Search Results (1,087)

Background: The gut microbiota of breast-fed infants is dominated by infant-type human-residential bifidobacteria (HRB) that contribute to infant health; thus, it is crucial to develop infant formulas that promote the establishment of a gut microbiota enriched with infant-type HRB, closely resembling that of breastfed infants. Methods: We compared various non-digestible prebiotic oligosaccharides and their combinations using a fecal culture system to explore which candidates could promote the growth of all infant-type HRB and rarely yield non-responders. The analysis included lactulose (LAC), raffinose (RAF), galactooligosaccharides (GOS), and short- and long-chain fructooligosaccharides. Fecal samples were collected from seven infants aged 1.5–10.2 months and cultured with each oligosaccharide individually or their combinations. Results: No single oligosaccharide effectively promoted the growth of all infant-type HRB, although GOS promoted the growth of HRB other than Bifidobacterium longum subsp. longum. Only the LAC/RAF/GOS group evenly and effectively promoted the growth of all infant-type HRB. Accordingly, acetate production was higher in fecal cultures supplemented with GOS or LAC/RAF/GOS than in the other cultures, suggesting that it is a superior combination for all infant-type HRB and rarely yields non-responders. Conclusions: This study can aid in developing infant formulas that help align the gut microbiota of formula-fed infants with that of breastfed infants. Full article

Numerical experiments using the WRF model were conducted to analyze the sensitivity of Typhoon Mangkhut intensification simulations to seven widely used planetary boundary layer (PBL) parameterization schemes, including YSU, MYJ, QNSE, MYNN2, MYNN3, ACM2, and BouLac. The results showed that all simulations generally reproduced the tropical cyclone (TC) track and intensity, with YSU, QNSE, and BouLac schemes better capturing intensification processes and closely matching observed TC intensity. In terms of surface layer parameterization, the QNSE scheme produced the highest C_k/C_d ratio, resulting in stronger TC intensity based on Emanuel’s potential intensity theory. In terms of PBL parameterization, the YSU and BouLac schemes, with the same revised MM5 surface layer scheme, simulated weaker turbulent diffusivity K_m and shallower mixing height, leading to stronger TC intensity. During the intensification period, the BouLac, YSU, and QNSE PBL schemes exhibited stronger tangential wind, radial inflow within the boundary layer, and updraft around the eye wall, consistent with TC intensity results. Both PBL and surface layer parameterization significantly influenced simulated TC intensity. The QNSE scheme, with the largest C_k/C_d ratio, and the YSU and BouLac schemes, with weaker turbulent diffusivity, generated stronger radial inflow, updraft, and warm core structures, contributing to higher storm intensity. Full article

Laccase, a copper-containing oxidoreductase, has close links with secondary metabolite biosynthesis in plants. Its activity can affect the synthesis and accumulation of secondary metabolites, thereby influencing plant growth, development, and stress resistance. This study aims to identify the grape laccases (VviLAC) gene family members in grape (Vitis vinifera L.) and explore the transcriptional regulatory network in berry development. Here, 115 VviLACs were identified and divided into seven (Type I–VII) classes. These were distributed on 17 chromosomes and out of 47 VviLACs on chromosome 18, 34 (72.34%) were involved in tandem duplication events. VviLAC1, VviLAC2, VviLAC3, and VviLAC62 were highly expressed before fruit color development, while VviLAC4, VviLAC12, VviLAC16, VviLAC18, VviLAC20, VviLAC53, VviLAC60 and VviLAC105 were highly expressed after fruit color transformation. Notably, VviLAC105 showed a significant positive correlation with important metabolites including resveratrol, resveratrol dimer, and peonidin-3-glucoside. Analysis of the transcriptional regulatory network predicted that the 12 different transcription factors target VviLACs genes. Specifically, WRKY and ERF were identified as potential transcriptional regulatory factors for VviLAC105, while Dof and MYB were identified as potential transcriptional regulatory factors for VviLAC51. This study identifies and provides basic information on the grape LAC gene family members and, in combination with transcriptome and metabolome data, predicts the upstream transcriptional regulatory network of VviLACs. Full article

Background/Objectives. The rise of antibiotic-resistant pathogens represents a significant global challenge in infectious disease control, which is amplified by the decline in the discovery of novel antibiotics. Staphylococcus aureus continues to be a highly significant pathogen, causing infections in multiple organs and tissues in both healthcare institutions and community settings. The bacterium has become increasingly resistant to all available antibiotics. Consequently, there is an urgent need for novel small molecules that inhibit the growth or impair the survival of bacterial pathogens. Given their large structural and chemical diversity, as well as often unique mechanisms of action, natural products represent an excellent avenue for the discovery and development of novel antimicrobial treatments. Anaephene A and B are two such naturally occurring compounds with significant antimicrobial activity against Gram-positive bacteria. Here, we report the rapid syntheses and biological characterization of five novel anaephene derivatives, which display low cytotoxicity against mammalian cells but potent antibacterial activity against various S. aureus strains, including methicillin-resistant S. aureus (MRSA) and the multi-drug-resistant community-acquired strain USA300LAC. Methods. A Sonogashira cross-coupling reaction served as the key step for the synthesis of the alkyl pyridinol products. Results/Conclusions. Using the compound JC-01-074, which displays bactericidal activity already at low concentrations (MIC: 16 μg/mL), we provide evidence that alkyl pyridinols target actively growing and biofilm-forming cells and show that these compounds cause disruption and deformation of the staphylococcal membrane, indicating a membrane-associated mechanism of action. Full article

Platelets are small cell fragments that play a crucial role in hemostasis, requiring fast response times and fine signaling pathway regulation. For this regulation, platelets require a balance between two pathway types: the activatory and negative signaling pathways. Activatory signaling mediators are positive responses that enhance stimuli initiated by a receptor in the platelet membrane. Negative signaling regulates and controls the responses downstream of the same receptors to roll back or even avoid spontaneous thrombotic events. Several blood-related pathologies can be observed when these processes are unregulated, such as massive bleeding in activatory signaling inhibition or thrombotic events for negative signaling inhibition. The study of each protein and metabolite in isolation does not help to understand the role of the protein or how it can be contrasted; however, understanding the balance between active and negative signaling could help develop effective therapies to prevent thrombotic events and bleeding disorders. Full article

Green hydrogen is becoming increasingly popular, with academics, institutions, and governments concentrating on its development, efficiency improvement, and cost reduction. The objective of the Ministry of Petroleum, Mines, and Energy is to achieve a 35% proportion of renewable energy in the overall energy composition by the year 2030, followed by a 50% commitment by 2050. This goal will be achieved through the implementation of feed-in tariffs and the integration of independent power generators. The present study focused on the economic feasibility of green hydrogen and its production process utilizing renewable energy resources on the northern coast of Mauritania. The current investigation also explored the wind potential along the northern coast of Mauritania, spanning over 600 km between Nouakchott and Nouadhibou. Wind data from masts, Lidar stations, and satellites at 10 and 80 m heights from 2022 to 2023 were used to assess wind characteristics and evaluate five turbine types for local conditions. A comprehensive techno-economic analysis was carried out at five specific sites, encompassing the measures of levelized cost of electricity (LCOE) and levelized cost of green hydrogen (LCOGH), as well as sensitivity analysis and economic performance indicators. The results showed an annual average wind speed of 7.6 m/s in Nouakchott to 9.8 m/s in Nouadhibou at 80 m. The GOLDWIND 3.0 MW model showed the highest capacity factor of 50.81% due to its low cut-in speed of 2.5 m/s and its rated wind speed of 10.5 to 11 m/s. The NORDEX 4 MW model forecasted an annual production of 21.97 GWh in Nouadhibou and 19.23 GWh in Boulanoir, with the LCOE ranging from USD 5.69 to 6.51 cents/kWh, below the local electricity tariff, and an LCOGH of USD 1.85 to 2.11 US/kg H₂. Multiple economic indicators confirmed the feasibility of wind energy and green hydrogen projects in assessed sites. These results boosted the confidence of the techno-economic model, highlighting the resilience of future investments in these sustainable energy infrastructures. Mauritania’s north coast has potential for wind energy, aiding green hydrogen production for energy goals. Full article

Genetic constructs must be delivered selectively to target tissues and intracellular compartments at the necessary concentrations in order to achieve the maximum therapeutic effect in gene therapy. Development of targeted carriers for non-viral delivery of nucleic acids into cells, including those in muscle, which is one of the most challenging tissues to transfect in vivo, remains a topical issue. We have studied ternary complexes of plasmid DNA and an arginine–histidine-rich peptide-based carrier coated with a glutamate–histidine-rich polymer bearing skeletal muscle targeting peptide (SMTP) for the gene delivery to muscle tissue. The relaxation of the ternary complexes after polyanion treatment was assessed using the ethidium bromide displacement assay. The developed polyplexes were used to transfect C2C12 myoblasts in full-media conditions, followed by analysis of their toxic properties using the Alamar Blue assay and expression analysis of lacZ and GFP reporter genes. After delivering plasmids containing the GFP and lacZ genes into the femoral muscles of mdx mice, which are model of Duchenne muscular dystrophy, GFP fluorescence and β-galactosidase activity were detected. We observed that the modification of ternary polyplexes with 10 mol% of SMTP ligand resulted in a 2.3-fold increase in lacZ gene expression when compared to unmodified control polyplexes in vivo. Thus, we have demonstrated that the developed DNA/carrier complexes and SMTP-modified coating are nontoxic, are stable against polyanion-induced relaxation, and can provide targeted gene delivery to muscle cells and tissues. The results of this study are useful for a range of therapeutic applications, from immunization to amelioration of inherited neuromuscular diseases. Full article

Stems are prone to bending or lodging due to inadequate stem strength, which seriously reduces the cut-flower ornamental quality of herbaceous peony (Paeonia lactiflora Pall.). Plant LACCASE (LAC), a copper-containing polyphenol oxidase, has been shown to participate in the polymerization process of monolignols; however, the role of LAC in regulating the stem strength of P. lactiflora remains unclear. Here, the full-length cDNA of PlLAC15, which demonstrated a positive association with stem strength, was isolated. It consisted of 1790 nucleotides, encoding 565 amino acids that had four typical laccase copper ion-binding domains. Moreover, PlLAC15 was highly expressed in the stem, and its expression level gradually significantly increased during stem development. Furthermore, PlLAC15 was found to be localized specifically to the cell wall, and its recombinant protein exhibited laccase activity. Additionally, the role of PlLAC15 in regulating the stem strength of P. lactiflora was confirmed by transgenic studies. When PlLAC15 was overexpressed in tobacco, stem strength increased by more than 50%, S-lignin was significantly deposited, and the lignification degree of stem xylem fiber cells increased. These results suggested that PlLAC15 facilitated S-lignin deposition to enhance stem strength in P. lactiflora, which would provide precious information that benefits future exploration of stem bending or lodging resistance in plants. Full article

We present a comprehensive investigation of mid-infrared (MIR) flux variability at 3.4 μm (W1 band) for a large sample of 3816 blazars, using Wide-field Infrared Survey Explorer (WISE) data through December 2022. The sample consists of 1740 flat-spectrum radio quasars (FSRQs), 1281 BL Lac objects (BL Lacs), and 795 blazars of uncertain type (BCUs). Considering Fermi Large Area Telescope detection, we classify 2331 as Fermi blazars and 1485 as non-Fermi blazars. Additionally, based on synchrotron peak frequency, the sample includes 2264 low-synchrotron peaked (LSP), 512 intermediate-synchrotron peaked (ISP), and 655 high-synchrotron peaked (HSP) sources. We conduct a comparative analysis of short- and long-term intrinsic variability amplitude (${\sigma }_m$), duty cycle (DC), and ensemble structure function (ESF) across blazar subclasses. The median short-term ${\sigma }_m$ values were $0.{181}_{-0.106}^{+0.153}$, $0.{104}_{-0.054}^{+0.101}$, $0.{135}_{-0.076}^{+0.154}$, $0.{173}_{-0.097}^{+0.158}$, $0.{177}_{-0.100}^{+0.156}$, $0.{096}_{-0.050}^{+0.109}$, and $0.{106}_{-0.058}^{+0.100}$ mag for FSRQs, BL Lacs, Fermi blazars, non-Fermi blazars, LSPs, ISPs, and HSPs, respectively. The median DC values were $71.{03}_{-22.48}^{+14.17}$, $64.{02}_{-22.86}^{+16.97}$, $68.{96}_{-25.52}^{+15.66}$, $69.{40}_{-22.17}^{+14.42}$, $71.{24}_{-21.36}^{+14.25}$, $63.{03}_{-33.19}^{+16.93}$, and $64.{63}_{-24.26}^{+15.88}$ percent for the same subclasses. The median long-term ${\sigma }_m$ values were $0.{137}_{-0.105}^{+0.408}$, $0.{171}_{-0.132}^{+0.206}$, $0.{282}_{-0.184}^{+0.332}$, $0.{071}_{-0.062}^{+0.143}$, $0.{218}_{-0.174}^{+0.386}$, $0.{173}_{-0.132}^{+0.208}$, and $0.{101}_{-0.077}^{+0.161}$ mag for the same subclasses, respectively. Our results reveal significant differences in 3.4 $\mathsf{\mu }$m flux variability among these subclasses. FSRQs (LSPs) exhibit larger ${\sigma }_m$ and DC values compared to BL Lacs (ISPs and HSPs). Fermi blazars display higher long-term ${\sigma }_m$ but lower short-term ${\sigma }_m$ relative to non-Fermi blazars, while DC distributions between the two groups are similar. ESF analysis further confirms the greater variability of FSRQs, LSPs, and Fermi blazars across a wide range of time scales compared to BL Lacs, ISPs/HSPs, and non-Fermi blazars. These findings highlight a close correlation between MIR variability and blazar properties, providing valuable insights into the underlying physical mechanisms responsible for their emission. Full article

Human lactoferrin (hLf) is an innate host defense protein that inhibits microbial H⁺-ATPases. This protein includes an ancestral structural motif (i.e., γ-core motif) intimately associated with the antimicrobial activity of many natural Cys-rich peptides. Peptides containing a complete γ-core motif from hLf or other phylogenetically diverse antimicrobial peptides (i.e., afnA, SolyC, PA1b, PvD₁, thanatin) showed microbicidal activity with similar features to those previously reported for hLf and defensins. Common mechanistic characteristics included (1) cell death independent of plasma membrane (PM) lysis, (2) loss of intracellular K⁺ (mediated by Tok1p K⁺ channels in yeast), (3) inhibition of microbicidal activity by high extracellular K⁺, (4) influence of cellular respiration on microbicidal activity, (5) involvement of mitochondrial ATP synthase in yeast cell death processes, and (6) increment of intracellular ATP. Similar features were also observed with the BM2 peptide, a fungal PM H⁺-ATPase inhibitor. Collectively, these findings suggest host defense peptides containing a homologous γ-core motif inhibit PM H⁺-ATPases. Based on this discovery, we propose that the γ-core motif is an archetypal effector involved in the inhibition of PM H⁺-ATPases across kingdoms of life and contributes to the in vitro microbicidal activity of Cys-rich antimicrobial peptides. Full article

Background: The prognostic value of baseline inflammatory markers in sepsis remains controversial, with conflicting evidence regarding their association with mortality. The dynamic changes in these markers over time might offer additional insights into disease progression and patient outcomes. Methods: This retrospective observational study included 138 patients with severe infections. The inflammatory biomarkers procalcitonin (PCT), C-reactive protein (CRP), and lactate (LAC) were measured at three time points: upon hospital admission (baseline), approximately 24–48 h after admission (second measurement; M2), and 48–72 h after admission (third measurement; M3). The primary outcome was 30-day mortality. A Mann–Whitney U test was used to compare the biomarker levels between the survivors and non-survivors. A Spearman’s correlation was used to assess the relationships between the baseline parameters. A logistic regression and a receiver operating characteristic (ROC) curve analysis were employed to evaluate the prognostic value of the baseline markers and their dynamic changes. Results: The baseline LAC and SOFA score were significantly associated with 30-day mortality. The percentage decrease in PCT, CRP, and LAC from the baseline to M3 emerged as strong predictors of survival, with the ROC curve analysis demonstrating superior discriminatory ability compared to the baseline values. CRP_Delta exhibited the highest AUC (0.903), followed by PCT_Delta (0.843) and LAC_Delta (0.703). Conclusions: The dynamic changes in these inflammatory biomarkers, particularly PCT, CRP, and LAC, offer valuable prognostic information beyond their baseline levels in predicting 30-day mortality in severe infections. These findings highlight the importance of monitoring biomarker trends for early risk stratification and potential treatment guidance. Full article

In this study, we propose a mechanism for tuning the modal characteristics of a wedge plasmonic waveguide. The wedge plasmonic waveguide is composed of a thin metallic layer deposited on a wedge-shaped dielectric waveguide. The tuning mechanism is based on controlling the surface plasmon polariton (SPP) mode at the interface between the metal layer and the dielectric waveguide instead of controlling the SPP mode at the interface between the wedge-shaped metal layer and the surrounding media. This mechanism is performed by modulating the effective refractive index of the dielectric waveguide using a closely coupled tuning waveguide. The numerically investigated results show that the propagation length of the device can be tuned more than 100%; this characteristic has not been explored yet in previous studies. The effective mode area with deep-subwavelength size is almost kept constant while tuning the propagation length. This study offers new insights into tailoring the modal characteristics of plasmonic waveguides based on controlling the mode property at the interface between the metal layer and the dielectric waveguide. This study is also a guideline for developing active plasmonic devices such as tunable nanoscale lightwave guiding waveguides and THz optic modulators. Full article

Frailty and cardiovascular diseases are increasingly prevalent in aging populations, sharing common pathological mechanisms, such as oxidative stress. The evidence shows that these factors predispose frail individuals to cardiovascular diseases but also increase the risk of thrombosis. Considering this background, this review aims to explore advances regarding the relationship between oxidative stress, platelet alterations, and cardiovascular diseases in frailty, examining the role of reactive oxygen species overproduction in platelet activation and thrombosis. The current evidence shows a bidirectional relationship between frailty and cardiovascular diseases, emphasizing how frailty not only predisposes individuals to cardiovascular diseases but also accelerates disease progression through oxidative damage and increased platelet function. Thus, oxidative stress is the central axis in the increase in platelet activation and secretion and the inadequate response to acetylsalicylic acid observed in frail people by mitochondrial mechanisms. Also, key biomarkers of oxidative stress, such as isoprostanes and derivate reactive oxygen metabolites, can be optimal predictors of cardiovascular risk and potential targets for therapeutic intervention. The potential of antioxidant therapies in mitigating oxidative stress and improving cardiovascular clinical outcomes such as platelet function is promising in frailty, although further research is necessary to establish the efficacy of these therapies. Understanding these mechanisms could prove essential in improving the health and quality of life of an aging population faced with the dual burden of frailty and cardiovascular diseases. Full article

The bHLH (basic helix–loop–helix) transcription factor AtCFLAP2 regulates epidermal wax accumulation, but the underlying molecular mechanism remains unknown. We obtained BnUC1^mut (BnaA05g18250D homologous to AtCFLAP2) from a Brassica napus mutant with up-curling leaves (Bnuc1) and epidermal wax deficiency via map-based cloning. BnUC1^mut contains a point mutation (N200S) in the conserved dimerization domain. Overexpressing BnUC1^mut in ZS11 (Zhongshuang11) significantly decreased the leaf epidermal wax content, resulting in up-curled and glossy leaves. In contrast, knocking out BnUC1^mut in ZS11-NIL (Zhongshuang11-near-isogenic line) restored the normal leaf phenotype (i.e., flat) and significantly increased the leaf epidermal wax content. The point mutation weakens the ability of BnUC1^mut to bind to the promoters of VLCFA (very-long-chain fatty acids) synthesis-related genes, including KCS (β-ketoacyl coenzyme synthase) and LACS (long-chain acyl CoA synthetase), as well as lipid transport-related genes, including LTP (non-specific lipid transfer protein). The resulting sharp decrease in the transcription of genes affecting VLCFA biosynthesis and lipid transport disrupts the normal accumulation of leaf epidermal wax. Thus, BnUC1 influences epidermal wax formation by regulating the expression of LTP and genes associated with VLCFA biosynthesis. Our findings provide a foundation for future investigations on the mechanism mediating plant epidermal wax accumulation. Full article

Epidermolysis bullosa (EB) is a clinically and genetically heterogeneous group of mechanobullous diseases characterized by non-scarring blisters and erosions on the skin and mucous membranes upon mechanical trauma. The simplex form (EBS) is characterized by recurrent blister formation within the basal layer of the epidermis. It most often results from dominant mutations in the genes coding for keratin (K) 5 or 14 proteins (KRT5 and KRT14). A disruptive mutation in KRT5 or KRT14 will not only structurally impair the cytoskeleton, but it will also activate a cascade of biochemical mechanisms contributing to EBS. Skin lesions are painful and disfiguring and have a significant impact on life quality. Several gene expression studies were accomplished on mouse model and human keratinocytes to define the gene expression signature of EBS. Several key genes associated with EBS were identified as specific immunological mediators, keratins, and cell junction components. These data deepened the understanding of the EBS pathophysiology and revealed important functional biological processes, particularly inflammation. This review emphasizes the three EBS subtypes caused by dominant mutations on either KRT5 or KRT14 (localized, intermediate, and severe). It aims to summarize current knowledge about the EBS expression profiling pattern and predicted molecular mechanisms involved and to outline progress in therapy. Full article