Picometer-Scale Atomic Shifts Governing Subdisordered Structures in Diamond.

Diamond is considered the most promising next-generation semiconductor material due to its excellent physical characteristics. It has been more than three decades since the discovery of a special structure named n-diamond. However, despite extensive efforts, its crystallographic structure and properties are still unclear. Here, we show that subdisordered structures in diamond provide an explanation for the structural feature of n-diamond. Monocrystalline diamond with subdisordered structures is synthesized via the chemical vapor deposition method. Atomic-resolution scanning transmission electron microscopy characterizations combined with the picometer-precision peak finder technology and diffraction simulations reveal that picometer-scale shifts of atoms within cells of diamond govern the subdisordered structures. First-principles calculations indicate that the bandgap of diamond decreases rapidly with increasing shifting distance, in accordance with experimental results. These findings clarify the crystallographic structure and electronic properties of n-diamond and provide new insights into the bandgap adjustment in diamond.

Aberrant cortical morphology patterns are associated with cognitive impairment in patients with chronic heart failure.

A mounting body of evidences suggests that patients with chronic heart failure (HF) frequently experience cognitive impairments, but the neuroanatomical mechanism underlying these impairments remains elusive. In this retrospective study, 49 chronic HF patients and 49 healthy controls (HCs) underwent brain structural MRI scans and cognitive assessments. Cortical morphology index (cortical thickness, complexity, sulcal depth and gyrification) were evaluated. Correlations between cortical morphology and cognitive scores and clinical variables were explored. Logistic regression analysis was employed to identify risk factors for predicting 3-year major adverse cardiovascular events. Compared with HCs, patients with chronic HF exhibited decreased cognitive scores (p < .001) and decreased cortical thickness, sulcal depth and gyrification in brain regions involved cognition, sensorimotor, autonomic nervous system (family-wise error correction, all p values <.05). Notably, HF duration and New York Heart Association (NYHA) demonstrated negative correlations with abnormal cortex morphology, particularly HF duration and thickness in left precentral gyrus (r = -.387, p = .006). Cortical morphology characteristics exhibited positive associations with global cognition, particularly cortical thickness in left pars opercularis (r = .476, p < .001). NYHA class is an independent risk factor for adverse outcome (p = .001). The observed correlation between abnormal cortical morphology and global cognition suggested that cortical morphology may serve as a promising imaging biomarker and provide insights into neuroanatomical underpinnings of cognitive impairment in patients with chronic HF.

Coronary CTA-based Vascular Radiomics Predicts Atherosclerosis Development Proximal to LAD Myocardial Bridging.

BACKGROUND: Cardiac cycle morphological changes can accelerate plaque growth proximal to myocardial bridging (MB) in the left anterior descending artery (LAD). OBJECTIVE: To assess coronary CT angiography (CCTA)-based vascular radiomics for predicting proximal plaque development in LAD MB. METHODS: Patients with repeated CCTA scans showing LAD MB without proximal plaque in index CCTA were included from Jinling Hospital as development set. They were divided into training and internal testing in an 8:2 ratio. Patients from 4 other tertiary hospitals were set as external validation set. The endpoint was proximal plaque development of LAD MB in follow-up CCTA. Four vascular radiomics models were built: MB centerline (MB CL), proximal MB CL (pMB CL), MB cross section (MB CS), and proximal MB CS (pMB CS), whose performances were evaluated using area under the curve (AUC), integrated discrimination improvement (IDI) and net reclassification improvement (NRI). RESULTS: 295 patients were included in the development (n=192; median age, 54±11 years; 137 men) and external validation sets (n=103; median age, 57±9 years; 57 men). The pMB CS vascular radiomics model exhibited higher AUCs in training, internal test, and external sets (AUC=0.78, 0.75, 0.75) than the clinical and anatomical model (all p<0.05). Integration of the pMB CS vascular radiomics model significantly raised the AUC of the clinical and anatomical model from 0.56 to 0.75 (p=0.002), along with enhanced NRI (0.76 [0.37-1.14], p<0.001) and IDI (0.17 [0.07-0.26], p<0.001) in the external validation set. CONCLUSION: The CCTA-based pMB CS vascular radiomics model can predict plaque development in LAD MB.

Attention-deficit/hyperactivity disorder and dopamine receptor D4 (DRD4) exon 3 variable number of tandem repeats (VNTR) 2-repeat allele.

To investigate the association of attention-deficit/hyperactivity disorder (ADHD) with the 48-base pair (bp) variable number of tandem repeats (VNTR) in exon 3 of the dopamine receptor D4 (DRD4) gene, we genotyped 240 ADHD patients and their parents from Hong Kong. The 4R allele was most common, followed by 2R. We examined association between the 2R allele (relative to 4R) and ADHD by Transmission Disequilibrium Test (TDT). The odds ratio (OR) (95% confidence interval) was 0.90 (0.64-1.3). The p-value was 0.6. Examining subgroups revealed nominally significant association of 2R with inattentive ADHD: OR = 0.33 (0.12-0.92) and p = 0.03. Because our study used TDT analysis, we meta-analyzed the association of 2R with ADHD in Asians (1329 patient alleles), revealing results similar to ours: OR = 0.97 (0.80-1.2) and p = 0.8. To examine the association of 2R with inattentive ADHD, we meta-analyzed all studies (regardless of analysis type or ethnicity, in order to increase statistical power): 702 patient alleles, 1420 control alleles, OR = 0.81 (0.57-1.1) and p = 0.2. Overall, there is no evidence of association between ADHD and the 2R allele, but the suggestive association with the inattentive type warrants further investigation.

Metal-Assisted Carbohydrate Assembly.

The sequence-controlled assembly of nucleic acids and amino acids into well-defined superstructures constitutes one of the most revolutionary technologies in modern science. The elaboration of such superstructures from carbohydrates, however, remains elusive and largely unexplored on account of their intrinsic constitutional and configurational complexity, not to mention their inherent conformational flexibility. Here, we report the bottom-up assembly of two classes of hierarchical superstructures that are formed from a highly flexible cyclo-oligosaccharide─namely, cyclofructan-6 (CF-6). The formation of coordinative bonds between the oxygen atoms of CF-6 and alkali metal cations (i) locks a myriad of flexible conformations of CF-6 into a few rigid conformations, (ii) bridges adjacent CF-6 ligands, and (iii) gives rise to the multiple-level assembly of three extended frameworks. The hierarchical superstructures present in these frameworks have been shown to modulate their nanomechanical properties. This research highlights the unique opportunities of constructing convoluted superstructures from carbohydrates and should encourage future endeavors in this underinvestigated field of science.

Rational development of topical climbazole formulations.

Dandruff, or pityriasis capitis simplex, is a common scalp condition associated with excessive flaking and scaling of the epidermal tissue. Other features include irregular corneocyte turnover, irritation, itching and an impaired skin barrier function. Previously we reported the characterization of climbazole (CBZ), an antifungal agent used in the management of dandruff. Skin permeation of CBZ from neat solvents was also investigated. In the present work we evaluated CBZ permeation in human skin in vitro from more complex formulations that better represent products used by consumers. The various systems studied were composed of propylene glycol (PG), Transcutol®P (TC), octyl salicylate (OSal) and isopropyl alcohol (IPA). As well as measurement of skin uptake and penetration of CBZ, where possible, the skin retention and permeation of the various solvents was also determined. All vehicles promoted skin permeation of CBZ but no significant differences in amount permeated were evident between the binary vehicles (PG:TC, TC:OSal) and the ternary vehicle studied (PG:IPA:OSal). The binary vehicles generally promoted more skin uptake of CBZ compared with the neat solvents (PG, TC, OSal) studied previously. Permeation and skin extraction of CBZ from the PG:TC vehicles increased with increasing PG content; a similar trend was evident for the PG:IPA:OSal systems. New methods were developed and validated for measurement of PG, TC and OSal. Analysis of the individual solvents indicated that PG permeation was also independent of the amounts of other solvents in the binary or ternary systems. Consistent with previous findings higher proportions of TC permeated compared with PG for the PG:TC binary systems; TC also permeated the skin more rapidly than PG from these vehicles. For OSal, skin extraction was generally higher for TC:OSal compared with the PG:IPA:OSal vehicle. However, increasing the content of OSal did not appear to influence CBZ skin uptake nor permeation. Interestingly, the effects of the various PG:TC vehicles on CBZ skin delivery contrast with results we previous reported for the same systems for a different active. This confirms that with reference to skin permeation, formulation effects and/or skin penetration enhancement should be expected to vary and may not be predicted for specific vehicles.

All-fiber hectowatt radially polarized laser system.

A high-power all-fiber radially polarized laser system is demonstrated, in which an integrated nanograting mode convertor (S-wave plate) is used for the generation of radially polarized beam. Experimentally, a 1-W radially polarized beam was used as the seed laser, whose mode purity and mode extinction ratio (MER) were 96.5% and 98.3%, respectively. A single-stage few-mode fiber amplifier was employed to boost the 1-W seed laser to an average power of 113.2 W, when the pump power was 160 W. The corresponding slope efficiency and beam quality factor (M2) were approximately 72% and 2.3%, respectively. Moreover, the mode purity and MER of the amplified radially polarized laser were measured to be 95.7% and 97%, respectively. To the best of our knowledge, this is the highest output power from an all-fiber radially polarized laser system without obvious degradations of the mode purity and MER.

Effects of Saccharomyces cerevisiae and Kluyveromyces marxianus on the Physicochemical, Microbial, and Flavor Changes of Sauce Meat during Storage.

Saccharomyces cerevisiae (S. cerevisiae) and Kluyveromyces marxianus (K. marxianus) are often used as fermenters in yogurt and alcohol, and have been less studied within meat products. The yeasts were added to sauce meat, and the uninoculated group served as a control in this study to examine and compare the changing patterns of physicochemical and flavor characteristics of S. cerevisiae and K. marxianus on sauce meat during storage. The changes in moisture content, aw, pH, thiobarbituric acid reactive substances (TBARS), and other flavor characteristics were measured in sauce meat during the first, second, fourth, and sixth months after production. The following factors were examined: moisture content, aw, pH, TBARS, peroxide value (POV), acid value (AV), soluble protein (SP), free amino acid (FAA), and volatile flavoring compounds. With VIP > 1 and p < 0.05 as the screening conditions, the partial least squares model (PLS-DA) was used to assess the distinctive flavor components in the sausages. The findings demonstrated that the three groups' changes in sauce meat were comparable during the first two months of storage but differed significantly between the 4th and 6th months. The moisture content, water activity, and pH of the sauce meat decreased gradually with the storage time; TBARS, AV, and FAA increased significantly; SP decreased significantly from 2.61 to 1.72, while POV increased to 0.03 and then decreased to 0.02. The POV and TBARS values of the yeast-infected meat were substantially lower than those of the control group, and the POV and TBARS values of the meat inoculated with S. cerevisiae were particularly decreased (p < 0.05). The POV and TBARS values of SC (S. cerevisiae group) decreased by 49.09% and 40.15%, respectively, compared to CK (the control group) at the time of storage until June. The experimental group (KM: K. marxianus group) significantly increased the SP and FAA values of the sauce meat (p < 0.05) by 32.4% and 29.84% compared to the CK group, respectively. Esters and olefins as well as alcohols and esters were much greater in meat that had been supplemented with S. cerevisiae and K. marxianus than in meat from the control group. In conclusion, inoculating sauce meat with S. cerevisiae can significantly enhance the quality and flavor of sauce meat while it is being stored.

Assessment of Two Restraint Potentials for Coarse-Grained Chemical-Cross-Link-Assisted Modeling of Protein Structures.

The influence of distance restraints from chemical cross-link mass spectroscopy (XL-MS) on the quality of protein structures modeled with the coarse-grained UNRES force field was assessed by using a protocol based on multiplexed replica exchange molecular dynamics, in which both simulated and experimental cross-link restraints were employed, for 23 small proteins. Six cross-links with upper distance boundaries from 4 Å to 12 Å (azido benzoic acid succinimide (ABAS), triazidotriazine (TATA), succinimidyldiazirine (SDA), disuccinimidyl adipate (DSA), disuccinimidyl glutarate (DSG), and disuccinimidyl suberate (BS3)) and two types of restraining potentials ((i) simple flat-bottom Lorentz-like potentials dependent on side chain distance (all cross-links) and (ii) distance- and orientation-dependent potentials determined based on molecular dynamics simulations of model systems (DSA, DSG, BS3, and SDA)) were considered. The Lorentz-like potentials with properly set parameters were found to produce a greater number of higher-quality models compared to unrestrained simulations than the MD-based potentials, because the latter can force too long distances between side chains. Therefore, the flat-bottom Lorentz-like potentials are recommended to represent cross-link restraints. It was also found that significant improvement of model quality upon the introduction of cross-link restraints is obtained when the sum of differences of indices of cross-linked residues exceeds 150.

In vitro and in vivo Biological Evaluation of Newly Tacrine-Selegiline Hybrids as Multi-Target Inhibitors of Cholinesterases and Monoamine Oxidases for Alzheimer's Disease.

Purpose: Alzheimer's disease (AD) is the most common neurodegenerative disease, and its multifactorial nature increases the difficulty of medical research. To explore an effective treatment for AD, a series of novel tacrine-selegiline hybrids with ChEs and MAOs inhibitory activities were designed and synthesized as multifunctional drugs. Methods: All designed compounds were evaluated in vitro for their inhibition of cholinesterases (AChE/BuChE) and monoamine oxidases (MAO-A/B) along with their blood-brain barrier permeability. Then, further biological activities of the optimizing compound 7d were determined, including molecular model analysis, in vitro cytotoxicity, acute toxicity studies in vivo, and pharmacokinetic and pharmacodynamic property studies in vivo. Results: Most synthesized compounds demonstrated potent inhibitory activity against ChEs/MAOs. Particularly, compound 7d exhibited good and well-balanced activity against ChEs (hAChE: IC50 = 1.57 µM, hBuChE: IC50 = 0.43 µM) and MAOs (hMAO-A: IC50 = 2.30 µM, hMAO-B: IC50 = 4.75 µM). Molecular modeling analysis demonstrated that 7d could interact simultaneously with both the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE in a mixed-type manner and also exhibits binding affinity towards BuChE and MAO-B. Additionally, 7d displayed excellent permeability of the blood-brain barrier, and under the experimental conditions, it elicited low or no toxicity toward PC12 and BV-2 cells. Furthermore, 7d was not acutely toxic in mice at doses up to 2500 mg/kg and could improve the cognitive function of mice with scopolamine-induced memory impairment. Lastly, 7d possessed well pharmacokinetic characteristics. Conclusion: In light of these results, it is clear that 7d could potentially serve as a promising multi-functional drug for the treatment of AD.

FFR CT and Static Computed Tomography Myocardial Perfusion Imaging for Therapeutic Decision-making and Prognosis in Patients With Coronary Artery Disease.

PURPOSE: The purpose of this study was to investigate the effect of integrated evaluation of resting static computed tomography perfusion (CTP) and coronary computed tomography angiography (CCTA)-derived fractional flow reserve (FFR CT ) on therapeutic decision-making and predicting major adverse cardiovascular events (MACEs) in patients with suspected coronary artery disease. MATERIALS AND METHODS: In this post hoc analysis of a prospective trial of CCTA in patients assigned to either CCTA or CCTA plus FFR CT arms, 500 patients in the CCTA plus FFR CT arm were analyzed. Both resting static CTP and FFR CT were evaluated by using the conventional CCTA. Perfusion defects in the myocardial segments with ≥50% degree of stenosis in the supplying vessels were defined as resting static CTP positive, and any vessel with an FFR CT value of ≤0.80 was considered positive. Patients were divided into 3 groups: (1) negative CTP-FFR CT match group (resting static CTP-negative and FFR CT -negative group); (2) mismatch CTP-FFR CT group (resting static CTP-positive and FFR CT -negative or resting static CTP-negative and FFR CT -positive group); and (3) positive CTP-FFR CT match group (resting static CTP-positive and FFR CT -positive group). We compared the revascularization-to-invasive coronary angiography ratio and the MACE rate among 3 subgroups at 1- and 3-year follow-ups. The adjusted Cox hazard proportional model was used to assess the prognostic value of FFR CT and resting static CTP to determine patients at risk of MACE. RESULTS: Patients in the positive CTP-FFR CT match group were more likely to undergo revascularization at the time of invasive coronary angiography compared with those in the mismatch CTP-FFR CT group (81.4% vs 57.7%, P =0.033) and the negative CTP-FFR CT match group (81.4% vs 33.3%, P= 0.001). At 1- and 3-year follow-ups, patients in the positive CTP-FFR CT match group were more likely to have MACE than those in the mismatch CTP-FFR CT group (10.5% vs 4.2%, P= 0.046; 35.6% vs 9.4%, P <0.001) and the negative CTP-FFR CT match group (10.5% vs 0.9%, P <0.001; 35.6% vs 5.4%, P <0.001). A positive CTP-FFR CT match was strongly related to MACE at 1-year (hazard ratio=8.06, P= 0.003) and 3-year (hazard ratio=6.23, P <0.001) follow-ups. CONCLUSION: In patients with suspected coronary artery disease, the combination of FFR CT with resting static CTP could guide therapeutic decisions and have a better prognosis with fewer MACE in a real-world scenario.

Late gadolinium enhanced cardiac MR derived radiomics approach for predicting all-cause mortality in cardiac amyloidosis: a multicenter study.

OBJECTIVES: To evaluate the prognostic value of radiomics features based on late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) images in patients with cardiac amyloidosis (CA). METHODS: This retrospective study included 120 CA patients undergoing CMR at three institutions. Radiomics features were extracted from global and three different segments (base, mid-ventricular, and apex) of left ventricular (LV) on short-axis LGE images. Primary endpoint was all-cause mortality. The predictive performance of the radiomics features and semi-quantitative and quantitative LGE parameters were compared by ROC. The AUC was used to observe whether Rad-score had an incremental value for clinical stage. The Kaplan-Meier curve was used to further stratify the risk of CA patients. RESULTS: During a median follow-up of 12.9 months, 30% (40/120) patients died. There was no significant difference in the predictive performance of the radiomics model in different LV sections in the validation set (AUCs of the global, basal, middle, and apical radiomics model were 0.75, 0.77, 0.76, and 0.77, respectively; all p > 0.05). The predictive performance of the Rad-score of the base-LV was better than that of the LGE total enhancement mass (AUC:0.77 vs. 0.54, p < 0.001) and LGE extent (AUC: 0.77 vs. 0.53, p = 0.004). Rad-score combined with Mayo stage had better predictive performance than Mayo stage alone (AUC: 0.86 vs. 0.81, p = 0.03). Rad-score (≥ 0.66) contributed to the risk stratification of all-cause mortality in CA. CONCLUSIONS: Compared to quantitative LGE parameters, radiomics can better predict all-cause mortality in CA, while the combination of radiomics and Mayo stage could provide higher predictive accuracy. CLINICAL RELEVANCE STATEMENT: Radiomics analysis provides incremental value and improved risk stratification for all-cause mortality in patients with cardiac amyloidosis. KEY POINTS: • Radiomics in LV-base was superior to LGE semi-quantitative and quantitative parameters for predicting all-cause mortality in CA. • Rad-score combined with Mayo stage had better predictive performance than Mayo stage alone or radiomics alone. • Rad-score ≥ 0.66 was associated with a significantly increased risk of all-cause mortality in CA patients.

Effect of macrophage polarization on parasitic protection against type 1 diabetes mellitus.

Type 1 diabetes mellitus is a chronic disease caused by the destruction of pancreatic beta cells. Based on the hygiene hypothesis, a growing body of evidence suggests a negative association between parasitic infections and diabetes in humans and animal models. The mechanism of parasite-mediated prevention of type 1 diabetes mellitus may be related to the adaptive and innate immune systems. Macrophage polarization is a new paradigm for the treatment of type 1 diabetes mellitus, and different host macrophage subsets play various roles during parasite infection. Proinflammatory cytokines are released by M1 macrophages, which are important in the development of type 1 diabetes mellitus. Parasite-activated M2 macrophages prevent the development of type 1 diabetes mellitus and can influence the development of adaptive immune responses through several mechanisms, including Th2 cells and regulatory T cells. Here, we review the role and mechanism of macrophage polarization in parasitic protection against type 1 diabetes mellitus.

Phytic acid improves osteogenesis and inhibits the senescence of human bone marrow mesenchymal stem cells under high-glucose conditions via the ERK pathway.

Hyperglycaemia causes impairment of osteogenic differentiation and accelerates stem cell senescence, resulting in weakened osteogenesis and disordered bone metabolism. Phytic acid (PA) is an antioxidant that is reportedly beneficial to bone homeostasis. The present study aims to clarify how PA affects the osteogenic capacity and cellular senescence of bone marrow mesenchymal stem cells (BMSCs) exposed to high-glucose environments, as well as the potential molecular mechanisms. Our results indicate that osteogenic differentiation in BMSCs cultivated in high-glucose conditions is enhanced by PA, as evidenced by increased alkaline phosphatase activity and staining, Alizarin Red S staining, osteogenic marker in in vitro studies, and increased osteogenesis in animal experiments. PA also prevented high-glucose-induced senescence of BMSCs, as evidenced by the repression of reactive oxygen species production, senescence-associated ß-galactosidase staining, and P21 and P53 expression. Furthermore, it was found that PA rescued the high-glucose-inhibited expression of phosphorylated extracellular regulated protein kinases (p-ERK). The inhibition of ERK pathway by the specific inhibitor PD98059 blocked the PA-enhanced osteogenesis of BMSCs and promoted cell senescence. Our results revealed that PA enhances osteogenic differentiation and inhibits BMSC senescence in a high-glucose environment. In addition, the activation of the ERK pathway seems to mediate the beneficial effects of PA. The findings provide novel insights that could facilitate bone regeneration in patients with diabetes.

Schistosoma-related molecules as a new strategy to combat type 1 diabetes through immune regulation.

The study of immune regulation mechanisms induced by parasites may help develop new treatment methods for inflammatory diseases including type 1 diabetes, which is related to type 1 immune responses. The negative correlation between schistosomiasis infection and type 1 diabetes has been confirmed, and the mechanism of Schistosoma-mediated prevention of type 1 diabetes may be related to the adaptive and innate immune systems. Schistosoma-related molecules affect immune cell composition and macrophage polarization and stimulate an increase in natural killer T cells. Furthermore, Schistosoma-related molecules can regulate the adaptive immune responses related to the prevention of type 1 diabetes and change the Th1/Th2 and Th17/Treg axis. Our previous review showed the role of regulatory T cells in the protective of type 1 diabetes mediated by Schistosoma. Here, we aim to review the other mechanisms of schistosomiasis infection and Schistosoma-related products in regulating the immune response associated with the treatment of type 1 diabetes.

1.36 J nanosecond laser at 1 kHz repetition based on a slab amplifier chain.

A high beam quality diode-pumped Nd:YAG master oscillator power-amplifier (MOPA) laser with three end-pumped slab amplifiers is developed. The Q-swtiched side-pumped rod oscillator presented a pulse energy 3.1 mJ with beam quality factors of M x2=1.17 and M y2=1.15 at a repetition of 1 kHz. The MOPA system delivered a pulse energy of 1.36 J with a pulse width of 48.2 ns and an extraction efficiency of 44.8%. The beam quality factors of M x2=1.72 and M y2=3.85 are measured without any phase-conjugators or adaptive optics.

Bioinspired Synthesis of Ag Nanoparticles onto Polytetrafluoroethylene with Enhanced Antibacterial Activity for Dental Implant Application.

BACKGROUND: Endosseous implants are widely used as a treatment for tooth loss, but gaps in the implant-abutment interface, and the cavity inside the implant, can cause inflammation of the tissue surrounding the implant. Currently available filling materials, however, cannot solve these problems. Therefore, the development of new antibacterial materials is key. In this study, we synthesized Ag nanoparticle-coated polytetrafluoroethylene (PTFE), analyzed the effect of Ag ion concentration, and estimated the antibacterial effects against oral pathogens in vitro. Method: The Ag nanoparticles (AgNPs)-modified PTFE was achieved using self-polymerized dopamine in an alkaline solution (2 mg/mL) and reduction reaction of Ag ions (0.01 mol/L and 0.05 mol/L). The surface features, chemical components, and wettability were characterized by scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS) and contact angle measurement. The antibacterial effect against Streptococcus mutans and Porphyromonas gingivalis was evaluated by counting colony-forming units on agar media and the visualization of bacteria present on the specimens by SEM and confocal laser scanning microscope (CLSM). RESULTS: The surface characterization results indicated that a polydopamine film was successfully formed on the PTFE membrane, and spherical AgNPs were successfully reduced. With increasing concentration of the Ag precursor, the contents of the AgNPs increased (p < 0.05). The antibacterial ratio of AgNP-coated PTFE against Streptococcus mutans and Porphyromonas gingivalis reached 94.2% and 80.6%, respectively. The results of antibacterial testing analyzed via SEM and CLSM also demonstrated the robust antibacterial ability of AgNPs-modified PTFE (p < 0.05). CONCLUSIONS: AgNPs-modified PTFE has great potential to function as an implant filling material with enhanced antibacterial properties, and has the potential to be a novel antimicrobial material for the prevention of peri-implantitis in the clinic.

Investigation of piroctone olamine delivery to the skin from single, binary and ternary solvent systems.

OBJECTIVE: Disruption of the protective stratum corneum barrier increases the skin's vulnerability to microorganisms and facilitates conditions such as dandruff. Dandruff is a disorder of the scalp that causes increased scaling of the SC and is associated with Malassezia fungus. Consequently, many anti-dandruff commercial products use anti-fungal active ingredients such as piroctone olamine also known as Octopirox (OPX). OPX is an active ingredient used in a number of topical preparations for the management of dandruff. The characterization of the physicochemical properties of OPX was previously reported. The aim of the present work was to investigate a range of solvent systems for their effects on OPX interaction with human skin. METHODS: The solvents used in this study were propylene glycol (PG), diethylene glycol monoethyl ether or Transcutol® (TC), PG monolaurate (PGML), isopropyl myristate (IPM), caprylic/capric triglyceride or Labrafac™ Lipophile WL 1349 (LAB), PG caprylate or Capryol® 90 (CAP), isostearyl isostearate (ISIS) and Plurol® Oleique CC 497 (PIOI). The single solvent systems evaluated were PG, TC, PGML, IPM, ISIS and CAP. For the binary solvent systems, PG and TC were examined. Ternary solvent systems consisted of: PG, TC and LAB; PG, PGML and LAB; and PG, TC and IPM. The concentration of OPX used was 1% (w/v). Heat-separated human epidermis was used for 24 h permeation experiments performed under finite dose conditions; mass balance studies were also conducted. RESULTS: For the six single solvents examined no permeation was evident. Skin permeation of OPX was observed for binary and ternary solvent systems. The highest permeation for all PG:TC binary solvent system ratios tested was from the PG:TC (75:25) system. For the ternary solvent systems investigated, highest cumulative permeation of OPX was observed for PG:PGML:LAB (60:30:10). Considering all systems, PG:TC (75:25) delivered the greatest amount of OPX through the skin. Although OPX is deposited in the skin following the application of neat solvents, higher skin retention values were generally observed for binary and ternary systems. CONCLUSION: To our knowledge, this is the first study to examine the permeation behaviour of OPX for a range of single, binary and ternary solvent systems.

OBJECTIF: La perturbation de la barrière protectrice de la couche cornée augmente la vulnérabilité de la peau aux micro-organismes et facilite des affections telles que les pellicules. Les pellicules sont un trouble du cuir chevelu qui provoque une augmentation de la desquamation de la couche cornée et qui est associé au champignon Malassezia. Par conséquent, de nombreux produits commerciaux antipelliculaires utilisent des principes actifs antifongiques, tels que la piroctone olamine, également appelée Octopirox (OPX). L'OPX est un principe actif utilisé dans un certain nombre de préparations topiques pour la prise en charge des pellicules. La caractérisation des propriétés physicochimiques de l'OPX a été précédemment rapportée. L'objectif de ce travail était d'étudier un éventail de systèmes de solvants pour leurs effets sur l'interaction de l'OPX avec la peau humaine. MÉTHODES: Les solvants utilisés dans cette étude étaient le propylène glycol (PG), l'éther monoéthylique de diéthylèneglycol ou Transcutol® (TC), le monolaurate de propylène glycol (PGML), le myristate d'isopropyle (IPM), le triglycéride caprylique/caprique ou Labrafac™ lipophile WL 1349 (LAB), le caprylate de propylène glycol ou Capryol® 90 (CAP), l'isostéarate d'isostéaryle (ISIS) et Plurol® Oleique CC 497 (PIOI). Les systèmes à solvant unique évalués étaient le PG, le TC, le PGML, l'IPM, l'ISIS et le CAP. Pour les systèmes de solvants binaires, le PG et le TC ont été examinés. Les systèmes de solvants ternaires comprenaient : PG, TC et LAB ; PG, PGML et LAB ; et PG, TC et IPM. La concentration d'OPX utilisée était de 1 % (p/v). L'épiderme humain séparé par la chaleur a été utilisé pour des expériences de perméation de 24 heures réalisées dans des conditions de dose finie ; des études d'équilibre de masse ont également été menées. RÉSULTATS: Pour les six solvants uniques examinés, aucune perméation n'était manifeste. Une perméation cutanée de l'OPX a été observée pour les systèmes de solvants binaires et ternaires. La perméation la plus élevée pour tous les rapports du système de solvant binaire PG:TC testés a été obtenue avec le système PG:TC (75:25). Pour les systèmes de solvants ternaires étudiés, la perméation cumulée la plus élevée d'OPX a été observée pour PG:PGML:LAB (60:30:10). Parmi tous les systèmes, PG:TC (75:25) a délivré la plus grande quantité d'OPX à travers la peau. Bien que l'OPX se dépose dans la peau après l'application de solvants purs, des valeurs de rétention cutanée plus élevées ont généralement été observées pour les systèmes binaire et ternaire. CONCLUSION: À notre connaissance, il s'agit de la première étude visant à examiner le comportement de perméation de l'OPX pour un éventail de systèmes de solvants uniques, binaires et ternaires.

Combination treatment with telitacicept, cyclophosphamide and glucocorticoids for severe Granulomatous polyangiitis: a case report and literature review.

Granulomatous polyangiitis (GPA) is a rare autoimmune disease that can involve multiple systems throughout the body, including the ear, nose, upper and lower respiratory tracts. It is classified as an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Telitacicept is a novel recombinant fusion protein targeting B-lymphocyte stimulator (BLyS). Telitacicept can inhibit the development and maturation of abnormal B cells by blocking BLyS, and inhibit the production of antibodies by abnormal plasma cells by blocking APRIL (A proliferation-inducing ligand), which is expected to become a new drug for the treatment of GPA. We report a 64-year-old man diagnosed at our hospital with GPA involving multiple systems including kidneys, lungs, nose and ears. Renal involvement was severe, with a clinical characteristic of rapidly progressive glomerulonephritis and a pathologic manifestation of crescentic nephritis with plasma cell infiltration. The patient was treated with hormones, immunoglobulins and cyclophosphamide (CYC) with the addition of telitacicept and a rapid reduction in hormone dosage. The patient's renal function improved significantly within a short period of time, and his hearing and lung lesions improved significantly. At the same time, he did not develop serious infections and other related complications. Our report suggests that short-term control of the patient's conditions is necessary in GPA patients with organ-threatening disease. Telitacicept combined with CYC and glucocorticoids may be an induction therapy with safety and feasibility. However, more clinical trials are needed to validate the efficacy and safety of the therapeutic regimen.

Diagnostic Values of METTL1-Related Genes and Immune Characteristics in Systemic Lupus Erythematosus.

Purpose: Methyltransferase like 1 (METTL1) regulates epitranscriptomes via the m7G modification in mammalian mRNA and microRNA. Systemic lupus erythematosus (SLE) is caused by abnormal immune reactivity and has diverse clinical manifestations. RNA methylation as a mechanism to regulate gene expression is widely implicated in immune regulation. However, the role of m7G in immune response of SLE has not been extensively studied. Patients and Methods: Expression of METTL1 was identified in the public dataset GSE122459 and validated in an independent cohort of SLE patients. We investigated the association between METTL1-expression and clinical manifestations of SLE. Subsequently, differentially expressed genes (DEG) that were correlated with METTL1-expression in GSE122459 were used for functional enrichment analysis. The correlation between infiltrating immune cells and METTL1, as well as candidate biomarkers identified to be correlated with either METTL1 or immune cell infiltration were assessed by single-sample GSEA. Potential mechanisms were explored with Gene ontology and KEGG pathway enrichment. Diagnostic performances of candidate biomarkers in SLE were analyzed. Results: The mRNA and protein expression of METTL1 in SLE patients were significantly decreased in both datasets. METTL1-coexpressed DEGs were enriched in several key immune-related pathways. Activated CD8 T cells, activated CD4 T cells, memory B cells and type 2 helper T cells were different between patients with high and low METTL1 expression. Further, activated CD8 T-cells, activated CD4 T-cells, memory B-cells were correlated with METTL1. The genes of LAMP3, CD83, PDCD1LG2, IGKVD3D-20, IGKV5-2, IGKV2D-30, IGLV3-19 and IGLV4-60 were identified as candidate targets that were correlated with immune cell proportion. Moreover, LAMP3, CD83, and PDCD1LG2 expression were of diagnostic value in SLE as indicated by ROC analysis. Conclusion: Our findings suggested that METTL1 and its candidate targets LAMP3, CD83, PDCD1LG2 may be used for diagnosing SLE and could be explored for developing targeted molecular therapy for SLE.