDTU-IDI at 10, 15, and 20 wt% significantly reduced the polymerization volumetric shrinkage of the experimental resin composites, without compromising the degree of conversion, mechanical and physicochemical properties. Remarkably, at a monomer content of 20 wt%, the polymerization shrinkage was reduced to 1.83 ± 0.53%. Composites containing 10, 15, and 20 wt% DDTU-IDI exhibited lower water sorption and higher contact angle. Following thermal cycling, the composites exhibited no significant decrease in mechanical properties, except for the flexural properties. SIGNIFICANCE: DDTU-IDI has favorable potential as a component which could produce volume expansion and increase rigidity in the development of low-shrinkage dental resin composites. The development of low-shrinkage composites containing DDTU-IDI appears to be a promising strategy for reducing polymerization shrinkage, thereby potentially enhancing the longevity of dental restorations.

Clinical efficacy of metformin in familial adenomatous polyposis and the effect of intestinal flora.

BACKGROUND AND AIMS: Metformin has been reported to inhibit the occurrence and development of colorectal cancer (CRC) by mediating changes in intestinal flora. Studies have also indicated that the occurence of familial adenomatous polyposis (FAP) may also be associated with changes in the intestinal flora. Therefore, we investigated the efficacy and safety of metformin in treating FAP and the association with intestinal flora. RESULTS: Compared with the baseline, the mean number and load of polyps in the areas of nanocarbon labeling and postoperative residuals in the test group were lower than those in the placebo group, while the diversity of intestinal flora species was increased. At the genus level, the relative abundance of g_Ruminococcus in the test group was lower than that at baseline, whereas the relative abundance of g_Lactobacillus was higher. These changes were statistically significant (P < 0.05). CONCLUSION: One-year metformin therapy for FAP is safe and effective, potentially mediated by modulating the intestinal flora. This study provides new insights and strategies for preventing adenomatous polyp carcinogenesis in FAP and explores possible preventive action.

DUSP4 maintains the survival and LSD1 protein stability in esophageal squamous cell carcinoma cells by inhibiting JNK signaling-dependent autophagy.

DUSP4 is a biomarker of esophageal squamous cell carcinoma (ESCC), which is responsible for the prognosis in ESCC. However, the underlying mechanism of DUSP4-regulated ESCC carcinogenesis is unknown. As a negative regulator of JNK, DUSP4 can inhibit autophagy, which contributes to tumorigenesis. This study aimed to explore the role of autophagy in DUSP4-regulated ESCC carcinogenesis. Our results showed that DUSP4 overexpression inhibited autophagy and promoted LSD1 protein expression in ESCC cells, while DUSP4 silencing showed the opposite effects. However, DUSP4 overexpression and silencing did not affect LSD1 mRNA expression. But the regulatory ability of DUSP4 overexpression on autophagy, death level, and LSD1 protein was reversed by rapamycin. In addition, DUSP4 overexpression inhibited JNK and Bcl2 phosphorylation and the dissociation of Bcl2-Beclin1 complex, while DUSP4 silencing promoted JNK and Bcl2 phosphorylation. Moreover, the regulatory ability of DUSP4 overexpression on autophagy, death, and LSD1 protein was reversed by JNK activator anisomycin. The xenograft assays also showed that DUSP4 overexpression-promoted ESCC tumor growth in vivo and LC3II and LSD1 protein expression in tumor tissues were reversed by rapamycin or anisomycin. Overall, DUSP4 inhibits Bcl2-Beclin1-autophagy signal transduction through the negative regulation of JNK, thus suppressing autophagic death and the autophagic degradation of LSD1 in ESCC, by which DUSP4 promotes ESCC carcinogenesis.

Biodegradable Zn-5Dy Alloy with Enhanced Osteo/Angio-Genic Activity and Osteointegration Effect via Regulation of SIRT4-Dependent Mitochondrial Function.

Zinc (Zn)-dysprosium (Dy) binary alloys are promising biodegradable bone fracture fixation implants owing to their attractive biodegradability and mechanical properties. However, their clinical application is a challenge for bone fracture healing, due to the lack of Zn-Dy alloys with tailored proper bio-mechanical and osteointegration properties for bone regeneration. A Zn-5Dy alloy with high strength and ductility and a degradation rate aligned with the bone remodeling cycle is developed. Here, mechanical stability is further confirmed, proving that Zn-5Dy alloy can resist aging in the degradation process, thus meeting the mechanical requirements of fracture fixation. In vitro cellular experiments reveal that the Zn-5Dy alloy enhances osteogenesis and angiogenesis by elevating SIRT4-mediated mitochondrial function. In vivo Micro-CT, SEM-EDS, and immunohistochemistry analyses further indicate good biosafety, suitable biodegradation rate, and great osteointegration of Zn-5Dy alloy during bone healing, which also depends on the upregulation of SIRT4-mediated mitochondrial events. Overall, the study is the first to report a Zn-5Dy alloy that exerts remarkable osteointegration properties and has a strong potential to promote bone healing. Furthermore, the results highlight the importance of mitochondrial modulation and shall guide the future development of mitochondria-targeting materials in enhancing bone fracture healing.

Codelivery of TGFß and Cox2 siRNA inhibits HCC by promoting T-cell penetration into the tumor and improves response to Immune Checkpoint Inhibitors.

Upregulation of TGFß and Cox2 in the tumor microenvironment results in blockade of T-cell penetration into the tumor. Without access to tumor antigens, the T-cell response will not benefit from administration of the immune checkpoint antibodies. We created an intravenous polypeptide nanoparticle that can deliver two siRNAs (silencing TGFß and Cox2). Systemic administration in mice, bearing a syngeneic orthotopic hepatocellular carcinoma (HCC), delivers the siRNAs to various cells in the liver, and significantly reduces the tumor. At 2 mg/kg (BIW) the nanoparticle demonstrated a single agent action and induced tumor growth inhibition to undetectable levels after five doses. Reducing the siRNAs to 1mg/kg BIW demonstrated greater inhibition in the presence of PD-L1 mAbs. After only three doses BIW, we could still recover a smaller tumor and, in tumor sections, showed an increase in penetration of CD4+ and CD8+ T-cells deeper into the remaining tumor that was not evident in animals treated with non-silencing siRNA. The combination of TGFß and Cox2 siRNA co-administered in a polypeptide nanoparticle can act as a novel therapeutic alone against HCC and may augment the activity of the immune checkpoint antibodies. Silencing TGFß and Cox2 converts an immune excluded (cold) tumor into a T-cell inflamed (hot) tumor.

LIF Aggravates Pulpitis by Promoting Inflammatory Response in Macrophages.

Leukemia inhibitory factor (LIF) has been recognized as a novel inflammatory modulator in inflammation-associated diseases. This study aimed to investigate the modulation of LIF in dental pulp inflammation. Experimental pulpitis was established in wild-type (WT) and Lif-deficient (Lif-/-) mice. Histological and immunostaining analyses were conducted to assess the role of LIF in the progression of pulpitis. Mouse macrophage cell line (RAW264.7) was treated with LPS to simulate an inflammatory environment. Exogenous LIF was added to this system to examine its modulation in macrophage inflammatory response in vitro. Primary bone marrow-derived macrophages (BMDMs) from WT and Lif-/- mice were isolated and stimulated with LPS to confirm the effect of Lif deletion on macrophage inflammatory response. Supernatants from LIF and LPS-treated human dental pulp cells (hDPCs) were collected and added to macrophages. Macrophage chemotaxis was assessed using transwell assays. The results showed an increased expression of LIF and LIFR with the progression of pulpitis, and LIFR was highly expressed in macrophages. Lif deficiency alleviated experimental pulpitis with the reduction of pro-inflammatory cytokines and macrophage infiltration. Exogenous LIF promoted inflammatory response of LPS-induced macrophages through a STAT3/p65-dependent pathway. Consistently, Lif deletion inhibited macrophage inflammatory response in vitro. Supernatants of LIF-treated hDPCs enhanced macrophage migration in LPS-induced inflammatory environment. Our findings demonstrated that LIF aggravates pulpitis by promoting macrophage inflammatory response through a STAT3/p65-dependent pathway. Furthermore, LIF plays a crucial role in driving the recruitment of macrophages to inflamed pulp tissue by promoting chemokine secretion in DPCs.

Cleavage and Noncleavage Chemistry in Reactive Oxygen Species (ROS)-Responsive Materials for Smart Drug Delivery.

The design and development of advanced drug delivery systems targeting reactive oxygen species (ROS) have gained significant interest in recent years for treating various diseases, including cancer, psychiatric diseases, cardiovascular diseases, neurological diseases, metabolic diseases, and chronic inflammations. Integrating specific chemical bonds capable of effectively responding to ROS and triggering drug release into the delivery system is crucial. In this Review, we discuss commonly used conjugation linkers (chemical bonds) and categorize them into two groups: cleavable linkers and noncleavable linkers. Our goal is to clarify their unique drug release mechanisms from a chemical perspective and provide practical organic synthesis approaches for their efficient production. We showcase numerous significant examples to demonstrate their synthesis routes and diverse applications. Ultimately, we strive to present a comprehensive overview of cleavage and noncleavage chemistry, offering insights into the development of smart drug delivery systems that respond to ROS.

Glucose-Triggered Gelation of Supramolecular Peptide Nanocoils with Glucose-Binding Motifs.

Peptide self-assembly is a powerful tool to prepare functional materials at the nanoscale. Often, the resulting materials have high aspect-ratio, with intermolecular ß-sheet formation underlying 1D fibrillar structures. Inspired by dynamic structures in nature, peptide self-assembly is increasingly moving toward stimuli-responsive designs wherein assembled structures are formed, altered, or dissipated in response to a specific cue. Here, a peptide bearing a prosthetic glucose-binding phenylboronic acid (PBA) is demonstrated to self-assemble into an uncommon nanocoil morphology. These nanocoils arise from antiparallel ß-sheets, with molecules aligned parallel to the long axis of the coil. The binding of glucose to the PBA motif stabilizes and elongates the nanocoil, driving entanglement and gelation at physiological glucose levels. The glucose-dependent gelation of these materials is then explored for the encapsulation and release of a therapeutic agent, glucagon, that corrects low blood glucose levels. Accordingly, the release of glucagon from the nanocoil hydrogels is inversely related to glucose level. When evaluated in a mouse model of severe acute hypoglycemia, glucagon delivered from glucose-stabilized nanocoil hydrogels demonstrates increased protection compared to delivery of the agent alone or within a control nanocoil hydrogel that is not stabilized by glucose.

Multifunctional nanocoating for enhanced titanium implant osseointegration.

Preventing bacterial infection and promoting osseointegration are essential for the long-term success of titanium (Ti) implants. In this study, we developed a multifunctional nanocoating on Ti mini-implants to simultaneously address these challenges. The nanocoating consists of self-assembled antimicrobial peptides GL13K and silver nanoparticles, referred to as Ag-GL. Our results showed that the Ag-GL coating did not alter the surface morphology of the mini-implants. Ag-GL coated mini-implants demonstrated a two orders of magnitude reduction in colony-forming unit (CFU) values compared to the noncoated eTi group, resulting in minimal inflammation and no apparent bone destruction in a bacterial infection in vivo model. When evaluating osseointegration properties, micro-CT analysis, histomorphometric analysis, and pull-out tests revealed that the Ag-GL coating significantly enhanced osseointegration and promoted new bone formation in vivo.

What is the stable internal fixation for the unstable and osteoporotic supracondylar femoral fractures: a finite element analysis.

BACKGROUND: Osteoporotic supracondylar femoral fractures (OSFF) have historically been managed by the lateral anatomical locking plate with reasonable success. However, for some kinds of unstable and osteoporotic supracondylar femoral fractures (UOSFF), especially with bone defects, unilateral locking plate (ULLP) fixation failed or resulted in implant breakage. This paper is going to explore what is the stable internal fixation for UOSFF by adding the bilateral locking plate (BLLP) fixation. METHODS: OSFF models were divided into two groups according to the fracture line type, which would be further subdivided according to their angle of fracture line, presence of bone defect, location, and degree of bone defect. Thereafter, kinds of locking plate fixation were constructed. A 2010-N load was applied to the femoral head, and a 1086-N load was applied to the greater trochanter. In this condition, the maximum von Mises stress distribution of models were investigated. RESULTS: Firstly, it was obviously found that the stress concentration in the BLLP group was more dispersed than that in the ULLP group. Secondly, according to the fracture line analysis, the stress value of fracture line type in "\" model group was higher than that of "/" model group. Moreover, with the increase in fracture line angle, the stress value of the model increased. Thirdly, from the bone defect analysis, the stress value of the medial bone defect (MBD) model group was higher than that of the lateral bone defect (LBD) model group. And as the degree of bone defect increased, the stress value increased gradually in the model group. CONCLUSION: In the following four cases, lateral unilateral locking plate fixation cannot effectively stabilize the fracture end, and double locking plate internal fixation is a necessary choice. First, when the angle of the fracture line is large (30, 45). Second, when the fracture line type is "/." Third, when the bone defect is large. Fourth, when the bone defect is medial.

Low T3 syndrome predicts more adverse events in patients with hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a common cardiac genetic disorder that clinically manifests with sudden death and progressive heart failure. Moreover, thyroid dysfunction is associated with increased cardiovascular morbidity and mortality risks. Therefore, this study aimed to clarify whether thyroid hormones could serve as an independent predictor of adverse events in patients with HCM. METHODS: The cohort consisted of 782 patients with HCM who had thyroid hormones baseline data and were admitted to the Affiliated Hospital of Jiaxing University. Patients were divided into two groups according to serum levels of free triiodothyronine (fT3): the normal fT3 and low triiodothyronine (T3) syndrome groups. Low T3 syndrome was defined as fT3 < 2.43 pmol/L with a normal thyroid-stimulating hormone (TSH) level. Patients whose TSH levels were abnormally high or abnormally low were excluded from this study. The primary endpoint was the occurrence of sudden cardiac death (SCD) events, and the secondary endpoint was a composite of worsening heart failure (WHF) events, including heart failure death, cardiac decompensation, hospitalization for heart failure, and HCM-related stroke. The Kaplan-Meier and Cox regression were performed for the survival analysis. RESULTS: After a median follow-up of 52 months, 75 SCD events and 134 WHF events were recorded. The Kaplan-Meier survival curves showed that the cumulative incidence of SCD events and WHF events were significantly higher in patients with low T3 syndrome (log-rank p = .02 and log-rank p = .001, respectively). Furthermore, multivariate Cox regression analysis demonstrated that low T3 syndrome is a strong predictor of SCD events and WHF events (adjusted hazard ratio [HR: 1.53, 95% confidence interval [CI]: 1.13-2.24, p < .01; HR: 3.87, 95% CI: 2.91-4.98, p < .001, respectively). CONCLUSIONS: Low T3 syndrome is highly prevalent among patients with HCM and was independently associated with an increased risk of SCD events and WHF events. The routine assessment of serum fT3 levels may provide risk stratification in this population.

Intrinsic and external active sites of single-atom catalysts.

Active components with suitable supports are the common paradigm for industrial catalysis, and the catalytic activity usually increases with minimizing the active component size, generating a new frontier in catalysis, single-atom catalysts (SACs). However, further improvement of SACs activity is limited by the relatively low loading of single atoms (SAs, which are heteroatoms for most SACs, i.e., external active sites) because of the highly favorable aggregation of single heteroatoms during preparation. Research interest should be shifted to investigate SACs with intrinsic SAs, which could circumvent the aggregation of external SAs and consequently increase the SAs loading while maintaining them individual to further improve the activity. In this review, SACs with external or intrinsic SAs are discussed and, at last, the perspectives and challenges for obtaining high-loading SACs with intrinsic SAs are outlined.

Prediction of overall survival after radical gastrectomy using nomograms created by tumor markers.

Prediction of prognosis after radical resection of gastric cancer has not been well established. Therefore, we aimed to establish a prognostic model based on a new score system of patients with gastric cancer. A total of 1235 patients who underwent curative gastrectomy at our hospital from October 2015 to April 2017 were included in this study. Univariate and multivariate analyses were used to screen for prognostic risk factors. Construction of the nomogram was based on Cox proportional hazard regression models. The construction of the new score models was analyzed by the receiver operating characteristic curve (ROC curve), calibration curve, and decision curve. Multivariate analysis showed that tumor size, T, N, carcinoembryonic antigen, CA125, and CA19-9 were independent prognostic factors. The new score model had a greater AUC (The area under the ROC curve) than other systems, and the C-index of the nomogram was highly reliable for evaluating the survival of patients with gastric cancer. Based on the tumor markers and other clinical indicators, we developed a precise model to predict the prognosis of patients with gastric cancer after radical surgery. This score system can be helpful to both surgeons and patients.

Bioactive Dental Resin Composites with MgO Nanoparticles.

Photoactivating dental resin composites have been the most prevailing material for repairing dental defects in various clinical scenarios due to their multiple advantages. However, compared to other restorative materials, the surface of resin-based composites is more susceptible to plaque biofilm accumulation, which can lead to secondary caries and restoration failure. This study introduced different weight fractions (1, 2, 5, 10, and 15%) of magnesium oxide nanoparticles (MgONPs) as antibacterial fillers into dental resin composites. Multifarious properties of the material were investigated, including antibacterial activity against a human salivary plaque-derived biofilm, cytotoxicity on human gingival fibroblasts, mechanical and physicochemical properties as well as the performance when subjected to thermocycling aging treatment. Results showed that the incorporation of MgONPs significantly improved the composites' anti-biofilm capability even at a low amount of 2 wt % without compromising the mechanical, physicochemical, and biocompatibility performances. The results of the thermocycling test suggested certain of aging resistance. Moreover, a small amount of MgONPs possibly made a difference in enhancing photoactivated polymerization and increasing the curing depth of experimental resin composites. Overall, this study highlights the potential of MgONPs as an effective strategy for developing antibacterial resin composites, which may help mitigating cariogenic biofilm-associated secondary caries.

Nomogram established using risk factors of early gastric cancer for predicting the lymph node metastasis.

BACKGROUND: For the prognosis of patients with early gastric cancer (EGC), lymph node metastasis (LNM) plays a crucial role. A thorough and precise evaluation of the patient for LNM is now required. AIM: To determine the factors influencing LNM and to construct a prediction model of LNM for EGC patients. METHODS: Clinical information and pathology data of 2217 EGC patients downloaded from the Surveillance, Epidemiology, and End Results database were collected and analyzed. Based on a 7:3 ratio, 1550 people were categorized into training sets and 667 people were assigned to testing sets, randomly. Based on the factors influencing LNM determined by the training sets, the nomogram was drawn and verified. RESULTS: Based on multivariate analysis, age at diagnosis, histology type, grade, T-stage, and size were risk factors of LNM for EGC. Besides, nomogram was drawn to predict the risk of LNM for EGC patients. Among the categorical variables, the effect of grade (well, moderate, and poor) was the most significant prognosis factor. For training sets and testing sets, respectively, area under the receiver-operating characteristic curve of nomograms were 0.751 [95% confidence interval (CI): 0.721-0.782] and 0.786 (95%CI: 0.742-0.830). In addition, the calibration curves showed that the prediction model of LNM had good consistency. CONCLUSION: Age at diagnosis, histology type, grade, T-stage, and tumor size were independent variables for LNM in EGC. Based on the above risk factors, prediction model may offer some guiding implications for the choice of subsequent therapeutic approaches for EGC.

Nono deficiency impedes the proliferation and adhesion of H9c2 cardiomyocytes through Pi3k/Akt signaling pathway.

Congenital heart disease (CHD) is the most common type of birth defect and the main noninfectious cause of death during the neonatal stage. The non-POU domain containing, octamer-binding gene, NONO, performs a variety of roles involved in DNA repair, RNA synthesis, transcriptional and post-transcriptional regulation. Currently, hemizygous loss-of-function mutation of NONO have been described as the genetic origin of CHD. However, essential effects of NONO during cardiac development have not been fully elucidated. In this study, we aim to understand role of Nono in cardiomyocytes during development by utilizing the CRISPR/Cas9 gene editing system to deplete Nono in the rat cardiomyocytes H9c2. Functional comparison of H9c2 control and knockout cells showed that Nono deficiency suppressed cell proliferation and adhesion. Furthermore, Nono depletion significantly affected the mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis, resulting in H9c2 overall metabolic deficits. Mechanistically we demonstrated that the Nono knockout impeded the cardiomyocyte function by attenuating phosphatidyl inositol 3 kinase-serine/threonine kinase (Pi3k/Akt) signaling via the assay for transposase-accessible chromatin using sequencing in combination with RNA sequencing. From these results we propose a novel molecular mechanism of Nono to influence cardiomyocytes differentiation and proliferation during the development of embryonic heart. We conclude that NONO may represent an emerging possible biomarkers and targets for the diagnosis and treatment of human cardiac development defects.