Search Results (149)

Background: Heparan sulfate (HS) is widely implicated as a receptor for Chlamydia cell attachment and infectivity. However, the enzymatic modification of HS modified by the 3-O sulfotransferase-3 (3-OST-3) enzyme in chlamydial cell entry remains unknown. Methodology: To rule out the possibility that host cell 3-O sulfated heparan sulfate (3-OS HS) plays a significant role in C. muridarum entry, a Chinese hamster ovary (CHO-K1) cell model lacking endogenous 3-OST-3 was used. In addition, we further tested the efficacy of the phage-display-derived cationic peptides recognizing heparan sulfate (G1 peptide) and the moieties of 3-O sulfated heparan sulfate (G2 peptide) against C. muridarum entry using human cervical adenocarcinoma (HeLa 229) and human vaginal epithelial (VK2/E6E7) cell lines. Furthermore, molecular dynamics simulations were conducted to investigate the interactions of the Chlamydia lipid bilayer membrane with the G1 and G2 peptides, focusing on their binding modes and affinities. Results: The converse effect of 3-OST-3 expression in the CHO-K1 cells had no enhancing effect on C. muridarum entry. The G2 peptide significantly (>80%) affected the cell infectivity of the elementary bodies (EBs) at all the tested concentrations, as evident from the reduced fluorescent staining in the number of inclusion bodies. The observed neutralization effect of G2 peptide on C. muridarum entry suggests the possibility of sulfated-like domains being present on the EBs. In addition, data generated from our in silico computational structural modeling indicated that the G2 peptide ligand had significant affinity towards the C. muridarum lipid bilayer. Conclusions: Taken together, our findings show that the pretreatment of C. muridarum with 3-O sulfated heparan sulfate recognizing G2 peptide significantly prevents the entry of EBs into host cells. Full article

In this study, borophene and nickel phthalocyanine (NiPc): borophene nanocomposites were prepared using the sonication method. The NiPc: borophene nanocomposite was uniformly obtained as a 10–80 nm-sized spherically shaped particle. Electrical conductivities (s) were measured as 3 × 10⁻¹³ Scm⁻¹ and 9.5 × 10⁻⁹ Scm⁻¹ for NiPc and the NiPc: borophene nanocomposite, respectively. The SEM image showed that borophene was homogeneously distributed in the NiPc matrix and increased the charge transport pathways. This is the main reason for a 10⁶-fold increase in electrical conductivity. An indium tin oxide (ITO)/NiPc: borophene nanocomposite-based thermoelectric generator (TEG) was prepared and characterized. The Seebeck coefficients (S) were calculated to be 5 μVK⁻¹ and 30 μVK⁻¹ for NiPc and the NiPc: borophene nanocomposite, respectively. A positive Seebeck coefficient value for the NiPc: borophene showed the p-type nature of the nanocomposite. The power factors (PF = sS2) were calculated as 7.5 × 10⁻¹⁶ μW m⁻¹ K⁻² and 8.6 × 10⁻¹⁰ μW m⁻¹ K⁻² for NiPc and the NiPc: borophene nanocomposite, respectively. Compositing NiPc with borophene increased the power factor by ~10⁶-fold. It has been concluded that the electrical conductivity and Seebeck coefficient of the NiPc: borophene material increases due to energy band convergence because of combining p-type NiPc with p-type borophene. Therefore, the NiPc: borophene nanocomposite is a promising material for TEG. Full article

Background: The efflux system is one of the resistance mechanisms that bacteria use to reduce the effectiveness of antibiotics, leading to the development of multidrug resistance. To evaluate other treatment choices, esomeprazole (ESO), omeprazole (OME), pantoprazole (PAN), vitamin D (VD), and vitamin K (VK) were tested for potential efflux pump (EP)-inhibiting activity. Methods: The minimum inhibitory concentrations (MICs) of the tested drugs were determined against K. pneumoniae ATCC 51503 and P. aeruginosa PAO1. Quantitative estimation of the EP-inhibiting activity of the tested medications was phenotypically investigated with a semi-automated fluorometric system and genotypically confirmed by real-time polymerase chain reaction (RT-PCR). Data were confirmed through docking study. Results: K. pneumoniae ATCC 51503 and P. aeruginosa PAO1 were positive efflux standard strains. VD and VK revealed an MIC_VD of 625–1250 µg/mL and MIC_VK of 2500–5000 µg/mL, lower than what was detected for PPIs (MIC_PPIs = 16,000–32,000 µg/mL). Vitamins showed powerful anti-efflux activity with remarkable ethidium bromide accumulation in K. pneumoniae ATCC 51503 and P. aeruginosa PAO1. Also, VD and VK significantly lowered the MIC of ciprofloxacin by 64-fold. On the molecular level, OME showed a notable decrease in the relative expression of the efflux-encoding genes acrB and mexA by 91.5% and 99.7% in ATCC 51503 and PAO1, respectively. Conclusion: This study highlights the anti-efflux activity of ESO, OME, PAN, VD, and VK against the tested Gram-negative strains. Hence, these PPIs and vitamins could be valuable adjuvant treatments to enhance the effectiveness of curing infections caused by MDR strains. Full article

Porcine epidemic diarrhea virus (PEDV) is a major pathogen responsible for viral diarrhea in pigs, causing particularly high mortality in neonatal piglets. In recent years, genetic variations in PEDV have resulted in alterations in both its virulence and antigenicity, leading to a reduced efficacy of existing vaccines. In this study, diarrheal samples were collected from four commercial pig farms in the Hubei, Guangxi, and Jiangxi provinces, China, which experienced vaccine failure. RT-qPCR confirmed PEDV infection, and three PEDV strains, 2021-HBMC, 2024-JXYX, and 2024-JXNC, were successfully isolated. Sequence analysis and phylogenetic tree construction classified these strains into the G2c genotype, the predominant subtype in China. The neutralization assays revealed a significant reduction in the neutralizing titers of these strains against the immune serum compared with the AJ1102 reference strain. Further amino acid sequence analysis of the spike (S) protein identified several mutations in key neutralizing epitopes compared with the AJ1102 strain, including S27L, E57A, N139D, M214T, and P229L in the S-NTD epitope; A520S, F539L, K566N, D569E, G612V, P634S, E636V/K in the COE epitope; and Y1376H in the 2C10 epitope, along with several deletions at N-glycosylation sites (347NSSD and 510NITV). Additionally, whole-genome sequencing and recombination analysis indicated that the 2021-HBMC strain may have resulted from a recombination event. The findings of this study underscore the challenge posed by the continuous genetic evolution of PEDV to vaccine efficacy and provide valuable insights for future vaccine development and control strategies. Full article

Vitamin K₃ (VK₃) is an essential micronutrient for fish growth and metabolism. To determine the optimal required dietary concentration of VK, a 12-week-long trial was planned to investigate the impact of VK₃ on growth performance, muscle composition, liver menaquinone-4 (MK-4), whole-body MK-4 concentration, and antioxidant capacity (T-AOC) in coho salmon alevins. A total of 2100 coho salmon alevins were divided into twenty-one tanks, with 100 alevins in each tank, and three tanks represented one group. Each of the seven groups were randomly assigned to one of the experimental diets formulated with varying levels of menadione nicotinamide bisulphite (VK₃), i.e., 0.16 (control), 5.25, 10.22, 14.93, 20.51, 40.09, and 59.87 mg/kg, respectively. The results revealed that the inclusion of VK₃ from 5.25 to 40.09 mg/kg improved (p < 0.05) the survival rate (SR), weight gain (WG), specific growth rate (SGR), and feed conversion ratio (FCR), while no effect (p > 0.05) was observed on the hepatosomatic index (HSI), viscerosomatic index (VSI), Fulton’s condition factor (K), and muscle composition. The whole-body MK-4, liver MK-4, liver T-AOC, total superoxide dismutase (T-SOD), and catalase (CAT) enzymes were also increased (p < 0.05). Malondialdehyde (MDA) contents were reduced (p < 0.05) in all supplemented groups with a decreasing trend. The predicted optimal required dietary concentrations of VK₃ were found to be 34.0, 43.5, 38.54, and 31.97 mg/kg based on WG, SGR, liver MK-4 concentration, and T-AOC, respectively, by quadratic regression analysis. It is concluded that the dietary VK₃ has improved the growth performance and antioxidant status in alevins during early development in the range of 31.97 to 43.5 mg/kg diet. Full article

Accurately forecasting CO₂ emissions in the transportation sector is essential for developing effective mitigation strategies. This study uses an annually spanning dataset from 1993 to 2022 to evaluate the predictive performance of three methods: NAR, NARX, and GA-T2FIS. Among these, NARX-VK, which incorporates vehicle kilometers (VK) and economic variables, demonstrated the highest predictive accuracy, achieving a MAPE of 2.2%, MAE of 1621.449 × 10³ tons, and RMSE of 1853.799 × 10³ tons. This performance surpasses that of NARX-RG, which relies on registered vehicle data and achieved a MAPE of 3.7%. While GA-T2FIS exhibited slightly lower accuracy than NARX-VK, it demonstrated robust performance in handling uncertainties and nonlinear relationships, achieving a MAPE of 2.6%. Sensitivity analysis indicated that changes in VK significantly influence CO₂ emissions. The Green Transition Scenario, assuming a 10% reduction in VK, led to a 4.4% decrease in peak CO₂ emissions and a 4.1% reduction in total emissions. Conversely, the High Growth Scenario, modeling a 10% increase in VK, resulted in a 7.2% rise in peak emissions and a 4.1% increase in total emissions. Full article

The edible value of crabapple flowers remains unreported. In this study, the flower buds of three crabapple cultivars with different flower colors, Malus ‘Royalty’ (purple-red), ‘May’s Delight’ (pink), and ‘Snowdrift’ (white), were processed via hot-air drying at different temperatures and durations. The results showed that the sensory scores of ‘Royalty’ (4 h at 50 °C or 6 h at 40 °C), ‘Snowdrift’ (5 h at 50 °C), and ‘May’s Delight’ (4 h at 60 °C or 6 h at 50 °C) were higher (score > 90 points). The contents of phloridzin, total flavonoids (TFC), and total free amino acids (TFAC) in ‘May’s Delight’ under 50 or 60 °C were significantly higher than in other treatments. The differences in functional constituents among the different treatments of ‘Royalty’ were the smallest (C.V < 7%). The influences (C.V_k > 35%) of cultivar and drying temperature on the phlorizin content (PC) and TFAC were significantly higher than those of other treatments. The PC maintained the highest stability (C.V_k < 10%) under different temperatures and durations. The value of color parameter a* of dry flowers was significantly positively correlated with TFC, PC, and TFAC, and the total score of the sensory evaluation was positively correlated with the TFC. Based on functional constituents and sensory evaluation, ‘May’s Delight’ with air-drying at 50 °C for 6 h was the best option for crabapple flower tea. Full article

Effective tools to prevent mosquito bites are essential for malaria control. The Lehmann Funnel Entry Trap (LFET), a window screen proven effective in reducing mosquito density, was tested for its large-scale impact on malaria vector control and community acceptance. A total of 1313 traps were deployed in Vallée du Kou 3 (VK3), with 12 traps randomly selected for detailed evaluation against untrapped houses in Vallée du Kou 5 (VK5). Traps were placed in windows with doors blocked by curtains. From July to October, mosquitoes were collected for nine days per month from VK3 traps and VK5 control houses. Morphological identification, density analysis, resistance gene screening, and female age structure determination were conducted. The trap’s impact was assessed via pyrethrum spray catch (PSC) and for nine days per month, while trap fabric integrity and community perceptions were also evaluated. Traps reduced mosquito entry density by more than 90% in VK3 houses. VK3 had 33% higher house mosquito density pre-intervention and 47% lower house mosquito density post-intervention than VK5. Old female mosquito numbers rose in VK5 but not VK3. Pyrethroid resistance was high (kdr mutation frequency > 0.9) in both control and intervention sites. VK3 residents appreciated the traps for reducing bites and improving sleep. The LFET effectively controls malaria vectors and is well-suited for widespread use in malaria elimination efforts. Full article

Aging is an inevitable aspect of life, but age-related diseases are not an inseparable part of the aging process, and their risk can be reduced through a healthy lifestyle. Vitamin K has a broader impact than just blood clotting, and yet it remains overshadowed by other vitamins and underestimated by both doctors and consumers. Vitamin K (VK) is a multifunctional micronutrient with anti-inflammatory and antioxidant properties, whose deficiency may cause age-related diseases such as cardiovascular diseases, neurodegenerative diseases and osteoporosis. There is a growing body of evidence supporting the role of vitamin K as a protective nutrient in aging and inflammation. This review summarizes the current knowledge regarding the molecular aspects of the protective role of vitamin K in aging and age-related diseases and its clinical implications. Full article

Islatravir (ISL) is the first-in-class nucleoside reverse transcriptase translocation inhibitor (NRTtI) with novel modes of action. Data on ISL resistance are currently limited, particularly to HIV-1 non-B subtypes. This study aimed to assess prevalent nucleos(t)ide reverse transcriptase inhibitor (NRTI)-resistant mutations in HIV-1 subtype C for their phenotypic resistance to ISL. Prevalent single and combinations of NRTI-resistant mutations were selected from a routine HIV-1 genotypic drug resistance testing database and introduced into HIV-1 subtype C-like pseudoviruses, which were then tested for ISL susceptibility. Single NRTI-resistant mutations were susceptible or showed only a low level of resistance to ISL. This included thymidine analogue mutations (TAMs, i.e., M41L, D67N, K70R, T215FY, and K219EQ) and non-TAMs (i.e., A62V, K65R, K70ET, L74IV, A114S, Y115F, and M184V). Combinations of M184V with one or more additional NRTI-resistant mutations generally displayed reduced ISL susceptibilities. This was more prominent for combinations that included M184V+TAMs, and particularly M184V+TAM-2 mutations. Combinations that included M184V+K65R did not impact significantly on ISL susceptibility. Our study suggests that ISL would be effective in treating people living with HIV (PLWH) failing tenofovir disoproxil fumarate (TDF)/lamivudine (3TC) or TDF/emtricitabine (FTC)-containing regimens, but would be less effective in PLH failing zidovudine (AZT) with 3TC or FTC-containing regimens. Full article

This in vitro study investigated how varying magnifications (5×, 10×, 20×, and 50×) using a confocal laser scanning microscope (CLSM) influence the measured surface roughness parameters, R_a/S_a and R_z/S_z, of various materials with two surface treatments. Cylindrical specimens (d ≈ 8 mm, h ≈ 3 mm, n = 10) from titanium, zirconia, glass-ceramic, denture base material, and composite underwent diamond treatment (80 μm; wet) and polishing (#4000; wet; Tegramin-25, Struers, G). The surface roughness parameters (R_a/S_a, R_z/S_z) were measured with a CLSM (VK-100, Keyence, J) at 5×, 10×, 20×, and 50× magnifications. Line roughness (R_a/R_z) was measured along a 1000 μm distance in three parallel lines, while area roughness (S_a/S_z) was evaluated over a 2500 μm × 1900 μm area. The statistical analysis included ANOVA, the Bonferroni post hoc test, and Pearson correlation (SPSS 29, IBM, USA; α = 0.05). R_a/S_a and R_z/S_z showed significant differences (p ≤ 0.001, ANOVA) across magnifications, with values decreasing as magnification increased, highest at 5× and lowest at 50×. Titanium, zirconia, and glass-ceramic showed significant measured roughness values from 5× to 50×. Denture base material and composite had lower measured roughness values, especially after polishing. Line and area roughness varied significantly, indicating that magnification affects measured values. Standardizing magnifications is essential to ensure comparability between studies. A 50× magnification captures more detailed profile information while masking larger defects. Full article

To investigate the relationship between microstructure, chemical composition, and thermoelectric properties, we have applied graded temperature heat treatments to recently developed τ₁-Al₂Fe₃Si₃-based thermoelectric (FAST) materials formed by a peritectic reaction. We investigated microstructures, chemical compositions, and Seebeck coefficients as continuous functions of heat treatment temperature. The τ1 phase can become p- and n-type semiconductors without doping by changing the Al/Si ratio. The Seebeck coefficient was maximized, exceeding |S| > 140 μVK⁻¹ for both p- and n-type materials, by heat treatment at 1173 K for 24 h through microstructural optimization. These results show that combining the graded temperature heat treatments and spatial mapping measurements of thermoelectric properties gives effective routes to determine the suitable heat treatment temperature for materials with multiphase microstructure. Full article

In this study, the effects of cutting speed and feed rate on the roughness parameters R_a, R_z, R_sk, R_ku, R_pk, R_vk, and A₂ were examined during machining with coated carbide tools in a dry environment. The authors introduced the R_vk/R_pk ratio, a coefficient that facilitates a simpler evaluation of surface wear resistance. Specifically, if this ratio is greater than 1, the surface is more wear-resistant, while values less than 1 indicate a higher tendency for surface wear. The Taguchi OA method was used to analyze and identify the significance of technological parameters on output characteristics. Based on the results, it was established that feed rate has the greatest impact on all output characteristics. The highest cutting force was measured at a cutting speed of 60 m/min and a feed rate of 0.15 mm/rev, attributed to the fact that at lower cutting speeds, the base material does not soften while the cross-sectional area of the chip increases. To achieve the lowest R_a and R_z surface roughness, a cutting speed of 100 m/min and a feed rate of 0.05 mm/rev are recommended. If the goal is to enhance surface wear resistance and improve oil retention capability, machining with a cutting speed of 80–100 m/min and a feed rate of 0.15 mm/rev is advisable, as the coarser machining increases both the R_vk/R_pk ratio and the oil-retaining pocket size, which together improve the wear resistance of the machined surface. Full article

Background: Research into key performance factors in trail running, particularly in vertical kilometer (VK) races, is crucial for effective training and periodization. However, recent studies on metabolic and cardiorespiratory responses during VK races, especially using field tests, are limited. Objectives: Therefore, the aim of this study is to evaluate the metabolic and cardiorespiratory responses during a VK field test, identifying differences based on sex and performance level, as well as key performance factors and their deterioration due to fatigue. Fifteen trained trail runners (ten males and five females, 19 to 38 years old) perform a VK race. Methods: The global physiological response is evaluated using the portable gas analyzer Cosmed K5 and the local response using near-infrared spectroscopy technology. Results: In gender comparisons, the ANCOVA test shows significant differences (p < 0.05) in the ventilation, tidal volume, expiratory time-to-inspiratory time ratio, inspiratory flow rate, end-tidal CO₂ partial pressure, heart rate, oxygen pulse, and total hemoglobin. Additionally, the performance comparison reveals significant differences in the variables’ velocity, oxygen consumption, carbon dioxide production, ventilation, dead space-to-tidal volume ratio, total time of the breathing cycle, expiratory time-to-inspiratory time ratio, inspiratory duty cycle, expiratory fractions of CO₂, quadriceps saturation index, and VE/VCO₂ ratio. Finally, the correlation analysis shows oxygen consumption (r = −0.80 mean; r = −0.72 peak), carbon dioxide production (r = −0.91 mean; r = −0.75 peak), expiratory time-to-inspiratory time ratio (r = 0.68 peak), ventilation (r = −0.58 mean), and quadriceps saturation index (r = 0.54 mean; r = −0.76 coefficient of variation) as the key performance factors in the VK race. Conclusions: Overall, the physiological analysis indicates the importance of local muscular adaptations and respiratory system capacity in this type of short-duration race. Full article

Background/Objectives: Cytolytic vaginosis or, classically, Doderlein’s cytolysis is characterized by significant growth of species of the Lactobacillus genus, which leads to high amounts of lactic acid in the vaginal environment. Lactobacillus crispatus has been proposed as a key pathogen in this clinical condition. The symptomatology of cytolytic vaginosis is commonly confused with that of vulvovaginal candidosis, leading to inadequate and ineffective azole therapies. Nevertheless, historically, the use of sodium bicarbonate intimate baths was an effective way to reduce the symptoms of cytolytic vaginosis. Methods: In this study, four HPMC gel prototypes were developed, containing sodium bicarbonate concentrations ranging from 4% to 7% (w/w). These gels were evaluated for their physicochemical properties, antimicrobial activity, interference with lactobacilli adhering to cells, and cellular and tissue biocompatibility. Results: The gels presented pH values of around 9.0, and osmolality between 706 mOsm/kg (F4) and 1065 mOsm/kg (F7). The viscosity upon heating to physiologic temperature and dilution with simulated vaginal fluid was highly affected by the concentration of sodium bicarbonate. Gels with higher sodium bicarbonate concentrations (F6 and F7) were not shown to be stable in these conditions. All formulations exhibited effective antimicrobial activity against seven L. crispatus strains, with MIC values ranging from 6.25% to 25% (v/v) in terms of dilution. Additionally, the 4% (w/w) gel significantly interfered with the adhesion of L. crispatus to epithelial cells in competition and exclusion assays, reducing adhesion by more than 90% in relation to the control. Cytotoxicity tests on the Hec-1A, HeLa, and VK2/E6E7 cell lines indicated that the F4 and F5 gels demonstrated lower cytotoxicity levels compared to those with higher concentrations. Furthermore, ex vivo assays using porcine vaginal tissue confirmed that the 4% gel was non-toxic at a 25% (v/v) dilution. Conclusions: Based on these results, the 4% (w/w) sodium bicarbonate gel (F4) emerges as a promising therapeutic option for cytolytic vaginosis, offering effective bacterial interference, favourable physicochemical properties, and biocompatibility suitable for vaginal application. Full article