Evidence of ferroelectric features in low-density supercooled water from ab initio deep neural-network simulations.

Over the last decade, an increasing body of evidence has emerged, supporting the existence of a metastable liquid-liquid critical point in supercooled water whereby two distinct liquid phases of different densities coexist. Analyzing long molecular dynamics simulations performed using deep neural-network force fields trained to accurate quantum mechanical data, we demonstrate that the low-density liquid phase displays a strong propensity toward spontaneous polarization, as witnessed by large and long-lived collective dipole fluctuations. Our findings suggest that the dynamical stability of the low-density phase, and hence the transition from high-density to low-density liquid, is triggered by a collective process involving an accumulation of rotational angular jumps, which could ignite large dipole fluctuations. This dynamical transition involves subtle changes in the electronic polarizability of water molecules which affects their rotational mobility within the two phases. These findings hold the potential for catalyzing activity in the search for dielectric-based probes of the putative second critical point.

Postbiotic mediators derived from Lactobacillus species enhance riboflavin-mediated antimicrobial photodynamic therapy for eradication of Streptococcus mutans planktonic and biofilm growth.

BACKGROUND: Streptococcus mutans has been implicated as a primary causative agent of dental caries and one of its important virulence properties is an ability to form biofilm on tooth surfaces. Thus, strategies to prevent and control S. mutans biofilms are requested. The present study aimed to examine the eradication of S. mutans planktonic and biofilm cells using riboflavin (Rib)-mediated antimicrobial photodynamic therapy (aPDT) enhanced by postbiotic mediators derived from Lactobacillus species. MATERIALS AND METHODS: Minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of Rib and postbiotic mediators were determined. The antimicrobial and anti-biofilm effects of Rib-mediated aPDT (Rib plus blue light), Rib-mediated aPDT in combination with postbiotic mediators derived from Lactobacillus casei (LC) (aPDT+ LC), and Rib-mediated aPDT in combination with postbiotic mediators derived from Lactobacillus plantarum (LP) (aPDT+ LP) were evaluated. The anti-virulence potential of Rib-mediated aPDT, aPDT+ LC, and aPDT+ LP were assessed by measuring the expression of the gtfB gene using quantitative real-time polymerase chain reaction (qRT-PCR) at the highest concentrations of Rib, LC, and LP, at which the S. mutans had proliferation as the same as in the control (non-treated) group. RESULTS: According to the results, the MIC doses of LC, LP, and Rib were 64 µg/mL, 128 µg/mL, and 128 µg/mL, respectively, while the MBC values of LC, LP, and Rib were 128 µg/mL, 256 µg/mL, and 256 µg/mL, respectively. Rib-mediated aPDT, aPDT+ LP, and aPDT+ LC showed a significant reduction in Log10 CFU/mL of S. mutans compared to the control group (4.2, 4.9, and 5.2 Log10 CFU/mL, respectively; all P < 0.05). The most destruction of S. mutans biofilms was observed after treatment with aPDT+ LC followed by aPDT+ LP and Rib-mediated aPDT (77.5%, 73.3%, and 67.6%, respectively; all P < 0.05). The concentrations of 31.2 µg/mL, 62.5 µg/mL, and 62.5 µg/mL were considered as the highest concentrations of LC, LP, and Rib, respectively, at which S. mutans replicates as same as the control group and were used for gtfB gene expression assay using qRT-PCR during Rib-mediated aPDT, aPDT+ LP, and aPDT+ LC treatments. Gene expression results revealed that aPDT+ LP and aPDT+ LC could decrease the gene expression level of gtfB by 6.3- and 5.7-fold, respectively (P < 0.05), while only 5.1-fold reduction was observed after Rib-mediated aPDT (P < 0.05). CONCLUSION: Our findings indicate that aPDT+ LP and aPDT+ LC hold promise for use as a treatment to combat S. mutans planktonic and biofilms growth as well as anti-virulence as a preventive strategy to inhibit biofilms development via reduction of gtfB gene expression.

Beyond Local Structures in Critical Supercooled Water through Unsupervised Learning.

The presence of a second critical point in water has been a topic of intense investigation for the last few decades. The molecular origins underlying this phenomenon are typically rationalized in terms of the competition between local high-density (HD) and low-density (LD) structures. Their identification often requires designing parameters that are subject to human intervention. Herein, we use unsupervised learning to discover structures in atomistic simulations of water close to the liquid-liquid critical point (LLCP). Encoding the information on the environment using local descriptors, we do not find evidence for two distinct thermodynamic structures. In contrast, when we deploy nonlocal descriptors that probe instead heterogeneities on the nanometer length scale, this leads to the emergence of LD and HD domains rationalizing the microscopic origins of the density fluctuations close to criticality.

Exploring the Mechanisms behind Non-aromatic Fluorescence with the Density Functional Tight Binding Method.

Recent experimental findings reveal nonconventional fluorescence emission in biological systems devoid of conjugated bonds or aromatic compounds, termed non-aromatic fluorescence (NAF). This phenomenon is exclusive to aggregated or solid states and remains absent in monomeric solutions. Previous studies focused on small model systems in vacuum show that the carbonyl stretching mode along with strong interaction of short hydrogen bonds (SHBs) remains the primary vibrational mode explaining NAF in these systems. In order to simulate larger model systems taking into account the effects of the surrounding environment, in this work we propose using the density functional tight-binding (DFTB) method in combination with non-adiabatic molecular dynamics (NAMD) and the mixed quantum/molecular mechanics (QM/MM) approach. We investigate the mechanism behind NAF in the crystal structure of l-pyroglutamine-ammonium, comparing it with the related nonfluorescent amino acid l-glutamine. Our results extend our previous findings to more realistic systems, demonstrating the efficiency and robustness of the proposed DFTB method in the context of NAMD in biological systems. Furthermore, due to its inherent low computational cost, this method allows for a better sampling of the nonradiative events at the conical intersection which is crucial for a complete understanding of this phenomenon. Beyond contributing to the ongoing exploration of NAF, this work paves the way for future application of this method in more complex biological systems such as amyloid aggregates, biomaterials, and non-aromatic proteins.

Photoinactivation of Enterococcus faecalis Biofilm: In Vitro Antimicrobial Effect of Photoexcited Rutin-Gallium(III) Complex via Visible Blue Light.

INTRODUCTION: Endodontic infection is a common problem that can result in tooth loss if not effectively treated. This study focused on investigating the use of rutin-gallium (Ga)(III) complex-mediated antimicrobial photodynamic therapy (aPDT) for the photoinactivation of Enterococcus faecalis biofilm. METHODS: The minimum biofilm eradication concentration of the rutin-Ga(III) complex and the minimum biofilm eradication dose of light-emitting diode against E. faecalis were evaluated. The antimicrobial effect of rutin-Ga(III) complex-mediated aPDT against E. faecalis was assessed. Additionally, the expression of genes associated with E. faecalis virulence, such as ace, gelE, and esp, as well as the production of reactive oxygen species within the cells were evaluated. RESULTS: The minimum biofilm eradication concentration of the rutin-Ga(III) complex was determined to be 25 µmol/L, whereas the minimum biofilm eradication dose of light-emitting diode irradiation was defined as 5 minutes with an energy density of 300-420 J/cm2. Rutin-Ga(III) complex-mediated aPDT demonstrated a significant dose-dependent reduction in the growth of E. faecalis biofilms. Moreover, aPDT led to increased intracellular reactive oxygen species generation in treated E. faecalis cells. Furthermore, the messenger RNA levels of ace, gelE, and esp genes were significantly down-regulated in E. faecalis treated with rutin-Ga(III) complex-mediated aPDT (P < .05). CONCLUSIONS: Rutin-Ga(III) complex-mediated aPDT effectively reduces E. faecalis biofilm growth by disrupting biofilm structure and down-regulating virulence genes. These findings highlight the potential of aPDT with the rutin-Ga(III) complex as an adjuvant therapeutic approach against E. faecalis biofilms.

Lessons Learned from Multiobjective Automatic Optimizations of Classical Three-Site Rigid Water Models Using Microscopic and Macroscopic Target Experimental Observables.

The development of accurate water models is of primary importance for molecular simulations. Despite their intrinsic approximations, three-site rigid water models are still ubiquitously used to simulate a variety of molecular systems. Automatic optimization approaches have been recently used to iteratively refine three-site water models to fit macroscopic (average) thermodynamic properties, providing state-of-the-art three-site models that still present some deviations from the liquid water properties. Here, we show the results obtained by automatically optimizing three-site rigid water models to fit a combination of microscopic and macroscopic experimental observables. We use Swarm-CG, a multiobjective particle-swarm-optimization algorithm, for training the models to reproduce the experimental radial distribution functions of liquid water at various temperatures (rich in microscopic-level information on, e.g., the local orientation and interactions of the water molecules). We systematically analyze the agreement of these models with experimental observables and the effect of adding macroscopic information to the training set. Our results demonstrate how adding microscopic-rich information in the training of water models allows one to achieve state-of-the-art accuracy in an efficient way. Limitations in the approach and in the approximated description of water in these three-site models are also discussed, providing a demonstrative case useful for the optimization of approximated molecular models, in general.

Consecutive versus concomitant follicle-stimulating hormone and highly purified human menopausal gonadotropin: A milder response but better quality / 대한생식의학회지

Objective@#This study investigated the impact of two stimulation protocols using highly purified human menopausal gonadotropin (HP-hMG) on the endocrine profile, follicular fluid soluble Fas levels, and outcomes of intracytoplasmic sperm injection (ICSI) cycles. @*Methods@#This prospective clinical trial included 100 normal-responder women undergoing ovarian stimulation for ICSI; 55 patients received concomitant follicle-stimulating hormone (FSH) plus HP-hMG from the start of stimulation, while 45 patients received FSH followed by HP-hMG during mid/late follicular stimulation. The primary outcome was the number of top-quality embryos. The secondary outcomes were the number and percentage of metaphase II (MII) oocytes and the clinical pregnancy rate. @*Results@#The number of MII oocytes was significantly higher in the concomitant protocol (median, 13.0; interquartile range [IQR], 8.5–18.0 vs. 9.0 [8.0–13.0] in the consecutive protocol; p=0.009); however, the percentage of MII oocytes and the fertilization rate were significantly higher in the consecutive protocol (median, 90.91; IQR, 80.0–100.0 vs. 83.33 [75.0–93.8]; p=0.034 and median, 86.67; IQR, 76.9–100.0 vs. 77.78 [66.7–89.9]; p=0.028, respectively). No significant between-group differences were found in top-quality embryos (p=0.693) or the clinical pregnancy rate (65.9% vs. 61.8% in the consecutive vs. concomitant protocol, respectively). The median follicular fluid soluble Fas antigen level was significantly higher in the concomitant protocol (9,731.0 pg/mL; IQR, 6,004.5–10,807.6 vs. 6,350.2 pg/mL; IQR, 4,382.4–9,418.4; p=0.021). @*Conclusion@#Personalized controlled ovarian stimulation using HP-hMG during the late follicular phase led to a significantly lower response, but did not affect the quality of ICSI.

Prevalence of occult hepatitis b infection in iranian cancer patients before chemotherapy treatment / Prevalência de infecção oculta da hepatite B em pacientes iranianos com câncer antes do tratamento de quimioterapia

ABSTRACT Background Occult hepatitis B infection is characterized by negative hepatitis B surface antigen (HBsAg) and also detectable hepatitis B virus (HBV) -DNA, with or without hepatitis B core antibody (anti-HBc). HBV reactivation in individuals under immunosuppressive therapy is critical, occurring in occult HBV. Objective In this study, we aimed to determine the prevalence of occult HBV infection among hepatitis B surface antigen negative in cancer patients before receiving chemotherapy. Methods Sera from 204 cancer patients who were negative for HBsAg, were tested for anti-HBc antibodies. The samples that were negative for HBsAg but positive for anti-HBc also examined for HBV-DNA by polymerase chain reaction (PCR). Results Of the 204 HBsAg negative blood samples, 11 (5.4%) samples were positive for anti-HBc antibodies. HBV-DNA was detected in 9/11 (81%) of anti-HBc positive samples. Occult HBV infection in hematological cancers was more than solid cancers, 4.8% and 4.3% respectively. There was no significant difference in HBc antibody positivity based on vaccination, previous blood transfusions, history of familial hepatitis or biochemical parameters (ALT, AST, total and direct bilirubin levels) (P>0.05). Conclusion Screening of occult HBV infection by HBsAg, HBV DNA and anti HB core antibody should be suggested as a routine investigation in cancer patients before receiving chemotherapy.

RESUMO Contexto A infecção oculta da hepatite B caracteriza-se por antígeno de superfície da hepatite B (AgHBs) negativo com vírus detectável da hepatite B (HBV) -DNA, com ou sem anticorpo de núcleo da hepatite B (anti-HBc). A reativação do HBV em indivíduos sob terapia imunossupressora é crítica, originando a infecção oculta pelo VHB. Objetivo Este estudo teve como objetivo determinar a prevalência de infecção oculta pelo VHB entre em pacientes com câncer e com antígeno de superfície da hepatite B negativo antes de receber quimioterapia. Métodos Soro de 204 pacientes com câncer que foram negativos para AgHBs, foram testados para anticorpos anti-HBc. As amostras que foram negativos para AgHBs, mas positivo para anti-HBc foram também examinadas para HBV-DNA, por reação em cadeia da polimerase. Resultados Entre 204 amostras de sangue AgHBs negativas, 11 (5,4%) foram positivos para anticorpos anti-HBc. HBV-DNA foi detectado em 9/11 (81%) das amostras positivas de anti-HBc. Infecção oculta de VHB em câncer hematológico foi maior que em cânceres sólidos, 4,8% e 4,3% respectivamente. Não houve diferença significativa na positividade anti-HBc, com base na vacinação, transfusões de sangue anteriores, história de hepatite familiar ou parâmetros bioquímicos (ALT, AST, total e níveis de bilirrubina total) (P & gt; 0,05). Conclusão A triagem de infecção oculta por AgHBs, HBV-DNA e anti-anticorpo de núcleo HB deve ser sugerida como uma investigação de rotina em pacientes com câncer antes de receber a quimioterapia.

Cytokine Pattern is Affected by Training Intensity in Women Futsal Players

To find the relation between exercise and cytokines, we examined the effect of the training intensity on the levels of cytokines, including interferon-gamma (IFN-γ), interlukine-4 (IL-4) and interlukine-4/interferon-gamma ratio (IL-4/IFN-γ ratio) in female Futsal players. Twelve well-trained female college Futsal players aged 19~22 participated in this study. The athletes completed 30-min of running at 60~65% maximal heart rate [moderate-intensity exercise], and 30-min of running at 75~80% maximal heart rate [high-intensity exercise]. peripheral blood samples were collected 24 h before and 24 h and 48 h after each of the exercise bouts. finding showed that The 30-min bout of moderate-intensity exercise induced a significant increase in IFN-γ (p=0.01) and significant decreases in IL-4 (p=0.001) and IL-4/IFN-γ ratio (p=0.003). And also, 30-min of running at 75~80% maximal heart rate induced increase in IFN-γ (p=0.07) and decreased in IL-4 (p=0.01) and IL-4/IFN-γ ratio (p=0.06) that these changes not significantly. In summary, exercise intensity can effect on the magnitude of changes in cytokines. It seems that moderate intensity exercise enhances cytokine pattern in female college Futsal players.