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5-Aminolevulinic acid (5-ALA), a non-proteinogenic amino acid, is an intermediate in the biosynthesis of heme and exerts antiviral effects against feline coronavirus (FCoV); however, the underlying mechanisms remain unclear. In the biosynthesis of heme, 5-ALA is condensed and converted to protoporphyrin IX (PpIX), which is then transformed into heme by the insertion of ferrous iron. Previous research has suggested that the metabolites generated during heme biosynthesis contribute to the antiviral effects of 5-ALA. Therefore, the present study investigated the in vitro mechanisms responsible for the antiviral effects of 5-ALA. The results obtained revealed that 5-ALA and PpIX both effectively reduced the viral titer in the supernatant of FCoV-infected fcwf-4 cells. Moreover, PpIX exerted virucidal effects against FCoV. We also confirmed that 5-ALA increased PpIX levels in cells. While hemin induced heme oxygenase-1 gene expression, it did not reduce the viral titer in the supernatant. Sodium ferrous citrate decreased PpIX levels and suppressed the antiviral effects of 5-ALA. Collectively, these results suggest that the antiviral effects of 5-ALA against FCoV are dependent on PpIX.

The coronavirus disease 2019 (COVID-19) has significantly affected the mental health of healthcare workers (HCWs). The authors have provided psychosocial support to HCWs working in typical hospitals and nursing homes in Fukushima Prefecture, Japan, where major COVID-19 outbreaks have occurred since December 2020. This study retrospectively examines depressive symptoms before psychosocial interventions among HCWs working at typical hospitals and nursing homes experiencing in-house major COVID-19 outbreaks. We have offered psychosocial support in eight hospitals and nursing homes, obtaining data on the mental health status of 558 HCWs using the Patient Health Questionnaire-9. The study's results indicate that 29.4% of HCWs have exhibited moderate or higher depressive symptoms, and 10.2% had suicidal ideation. Multiple logistic regression analysis showed that being a nurse was associated with higher depressive symptoms and suicidal ideation compared to other HCWs. In addition, multiple logistic regression analysis of Polymerase Chain Reaction-positive HCWs showed that being a nurse and the number of COVID-19-related symptoms was associated with high depressive symptoms. These results suggest that HCWs in typical hospitals and nursing homes experiencing major COVID-19 outbreaks are more likely to exhibit severe depressive symptoms, which may worsen if infected with COVID-19. This study's findings expand the current understanding of HCWs' depressive symptoms and the importance of psychosocial support during unexpected major outbreaks in healthcare facilities.

To ensure human resource availability for a smooth response during various types of disasters, there is a need to improve the intent of those involved in responding to each hazard type. However, Disaster Medical Assistance Team personnel's intent to engage with specific hazards has yet to be clarified. This study therefore aimed to clarify the factors affecting Disaster Medical Assistance Team members' ( n = 178) intent to engage with each type of hazard through an anonymous web questionnaire survey containing 20 questions. Our results show that the intent to engage in disaster response activities was significantly lower for chemical (50), biological (47), radiological/nuclear (58), and explosive (52) incidents compared with natural (82) and man-made hazards (82) ( p < 0.01). Multiple regression analysis showed that incentives were the most common factor affecting responders' intent to engage with all hazard types, followed by self-confidence. Thus, creating a system that provides generous incentives could effectively improve disaster responders' intent to engage with specific hazards. Another approach could be education and training to increase disaster responders' confidence. We believe that the successful implementation of these measures would improve the intent of responders to engage with hazards and promote the recruitment of sufficient human resources.

Chemokines and cytokines in the tumor microenvironment influence immune cell infiltration and activation. To elucidate their role in immune cell recruitment during oral cancer development, we generated a mouse tongue cancer model using the carcinogen 4-nitroquinoline 1-oxide (4NQO) and investigated the carcinogenetic process and chemokine/cytokine gene expression kinetics in the mouse tongue. C57/BL6 mice were administered 4NQO in drinking water, after which tongues were dissected at 16 and 28 weeks and subjected to analysis using the RT 2 Profiler PCR Array, qRT-PCR, and pathologic and immunohistochemical analyses. We found that Th1-associated chemokine/cytokine ( Cxcl9 , Cxcl10 , Ccl5 , and Ifng ) and Treg-associated chemokine/cytokine ( Ccl17 , Ccl22 , and Il10 ) mRNA levels were simultaneously increased in premalignant lesions of 4NQO-treated mice at 16 weeks. Additionally, although levels of Gata3 , a Th2 marker, were not upregulated, those of Cxcr3 , Ccr4 , and Foxp3 were upregulated in the tongue tissue. Furthermore, immunohistochemical analysis confirmed the infiltration of CD4 + , CD8 + , and Foxp3 + cells in the tongue tissue of 4NQO-treated mice, as well as significant correlations between Th1- or Treg-associated chemokine/cytokine mRNA expression and T cell infiltration. These results indicate that CD4 + , CD8 + , and Foxp3 + cells were simultaneously recruited through the expression of Th1- and Treg-associated chemokines in premalignant lesions of 4NQO-induced mouse tongue tissue.

Simple Summary: Nuclear receptors (NRs) and specificity protein (Sp) transcription factors (TFs) play major roles in carcinogenesis through their regulation of procarcinogenic pathways and genes. This review summarizes an important sub-set of genes coregulated by NR/Sp in cancer cells and is focused on the mechanisms of these responses that involve NR acting as a ligand-dependent cofactor of DNA-bound Sp TFs. In addition, several NR-regulated genes involve both NRs and Sp TFs bound to GC-rich Sp binding sites that can be proximal or distal and this includes interactions with other nuclear cofactors and the basal transcriptional machinery. The human nuclear receptor (NR) superfamily consists of 48 genes that are ligand-activated transcription factors that play a key role in maintaining cellular homeostasis and in pathophysiology. NRs are important drug targets for both cancer and non-cancer endpoints as ligands for these receptors can act as agonists, antagonists or inverse agonists to modulate gene expression. With two exceptions, the classical mechanism of action of NRs involves their interactions as monomers, dimers or heterodimers with their cognate response elements (cis-elements) in target gene promoters. Several studies showed that a number of NR-regulated genes did not directly bind their corresponding cis-elements and promoter analysis identified that NR-responsive gene promoters contained GC-rich sequences that bind specificity protein 1 (Sp1), Sp3 and Sp4 transcription factors (TFs). This review is focused on identifying an important sub-set of Sp-regulated genes that are indirectly coregulated through interactions with NRs. Subsequent studies showed that many NRs directly bind Sp1 (or Sp3 and Sp4), the NR/Sp complexes bind GC-rich sites to regulate gene expression and the NR acts as a ligand-modulated nuclear cofactor. In addition, several reports show that NR-responsive genes contain cis-elements that bind both Sp TFs and NRs, and mutation of either cis-element results in loss of NR-responsive (inducible and/or basal). Regulation of these genes involves interactions between DNA-bound Sp TFs with proximal or distal DNA-bound NRs, and, in some cases, other nuclear cofactors are required for gene expression. Thus, many NR-responsive genes are regulated by NR/Sp complexes, and these genes can be targeted by ligands that target NRs and also by drugs that induce degradation of Sp1, Sp3 and Sp4. [ABSTRACT FROM AUTHOR]

Background: Polysaccharides produced by the edible fungus Cordyceps cicadae can regulate blood sugar levels and may represent a suitable candidate for the treatment of diabetes and its complications. However, there is limited information available about the mechanism of how C. cicadae polysaccharide (CCP) might improve diabetic conditions. Methods: This study investigated its effects on the intestinal microbiota, intestinal mucosal barrier, and inflammation in mice with type 2 diabetes mellitus (T2DM) induced by streptozotocin, and its potential mechanisms. Results: Compared with the DC (diabetes model control group), CCPH oral treatment significantly increased the number of beneficial bifidobacteria, bifidobacteria, and lactobacilli (p < 0.01), restored the diversity of intestinal microorganisms in diabetic mice, and the proportions of Firmicutes and Bacteroidetes (34.36%/54.65%) were significantly lower than those of the DC (52.15%/32.09%). Moreover, CCPH significantly reduced the content of endotoxin (lipopolysaccharide, LPS) and D-lactic acid(D-LA) (p < 0.05), the activities of antioxidant enzymes and total antioxidant capacity were significantly increased (p < 0.01), and the content of proinflammatory cytokines TNF-α, IL-6, and IL-1β were reduced by 42.05%, 51.28%, and 52.79%, respectively, compared with the DC. The TLR4/NF-κB signaling pathway, as a therapeutic target for diabetic intestinal diseases, plays a role in regulating the inflammatory response and protecting the intestinal barrier function. Molecular mechanism studies showed that oral treatment with CCPH down-regulated the expression of NF-κB, TLR-4, and TNF-α genes by 18.66%, 21.58%, and 34.87%, respectively, while up-regulating the expression of ZO-1 and occludin genes by 32.70% and 25.11%, respectively. CCPH regulates the expression of short-chain fatty acid levels, increases microbial diversity, and ameliorates mouse colon lesions by inhibiting the TLR4/NF-κB signaling pathway. Conclusions: In conclusion, it is demonstrated that in this murine model, the treatment of diabetes with C. cicadae polysaccharide can effectively regulate intestinal microbiota imbalance, protect intestinal mucosal barrier function, and reduce inflammation in vivo, suggesting this natural product can provide a suitable strategy for the treatment of T2D-induced gut dysbiosis and intestinal health. [ABSTRACT FROM AUTHOR]

The claustrum is a small but densely interconnected brain structure that is innervated by axons containing serotonin (5-HT), a neuromodulator that has been implicated in control of sleep and in the actions of psychedelic drugs. However, little is known about how 5-HT influences the claustrum. We have combined whole-cell patch-clamp measurements of ionic currents, flash photolysis, and receptor pharmacology to characterize the 5-HT responses of individual claustral projection neurons (PNs) in mouse brain slices. Serotonin application elicited a long-lasting outward current in claustral PNs. This current was due to an increase in membrane permeability to K+ ions and was mediated mainly by the type 1A 5-HT receptor (5-HTR-1A). The 5-HT-induced K+ current hyperpolarized, and thereby inhibited, the PNs by reducing action potential firing. Focal uncaging of 5-HT revealed that inhibitory 5-HTR-1As were located at both the soma and dendrites of PNs. We conclude that 5-HT creates a net inhibition in the claustrum, an action that should decrease claustrum sensitivity to excitatory input from other brain areas and thereby contribute to 5-HT action in the brain. [ABSTRACT FROM AUTHOR]

ABS plastic is an inexpensive material with attractive physical and chemical properties. Unfortunately, it is susceptible to degradation under UV radiation, so it limits the use of this material outdoors. In this paper, we demonstrate a low-cost approach to reduce the photodegradation of ABS plastic by using additives of kraft lignin and dioxane lignin as UV absorbers. Lignin is an abundant plant polymer, which is a waste product of the pulp and paper industry. Non-regular structure of lignin hampers its use in industry. However, there is possible use of lignin as an addition to enhance the properties of resulting materials. In this study, we obtained composites of ABS and lignin with the hot extrusion method. Adding up to 15% of lignin to ABS plastic does not have a significant negative impact on tensile properties. We irradiated the resulting composites with UV and studied the UV effects on their mechanical properties and chemical structure. Oxidative degradation was characterized by FTIR and 2D NMR methods. The results showed that small lignin additions reduced the photodegradation of ABS. The previously undescribed product of the degradation of the obtained composites was detected with the use of the set of 2D NMR spectra of the composites. We proposed a scheme for the formation of this photodegradation product based on the obtained data. [ABSTRACT FROM AUTHOR]

The shortage of fresh water resources and soil salinization restrict the sustainable development of oasis agriculture in Xinjiang, China. Magnetically treated brackish water can physically improve the quality of water used for irrigation, and this technology is being gradually applied in agricultural production. However, the infiltration characteristics of magnetized brackish water and its response to the distribution of soil water and salt are still unknown. We conducted infiltration tests using a one-dimensional soil column system, employing magnetized water at concentrations of 0.2, 1, 3, and 5 g·L⁻1, with a magnetization strength of 3000 gauss (GS), and explored the effects of salinity of magnetized water on water–salt transport and infiltration characteristics of soil under drip irrigation. The migration rate of the wetting front of magnetized water infiltration slowed, and the cumulative infiltration content increased. Specifically, compared to the unmagnetized control, the infiltration time at a depth of 40 cm for magnetized water concentrations of 0.2, 1, 3, and 5 g·L−1 increased by 17.42%, 42.16%, 47.02%, and 39.19%, respectively. Correspondingly, the cumulative infiltration volume increased by 7.88%, 8.09%, 10.60%, and 5.38%. Further, the infiltration of magnetized brackish water increased the water retention capacity of soil, effectively reduced the salt content of soil layers, and had a remarkable desalting effect. Salinity of the soil profile showed an L-shaped trend of salt accumulation in the lower layer and desalting in the upper layer. For water salinity of 3 g·L−1, soil desalting intensity was greatest. In addition, K S h f , suction rate, empirical coefficient a, initial infiltration rate, and stable infiltration rate all decreased under magnetization treatment with the same salinity. Thus, this study provides a new way to alleviate the shortage of fresh water resources in arid areas, a guideline for safely using brackish water and also increasing productivity of saline–alkali land. [ABSTRACT FROM AUTHOR]

Panfacial fractures are complex fractures involving multiple regions of the facial skeleton and may require multiple surgeries over a relatively short period. They are often associated with polytrauma and other injuries including neurotrauma, which require either immediate (ATLS) airway management, prolonged intubation, or repeated intubations for staged surgeries. The choice of airway for the surgical management of these fractures is difficult, as an assessment of the occlusion is required, and the central nasal complex and/or skull base may be involved, making classical orotracheal or nasotracheal intubation problematic. Submental intubation is increasingly reported as a method of airway management with the aim of avoiding a tracheostomy and its related complications. A review of the different techniques of airway management in the elective treatment of panfacial fractures was performed, focusing on the pros and cons of each method. Most articles were retrospective studies, with only one prospective study comparing submental intubation to tracheostomy in panfacial fractures. An algorithm for the management of the airway in panfacial fractures was presented, based on a sequential assessment of the existing airway, the surgical access required, and the need for prolonged or repeated intubation. Front of neck access, orotracheal and nasotracheal intubation, and submental intubation are all appropriate techniques in different circumstances, and the advantages and disadvantages of each are presented. [ABSTRACT FROM AUTHOR]

Featured Application: Automated Demand Response, Home Energy Management System, Demand Control. This research focuses on developing a low-cost automated demand response controller (DRC) with OpenADR 2.0a capability to enable existing infrared-controlled (IR-controlled) air conditioners (ACs) in homes and buildings to participate in automated demand response programs (ADRPs). The DRC consists of four modules: a smart socket module, an infrared module, a temperature sensor, and a voltage/current module. It can receive, analyze, and respond to demand response (DR) events and perform necessary demand and energy control strategies via IR. Power line communication (PLC) is used for communication without additional wiring. The system is tested under two conditions: participating in ADRPs via OpenADR and not participating in ADRPs. An 8.8% load reduction is observed with different temperature settings when not participating in ADRPs, and energy reductions of 21% to 46% are achieved using various cooling/fanning duty cycles in ADRPs. The proposed system can be integrated with any DR algorithm to meet demand management requirements under the OpenADR program, contributing to significant demand reductions. [ABSTRACT FROM AUTHOR]

The importance of studying the role of volatiles in flammability is well recognized, but the relationship between specific compounds and components of flammability is underestimated. In this study, volatiles emitted from Picea omorika (Pančić) Purk. needles were identified and quantified, and the relationship between volatile emission and moisture content, flammability characteristics and bioclimatic coefficients was investigated. Fresh needles from four different forest communities were analyzed for specific volatile organic compounds (using a gas chromatography-surface acoustic wave analyzer, GC-SAW), moisture content (based on fresh and oven-dried mass), and flammability components (using an epiradiator). Five monoterpenes, one sesquiterpene, and one alcohol were identified and their amounts, moisture content, and flammability components differed between the populations. The amounts of myrcene and β-pinene correlated significantly with moisture content and time to ignition. Myrcene content also correlated with flame duration, site altitude, mean annual temperature, variation in mean annual temperature, and the Ellenberg quotient. The emission of myrcene correlates with ecophysiological, flammability, topographic, and climatic variables. This suggests that myrcene-rich plant species may be of particular interest for research into flammability, especially from the point of view of rapid ignition. [ABSTRACT FROM AUTHOR]

Agunmu (ground herbal medicine) is a form of West African traditional medicine consisting of a cocktail of herbs. The goal of this study is to evaluate a formulation of Agunmu made from M. indica, A. repens, E. chlorantha, A. boonei, and B. ferruginea, sold in the open market and commonly used for the treatment of malaria by the locals, for its antimalarial effects and to determine the active principles that may contribute to the antimalarial effect. The ethanolic extract obtained from this formulation (Ag-Iba) was analyzed, using TLC, LC-MS, and Tandem-MS techniques, to determine its phytochemical properties. The extract was tested in vitro against representative bacteria strains, cancer and normal human cell lines, and susceptible (D6) and resistant (W2) Plasmodium falciparum. In subsequent in vivo experiments, graded doses of the extract were used to treat mice infected with chloroquine-susceptible (NK-65) and chloroquine-resistant (ANKA) strains of Plasmodium berghei. Bacteria growth was monitored with a disc diffusion assay, cancer cell viability was determined with MTS assay, and percentage parasitemia and parasite clearance were determined by microscopy. Bound heme content, host mitochondria permeability transition (mPT) pore opening, F0F1-ATPase, and lipid peroxidation were determined via spectrophotometry. Indices of oxidative stress, anti-oxidant activities, toxicity, cell death, and inflammatory responses were obtained using biochemical and ELISA techniques. The histology of the liver and spleen was performed using the standard method. We elucidated the structures of the critical active principles in the extract to be flavonoids: kaempferol, quercetin, myricetin, and their glycosides with little or no detectable levels of the toxic Aristolochic acids that are found in Aristolochia repens, one of the components of the formulation. The extract also showed anti-plasmodial activity in in vitro and in vivo models. Furthermore, the extract dose-dependently decreased mitochondrial dysfunction, cell death, and inflammatory and oxidative damage but increased antioxidant potentials. Presumably, the active principles in the extract work as a combinatorial therapy to elicit potent antimalarial activity. Overall, our study unraveled the active components from a commercial herbal formulation that could be reformulated for antimalarial therapy. [ABSTRACT FROM AUTHOR]

Recombinant aequorin has been extensively used in mammalian and plant systems as a powerful tool for calcium monitoring. While aequorin has also been widely applied in yeast research, a notable gap exists in the literature regarding comprehensive reviews of these applications. This review aims to address that gap by providing an overview of how aequorin has been used to explore calcium homeostasis, signaling pathways, and responses to stressors, heavy metals, and toxic compounds in Saccharomyces cerevisiae. We also discuss strategies for further developing the aequorin system in yeast, with particular emphasis on its use as a model for human calcium signaling studies, such as the reproduction of the mitochondrial calcium uniporter. By highlighting previous research and pinpointing potential future applications, we discuss the untapped potential of aequorin in yeast for drug screening, environmental toxicity testing, and disease-related studies. [ABSTRACT FROM AUTHOR]

Background: Biofilm-associated infections frequently span multiple body sites and represent a significant clinical challenge, often requiring a multidisciplinary approach involving surgery and antimicrobial therapy. These infections are commonly healthcare-associated and frequently related to internal or external medical devices. The formation of biofilms complicates treatment, as they create environments that are difficult for most antimicrobial agents to penetrate. Fluoroquinolones play a critical role in the eradication of biofilm-related infections. Numerous studies have investigated the synergistic potential of combining fluoroquinolones with other chemical agents to augment their efficacy while minimizing potential toxicity. Comparative research suggests that the antibiofilm activity of fluoroquinolones is superior to that of beta-lactams and glycopeptides. However, their activity remains less effective than that of minocycline and fosfomycin. Noteworthy combinations include fluoroquinolones with fosfomycin and aminoglycosides for enhanced activity against Gram-negative organisms and fluoroquinolones with minocycline and rifampin for more effective treatment of Gram-positive infections. Despite the limitations of fluoroquinolones due to the intrinsic characteristics of this antibiotic, they remain fundamental in this setting thanks to their bioavailability and synergisms with other drugs. Methods: A comprehensive literature search was conducted using online databases (PubMed/MEDLINE/Google Scholar) and books written by experts in microbiology and infectious diseases to identify relevant studies on fluoroquinolones and biofilm. Results: This review critically assesses the role of fluoroquinolones in managing biofilm-associated infections in various clinical settings while also exploring the potential benefits of combination therapy with these antibiotics. Conclusions: The literature predominantly consists of in vitro studies, with limited in vivo investigations. Although real world data are scarce, they are in accordance with fluoroquinolones' effectiveness in managing early biofilm-associated infections. Also, future perspectives of newer treatment options to be placed alongside fluoroquinolones are discussed. This review underscores the role of fluoroquinolones in the setting of biofilm-associated infections, providing a comprehensive guide for physicians regarding the best use of this class of antibiotics while highlighting the existing critical issues. [ABSTRACT FROM AUTHOR]

Tumor-associated macrophages (TAMs) are a major cellular component in the tumor microenvironment of many solid tumors. The functional competence of TAMs varies depending on the type of tumors and their respective microenvironments. The classically activated M1 macrophages exhibit antitumor functions, whereas the alternatively activated M2 macrophages exhibit protumor functions that contribute to tumor development and progression. Although TAMs have been detected in oral squamous cell carcinoma (OSCC), little is known about their phenotype. In the present study, we performed an immunohistochemical analysis to identify TAMs in surgically resected specimens from 50 patients with OSCC and evaluated the relationship between infiltrated TAMs and the pathological grade of OSCC. Positive staining for CD163, which has been used as a marker for M2 macrophages, was observed in OSCC specimens, and the percentages of CD163+ cells were significantly increased based on the pathological grade. CD163+ cells were detected in the tumor stroma in grade I tumors, whereas an increase in the CD163+ cells in the tumor nest was observed in higher grades of tumors. Although infiltrated CD4+ and CD8+ T cells were detected in all pathological grades of OSCC, no correlation between the infiltrated T cells and the CD163+ TAMs was observed. These results indicate that the infiltrated TAMs in OSCC have an M2 phenotype and that the M2 macrophages may participate in the development of OSCC.

Hydrochemical data were utilized in this study to elucidate the hydrogeochemical characteristics and genesis of high-arsenic groundwater in the North China Plain, employing both traditional hydrogeochemical analysis and unsupervised machine learning techniques. The findings indicate that the predominant hydrochemical types of groundwater in the study area are HCO3-Ca·Na and SO4·Cl-Na·Ca. The primary mechanism influencing groundwater chemistry has been identified as rock weathering. The unsupervised machine learning framework incorporates various methods, such as principal component analysis (PCA), non-negative matrix factorization (NMF), machine learning models (gradient boosting trees and random forests), and cluster analysis to explore the characteristics and genesis of groundwater hydrochemical types within the study area. This study demonstrated that the formation mechanism of high-arsenic groundwater results from multiple interacting factors. [ABSTRACT FROM AUTHOR]

The production of recombinant enzymes, primarily used for obtaining pure and functional target molecules, holds significant importance in modern biotechnology. This study aimed to obtain and characterize recombinant, extracellularly expressed α-amylases (Amy3500 and Amy1974), derived from B. amyloliquefaciens MDC1974 and B. subtilis MDC3500, respectively, using the pBE-S shuttle vector. Both α-amylase genes were molecularly cloned into the E. coli/B. subtilis pBE-S shuttle vector, both with (Amy1974sig and Amy3500sig) and without their signal peptides (Amy1974 and Amy3500), along with a signal peptide originating from the plasmid, and tested in flask fermentations. For recombinant Amy3500, the amylase variants resulted in similar levels of volumetric activity (700–750 U/mL). In contrast, the expression of Amy1974 nearly doubled compared to Amy1974sig with double signal peptides, reaching 2000 U/mL. SDS-PAGE estimated the molecular weight of Amy1974 α-amylase to be 54.6 kDa, which is consistent with the theoretical molecular mass calculations. However, the estimated molecular weight of Amy3500 α-amylase was significantly lower upon exiting the producer cells. Ca2⁺ ions exhibit a modest activating effect on the activities of Amy1974 and Amy3500 amylases, likely due to their tight binding to the protein scaffold. Both enzymes exhibited broad activity peaks between 45 and 70 °C, with a maximum at 65 °C. The Amy1974 and Amy3500 α-amylases demonstrated broad pH optima and pH-dependent thermostability, with optimum pH values at 6.5 and 5.8, and thermal stability peaks at pH 7.6 and 5.9, respectively. Both α-amylases displayed high relative activity against various starches, including corn amylopectin and potato amylose, while showing comparatively lower activity towards α-, β-, and γ-cyclodextrins. The Amy1974 amylase is effective in converting starch into dextrins of varying lengths, while Amy3500 primarily converts starch into glucose. These characteristics make them promising candidate enzymes for industrial applications. [ABSTRACT FROM AUTHOR]

This study investigates the isotopic composition of precipitation in Iran and its moisture sources, offering insights crucial for addressing water recharge and management in semi-arid regions. This study analyzes 150 precipitation events collected from 11 stations across Iran over multiple years. The HYSPLIT model was used to trace air mass trajectories contributing to these events. The isotopic composition of precipitation from each moisture source was examined to identify their distinct characteristics. Furthermore, the contribution of each air mass to groundwater and surface water recharge was quantified using the Simmr mixing model in R programming language, combining stable isotope data from precipitation and surface/groundwater samples. Precipitation in northern Iran is associated with low d-excess values, indicating moisture from high-latitude sources, particularly the Caspian Sea, while higher d-excess values in the west and south point to moisture mainly from the Persian Gulf and the Mediterranean Sea. Air mass trajectory analysis via the HYSPLIT model identified the dominant pathways of Continental Tropical (CT), Continental Polar (CP), and Mediterranean (MedT) air masses across Iran. Quantitative analysis using the Simmr mixing model revealed that the CT air mass contributes up to 33.6% to groundwater recharge in southern Iran's karstic regions, while the CP air mass dominates in the north, with up to 46.8% contribution. The MedT air mass, although significant in the west, decreases in influence towards the east. Isotope data from groundwater and surface water sites showed more depleted values than local precipitation, likely due to larger catchment areas. These findings contribute to water management strategies by identifying the variations in moisture sources that influence groundwater and surface water recharge in Iran. Understanding these variations enables the development of targeted strategies for managing water resources in semi-arid regions facing increasing water scarcity. The methodologies applied in this study can be adapted to other regions, providing a valuable framework for sustainable water management in areas where identifying moisture sources is critical. [ABSTRACT FROM AUTHOR]

Mycoplasma bovis (M. bovis) is capable of causing pneumonia, arthritis, mastitis, and various other ailments in cattle of all age groups, posing a significant threat to the healthy progression of the worldwide cattle industry. The invasion of non-phagocytic host cells serves as a pivotal mechanism enabling M. bovis to evade the immune system and penetrate mucosal barriers, thereby promoting its spread. To investigate the differences in M. bovis invasion into four types of non-phagocytic cells (Madin–Darby bovine kidney (MDBK) cells, embryonic bovine lung (EBL) cells, bovine embryo tracheal (EBTr) cells and bovine turbinate (BT) cells) and further elucidate its invasion mechanism, this study first optimized the experimental methods for M. bovis invasion into cells. Utilizing laser scanning confocal microscopy, transmission electron microscopy, and high-content live-cell imaging systems, the invasion process of M. bovis into four types of non-phagocytic cells was observed. The invasion rates of three different strains of M. bovis (PG45, 07801, 08M) were quantified through the plate counting method. In order to clarify the specific pathway of M. bovis invasion into cells, chlorpromazine (CPZ), amiloride (AMI), and methyl-β-cyclodextrin (M-β-CD) were used to inhibit CLR-mediated clathrin-dependent endocytosis (CDE) pathway, macropinocytosis, and lipid raft pathway, respectively. Subsequently, the invasion rates of PG45 into these four types of cells were measured. Using siRNA technology, the expression of clathrin (CLR) in EBL cells was knocked down to further verify the role of CLR in the invasion process of M. bovis. The results showed that the optimal conditions for M. bovis to invade non-phagocytic cells were a multiplicity of infection (MOI) of 1000 and an optimal invasion time of 4 h. All three strains of M. bovis have the ability to invade the four types of non-phagocytic cells, yet their invasion abilities vary significantly. Observations from transmission electron microscopy further confirmed that at 120 min post-infection, PG45 had successfully invaded EBL cells and was present within endocytic vesicles. It is noteworthy that almost all PG45 successfully escaped from the endocytic vesicles after 240 min of infection had passed. Through chemical inhibition experiments and CLR protein knockdown experiments, it was found that when the CDE and lipid raft pathways were blocked or CLR protein expression was reduced, the invasion rates of PG45, 07801, and 08M in MDBK, EBL, EBTr, and BT cells were significantly decreased (p < 0.05). The above results indicate that M. bovis can invade all types of non-phagocytic cells through endocytic pathways involving CDE (clathrin-dependent endocytosis) or lipid raft-mediated endocytosis, and possesses the ability to escape from phagosomes. [ABSTRACT FROM AUTHOR]

Earthquake forecasting is arguably one of the most challenging tasks in Earth sciences owing to the high complexity of the earthquake process. Over the past 40 years, there has been a plethora of work on finding credible, consistent and accurate earthquake precursors. This paper is a cumulative survey on earthquake precursor research, arranged into two broad categories: electromagnetic precursors and radon precursors. In the first category, methods related to measuring electromagnetic radiation in a wide frequency range, i.e., from a few Hz to several MHz, are presented. Precursors based on optical and radar imaging acquired by spaceborne sensors are also considered, in the broad sense, as electromagnetic. In the second category, concentration measurements of radon gas found in soil and air, or even in ground water after being dissolved, form the basis of radon activity precursors. Well-established mathematical techniques for analysing data derived from electromagnetic radiation and radon concentration measurements are also described with an emphasis on fractal methods. Finally, physical models of earthquake generation and propagation aiming at interpreting the foundation of the aforementioned seismic precursors, are investigated. [ABSTRACT FROM AUTHOR]

In recent decades, the risk of developing opportunistic infections has increased in parallel with the ever-increasing number of people suffering from chronic immunosuppressive diseases or undergoing prosthetic surgery. Staphylococcus warneri is a Gram-positive and coagulase-negative bacterium. Usually found as a component of the healthy human and animal microbiota of the skin and mucosae, it can take on the role of an opportunistic pathogen capable of causing a variety of infections, ranging from mild to life-threatening, not only in immunocompromised patients but even, although rarely, in healthy people. Here, in addition to a concise discussion of the identification and distinguishing features of S. warneri compared to other staphylococcal species, a systematic overview of the findings from case reports and clinical studies is provided. The paper highlights the virulence and antibiotic resistance profiles of S. warneri, the different clinical contexts in which it has proven to be a serious pathogen, emphasizing its ability to colonize artificial prosthetic materials and its tropism for musculoskeletal and cardiovascular tissues. Some original data on orthopedic implant infections by S. warneri complement the discussion. Finally, from a different perspective, the paper addresses the possibilities of industrial exploitation of this bacterium. [ABSTRACT FROM AUTHOR]

Extraction of lipids and high-value products from highly wet microalgae requires significant energy for the drying pretreatment. In this study, we examined the direct extraction of lipids, β-carotene, and polyphenolic compounds from wet Dunaliella salina using liquefied dimethyl ether (DME), which is effective in lipid extraction for biofuel production. The amount of DME-extracted β-carotene was 7.0 mg/g, which was higher than that obtained from the chloroform–methanol extraction. Moreover, the total phenolic content extracted with DME and its antioxidant capacity were slightly higher than those extracted with chloroform–methanol. DME removed almost all the water and extracted 29.2 wt% of total lipids and 9.7 wt% of fatty acids. More lipids were extracted from wet samples by liquefied DME than by chloroform–methanol extraction. The C/N ratio of lipids extracted with DME was 112.0, higher than that of chloroform–methanol. The high C/N ratio suggests that nitrogen-containing phosphatidylcholines may be less easily extracted by liquefied DME and may be highly selective. However, the ratio of saturated fatty acids was 34.8%, lower than that of chloroform–methanol. Na+ and Mg2+ in the culture medium were not extracted using DME. Thus, using the extract with DME has both advantages and disadvantages compared to using the extract with chloroform–methanol; however, it has satisfactory extraction properties. DME is expected to be an environment-friendly alternative solvent because it does not require drying, which is necessary for conventional extraction solvents. [ABSTRACT FROM AUTHOR]

Due to a heavy reliance on groundwater, Bangladesh is experiencing a severe decline in groundwater storage, with some areas even facing land subsidence. This study aims to investigate the relationship between groundwater storage changes and land subsidence in Bangladesh, utilizing a combination of GRACE and InSAR technologies. To clarify this relationship from a macro perspective, the study employs GRACE data merged with GLDAS to analyze changes in groundwater storage and SBAS-InSAR technology to assess land subsidence. The Dynamic Time Warping (DTW) method calculates the similarity between groundwater storage and land subsidence time series, incorporating precipitation and land cover types into the data analysis. The findings reveal the following: (1) Groundwater storage in Bangladesh is declining at an average rate of −5.55 mm/year, with the most significant declines occurring in Rangpur, Mymensingh, and Rajshahi. Notably, subsidence areas closely match regions with deeper groundwater levels; (2) The similarity coefficient between the time series of groundwater storage and land subsidence changes exceeds 0.85. Additionally, land subsidence in different regions shows an average lagged response of 2 to 6 months to changes in groundwater storage. This study confirms a connection between groundwater dynamics and land subsidence in Bangladesh, providing essential knowledge and theoretical support for further research. [ABSTRACT FROM AUTHOR]

Simple Summary: With advances in radiological imaging and its increased use, small nodules are being detected more frequently. Surgical resection is often the final option for diagnosis and treatment; however, small nodules may be too small to be detected during surgery. The lungs are soft, deformable organs that can change shape during respiratory phases and surgical procedures. Thus, surgeons rely on preoperative or intraoperative markings for nodule identification and precise resection. Furthermore, two randomized clinical trials found that sublobar resection could be an alternative treatment for early-stage non-small-cell lung cancer. Therefore, the demand for preoperative or intraoperative marking techniques is increasing, particularly for wedge resection or segmentectomy. In this study, we provide a narrative review of the current status and future perspectives of preoperative and intraoperative markings in thoracic surgery. The widespread implementation of lung cancer screening and thin-slice computed tomography (CT) has led to the more frequent detection of small nodules, which are commonly referred to thoracic surgeons. Surgical resection is the final diagnostic and treatment option for such nodules; however, surgeons must perform preoperative or intraoperative markings for the identification of such nodules and their precise resection. Historically, hook-wire marking has been performed more frequently worldwide; however, lethal complications, such as air embolism, have been reported. Therefore, several surgeons have recently attempted to develop novel preoperative and intraoperative markers. For example, transbronchial markings, such as virtual-assisted lung mapping and intraoperative markings using cone-beam computed tomography, have been developed. This review explores various marking methods that have been practically applied for a better understanding of preoperative and intraoperative markings in thoracic surgery. Recently, several attempts have been made to perform intraoperative molecular imaging and dynamic virtual three-dimensional computed tomography for the localization, diagnosis, and margin assessment of small nodules. In this narrative review, the current status and future perspectives of preoperative and intraoperative markings in thoracic surgery are examined for a better understanding of these techniques. [ABSTRACT FROM AUTHOR]

Human bocavirus (HBoV) has emerged as a significant pathogen primarily associated with respiratory infections in children. This study aimed to evaluate the clinical relevance of HBoV infection by quantifying viral loads in nasopharyngeal swabs from hospitalized children with acute respiratory infections (ARIs) and investigating correlations with clinical outcomes. A total of 957 children were tested, with HBoV detected in 73 cases (7.6%), either as a sole infection or co-infection with other respiratory viruses. Quantitative polymerase chain reaction (qPCR) was employed to measure viral load, and a threshold of 104 copies/mL was used to differentiate high and low viral concentrations. Results have shown that children with lower respiratory tract infections (LRTIs) had significantly higher viral loads, most notably in cases where HBoV was the sole pathogen. Additionally, children with pre-existing health conditions were more likely to have elevated HBoV concentrations compared to those who were previously healthy. Children with higher viral loads were more likely to require oxygen supplementation and receive empirical antibiotic therapy, indicating a more severe clinical course. This study underscores the importance of considering HBoV viral load in clinical diagnostics, as higher concentrations were associated with more severe presentations, including the need for oxygen support. Future research should focus on refining diagnostic thresholds and exploring HBoV's role in co-infections to enhance patient care strategies. [ABSTRACT FROM AUTHOR]

Continuous measurements of soil moisture in the deeper parts of the unsaturated zone remain an important challenge. This study examines the development of an integrated system for the continuous and 3-D monitoring of the vadose zone processes in a cost- and energy-efficient way. This system comprises TDR, ERT and GPR geophysical techniques. Their capacities to adequately image subsurface moisture changes with continuous and time-lapse measurements are assessed during an artificial infiltration experiment conducted in a characteristic urban site with anthropogenic fills and much compaction. A 3-D array was designed for each method to expand the information of a single TDR probe and obtain a broader image of the subsurface. Custom spatial TDR probes installed in boreholes made with a percussion drilling instrument were used for soil moisture measurements. Moisture profiles along the probes were estimated with a numerical one-dimensional inversion model and a standard calibration equation. High conductivity water used during all infiltration tests led to the detection of the flow by all techniques. Preferential flow was present throughout the experiment and imaged sufficiently by all methods. Overall, the integrated approach conceals each method's weaknesses and provides a reliable 3-D view of the subsurface. The results suggest that this approach can be used to monitor the unsaturated zone at even greater depths. [ABSTRACT FROM AUTHOR]

Purpose: This integrated review aims to identify and analyze the multifactorial contributors to the longevity of direct restorations, focusing on tooth-, patient-, and dentist-related factors. Materials and Methods: A search of the literature was performed using an electronic database, PubMed/Medline, Web of Science, and Scopus, on papers published between 1980 and 2024. The titles and abstracts of papers that evaluated aspects categorized into tooth-related, patient-related, and dentist-related factors influencing restoration failure were selected and screened. Full-text assessments were conducted, and the extracted data were compiled, summarized, and synthesized. The reference lists of the collected papers were also screened, and relevant citations were included in this review. Data were gathered from clinical and laboratorial studies, systematic reviews, and meta-analyses to provide a comprehensive understanding of restoration longevity. Results: Among the tooth-related factors, multiple-surface restorations, deep margins, tooth location, and tooth vitality significantly impact restoration survival. Patient-related factors such as medical conditions, risk predictors of caries, age, sex, parafunctional habits, smoking, periodontal health, number of restorations, and socioeconomic status all play crucial roles. Regarding dentist-related factors, the decision-making process, age, experience, and dentist manual dexterity are vital aspects. Furthermore, the technique used, including isolation methods for moisture control, as well as the type of dental practice (large group vs. small practice), notably influenced the restoration survival. Conclusions: The longevity of dental restorations is influenced by a complex interplay of tooth-related, patient-related, and dentist-related factors. Strategies to improve restoration outcomes should consider all these multifactorial contributors. Continuing professional education, diligent patient guidance on the factors that influence restoration survival, careful material selection and restorative technique, and tailored individual treatment are crucial factors to reduce failure rates and improve the lifespan of restorations. [ABSTRACT FROM AUTHOR]

Brazil, despite possessing the largest renewable freshwater reserves in the world (8.65 trillion m3 annually), faces growing challenges in water management due to increasing demand. Agriculture, responsible for 68.4% of water consumption, is one of the main drivers of this demand, especially in the São Francisco River Basin, where irrigation accounts for 81% of total water withdrawals. Water bodies play a crucial role in sustaining ecosystems and supporting life, particularly along the East-West axis of Alagoas, a water-rich region in the ENEB. This study aimed to map and quantify the spatiotemporal variations of water bodies in the ENEB region and assess the impacts of human activities using MODIS satellite data, applying hydrological indices such as NDWI, MNDWI, and AWEI. Between 2003 and 2022, significant variations in the extent of water bodies were observed, with reductions of up to 100 km2 during dry periods and expansions of up to 300 km2 during wet seasons compared to dry periods. AWEI and MNDWI proved to be the most effective indices for detecting water bodies with MODIS data, providing accurate insights into water dynamics. Additionally, the MapBiomas Rios dataset, despite being resampled from a 30 m to a 500 m resolution, offered the most accurate representation of water bodies due to its methodology for data acquisition. Changes in albedo and surface temperature were also detected, highlighting the influence of climate change on the region's water resources. These findings are crucial for guiding the sustainable management of water resources, not only in Alagoas but also in other regions of Brazil and similar semi-arid areas around the world. The study demonstrates the hydrological variability in the state of Alagoas, indicating the need for adaptive strategies to mitigate the impacts of climate change and anthropogenic pressures, supporting the need for informed decision-making in water resource management at both local and national levels. [ABSTRACT FROM AUTHOR]

Simple Summary: Birds are highly exposed to pathogens leading to high risk of low egg production, high mortality rates and high costs of veterinary care. Moreover, the intense breeding of avian species for desirable production traits causes immunosuppressive stress. Therefore, line selection requires thorough knowledge not only of genetics but also of the immunology of poultry. The function of secondary (peripheral) lymphoid organs is to activate the immune response through the accumulation of antigens for the activation of naive B and T cells. This review aims to present the morphological characterization of chickens' secondary immune organs along with the latest and more outstanding scientific discoveries and their relevance not only in veterinary medicine but also in human medicine. The authors hope that this review will represent a useful source of information for the design of future experiments with animal models in terms of more tailored protocols and heightened awareness. Recent discoveries have indicated the importance of developing modern strategies for vaccinations, more ethical research models, and effective alternatives to antibiotic treatment in farm animals. Chickens (Gallus gallus) play a crucial role in this context given the commercial and economic relevance of poultry production worldwide and the search for analogies between the immune systems of humans and birds. Specifically, chicken secondary lymphoid tissues share similar features to their human counterparts. Chickens have several secondary or peripheral lymphoid tissues that are the sites where the adaptive immune response is initiated. The more general classification of these organs divides them into the spleen and skin-, pineal-, or mucosa-associated lymphoid tissues. Each of these tissues is further subdivided into separate lymphoid structures that perform specific and different functions along the animal's body. A review summarizing the state of the art of research on chicken secondary lymphoid organs is of great relevance for the design of future studies. [ABSTRACT FROM AUTHOR]

Fish retinal ganglion cells (RGCs) can regenerate after optic nerve lesions (ONLs). We previously reported that heat shock factor 1 (HSF1) and Yamanaka factors increased in the zebrafish retina 0.5–24 h after ONLs, and they led to cell survival and the transformation of neuro-stem cells. We also showed that retinoic acid (RA) signaling and transglutaminase 2 (TG2) were activated in the fish retina, performing neurite outgrowth 5–30 days after ONLs. In this study, we found that RA signaling and TG2 increased within 0.5 h in the zebrafish retina after ONLs. We examined their interaction with the TG2-specific morpholino and inhibitor due to the significantly close initiation time of TG2 and HSF1. The inhibition of TG2 led to the complete suppression of HSF1 expression. Furthermore, the results of a ChIP assay with an anti-TG2 antibody evidenced significant anti-TG2 immunoprecipitation of HSF1 genome DNA after ONLs. The inhibition of TG2 also suppressed Yamanaka factors' gene expression. This rapid increase in TG2 expression occurred 30 min after the ONLs, and RA signaling occurred 15 min before this change. The present study demonstrates that TG2 regulates Yamanaka factors via HSF1 signals in the acute phase of fish optic nerve regeneration. [ABSTRACT FROM AUTHOR]

During gliotoxin biosynthesis in fungi, the cytochrome P450 GliF enzyme catalyzes an unusual C–N ring-closure step while also an aromatic ring is hydroxylated in the same reaction cycle, which may have relevance to drug synthesis reactions in biotechnology. However, as the details of the reaction mechanism are still controversial, no applications have been developed yet. To resolve the mechanism of gliotoxin biosynthesis and gain insight into the steps leading to ring-closure, we ran a combination of molecular dynamics and density functional theory calculations on the structure and reactivity of P450 GliF and tested a range of possible reaction mechanisms, pathways and models. The calculations show that, rather than hydrogen atom transfer from the substrate to Compound I, an initial proton transfer transition state is followed by a fast electron transfer en route to the radical intermediate, and hence a non-synchronous hydrogen atom abstraction takes place. The radical intermediate then reacts by OH rebound to the aromatic ring to form a biradical in the substrate that, through ring-closure between the radical centers, gives gliotoxin products. Interestingly, the structure and energetics of the reaction mechanisms appear little affected by the addition of polar groups to the model and hence we predict that the reaction can be catalyzed by other P450 isozymes that also bind the same substrate. Alternative pathways, such as a pathway starting with an electrophilic attack on the arene to form an epoxide, are high in energy and are ruled out. [ABSTRACT FROM AUTHOR]

Oral cancer (OC) presents a significant global health burden with rising incidence rates. Despite advancements in diagnosis and treatments, the survival rate for OC patients, particularly those with advanced or recurrent disease, remains low at approximately 20%. This poor prognosis is often due to a small population of cancer stem cells (CSCs) that are capable of self-renewal and immune evasion, playing pivotal roles in proliferation, tumor initiation, progression, metastasis, and therapy resistance. Exosomes, which are nano-sized extracellular vesicles (EVs), have emerged as crucial mediators of cell-to-cell communication within the tumor microenvironment (TME). These vesicles carry diverse molecules such as DNA, RNA, proteins, lipids, and metabolites, influencing various cellular processes. Emerging evidence suggests that CSC-derived EVs significantly promote tumor progression and metastasis and maintain the balance between CSCs and non-CSCs, which is vital for intracellular communication within the TME of oral cancer. Recent reports indicate that oral cancer stem cell-derived EVs (OCSC-EVs) influence stemness, immune evasion, metastasis, angiogenesis, tumor reoccurrence, and drug resistance. Understanding OCSC-EVs could significantly improve oral cancer diagnosis, prognosis, and therapy. In this mini-review, we explore OCSC-derived exosomes in oral cancer, examining their potential as diagnostic and prognostic biomarkers that reflect CSC characteristics, and delve into their therapeutic implications, emphasizing their roles in tumor progression and therapy resistance. However, despite their promising potential, several challenges remain, including the need to standardize isolation and characterization methods and to elucidate exosome-mediated mechanisms. Thus, a comprehensive understanding of OCSC-EVs could pave the way for innovative therapeutic strategies that have the potential to improve clinical outcomes for OC patients. [ABSTRACT FROM AUTHOR]

Parasitic diseases, such as malaria, are an immense burden to many low- and middle-income countries. In 2022, 249 million cases and 608,000 deaths were reported by the World Health Organization for malaria alone. Climate change, conflict, humanitarian crises, resource constraints and diverse biological challenges threaten progress in the elimination of malaria. Undeniably, the lack of a commercialized vaccine and the spread of drug-resistant parasites beg the need for novel approaches to treat this infectious disease. Most approaches for the development of antimalarials to date take inspiration from tropical or sub-tropical environments; however, it is necessary to expand our search. In this review, we highlight the origin of antimalarial treatments and propose new insights in the search for developing novel antiparasitic treatments. Plants and microorganisms living in harsh and cold environments, such as those found in the largely unexploited Northern Canadian boreal forest, often demonstrate interesting properties that are not found in other environments. Most prominently, the essential oil of Rhododendron tomentosum spp. Subarcticum from Nunavik and mortiamides isolated from Mortierella species found in Nunavut have shown promising activity against Plasmodium falciparum. [ABSTRACT FROM AUTHOR]

Elucidation of pathways regulating parasite cell death is believed to contribute to identification of novel therapeutic targets for protozoan diseases, and in this context, apoptosis-like cell death has been reported in different groups of protozoa, in which metacaspases seem to play a role. In the genus Plasmodium, apoptotic markers have been detected in P. falciparum and P. berghei, and no study focusing on P. vivax cell death has been reported so far. In the present study, we investigated the susceptibility of P. vivax to undergo apoptotic cell death after incubating mature trophozoites with the classical apoptosis inducer staurosporine. As assessed by flow cytometry assays, staurosporine inhibited parasite intraerythrocytic development, which was accompanied by a decrease in cell viability, evidenced by reduced plasmodial mitochondrial activity. However, typical signs of apoptosis, such as DNA fragmentation, chromatin condensation, and nuclear segregation, were not detected in the parasites induced to cell death, and no significant alteration in metacaspase gene expression (PvMCA1) was observed under cell death stimulus. Interestingly, dying parasites positively modulated cell death (eryptosis) of host erythrocytes, which was marked by externalization of phosphatidylserine and cell shrinkage. Our study shows for the time that P. vivax blood stages may not be susceptible to apoptosis-like processes, while they could trigger eryptosis of parasitized cells by undergoing cell death. Further studies are required to elucidate the cellular machinery involved in cell death of P. vivax parasites as well as in the modulation of host cell death. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVDs) are one of the main causes of mortality and morbidity worldwide. A healthy diet rich in plant-derived compounds such as (poly)phenols appears to have a key role in improving cardiovascular health. Flavan-3-ols represent a subclass of (poly)phenols of great interest for their possible health benefits. In this review, we summarized the results of clinical studies on vascular outcomes of flavan-3-ol supplementation and we focused on the role of the microbiota in CVD. Clinical trials included in this review showed that supplementation with flavan-3-ols mostly derived from cocoa products significantly reduces blood pressure and improves endothelial function. Studies on catechins from green tea demonstrated better results when involving healthy individuals. From a mechanistic point of view, emerging evidence suggests that microbial metabolites may play a role in the observed effects. Their function extends beyond the previous belief of ROS scavenging activity and encompasses a direct impact on gene expression and protein function. Although flavan-3-ols appear to have effects on cardiovascular health, further studies are needed to clarify and confirm these potential benefits and the rising evidence of the potential involvement of the microbiota. [ABSTRACT FROM AUTHOR]

Nosocomial pneumonia, including hospital-acquired pneumonia and ventilator-associated pneumonia, is the leading cause of death related to hospital-acquired infections among critically ill patients. A growing proportion of these cases are attributed to multi-drug-resistant (MDR-) Gram-negative bacteria (GNB). MDR-GNB pneumonia often leads to delayed appropriate treatment, prolonged hospital stays, and increased morbidity and mortality. This issue is compounded by the increased toxicity profiles of the conventional antibiotics required to treat MDR-GNB infections. In recent years, several novel antibiotics have been licensed for the treatment of GNB nosocomial pneumonia. These novel antibiotics are promising therapeutic options for treatment of nosocomial pneumonia by MDR pathogens with certain mechanisms of resistance. Still, antibiotic resistance remains an evolving global crisis, and resistance to novel antibiotics has started emerging, making their judicious use crucial to prolong their shelf-life. This article presents an up-to-date review of these novel antibiotics and their current role in the antimicrobial armamentarium. We critically present data for the pharmacokinetics/pharmacodynamics, the in vitro spectrum of antimicrobial activity and resistance, and in vivo data for their clinical and microbiological efficacy in trials. Where possible, available data are summarized specifically in patients with nosocomial pneumonia, as this cohort may exhibit 'critical illness' physiology that affects drug efficacy. [ABSTRACT FROM AUTHOR]

Climate change may increase the vulnerability of aquifers to contamination through extreme precipitation and extended drought periods. Therefore, the understanding of groundwater ecosystem dynamics is crucial, with bacterial assemblages playing a major role in biogeochemical cycles. The present research describes a geospatial study targeting the bacterial community structure of groundwaters from the largest karst aquifer in Portugal (the Maciço Calcário Estremenho), integrating hydrogeochemical and bacterial diversity data. A total of 22 samples were analyzed from a set of 11 geographically sparsely distributed groundwater sources in dry vs. wet seasons. The 16S rRNA gene barcoding data revealed bacterial community variability across samples in space and time. The phylum Proteobacteria was dominant across all samples (from 44 to 92% of total sequence reads), mainly represented by the classes Alphaproteobacteria (orders Sphingomonadales, BD7–3, Rhizobiales and Rhodospirillales), Betaproteobacteria (orders Burkholderiales, Rhodocyclales, Nitrosomonadales), Gammaproteobacteria (orders Pseudomonadales, Xanthomonadales, Alteromonadales, Legionellales) and Deltaproteobacteria (orders Myxococcales, Spirobacillales). Variation in the bacterial community was primarily attributed to parameters such as redox conditions (DO, ORP), Fe, Mn, SO4, PO4, Sr and Cl, but also some minor and trace elements (Al, V, Cr, Cu, Pb). Our results provide novel insights into bacterial diversity in relation to groundwater hydrogeochemistry. The strong dominance of OTUs related to bacterial taxa associated with nitrification/denitrification also highlights a potentially important role of these assemblages on nutrients (nitrogen sources) and groundwater quality dynamics at this karstic aquifer system. Moreover, the integration of bacterial assemblages information is emphasized as central for water quality monitoring programs. [ABSTRACT FROM AUTHOR]

The Pesaro-Urbino province (PUP) (northern Marche, central Italy) is one of the most seismically active areas in Italy, with the most recent earthquakes (5.2 and 5.5 Mw) having occurred on 9 November 2022 with an epicenter located in the Adriatic Sea. A detailed geochemical and isotopic characterization of 87 groundwaters (and dissolved gases) circulating in the PUP was carried out to (i) unravel the geochemical processes controlling the water circulation, (ii) investigate the interplay between deep originated fluids and shallow aquifers, (iii) evaluate the reliability of specific geochemical parameters as tracers for seismic activity, and (iv) select the most suitable sampling sites to deploy a monitoring network to highlight possible compositional changes related to the regional and local tectonic activity. The geochemical dataset includes waters showing five different hydrochemical compositional facies: (i) calcium bicarbonate with low Total Dissolved Solids (TDS); (ii) calcium bicarbonate with relatively high concentrations of sulfate (>200 mg/L); (iii) sodium bicarbonate with pH > 8.8; (iv) calcium sulfate; (v) sodium chlorine. Two distinct groups of dissolved gases can be recognized: (a) N2-dominated gases with N2/Ar ratios similar to those of Air-Saturated Water (ASW); (b) CO2- and CH4-rich gases associated with high TDS and springs rich in S-bearing reduced species. The isotopic values of δ13C-CO2 and δ13C-CH4 suggest a predominant biogenic origin for both species with a negligible contribution from deep-seated fluids. The Ca-HCO3(SO4), Ca(Na)-SO4(Cl), and Na-HCO3 waters, being likely related to deep hydrological pathways, are the best candidates to be included in the monitoring network in the Pesaro-Urbino province. This will be of paramount importance in addressing the challenge of unravelling fluid geochemical precursors of earthquakes, thus increasing and improving seismic surveillance practices and hazard mitigation. [ABSTRACT FROM AUTHOR]

As the medium of geological information, groundwater provides an indirect method to solve the secondary disasters of mining activities. Identifying the groundwater regime of overburden aquifers induced by the mining disturbance is significant in mining safety and geological environment protection. This study proposes the novel data-driven algorithm based on the combination of machine learning methods and hydrochemical analyses to predict anomalous changes in groundwater levels within the mine and its neighboring areas induced after mining activities accurately. The hydrochemistry analysis reveals that the dissolution of carbonate and evaporite and the cation exchange function are the main hydrochemical process for controlling the groundwater environment. The anomalous change in the hydrochemistry characteristic in different aquifers reveals that the hydraulic connection between different aquifers is enhanced by mining activities. The continuous wavelet coherence is used to reveal the nonlinear relationship between the groundwater level change and external influencing factors. Based on the above analysis, the groundwater level, precipitation, mine water inflow, and unit goal area could be considered as the input variables of the hydrological model. Two different data-driven algorithms, the Decision Tree and the Long Short-Term Memory (LSTM) neural network, are introduced to construct the hydrological prediction model. Four error metrics (MAPE, RMSE, NSE and R2) are applied for evaluating the performance of hydrological model. For the NSE value, the predictive accuracy of the hydrological model constructed using LSTM is 8% higher than that of Decision Tree algorithm. Accurately predicting the anomalous change in groundwater level caused by the mining activities could ensure the safety of coal mining and prevent the secondary disaster of mining activities. [ABSTRACT FROM AUTHOR]

Accurately characterizing rainfall runoff processes in plain farmland, especially at the plot scale with significant micro-topographic features, has presented challenges. Integrated surface–subsurface flow models with high-precision surface flow modules are appropriate tools, yet open-source versions are rare. To address this gap, we proposed an open-source integrated surface–subsurface flow model called the FullSWOF-Plain model, in which the one-dimensional subsurface module Hydrus-1D was integrated with a modified two-dimensional surface water flow module (FullSWOF-2D) using the sequential head method. Various experimental scenarios were simulated to validate the model's performance, including two outflow cases (i.e., 1D and 2D) without infiltration, a classical one-dimensional infiltration case, and two typical rainfall events at the experimental field. The results demonstrate the accuracy of this proposed model, with the Nash–Sutcliffe efficiency (NSE) of the simulated discharge exceeding 0.90 in the experimental field case and the root mean squared error (RMSE) values for soil moisture at five depths consistently below 0.03 cm3/cm3. However, we observed a lag in the simulated response time of soil moisture due to the neglect of preferential flow. The micro-topography significantly influenced ponding time and ponding areas. Lower local terrain normally experienced earlier surface ponding. Scattered surface ponding water first occurred in the ditch and followed in the relatively low areas in the main field. The concentration process of surface runoff exhibited hierarchical characteristics, with the drainage ditch contributing the most discharge initially, followed by the connection of scattered puddles in the main field, draining excess surface water to the ditch through rills. This quantitative study sheds light on the impact of micro-topography on surface runoff in plain farmland areas. [ABSTRACT FROM AUTHOR]

Electrical resistivity tomography (ERT) has turned out to be one of the most applied and user-friendly geophysical methods in geotechnical and geoenvironmental research. ERT is an emerging technology that is becoming popular nowadays for investigating subsurface conditions. Multiple attributes of the technology using various electrode configurations significantly reduce measurement time and are suitable for applications even in hardly accessible mountain areas. It is a noninvasive test for subsurface characterization and a very sensitive method used to determine geophysical properties, i.e., structural integrity, water content, fluid composition, etc. This paper aimed to elucidate the ERT technique's main features and applications in geotechnical and geoenvironmental engineering through four case studies. The first case study investigated the possible flow paths and areas of moisture accumulation after leachate recirculation in a bioreactor landfill. The second case study attempted to determine the moisture variation along highway pavement. The third case study explored the slope failure investigation by ERT. The fourth case study demonstrated the efficiency of the ERT method in the landfill evapotranspiration (ET) cover to investigate moisture variation on a broader scale and performance monitoring. In all of the four cases, ERT exhibited promising performance. [ABSTRACT FROM AUTHOR]

Simple Summary: PD-L1 expression determines patients' eligibility for immunotherapy. Current sampling does not consider the heterogeneity of PD-L1 expression in head and neck squamous cell carcinoma (HNSCC) within the primary tumor. Moreover, potential differences are not considered when comparing primary tumors and their associated metastases or local recurrences, hereby excluding potential responders to immunotherapy. Here, we investigated the inter-sample heterogeneity of PD-L1 expression by analyzing multiple samples from individual patients. Multisection staining revealed clinically relevant CPS changes, which would have potentially affected treatment decisions in 28.7% (intra-tumoral), 44.4% (tumor vs. metastases), and 61.5% (initial tumor vs. local recurrence) of patients, respectively, compared with single-region staining. Increased CPS in primary tumors and lymph node metastases were associated with improved 5-year overall survival. Our results suggest that multiple tumor sections should be evaluated in HNSCC patients when assessing PD-L1 expression prior to potential immunotherapy, particularly if the initial result was negative. For practical reasons, in many studies PD-L1 expression is measured by combined positive score (CPS) from a single tumor sample. This does not reflect the heterogeneity of PD-L1 expression in head and neck squamous cell carcinoma (HNSCC). We investigated the extent and relevance of PD-L1 expression heterogeneity in HNSCC analyzing primary tumors and recurrences (LRs), as well as metastases. Tumor tissue from 200 HNSCC patients was immunohistochemically stained for PD-L1 and analyzed using image-analysis software QuPath v3.4 with multiple specimens per patient. CPS was ≥20 in 25.6% of primary tumors. Intra-tumoral heterogeneity led to a therapeutically relevant underestimation of PD-L1 expression in 28.7% of patients, when only one specimen per patient was analyzed. Inter-tumoral differences in PD-L1 expression between primary tumors and lymph node metastasis (LNM) or LR occurred in 44.4% and 61.5% (CPS) and in 40.6% and 50% of cases (TPS). Overall survival was increased in patients with CPS ≥ 1 vs. CPS < 1 in primary tumors and LNM (hazard ratio: 0.46 and 0.35; p < 0.005); CPS in LR was not prognostic. Our analysis shows clinically relevant intra- and inter-sample heterogeneity of PD-L1 expression in HNSCC. To account for heterogeneity and improve patient selection for immunotherapy, multiple sample analyses should be performed, particularly in patients with CPS/TPS < 1. [ABSTRACT FROM AUTHOR]

After the Fukushima nuclear power plant accident in 2011, many types of survey meters were used, including Geiger–Müller (GM) survey meters, which have long been used to measure β-rays. Recently, however, a novel radiation survey meter that uses a plastic-scintillation sensor has been developed. Although manufacturers' catalog data are available for these survey meters, there have been no user reports on performance. In addition, the performance of commercial plastic-scintillation survey meters has not been evaluated. In this study, we experimentally compared the performance of a plastic-scintillation survey meter with that of a GM survey meter. The results show that the two instruments performed very similarly in most respects. The GM survey meter exhibited count losses when the radiation count rate was high, whereas the plastic-scintillation survey meter remained accurate under such circumstances, with almost no count loss at high radiation rates. For measurements at background rates (i.e., low counting rates), the counting rates of the plastic-scintillation and GM survey meters were similar. Therefore, an advantage of plastic-scintillation survey meters is that they are less affected by count loss than GM survey meters. We conclude that the plastic-scintillation survey meter is a useful β-ray measuring/monitoring instrument. [ABSTRACT FROM AUTHOR]

Molecular chaperones are highly conserved across evolution and play a crucial role in preserving protein homeostasis. The 60 kDa heat shock protein (HSP60), also referred to as chaperonin 60 (Cpn60), resides within mitochondria and is involved in maintaining the organelle's proteome integrity and homeostasis. The HSP60 family, encompassing Cpn60, plays diverse roles in cellular processes, including protein folding, cell signaling, and managing high-temperature stress. In prokaryotes, HSP60 is well understood as a GroEL/GroES complex, which forms a double-ring cavity and aids in protein folding. In eukaryotes, HSP60 is implicated in numerous biological functions, like facilitating the folding of native proteins and influencing disease and development processes. Notably, research highlights its critical involvement in sustaining oxidative stress and preserving mitochondrial integrity. HSP60 perturbation results in the loss of the mitochondria integrity and activates apoptosis. Currently, numerous clinical investigations are in progress to explore targeting HSP60 both in vivo and in vitro across various disease models. These studies aim to enhance our comprehension of disease mechanisms and potentially harness HSP60 as a therapeutic target for various conditions, including cancer, inflammatory disorders, and neurodegenerative diseases. This review delves into the diverse functions of HSP60 in regulating proteo-homeostasis, oxidative stress, ROS, apoptosis, and its implications in diseases like cancer and neurodegeneration. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) represents the deadliest tumor among brain cancers. It is a solid tumor characterized by uncontrolled cell proliferation generating the hypoxic niches in the cancer core. By inducing the transcription of hypoxic inducible factor (HIF), hypoxia triggers many signaling cascades responsible for cancer progression and aggressiveness, including enhanced expression of vascular endothelial growth factor (VEGF) or antioxidant enzymes, such as heme oxygenase-1 (HO-1). The present work aimed to investigate the link between HO-1 expression and the hypoxic microenvironment of GBM by culturing two human glioblastoma cell lines (U87MG and A172) in the presence of a hypoxic mimetic agent, deferoxamine (DFX). By targeting hypoxia-induced HO-1, we have tested the effect of a novel acetamide-based HO-1 inhibitor (VP18/58) on GBM progression. Results have demonstrated that hypoxic conditions induced upregulation and nuclear expression of HO-1 in a cell-dependent manner related to malignant phenotype. Moreover, our data demonstrated that the HO-1 inhibitor counteracted GBM progression by modulating the HIFα/HO-1/VEGF signaling cascade in cancer cells bearing more malignant phenotypes. [ABSTRACT FROM AUTHOR]

During the 2008 financial crisis, central banks (such as the Fed) adopted a quantitative easing (QE) policy to stimulate their countries' economies and overcome severe economic and financial recessions. However, apart from stimulating the economy by issuing a substantial amount of currency to purchase long-term bonds and suppress interest rates, QE policy also contributed to a boom in the real estate and construction sectors. Therefore, this study employs data envelopment analysis to measure the business performance (BP) of construction companies, and explore the impact of QE policy on the BP of construction companies, between 2004 and 2015, using hierarchical regression. We also examine the moderating role of the debt ratio on the relationship. Focused on publicly listed construction companies in Taiwan, this research reveals three encouraging findings. Firstly, QE policy indeed enhanced the BP of Taiwanese construction companies. Secondly, performance improvements in construction companies due to QE policy show a time-diminishing trend, suggesting the importance of seizing the initial policy benefits of QE implementation. Lastly, construction companies with appropriate financial leverage may exhibit better BP. These findings can provide valuable insights for relevant government entities and decision-makers in the industry for policy and investment decisions. [ABSTRACT FROM AUTHOR]

The development of global transport infrastructure is a crucial aspect of economic growth and prosperity. In this study, the main trends in the development of global transport infrastructure are analyzed, with a focus on the state and trends in the functioning of the national transport infrastructure of the Russian Federation. By identifying key problems and determinants of financial growth, a preliminary decomposition is made to guide future development. Proceeding from the fact that the innovative development of Russia's transport infrastructure should occur through state stimulation of the development of intellectual and partnership relationships and the formation of a digital environment for managing projects for its innovative transformation at the state level, this study identifies the goals, methods, and levels of ensuring the implementation of innovative transformations in transport infrastructure. Consideration of the historical aspects of the formation of the modern economy and comprehension of the mechanisms of state management and tools to ensure innovative transformations in the sphere of transport allowed us to identify three stages (dogmatic, strategic regulation, and innovative integration) of transformation regarding the theory of the state management for the innovative development of transport infrastructure in Russia. Taking into account the content of these periods of transformation allowed us to detail the specifics of the modern stage; highlight the shortcomings; and propose theoretical and methodological foundations for revising the provisions of the state regulation of innovative development in transport infrastructure. To determine the effectiveness of the processes of the state regulation of innovation activity in the transport industry, we propose a model for assessing the effectiveness of innovation activity in the transport complex, which is presented in the form of a three-level parametric system, where the first group of indicators allows us to assess the innovation activity of economic entities in the transport industry; the second allows us to assess innovation potential; and the third allows us to assess the effectiveness of innovation. The novelty of the proposed model is the consideration of the principles of dynamism, perspective, and expediency, and its application allows us to establish the level of innovative development in transport infrastructure. An important factor in ensuring the sustainable development of a country's economy and forming its positive image in the world is its financial attractiveness. Therefore, the assessment of financial attractiveness is a priority task for the development of modern sustainable transport infrastructure in Russia. [ABSTRACT FROM AUTHOR]

A method has been proposed for creating an operationally durable copper coating with antimicrobial properties for the buttons of electrical switches based on the gas dynamic spray deposition of copper on acrylonitrile butadiene styrene (ABS) plastic. It is shown that during the coating process, a polymer film is formed on top of the copper layer. Comparative in situ studies of microbial contamination have shown that the copper-coated buttons have a significant antimicrobial effect compared to standard buttons. Analysis of swabs over a 22-week study in a hospital environment showed that the frequency of contamination for a copper-coated button with various microorganisms was 2.7 times lower than that of a control button. The presented results allow us to consider the developed copper coating for plastic switches an effective alternative method in the fight against healthcare-associated infections. [ABSTRACT FROM AUTHOR]