Even with 100% certainty of a complete cure for breast cancer (BC), there is still a long way to go toward more efficient treatment. This requires sensitive and timely detection and accurate pre/post-clinical characterizations. Despite the availability of advanced diagnostic tools, many cancer patients lack access to efficient diagnostics that are both highly reliable and affordable. The fluorescence-based optical technique aims to make another significant leap forward in improving patient safety. It offers a convenient operation that reduces healthcare costs compared to visual examination tools (VETs). The primary and metastatic stages of BC consider different cancerous cell lines (MDAs), meaning the highest number of cells in this research (up to 300,000) represents the metastatic stages of BC, and 50,000 represents the primary level of BC developments have been studied based on fluorescence-enhanced photodynamic characterizations. The ability to characterize the fluorescence caused by MDA with 50,000 cells compared to the dominant radiation of MDA with 300,000 cells is emphatic proof of the high potential of fluorescence technique in timely BC detections, specifically before it spreads to the axillary lymph nodes. The specific cell numbers of 50,000 and 300,000 were chosen arbitrarily based on the cultivation of common biological limitations. Comparing the outcomes between 50,000 and 300,000 cells allows for evaluating the fluorescence technique’s diagnostic capability across various stages of breast cancer. This assessment provides valuable insights into the effectiveness of the fluorescence-based characterizing approach in detecting cancerous cells at different stages of the disease. Here, we have assessed fluorescence’s spectral shift and intensity difference as a diagnostic approach to distinguish between cancerous and normal breast cells. This study also presents a two-way structure of the 5-aminolevulinic acid (5-ALA) prodrug and Fluorescein Sodium (FS) effect in BC cell characterization from the perspective of photodynamical procedures and the detection side. 5-ALA induces an accumulation of protoporphyrin IX (PpIX) photosensitizer through a biosynthetic pathway, leading to red radiation of fluorescence measurements depending on different factors, such as temperature, incubation time, added glucose of the culturing medium, as well as photosynthesis processes. The presence and progression of breast cancer can be indicated by elevated levels of Reactive Oxygen Species (ROS), which are associated with the production of PpIX in cells following the administration of 5-ALA. Also, nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) fluorophores are recognized as the main factors for fluorescence emissions at around 420-580 nm emission intervals. Considering the MDA’s high metastatic potential, the impact of 5-ALA on MDA’s cellular morphology and viability has been investigated. The molecular fluorophores are the primary probes to MDA’s cellular photodynamic considerations, allowing this widespread pre/post-clinical approach. The fluorescence signal reduction due to decreased cell viability and increased MDA’s cellular death rate after 24 hours of the 5-ALA-induced staining corresponds to the changes in lipid metabolism enzymes of MDAs cultured at different doses, which could be known as a cell death inducer function. Furthermore, statistical concerns have been studied using PCA multivariate component analysis to differentiate MDA cell lines administrated by 5-ALA.

Laser-induced breakdown spectroscopy (LIBS) of pharmaceutical drugs that contain paracetamol is investigated in air and argon atmospheres. Characteristic neutral and ionic spectral lines of various elements and molecular signatures of CN violet and C₂ Swan band systems are observed. The relative hardness of all drug samples is measured as well. Principal component analysis, a multivariate method, is applied in data analysis for demarcation purposes of the drug samples. The CN violet and C₂ Swan spectral radiances are investigated for evaluation of possible correlation of the chemical and molecular structures of the pharmaceuticals. Complementary Raman and Fourier-transform-infra-red spectroscopies are used record molecular spectra of the drug samples. The applicationof the above techniques for the drug screening are important for identification and mitigation of drugs that reveal additives that may cause adverse side-effects.

Recognition, decoding and tracking of vortex patterns is of increasing importance in many fields reaching from astronomical observation of distant galaxies to turbulence phenomena in liquids or gases. Currently, coherent light beams with orbital angular momentum (OAM) are of particular interest for optical communication, metrology, micro-machining or particle manipulation. One common task is to identify characteristic spiral patterns in pixelated intensity maps at real-world signal-to-noise ratios. Recently, Fast Fourier Transform (FFT) was applied to the quantitative analysis of spiral interference patterns of OAM beams. Our study considers this approach in more detail. It is demonstrated that specific information can be extracted by combining conformal mapping by polar transform with determining one- or two-dimensional angular frequency spectra either in spatially fixed or scanning mode. Results of proof-of-principle experiments are presented.

The application of non-uniform spiral gratings to control structure, topological parameters and propagation of orbital angular momentum (OAM) beams was studied experimentally with coherent near-infrared light. Adapted digital spiral grating structures were programmed into the phase map of a high-resolution liquid-crystal-on-silicon spatial light modulator (LCoS-SLM). It is shown that characteristic spatio-spectral anomalies related to Gouy phase shift can be used as pointers to quantify rotational beam properties. Depending on sign and gradient of spatially variable periods of chirped spiral gratings (CSG), variations of rotation angle and angular velocity as a function of propagation distance were measured. Propagation-dependent self-torque is introduced in analogy to known local self-torque phenomena of OAM beams as obtained by the superposition of temporally chirped or phase modulated wavepackets.

This work examines atomic and molecular signatures in laser-induced plasma in standard ambient temperature and pressure environments, including background contributions to the spectra that depend on the laser pulse-width. Investigations include solids, gases, and nano-particles. Abel inversions of measured line-of-sight data reveal insight into the radial plasma distribution. For nominal 6 nanosecond laser pulses and for pulse-energies in the range of 100 to 800 milli-Joules, expansion dynamics and turbulence due to shock phenomena are elucidated to address local equilibrium details that are frequently assumed in spatially averaged emission spectroscopy. Chemical equilibrium computations reveal temperature dependence of selected plasma species. Specific interests include atomic hydrogen (H) and cyanide (CN). The atomic H spectra, collected following optical breakdown in ultra-high-pure hydrogen and 9:1 mixtures of ultra-pure hydrogen and nitrogen gases, indicate spherical shell structures and isentropic expansion of the plasma kernel over and above the usual shockwave. The recombination radiation of CN emanates within the first 100 nanoseconds for laser-induced breakdown in a 1:1 CO₂:N₂ gas mixture when using nanosecond laser pulses to create the micro-plasma. The micro-plasma is generated using 1064 nm, 150 mJ, 6 ns Q-switched Nd:YAG laser radiation. Measurements of the optical emission spectra utilize a 0.64 m Czerny-Turner type spectrometer and an intensified charge-coupled device.

A binary biomass-based solid electrolyte film (LSE) was successfully synthesized through the incorporation of lignin nanoparticles (LNP) with sodium alginate (SA). The impact of the mass ratio of SA to LNP on the microstructure, porosity, electrolyte absorption capacity, ionic conductivity, and electrochemical properties of the LSE was thoroughly investigated. The results indicated that as the proportion of SA increased from 5% to 15% LNP, the pore structure of the LSE became increasingly uniform and abundant. Consequently, enhancements were observed in porosity, liquid absorption capacity, ionic conductivity, and overall electrochemical performance. Notably, at a SA amount of 15% LNP, the ionic conductivity of resultant LSE-15 was recorded at 14.10 mS cm1, with porosity and liquid absorption rates reaching 308% and 58.4%, respectively. LSE-15 was employed as a solid electrolyte, while LNP-based carbon aerogel (LCA) served as the two electrodes in the construction of a symmetric all-solid-state supercapacitor (SSC). The SSC device demonstrated exceptional electrochemical storage capacity, achieving a specific capacitance of 197 F g1 at 0.5 A g1, along with maximum energy and power density of 27.33 W h kg1 and 4998 W kg1, respectively. Furthermore, the SSC device exhibited highly stable electrochemical performance under extreme conditions, including compression, bending, and both series and parallel connections. Therefore, the development and application of the binary biomass-based solid electrolyte film in supercapacitors represent a promising strategy for harnessing high-value biomass resources in the field of energy storage.

The achievement of size uniformity and monodispersity in perovskite quantum dots (QDs) requires the implementation of precise temperature control and the establishment of optimal reaction conditions. Nevertheless, the accurate control of a range of reaction variables represents a considerable challenge. This study addresses the aforementioned challenge by employing manganese (Mn) doping to achieve size uniformity in CsPbBr₃ perovskite QDs without the necessity for precise control of the reaction conditions. By optimizing the Mn:Pb ratio, it is possible to successfully dope CsPbBr₃ QDs with appropriate concentrations of Mn²⁺ and achieve a uniform size distribution. The spectroscopic measurements on single QDs indicate that the appropriate Mn²⁺ concentrations can result in a narrower spectral linewidth, a longer photoluminescence (PL) lifetime, and a reduced biexciton Auger recombination rate, thus positively affecting the PL properties. This study not only simplifies the size control of perovskite QDs, but also demonstrates the potential of Mn-doped CsPbBr₃ QDs for narrow linewidth light-emitting diode applications.

Crystalline silver thin layers were obtained by high-energy pulsed laser ablation without heating of the deposition substrate. The fluid Plateau-Rayleigh (PRI), Rayleigh – Taylor (RTI) and Richtmyer – Meshkov (RMI) instabilities, as well as crown splash induced during pulsed laser deposition (PLD) in high energy regime, resulting in ring and pearl shaped structures, offer the benefit of increased sorption surface. These morphological structures obtained for the silver thin layers make them of interest for catalytic applications. The study presented with this work addresses both the fundamental and applied issues on the morphological structures obtained for the silver thin layer and their catalytic function in organic processes. In this sense, the catalytic action of the thin silver layer was highlighted by modifications of the Reactive Blue 21 dye (C.I.) in aqueous solution with sodium bicarbonate. Specific investigations and analyzes were carried out by electron microscopy and elemental analysis (SEM-EDX), atomic force microscopy (AFM) and profilometry, mass spectrometry, ablation plasma diagnosis, diffractograms (XRD), as well as IR spectroscopy (FTIR). In addition to the experimental investigation and analyzes, simulation of the ionization energy threshold was conducted in COMSOL for complementary evaluation on the involved processes and phenomena.

This paper proposes a methodology for the development and its Verification and Validation(V&V) of safety-rated software. The development methodology is based on the structured analysis and structured design methodology, which has been proven in the field of safety software development during long period. The suggested the development and the V&V methodology additionally focuses on the quality attributes 3C+T (completeness, Correctness, Consistency and traceability), which are important criteria in IEC international standards. The software development life cycle is compiled from IEC international standardization, which are of the requirements analysis phase, design phase, implementation phase, testing phase, installation/commissioning phase, and operation & maintenance phases. The activities of the development process method were defined from requirements analysis to implementation, and the activities of the verification and validation were defined to include the scope of the developer's activities and then to include the test phase, installation/commissioning phase, and operation phases additionally. In other words, testing phase performed by the developer was defined as informal testing, and testing performed by the verifier according to test criteria, test plans, and test procedures was defined as formal testing. According to proposed methodology, the requirements phase defines the sequence of Entity Relationship Diagram (ERD)-Context Diagram-Data Flow Diagram (DFD), functional decomposition process and defines operational scenario. In the design phase, module design such as task analysis and task allocation were defined. In the implementation phase, we listed the coding guidelines that must be followed for safety-related system. The test phase defined the test criteria, test plan, test procedure, and test result report activities. In the installation/commissioning and operation phases, recommendations for improving reliability, quality, and safety were proposed for deliverables such as user documentation and technical documentation.

Familial Alzheimer’s disease (FAD) can be caused by mutations in PSEN1 that encodes presenilin-1, a component of the gamma-secretase complex that cleaves amyloid precursor protein. Alterations in calcium (Ca2+) homeostasis and glutamate signaling are implicated in the pathogenesis of FAD, however it has been difficult to assess in humans whether or not these phenotypes are the result of amyloid or tau pathology. This study aimed to assess early calcium and glutamate phenotypes of FAD by measuring the Ca2+ response of induced pluripotent stem cell (iPSC)-derived neurons bearing PSEN1 mutations to glutamate and the ionotropic glutamate receptor agonists NMDA, AMPA and kainate compared to isogenic control and healthy lines. The data shows that in early neurons, even in the absence of amyloid and tau phenotypes, FAD neurons exhibit increased Ca2+ responses to glutamate and AMPA, but not NMDA or kainate. Together this suggests that PSEN1 mutations alter Ca2+ and glutamate signaling as an early phenotype of FAD.

Obesity has increasingly become a worldwide epidemic, as demonstrated by epidemiological and clinical studies. Obesity may lead to development of a broad spectrum of cardiovascular diseases (CVDs), such as coronary heart disease (CHD), hypertension, heart failure (HF), cerebrovascular disease, atrial fibrillation (AF), ventricular arrhythmias, and sudden cardiac death (SCD). In addition to hypertension, there are other cardiometabolic risk factors (CRFs) such as visceral adiposity, dyslipidemia, insulin resistance, diabetes, elevated levels of fibrinogen, and C-reactive protein and others, all of which increase the risk of CVD events. Mechanisms involved between obesity and CVD mainly include insulin resistance, oxidative stress, inflammation, and adipokines dysregulation, which cause maladaptive structural and functional alterations of the heart, particularly left ventricular (LV) remodeling and diastolic dysfunction. Natural products of plants, provide a diversity of nutrients and different bioactive compounds, including phenolics, flavonoids, terpenoids, carotenoids, anthocyanins, vitamins, minerals, fibers, and others, which possess a wide range of biological activities including antihypertensive, antilipidemic, antidiabetic, and other activities, thus conferring cardiometabolic benefits. In this review, we discussed the main therapeutic interventions using extracts from herbs and plants in preclinical and clinical trials with protective properties targeting CRFs. Molecular mechanisms and therapeutic targets of herbs and plants extracts for the prevention and treatment of CRFs are also reviewed.

Recurrent Pregnancy Loss (RPL) affects 1-2% of women, and its triggering factors are unclear. Several studies have shown the vaginal, endometrial, and gut microbiota may play a role in RPL. A decrease in the quantity of Lactobacillus crispatus in local microbiota has been associated with an increase in local (vaginal and endometrial) inflammatory response and immune cell activation that leads to pregnancy loss. The inflammatory response may be triggered by gram-negative bacteria, lipopolysaccharides (LPS), viral infections, mycosis, or atypia (tumor growth). Bacterial structures and metabolites produced by microbiota could be involved in immune cell modulation and may be responsible for immune cell activation and molecular mimicry. Gut microbiota metabolic products may increase the amount of circulating pro-inflammatory lymphocytes, which, in turn, will migrate into vaginal or endometrial tissues. Local proinflammatory Th1 and Th17 subpopulations along with a decrease in Treg and tolerogenic NK cells are accountable for the increase in pregnancy loss. Local microbiota may modulate the local inflammatory response increasing pregnancy success. Analyzing local and gut microbiota may be necessary to characterize some RPL patients. Although oral supplementation of probiotics has not been shown to modify vaginal or endometrial microbiota, the metabolites produced by it may benefit patients. Lactobacillus crispatus transplantation into the vagina may enhance the required immune tolerogenic response to achieve a normal pregnancy. The effect of hormone stimulation and progesterone to maintain early pregnancy on microbiota has not been adequately studied, and more research is needed in this area. Well-designed clinical trials are needed to ascertain the benefit of microbiota modulation in RPL.

High-spin states of 192Tl are populated by the heavy ion fusion-evaporation reaction 181Ta(16O, 5n)192Tl at 97 MeV beam energy. A new level scheme with eight new levels is constructed and the level spins are tentatively assigned. The negative-parity yrast band is extended up to 23^{-}\hbar. Subsequently, the systematics of signature splitting and signature inversion are discussed for the negative-parity yrast band of odd-odd Tl isotopes including 192Tl, 194Tl, 196Tl, and 198Tl. With the increase of neutron number signature inversion is found in 196,198Tl at high-spin state in these four Tl isotopes. The reason may be due to the competition between neutron-proton interaction and Coriolis force.

Estrogen receptor-positive (ER+) breast cancer is common among postmenopausal women and is frequently treated with Letrozole. Letrozole inhibits aromatase from synthesizing estrogen from androgens. Decreased estrogen slows the growth of tumors and can be an effective treatment. Letrozole resistance is increasingly being observed, which poses a unique problem for patients. We reanalyzed transcriptomic data comparing individuals who responded to Letrozole therapy (responders) to those who were resistant to treatment (non-responders). We identified SOX11 and S100A9 as two genes that significantly differed between these patients; with “PLK1 signaling events” being the most significant signaling pathway. We also identified PRDX4 and E2F8 as the top transcriptional biomarkers for ER+ treatment resistance. Many of the other significant gene products play a known role in ER+ breast cancer or other types of cancer, which partially validate our results. Several of the gene products we identified do not have a characterized role in ER+ breast cancer. Our analysis identified a set of genes that warrant further research to elucidate the molecular mechanism of Letrozole resistance in this patient population, as well as novel high-performing biomarkers. We anticipate that these findings could contribute to improved therapeutic outcomes in human patients.

Hepatocellular carcinoma (HCC) development is associated with altered modifications in DNA methylation, changing transcriptional regulation. Emerging evidence indicates that DNA methyltransferase 1 (DNMT1) plays a key role in carcinogenesis process. This study aimed to investigate how pirfenidone (PFD) modifies this pathway and the effect generated by the association between c-Myc expression and DNMT1 activation. Rats F344 were used for HCC development using 50 mg/kg of diethylnitrosamine (DEN) and 25 mg/kg of 2-aminofluorene (2-AAF). HCC/PFD group received simultaneous doses of 300 mg/kg of PFD. All treatments lasted 12 weeks. On the other hand, HepG2 cells were used to evaluate the effects of PFD in restoring DNA methylation in the presence of the inhibitor 5-Aza. Histopathological, biochemical, immunohistochemical, and western blot analysis were carried out and our findings showed that PFD treatment reduced the amount and size of tumors along with decreased Glipican-3, β-catenin, and c-Myc expression in nuclear fractions. Also, this treatment improved lipid metabolism by modulating PPARγ and SREBP1 signaling. Interestingly, PFD augmented DNMT1 and DNMT3a protein expression, which restores global methylation, both in our in vivo and in vitro models. In conclusion, our results suggest that PFD could slow down HCC development by controlling DNA methylation.

LCK, a member of the Scr kinase family, is a non-receptor tyrosine kinase involved in immune cell activation, antigen recognition, tumor growth, and cytotoxic response. The enzyme has usually been linked to T lymphocyte activation upon antigen recognition. Lck activation is central to CD4, CD8, and NK activation. However, recently, it has become clearer that activating the enzyme in CD8 cells can be independent of antigen presentation and enhance cytotoxic response. The role of Lck in NK cytotoxic function has been controversial in a similar fashion as the role of the enzyme in CAR T cells. Inhibition of Lck has been mainly to treat hematologic malignancies with a high rate of success. They may be useful in treating other tumor types, and they may be useful to prevent cell exhaustion. New, more selective inhibitors have been documented, and they have shown inter-esting activities not only in tumor growth but in the treatment of autoimmune diseases, asthma, and graft vs host disease. Drug repurposing and bioinformatics can aid in solving several unsolved is-sues on the role of Lck in cancer. In summary, the role of Lck in immune response and tumor growth is not a simple event and requires more research.

Music has the innate potential to reach all parts of the brain, stimulates certain brain areas which are not achievable through other modalities. Music Therapy (MT) is being used for more than a century to treat individuals who needs personalized care. MT optimizes motor, speech and language responsibilities of the brain and improves cognitive performance. Pervasive developmentdisorder (PDD) is a multifaceted, neuro developmental disorder and autism spectrum disorder (ASD) comes under PDD, which is defined by deficiencies in three principal spheres: social connection with others, communicative and normal movement skills. The conventional imaging studies illustrate reduced brain area connectivity in people with ASD, involving selected parts of the brain cortex. People with ASD express much interest in musical activities which engages the brain network areas and improves communication and social skills.The main objective of this review is to analyze the potential role of MT in treating the neurological conditions, particularly ASD. Evidence based studies have reported the extensive therapeutic application of music on various part of the brain in a nonverbal child with autism through hearing or making music.Hence we hypothesized that MT intervention can improve the communication capacity in people with ASD, than customary neurorestoration therapy alone.

Background and Objectives: Most of the research of the BRCA1 inactivation is focused on monoallelic germline alterations and loss of heterozygosity in tumour. The aim of this study was to identify characteristic transcriptomic pattern of monoallelic somatic BRCA1 inactivation and estimate its impact to the event-free breast cancer survival prognosis. Materials and Methods: We conducted global transcriptome sequencing of breast cancer tissue samples to identify differentially expressed genes and signalling pathways associated with monoallelic somatic BRCA1 inactivation. The study group involved 36 patient samples categorized based on BRCA1 inactivation status. Subsequently, the differential gene expression and Kaplan-Meier analyses in the groups with and without monoallelic somatic BRCA1 inactivation were performed. Results: Kaplan-Meier analysis showed tendency for longer event-free survival in patients with monoallelic somatic BRCA1 inactivation, suggesting somatic BRCA1 inactivation is favourable prognostic. Differential gene expression analysis followed by the STRING tool enrichment analysis showed significant enrichment of proteins in the extracellular region and extracellular space. Conclusion: In this study we identified transcriptomic profile of differentially expressed genes TPSD1, FABP4, CARTPT and MMP9 as indicative for homologous recombination impaired tumours with tendency for better therapy results.

Acting as the most abundant and widely distributed volatile secondary metabolites in plants, terpenoids play crucial roles in diverse physiological regulations and metabolic processes. Terpene synthases occupy a decisive proportion in determining the composition and diversity of terpenoids; though their regulatory effects have been extensively investigated across various plant species, limited studies have focused on the upstream transcriptional regulation of terpene synthases. In this study, we unveil linalool as the predominant volatile compound in Freesia hybrida flowers, demonstrating a gradual release pattern during flower blooming. In the context of the transcriptome, a typical MYB transcription factor, FhMYB108, was screened based on digital expression profile correlation analysis and homologous gene comparison. FhMYB108 is capable of regulating the expression of terpene synthase FhTPS1, and both their expression levels exhibit a gradual increase concomitant with flower opening. Moreover, transcriptional regulation and transient expression assays revealed that FhMYB108 exerts a stimulatory effect on the transcription of A. thaliana AtTPS14, while no significant increase in AtTPS14 expression was observed upon stabilization of FhMYB108 in Arabidopsis. Investigate its reason, the highly expressed AtMYC2 in A. thaliana can interact with FhMYB108 to suppress the activation of AtTPS14 by FhMYB108. The present study not only elucidated the regulatory mechanism underlying linalool synthesis, but also discovered the synergistic effect of MYB and bHLH transcription factors in governing the biosynthesis of volatile terpenoids.

Mesenchymal stem cells due to their multipotent ability are considered one of the best candidates to be used in regenerative medicine. The most used source of those stem cells long the last decades was the bone marrow, despite its limited cell resources and the painful and very invasive surgical treatment. Therefore, the scientific community investigated many alternative sources for the harvesting of these stem cell subpopulations. Adipose tissue attracted the biggest interest thanks to special features, such as great tissue abundance, easy availability, and in the end the large amount of positive mesenchymal stem cells. Once it was verified that these stem cell subpopulations possess the same bone marrow differentiation potential, it became evident that they would be the ideal candidate to be used in regenerative and tissue engineering applications. Even the regenerative use of these cells long become a sensitive point because not all the acquired phenotypes resulted in the best source for plastic procedures. As documented in the literature, the ideal fillers for regenerative is represented by stem cell population. Therefore, it became crucial to investigate any kind of biological mechanism on the differentiative ability of those mesenchymal stem cells, especially their regulative factors. One of the most studied and important regulators are the miRNAs. Indeed, miRNA play a crucial role in the differentiation process of adipose stem cell cultures isolated from patients or obtained by commercial cell lines toward osteocytes, chondrocytes, and adipocytes differentiated populations.

Continuing the investigation already started (See Farcaş, A.-A.; Bende, A. PCCP 2024, 26, 14937), the light absorption and charge-transfer properties of the dopamine (DA), dopamine zwitterion (called as dopamine-semi-quinone or DsQ) and dopamine-o-quinone (DoQ) adsorbed on the graphene nanoparticle surface have been investigated using the ground state and linear-response time-dependent density functional theories, considering the B97X-D3BJ/def2-TZVPP level of theory. In terms of the strength of molecular adsorption on the surface, the DsQ form has 50 % higher binding energy than that for the DA or DoQ cases (-20.24 kcal/mol vs. -30.41 kcal/mol). The results obtained for electronically excited states and UV-Vis absorption spectra show that the photochemical behavior of DsQ is more similar to DA than that observed for DoQ. Of the three systems analyzed, the DsQ-based complex showed the most active CT phenomenon, both in terms of the number of CT-like states and the amount of charge transferred. Of the first thirty electronically excited states computed for the DsQ case, eleven are purely CT-type and nine are mixed CT and localized (or Frenkel) excitations. By varying the adsorption distance between the molecule and the surface vertically, the amount of charge transfer obtained for DA decreases significantly as the distance increases, for DoQ it remains stable, while for DsQ there are states for which little change is observed, while for others there is a significant change. Furthermore, the mechanistic compilation of the electron orbital diagrams of the individual components cannot describe in detail the nature of the excitations inside the complex.

Presynaptic Ca²⁺-influx through voltage-gated Ca²⁺ channels (VGCC) is a key signal for synaptic vesicle release. Synaptic neurexins can partially determine the strength of transmission by regulating VGCCs. However, it is unknown whether neurexins modulate Ca²⁺-influx via all VGCC subtypes similarly. Here, we performed live cell imaging of synaptic boutons from primary hippocampal neurons with a Ca²⁺-indicator. We used the expression of inactive and active Cre recombinase to compare control to conditional knockout neurons lacking either all or selected neurexin variants. We found that reduced total presynaptic Ca²⁺-transients caused by the deletion of all neurexins were primarily due to the reduced contribution of P/Q-type VGCCs. The deletion of neurexin1α alone also reduced the total presynaptic Ca²⁺-influx but increased Ca²⁺-influx via N-type VGCCs. Moreover, we tested whether the decrease of Ca²⁺-influx induced by activation of cannabinoid receptor 1 (CB1-receptor) is modulated by neurexins. Unlike earlier observations emphasizing a role for β-neurexins, we found that the decrease of presynaptic Ca²⁺-transients induced by CB1-receptor activation depended more strongly on the presence of α-neurexins in hippocampal neurons. Together, our results suggest that neurexins have unique roles in the modulation of presynaptic Ca²⁺-influx through VGCC subtypes and that different neurexin variants may affect specific VGCCs.

Introduction Sepsis-associated encephalopathy (SAE) is common in sepsis and is linked to high mortality and impaired neurologic outcome. Brain ultrasonography (US), including transcranial Doppler (TCD) and transcranial color-coded duplex sonography (TCCS), is a non-invasive tool for cerebral monitoring and might be useful in sepsis. The aims of this review are: 1) to explore whether brain perfusion is altered in sepsis, 2) to determine the role of brain US in guiding resuscitation, and 3) its ability to predict neurological outcomes in septic patients. Materials and methods This scoping review adhered to the PRISMA-ScR protocol and JBI methodology. A comprehensive literature search was conducted across MEDLINE, Scopus, and Web of Science. The review included studies on adults with sepsis or septic shock in the ICU. Randomised controlled trials, clinical trials, observational studies and systematic reviews were included. All the data related to the review's key questions were extracted and charted independently by two authors. Results 625 articles were screened, and 34 were ultimately included after application of exclusion criteria. 85% of the studies were observational 15% were systematic reviews with or without meta-analysis. The studies primarily focused on cerebral blood flow (CBF) alterations in sepsis, reporting variable results. Findings showed variable cerebral autoregulation (CAR) impairment, with higher incidence in the early stages of sepsis and associations with poor neurological outcomes. However, while alterations in CAR and CBF are common in septic patients, their impact on neurological outcomes and mortality is not clear. Regarding resuscitation, only a paucity of studies were found and no conclusions can be drawn. Conclusions The current body of evidence has a poor grade, but it is possible to say that brain US can identify cerebral perfusions alterations. Its usage during resuscitation is feasible and warrants further investigations. Use of brain US during resuscitation and for prediction of outcome is not currently supported by evidence. Further studies on brain perfusion, acquisition of 2D images of parenchyma (TCCS) and application of a multimodal brain monitoring might be useful in these contexts.

Diffusion magnetic resonance imaging (dMRI) is an imaging technique that provides information on the microstructural organization of biological tissue. dMRI allows for non-invasive visualization and quantitative assessment of white matter architecture in the brain by characterizing restrictions on the random motion of water molecules. Ultra-high field MRI scanners, such as those operating at 7 Tesla (7T) or higher, can boost signal-to-noise ratio (SNR) to improve dMRI compared with what is attainable at conventional field strengths such as 3T or 1.5T. However, at 7T wavelength effects cause lower transmit magnetic field efficiency in the human brain, mainly in the posterior fossa region, manifesting as signal dropouts in this region. Recently, we reported a simple approach of using a wireless radiofrequency (RF) surface array to improve transmit efficiency and signal sensitivity at 7T. Here we demonstrate the feasibility and effectiveness of using this RF enhancer for in-vivo dMRI at 7T. The use of the RF enhancer can effectively recover signal dropouts in the regions with intrinsically lower SNR such as cerebellum, leading to a better depiction of principal fiber orientations and enhanced visualization of extended tracts to the brainstem and pons enabling more comprehensive delineation of the full white matter architecture.

Reconstructing the Tree of Life remains a central goal in biology. Early methods, relying on small numbers of morphological or genetic characters, often yielded conflicting evolutionary histories, undermining confidence in the results. Investigations based on phylogenomics, which use hundreds to thousands of loci for phylogenetic inquiry, have provided a clearer picture of life's history, but certain branches remain problematic. To resolve difficult nodes on the Tree of Life, two recent studies tested the utility of synteny, the conserved collinearity of orthologous genetic loci in two or more organisms, for phylogenetics. Synteny exhibits compelling phylogenomic potential while also raising new challenges. We identify and discuss specific opportunities and challenges that bear on the value of synteny data and other rare genomic changes for phylogenomic studies. Synteny-based analyses of highly contiguous genome assemblies mark a new chapter in the phylogenomic era and the quest to reconstruct the Tree of Life.

The keratinocyte carcinomas, basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), are the most common cancers in humans. Recently, an increasing body of literature has investigated the role of miRNAs in keratinocyte carcinoma pathogenesis, progression and their use as therapeutic agents and targets, or biomarkers. However, there is very little consistency in the literature regarding the identity of and/or role of individual miRNAs in cSCC (and to a lesser extent BCC) biology. miRNA analyses that combine clinical evidence with experimental elucidation of targets and functional impact provide far more compelling evidence than studies purely based on clinical findings or bioinformatic analyses. In this study, we review the clinical evidence associated with miRNA dysregulation in KCs assessing the quality of validation evidence provided, identify gaps, and provide recommendations for future studies based on relevant studies that investigated miRNA levels in human cSCC and BCC. Furthermore, we demonstrate how miRNAs contribute to the regulation of a diverse network of cellular functions, and that large-scale changes in tumor cell biology can be attributed to miRNA dysregulation. We highlight the need for further studies investigating the role of miRNAs as communicators between different cell types in the tumor microenvironment. Finally, we explore the clinical benefits of miRNAs as biomarkers of keratinocyte carcinoma prognosis and treatment.

Oligopeptide transporters (OPTs) are a group of membrane localized proteins that have a broad range of substrate transport capabilities and contribute to numerous biological processes. However, limited information has been reported on OPTs in higher plants. In this study, a comprehensive analysis of the OPT gene family in Medicago truncatula was performed. A total of 26 OPT genes (MtOPT01-MtOPT26) have been identified in the Medicago truncatula genome. Phylogenetic analyses indicated that MtOPTs consisted of two distinct subgroups, 12 MtOPTs belonged to the peptide transport subgroup (PT-OPT) based on their predicted amino acid sequences containing the two highly conserved motifs (NPG and KIPPR) and 14 MtOPTs belonged to yellow stripe subgroup (YS-OPT). The MtOPTs distributed on each of 8 chromosomes in Medicago truncatula. Sequence analysis verified that MtOPTs significant similar to those in other plants. The copy number of MtOPTs was low and the multiply of MtOPTs was simple relatively. Gene structure analysis showed that most of the MtOPTs have various numbers of introns. The multiple of MtOPTs might play different biological roles which were supported by the fact that MtOPTs have a distinct tissue-specific expression pattern. The data obtained in this study will help to better understand the complexity of the MtOPTs gene family and provide new evidence for the function and evolution of the OPT gene family in higher plants.

Cancer develops from abnormal cell growth in the body, causing significant mortalities every year. To date, potent therapeutic approaches have been developed to eradicate tumor cells, but intolerable toxicity and drug resistance can occur in treated patients, limiting the efficiency of existing treatment strategies. Therefore, searching for novel genes critical for cancer progression and therapeutic response is urgently needed for successful cancer therapy. Recent advances in bioinformatic and proteomic techniques have allowed the identification of a novel category of peptides encoded by non-canonical open reading frames (ncORFs) from historically non-coding genomic regions. Surprisingly, many of the ncORFs express functional microproteins that play a vital role in human cancers. In this review, we provide a comprehensive description of different ncORF types with coding capacity and technological methods in discovering ncORFs among human genomes. We also summarize the diagnostic and prognostic value of these ncORF as well as their carcinogenic role in cancer progression and underestimated potential as therapeutic targets.

The interpretation of optical spectra requires thorough comprehension of quantum mechanics, especially understanding the concept of angular momentum operators. Suppose now that a transformation from laboratory-fixed to molecule-attached coordinates, by invoking the correspondence principle, induces reversed angular momentum operator identities. However, the foundations of quantum mechanics and the mathematical implementation of specific symmetries assert that reversal of motion or time reversal includes complex conjugation as part of anti-unitary operation. Quantum theory contraindicates sign changes of the fundamental angular momentum algebra. Reversed angular momentum sign changes are of heuristic nature and are actually not needed in analysis of diatomic spectra. This work addresses sustenance of usual angular momentum theory, including presentation of straightforward proofs leading to falsification of the occurrence of reversed angular momentum identities. This review also summarises aspects of a consistent implementation of quantum mechanics for spectroscopy with selected diatomic molecules of interest in astrophysics and in engineering applications.

Background: Obesity remains a widely debated issue, often criticized for the limitations in its identification and classification. This study aims to compare two distinct systems for classifying obesity: Body Mass Index (BMI) and body fat percentage (BFP) as assessed by bioelectrical impedance analysis (BIA). By examining these measures, the study seeks to clarify how different metrics of body composition influence the identification of obesity-related risk factors. Methods: The study enrolled 1255 adults, comprising 471 males and 784 females, with a mean age of 36 ± 11.90 years. Participants exhibited varying degrees of weight status, including optimal weight, overweight, and obesity. Body composition analysis was conducted using the TANITA Body Composition Analyzer BC-418 MA III device (T5896, Tokyo, Japan), evaluating the following parameters: current weight, basal metabolic rate (BMR), adipose tissue (%), muscle mass (%), and hydration status (%). Results: Age and psychological factors like cravings, fatigue, stress, and compulsive eating were significant predictors of obesity in the BMI model but not in the BFP model. Additionally, having a family history of diabetes was protective in the BMI model (OR: 0.33) but increased risk in the BFP model (OR: 1.66). The BMI model demonstrates exceptional predictive ability (AUC=0.998). In contrast, the BFP model, while still performing well, exhibits a lower AUC (0.975), indicating slightly reduced discriminative power compared to the BMI model. Conclusions:BMI classification demonstrates superior predictive accuracy, specificity, and sensitivity. This suggests that BMI remains a more reliable measure for identifying obesity-related risk factors compared to the BFP model.

The continues evolution of coronaviruses has gained considerable attention prior to the outbreak of COVID 19. Although, COVID-19 is currently not recognized as a global pandemic, the virus's ability to evolve and cause disease outbreaks in both humans and animals necessitates ongoing research into its genetic and structural characteristics. Therefore, understanding the molecular origin, rapid evolution, as were as the immunogenicity of coronaviruses is a critical step towards preparing for and preventing future outbreaks. This study aimed to uncover the genetic diversity and evolutionary relationships among the main viral proteins of SARS-CoV-2 and other related coronaviruses. Amino acid sequences of structural viral proteins spike glycoprotein, nucleocapsid protein, membrane protein, and envelope protein were retrieved from the NCBI database for SARS-CoV-2 and 13 other coronaviruses. Here, we identified that SARS-CoV-2 is closely related to BatCoV RaTG13 and Pangolin-CoV, suggesting their potential role in the emergence of the virus. Additionally, we predicted novel epitopes, glycosylation sites, and cleavage sites, identifying three novel glycosylation sites (NATR, NXSN, and NGTK) and six new CTL epitopes (XSNQVAVLY, NSFTRGVYY, NATRFASVY, STQDLFLPF, NSASFSTFK, and ASFSTFKCY). Our comparative analysis revealed that BatCoV RaTG13 has the closest cleavage site to SARS-CoV-2, with significant similarities also observed with Pangolin-CoV. The study highlighted the unique features of SARS-CoV-2, including its furin cleavage site, which may account for its high infectivity during the pandemic. These findings contribute to the understanding of SARS-CoV-2 evolution and its relationship with other coronaviruses, providing critical insights for the development of broad-spectrum vaccines and antiviral therapies.

The Aspergillus genus comprises fungi that are widely distributed in nature. The Terrei section is particularly important due to its functions in recycling organic matter. Aspergillus hortae is a species from this section that has been isolated from clinical samples, but its role as a pathogenic agent is unclear. In this study, three clinical A. hortae isolates from Colombia, initially identified as A. terreus, were characterised by micro and macro-morphological analysis at 26°C and 37°C. A bioinformatic pipeline was used for molecular typing, which included analysis of whole genome sequences for accurate species identification. Susceptibility assays were also conducted using the microdilution broth method (EUCAST). It was confirmed that this species is intrinsically resistant to Amphotericin B with a minimum inhibitory concentration (MIC) of 2-4 mg/L, and is also thermotolerant. We obtained the in vitro susceptibility profiles for three azole drugs (MIC, 0.25-1 mg/L). The three isolates showed phylogenetic divergence from the reference genome strain. A mutation (M769K) in the MelA ortholog of a hypopigmented isolate, which had the lowest MIC value for AmB (2 mg/L), was identified. This study presents the morphological characterization, molecular typing through whole-genome analysis and identification of susceptibility profiles to azoles and amphotericin B of three clinical isolates of A. hortae from Colombia.

More than 20 years after the discovery of the first anelloviruses (AVs), they still remain a mysterious group of viruses. To date, there is no clear understanding of their impact on the host organism, although information is emerging about their participation in various pathologies. However, it is well known that AVs are an important component of the human virome. In the current study we assessed the abundance of AVs in viromes from four nasal and pharyngeal samples from children with respiratory symptoms using a metagenomic approach. It is worth noting that three patients had known respiratory viruses and one did not have any. Regarding AVs, they were detected in all samples, namely Torque teno mini virus (TTMV). The greatest abundance and diversity of AVs (Torque teno virus (TTV), TTMV and Torque teno midi virus (TTMDV)) were shown in a diseased patient with an absence of respiratory viruses, which may indicate the potential involvement of AVs in the maintenance of respiratory symptoms. An activated immune system to combat the main pathogens, against the background of which the number of AVs decreases, is discussed as a possible reason for the reduced diversity of anellome in other patients. We also compared the results of the metagenomic approach and qPCR for major respiratory viruses, which were in agreement. In addition, metagenomic sequencing made it possible to obtain additional data on viral genomes in order to establish their taxonomic identification and characterize individual viral profiles in patients from the Siberian part of Russia.

Circulating tumor cells (CTCs) are cells released from the primary tumor and intravasate into the blood or lymphatic vessels, where they are transported to distant sites and act as seeds that initiate cancer metastases. Recent advances in CTC research have shown their relevance as prognostic markers for early and metastatic disease detection, predictive biomarkers for relapse, and response to medical intervention or therapy. The rapidly evolving landscape of CTC biology has opened new avenues for understanding cancer progression, metastasis, and treatment response. Additionally, translating these findings into clinical applications holds promise for improving cancer diagnostics, prognosis, and personalized therapeutic strategies. This review discusses the significance of CTCs in cancer research and their associated challenges. We explore recent developments in the detection and characterization of CTCs and their implications in cancer research and clinical practice.

Numerous varieties of Capsicum annuum L. with multiple valuable traits, such as adaptation to biotic and abiotic stress factors, can be found in south-east Romania, well known for vegetable cultivation and an important area of biodiversity conservation. To obtain useful information toward a sustainable agriculture, management and conservation of local pepper varieties, we analyzed the genetic diversity and we did deep molecular characterization using Whole Genome Resequencing (WGS) for variant/mutation detection. The pepper varieties used in the present study were registered by VRDS in the ISTIS catalog between 1974 and 2019 and maintained in conservative selection, however, no studies have been published yet using WGS analysis in order to characterize this specific germplasm. The genome sequences, annotation and alignments provided in this study offer essential resources for genomic research as well as for future breeding efforts using the C. annuum local varieties.

The extensive metabolic diversity of microalgae, coupled with their rapid growth rates and cost-effective production, position these organisms as highly promising resources for a wide range of biotechnological applications. These characteristics allow microalgae to address crucial needs in both the agricultural, medical, and industrial sectors. Microalgae are proving to be val-uable in various fields, including the remediation of diverse wastewater types, the production of biofuels and biofertilizers, and the extraction of various products from their biomass. For decades, the microalga Chlamydomonas has been widely used as a fundamental research model organism in various areas such as photosynthesis, respiration, sulfur and phosphorus metabolism, nitrogen metabolism, and flagella synthesis, among others. However, in recent years, the potential of Chlamydomonas as a biotechnological tool for bioremediation, biofertilization, biomass, and bio-products production has been increasingly recognized. Bioremediation of wastewater using Chlamydomonas presents significant potential for sustainable reduction of contaminants and fa-cilitates resource recovery and valorization of microalgal biomass, offering important economic benefits. Chlamydomonas has also established itself as a platform for the production of a wide va-riety of biotechnologically interesting products, such as different types of biofuels, and high-value-added products. The aim of this review is to achieve a comprehensive understanding of the potential of Chlamydomonas in these aspects, and to explore their interrelationship, which would offer significant environmental and biotechnological advantages.

The mutation in NF2 is the most common alteration associated with meningioma oncogenesis, and it is related to the loss of a suppressing protein called merlin. At the same time, alterations in energy production are visible in cancer cells where increased demand for energy is observed. Fatty acid oxidation could be one of the ways cancer cells obtain energy. This metabolic pathway uses the acylcarnitine shuttle system, which is responsible for the acylation of fatty acids and their transport through mitochondria. Therefore, this study aimed to profile acylcarnitines with short-, medium- and long-acyl chain length in meningiomas to assess their changes in tumors with different NF2 mutation statuses. For the analysis, solid-phase microextraction (SPME) coupled with liquid chromatography high resolution mass spectrometry (LC-HRMS) was used. The presented sampling method enables low invasive and easy collection of the analytes from the studied lesions, which can be crucial for future analysis of potential biomarkers in the surgery room. It was observed that higher levels of these analytes characterized meningiomas with NF2 mutation. Moreover, increased energy consumption and elevated levels of acylcarnitines show that these analytes can be considered as a marker of increased fatty acid oxidation in NF2 mutated cells.

The p53 tumor suppressor protein shows antiviral activity. The replication of viruses is also antagonized by interferons (IFNs) – cytokines, which control immunity genes by the STAT transcription factors. The best studied interferons belong to type I (e.g. IFNα) and type II (IFNγ) groups. IFNα and IFNγ both induce activating phosphorylation of STAT1 on Tyr701. Previously, we noticed that p53 activates SOCS1, which is a negative regulator of STAT1 phosphorylation. Thus, we hypothesized that p53 by activating SOCS1 expression reduces phosphorylation of STAT1 and attenuates activation of genes stimulated either by IFNα or IFNγ. To test this hypothesis, we exposed p53-proficient and p53-deficient cells to strong p53 activators, and either to IFNα or IFNγ. Subsequently, we estimated the phosphorylation status of STAT1 and the expression of genes regulated by either of these cytokines. Strong activation of p53 reduced the phosphorylation of STAT1 on Tyr701, however surprisingly it did not lead to reduced expression of most tested interferon-stimulated genes. On contrary, p53 and IFNγ synergized in the activation of CASP1, IFIT1 and IFIT3 genes. We conclude that the interactions between p53 and interferon-activated pathways are more complicated than initially expected, but the apparent cooperation between p53 and IFNγ deserves further studies.

In Cameroon, Aedes mosquitoes transmit various arboviruses, posing significant health risks. We aimed to characterize the Aedes virome in southwestern Cameroon and identify potential core viruses which might be associated with vector competence. A total of 398 Aedes mosquitoes were collected from four locations (Bafoussam, Buea, Edea and Yaounde). Aedes albopictus dominated all sites except for Bafoussam where Aedes africanus prevailed. Metagenomic analyses of mosquitoes grouped per species into 54 pools revealed notable differences in eukaryotic viromes between Ae. africanus and Ae. albopictus, with the former exhibiting greater richness and diversity. Thirty-seven eukaryotic virus species from 16 families were identified, including six novel viruses with near complete genome sequences. Seven viruses were further quantified in individual mosquitoes via qRT-PCR. Although none of them could be identified as core viruses, Guangzhou sobemo-like virus and Bafoussam mosquito solemovirus virus were highly prevalent regionally in Ae. albopictus and Ae. africanus, respectively. This study highlights the diverse eukaryotic virome of Aedes species in southwestern Cameroon. Despite their shared Genus, Aedes species exhibit limited viral sharing, with varying viral abundance and prevalence across locations. Ae. africanus, an understudied vector, harbors a rich and diverse virome, suggesting potential implications for arbovirus vector competence.

It is of great academic significance to understand how the atomic structure of interfaces and boundaries in materials impacts the magnetic coupling nature across the boundaries and encourage development of state-of-the-art magnetic devices. Here, we carry out a systematic investigation of the atomic and electronic structures of twin boundaries (TBs) in LiFe5O8 thin films and determine their concurrent magnetic couplings using atomic-resolution transmission electron microscopy and atomistic first-principles calculations. The results show ferromagnetic or antiferromagnetic coupling can exist across the different TBs in LiFe5O8 (LFO) thin films and electrical structures within a few atomic layers directly rely on the TB atomic core structures. Uncovering one-to-one relationship between the magnetic properties of individual TB and the local atomic structures will clarify a thorough comprehension of numerous fascinating magnetic properties of commonly utilized magnetic materials, which will undoubtedly encourage the progress of sophisticated magnetic materials and devices.

Non-coding RNAs have been described as crucial regulators of gene expression and guards for cellular homeostasis. Some recent papers are focused on vault RNAs, one of the classes of non-coding RNA, and their role in cell proliferation, tumorigenesis, apoptosis, cancer response to therapy, and autophagy, which made them potential therapy targets in oncology. In the human genome, four vault RNA paralogues can be distinguished. They are associated with vault complexes, considered the largest ribonucleoprotein complex. The protein part of these complexes consists of a major vault protein (MVP) and two minor vault proteins (vPARP and TEP1). The name of the complex, as well as vault RNA, comes from the hollow barrel-shaped structure that reminds a vault. Their sequence and structure are highly evolutionary conserved and show many similarities in comparison with different species, but vault RNAs show various roles. Vaults were discovered in 1986, and their functions remained unclear for many years. Although not much is known about their contribution to cell metabolism, it has become clear that vault RNAs are involved in various processes and pathways associated with cancer progression and modulating cell functioning in normal and pathological stages. In this review, we discuss known functions of the human vault RNAs in the context of cellular metabolism, emphasizing processes related to cancer and cancer therapy efficacy.

From their discovery in 2002, BRAF mutations have been identified as clear drivers of oncogenesis in several cancer types. Currently, their incidence rate is nearly 7% of all solid tumors with BRAF V600E constituting approximately 90% of these diagnoses [1]. In melanoma, thyroid cancer, and histiocytic neoplasms, BRAF hotspot mutations are found at a rate of about 50%, while in lung and colorectal cancers they range from 3 to 10% of reported cases [2-5]. Though present in other malignancies such as breast and ovarian cancers, they constitute a small portion of diagnoses (<1%). Given their frequency along with advancements in screening technologies, various methods are used for the detection of BRAF-mutant cancers. Among these are targeted next-generation sequencing (NGS) on tumor tissue or circulating tumor DNA (ctDNA) and immunohistochemistry (IHC)-based assays. With advancements in detection technologies, several approaches have been taken for the treatment of BRAF mutant cancers. In this review we retrace the milestones that led to the clinical development of targeted therapies currently available for these tumors.

Additive manufacturing processes offer various options to fabricate metal parts, which show numerous ecological and technological advantages compared to formative and subtractive manufacturing methods. Due to quick availability and high accuracy, they are particularly suitable to produce complex prototypes. Metal fused deposition modeling is a relatively new material extrusion additive manufacturing technique based on the widely used fused filament deposition process. This study focuses on the Inconel 625 metal filament from Markforged Inc., it consists of a mixture of metal powder and a binder system, the latter being removed during washing and sintering. In this article, the mechanical properties of printed and sintered Inconel were investigated using tensile testing specimens with three different infill patterns, solid, triangular, and gyroid, printed in flatwise and upright direction. In addition, investigations into the dimensional accuracy of the printed specimens and the sintering shrinkage were carried out. The results showed that neither the dimensional accuracy nor the sintering shrinkage was significantly influenced by the printing orientation. In the context of lightweight engineering, the structures proofed beneficial especially within the elastic region. Generally, triangular infill patterns resulted in higher stiffness, while gyroids led to more ductile specimens. A mass-related evaluation of tensile testing elucidates that with aid of the infill structures weight savings of 40 % resulted in mechanical performance decreased by only 20 % on average.

Some peptide-based drugs including oxytocin, vasopressin, ziconotide, pramlintide, nesiritide, and octreotide, contain one intramolecular disulfide bonds. A novel and reusable monodispersed silica nanosphere-supported Pt(IV) complex (SiO2@TPEA@Pt(IV)) was synthesized via a four-step procedure and used for formation of intramolecular disulfide bonds in peptides. TEM and chemical mapping results for the Pt(II) intermediates and for SiO2@TPEA@Pt(IV) show that the silica nanospheres possess a monodisperse spherical structure and contain uniformly distributed Si, O, C, N, Cl, and Pt. The valence state of Pt on the silica nanospheres was characterized by XPS. The Pt(IV) loaded on SiO2@TPEA@Pt(IV) was 0.15 mmol/g, as determined by UV-vis spectrometry. Formation of intramolecular disulfides in six dithiol-containing peptides of variable lengths by use of SiO2@TPEA@Pt(IV) was investigated and the relative oxidation yields were determined by HPLC. In addition, peptide 1 (Ac-CPFC-NH2) was utilized to study the reusability of SiO2@TPEA@Pt(IV). No significant decrease in the relative oxidation yield was observed after ten reaction cycles. Moreover, the structure of SiO2@TPEA@Pt(IV) after being used ten cycles was determined to be similar to its initial one, demonstrating the cycling stability of the complex.

Viral contamination in the aquaculture industry is a significant challenge that requires further research. Emerging evidence suggests that long noncoding RNAs (lncRNAs) play a role in regulating various biological processes, including immunity. However, most studies have focused on model organisms, and little is known about non-coding RNAs in the immune response to viral hemorrhagic septicemia (VHS) in rainbow trout. In this study, we investigated the listing of non-coding RNAs (ncRNAs) in rainbow trout challenged with VHS virus. We explored their potential role in defense-like responses based on transcriptomic analysis of the virus-treated and control groups. As a result of this research, 4207 lncRNAs were identified, of which 182 lncRNAs were differentially expressed between treated and untreated samples. Among 7753 lncRNA transcripts, 1920 were novel intergenic (class code “u”), and 3748 transcripts were potentially novel isoform of lncRNAs. Gene ontology analysis revealed biological pathways associated with the stress response and immune signaling. Pairs of genes such as TP63-MSTRG.62, IL10-MSTRG.9783, IL10-MSTRG.9784, TK1-MSTRG.22826, and MSTRG.17881-GLI1 showed cis interactions, while DOCK10-MSTRG.30015, MSTRG.36357-LOC101268921, and MSTRG.34190-ENPP2 showed trans interactions. In this study, the role of lncRNAs in regulating the expression of the target genes was clearly identified. This finding is consistent with the regulatory processes of immune system responses mediated by cytokines, as well as the regulation of oxygen levels in response to viral infection. The information presented here highlights the various regulatory mechanisms of lncRNAs in the expression of immune system genes in fish treated with VHS virus.

Lyme disease is a highly prevalent tick-borne infection caused by Borrelia burgdorferi spirochetes in North America and Eurasia. Diagnosis of the early disease remains difficult with the currently approved serological tests in the absence of noticeable tick bite or erythema migrans due to presentation of non-specific symptoms and the absence of antibodies early in infection. Furthermore, it is difficult to distinguish persistence of disease and reinfection in the endemic regions. If not treated early, infection spreads throughout the body and affects most organs with disease manifestations including arthritis, musculoskeletal pain, neuroborreliosis and acrodermatitis chronicum atrophicans. Although most patients recover after antibiotic treatment, ~10-12% of show recurrence of symptoms known as post-treatment Lyme disease syndrome (PTLDS). Various causes of PTLDS are not well-defined; however, the spirochete persisters, antigenic debris, dysregulation of immunological response in individuals or a combination of these factors are proposed to result in continuation of Lyme disease manifestations. Based on these considerations, this review highlights currently employed treatment approaches with antimicrobials and vaccines being tried for prevention of B. burgdorferi infection. We also summarize combinatorial approaches that could be employed to alleviate symptoms to improve the quality of life of the individuals suffering from long Lyme disease.

Huperzine A is an herbal reversible inhibitor of Acetylcholinesterase (AChE). A molecular docking analysis on Huperzine A molecule has been carried out to understand its structure, conformational flexibility, intermolecular interaction and the binding affinity in the active site of AChE enzyme. Further, the charge density distribution of huperzine A molecule (lifted from the active site of AChE) was determined from the high level quantum chemical calculations coupled with charge density analysis. The binding affinity of Huperzine A towards AChE was calculated from the molecular docking; the lowest docked energy is -8.46 kcal/mol. In the active site, huperzine A molecule interacts with acyl binding pocket-Phe330 of AChE, that is, the bicyclo ring group of huperzine A forms an intermolecular interaction with the oxygen atom of main chain of the amino acid residue Phe330 at the distances 3.02 and 3.25 Å respectively. On the other hand, a gas phase study on huperzine A molecule also performed using HF and DFT (B3LYP) methods with the basis set 6-311G**. The molecular structure, conformation, and the charge density distribution of huperzine A molecule in the gas phase have determined using quantum chemical calculations and the charge density analysis. The comparative studies between the gas phase and the active site forms of huperzine A molecule, explicitly reveals the degree of conformational modification and the charge density redistribution of huperzine A when present in the active site. The dipole moment of the molecule in the active site is 6.85 D, which is slightly higher than its gas phase value (5.91 D). The electrostatic potential (ESP) surface of active site molecule clearly shows the strong electronegative and positive ESP regions of the molecule, which are the expected strong reactive locations of the molecule.

The rural population in the Dry Zone of Sri Lanka is largely affected by Chronic Kidney Disease of Unknown etiology (CKDu). According to the multidisciplinary research carried out so far, quality of groundwater was considered one of the possible causative factors for CKDu. Therefore, the assessment of water quality variations and evolution mechanism of water quality parameters of drinking water sources is important for identifying any relationships between CKDu and the drinking water quality. The current study aimed to perform a detailed hydrogeochemical investigation using isotopic and chemical methods on selected groundwater sources in the CKDu-endemic, non-endemic and control areas. TDS, hardness, Mg2+, Na+ and F- are the main parameters that cause water quality deterioration but, their derived mechanism in these three regions are completely different. The excess concentrations of F- and Mg2+ in the CKDu endemic area, low F- and high Mg2+in the CKDu non-endemic sedimentary formation, and either combinations of low F- and low Mg2+, high F- and low Mg2+ or low F- with high Mg2+ in the control area are the distinct features. The primary processes that regulate the evolution of groundwater types in CKDu endemic and control area is the weathering of silicates. Similarly, in the CKDu endemic area, carbonate dissolution and reverse ion exchange are prominent. Cation exchange and evaporite dissolution are more pronounced in the control area. Shallow groundwaters are evapo-concentrated hence it further deteriorates quality when compared to the deep groundwater with non-mixed, non-evaporated, and higher elevation recharge effect (from 100 m altitude) in the CKDu endemic area. Dilution decreases the ion content in the CKDu endemic area while evaporite dissolution further increase it in the control area after the rainy season. Evaporation, and seawater mixing affected the quality of groundwater in the non-endemic sedimentary formation. A statistically significant difference of F- ionic ratio with Na+, Mg2+, Ca2+ in the endemic and control areas. Intense rock weathering combined with the desorption added excess F- to the groundwater in the CKDu endemic area while the cation exchange and fluorite dissolution is contributing factor in CKDu control area. All the groundwater samples analyzed have exceeded the moderate hardness threshold. However, prominent Mg hardness proportion together with excess F- in the CKDu endemic area may produce nephrotoxic MgF2 complexes that may trigger renal damage. In contrast, produced NaF complexes in the CKDu control area leads to reduction of F- toxicity in the human body. Therefore, increased levels of magnesium, fluoride and TDS in the shallow groundwater, along with geochemical, hydrogeological and climatic factors, may contribute to the CKDu in the Dry Zone of Sri Lanka.

Metallo-β-lactamases (MBLs) are members of the structurally conserved but functionally diverse MBL-fold superfamily of metallohydrolases. MBLs are a major concern for global health care as they efficiently inactivate β-lactam antibiotics, including the “last-resort” carbapenems, and no clinically suitable inhibitors are currently available. Increasingly, promiscuous β-lactamase activity is also observed in other members of the superfamily, including from viruses, which represents an underexplored reservoir for future pathways to antibiotic resistance. Here, two such MBL-fold enzymes from Bacillus phages, the cyclic mononucleotide-degrading proteins ApycGoe3 and ApycGrass, are shown to efficiently degrade β-lactam substrates in vitro. In particular, ApycGrass displays a distinct preference for carbapenem substrates with a catalytic efficiency that is within one order of magnitude of that of the clinically relevant MBL NDM-1. Mutagenesis experiments also demonstrate that the loss of a metal-bridging aspartate residue reduces nuclease activity up to 35-fold, but improves carbapenemase activity. In addition, we propose that the oligomeric state significantly influences β-lactamase activity by modifying access to the active site pocket. Together, these observations hint at a possible new avenue of resistance via the spread of phage-borne MBL-fold enzymes with β-lactamase activity.

Systemic Lupus Erythematosus (lupus) and B-cell lymphoma (lymphoma) are serious diseases. Lupus and lymphoma co-occur at higher-than-expected rates and primarily depend on B-cells for their pathology, implicating shared inflammation-related B-cell molecular mechanisms as a potential cause of co-occurrence. We consequently implemented a novel Immune Imbalance Transcriptomics (IIT) algorithm and applied IIT to lupus, lymphoma, and healthy B-cell RNA-seq data to find shared- and contrasting mechanisms potentially targetable for treatment. We observed 8,562 genes significantly dysregulated in both lupus and lymphoma. Of those genes, we found 5,335 to have a significant immune imbalance, defined as significant dysregulation by both diseases, as determined by IIT. Gene Ontology (GO) term and pathway enrichment of IIT genes yielded immune-related “Neutrophil Degranulation” and “Adaptive Immune System”, validating that the IIT algorithm isolates biologically relevant genes in immunity and inflammation. We found that 389 IIT gene products are drug-targetable with established or repurposed drugs. Among our results, we found 40 known and 349 novel lupus targets, along with 151 known and 238 novel lymphoma targets. Known disease drug targets in our IIT results further validate that IIT isolates genes with disease-relevant mechanisms. We anticipate the IIT algorithm and shared and contrasting gene mechanisms uncovered here will contribute to the development of immune-related therapeutic options for lupus and lymphoma patients.

A large diversity of epigenetic factors, such as microRNAs and histones modifications, are known to be capable of regulating gene expression without altering DNA sequence itself. In particular, miR-1 is considered the first essential microRNA in cardiac development. In this study, miR-1 potential role in early cardiac chamber differentiation is analyzed through specific signaling pathways. For this, we performed in chick embryos functional experiments by means of miR-1 microinjections into the posterior cardiac precursors -of both primitive endocardial tubes- committed to sinoatrial region fates. Subsequently, embryos were subjected to whole mount in situ hybridization, immunohistochemistry and RT-qPCR analysis. As a relevant nov-elty, our results revealed that miR-1 increases Tbx5, Gata4 and AMHC1, while this microRNA diminishes Mef2c expression, during early differentiation of cardiac sinoatrial region. Further-more, we observed in this developmental context that miR-1 upregulates CRABPII and RARß, and downregulates CRABPI, which are three crucial factors in retinoic acid signaling pathway. Interestingly, we also noticed that miR-1 directly interacts with HDAC4 and Calmodulin, as well as with Erk2/MAPK1, which are three key factors actively involved in Mef2c regulation. Our study shows, for the first time, a key role of miR-1 as an epigenetic regulator in early differenti-ation of cardiac sinoatrial region through orchestrating opposite actions between retinoic acid and Mef2c, fundamental to properly assign cardiac cells to their respective heart chambers. A better understanding of those molecular mechanisms modulated by miR-1 will definitely help in fields applied to therapy and cardiac regeneration and repair.

The chiral optical Tamm state (COTS) is a special localized state at the interface of a handedness-preserving mirror and a structurally chiral medium such as a cholesteric liquid crystal or a chiral sculptured thin film. The spectral behavior of COTS, observed as reflection resonances, is described by the temporal coupled-mode theory. Mode coupling is different for two circular light polarizations because COTS has a helix structure replicating that of the cholesteric. The mode coupling for co-handed circularly polarized light exponentially attenuates with the cholesteric layer thickness since the COTS frequency falls into the stop band. Cross-handed circularly polarized light freely goes through the cholesteric layer and can excite COTS when reflected from the handedness-preserving mirror. The coupling in this case is proportional to anisotropy of the cholesteric and theoretically it is only anisotropy of magnetic permittivity that can ultimately cancel this coupling. These two couplings being equal results in a polarization crossover (the Kopp--Genack effect) for which a linear polarization is optimal to excite COTS. The corresponding cholesteric thickness and scattering matrix for COTS are generally described by simple expressions.

The study of the change in entropy during the formation of stars in collapsing molecular clouds is an important area of research in astrophysics. As the cloud decreases in size, the presence of gases leads to an increase in entropy. However, the extent of this change in entropy is influenced by the amount of space available for the gases. In this scientific investigation, I conduct a detailed analysis of entropy on a small scale within the contracting cloud, following the principles of the second law of thermodynamics. Initially, my focus is on a turbulent cloud composed of N particles with a mass of M, which collapses under the force of gravity. It becomes clear that in order for the collapse to occur, gravitational energy must overcome other pressure forces that oppose it. This process results in the rapid movement of particles within the cloud, ultimately leading to a change in entropy

The immune response is crucial in Pregnancy Loss (RPL), which affects 1-2% of women. In RPL, peripheral blood lymphocytes and local immune cells are activated with a concomitant decrease in the leukocyte tolerogenic response in the uterus and decidua. IL-17 plays an essential role in T cell activation, weakening tolerogenic responses of the T cells. The report aims to analyze the IL-17 genetic polymorphism, circulating IL-17 lymphocyte populations, the reaction upon lymphocyte priming, the amount of cytokine in serum, and the number of T-reg cells in a group of 50 RPL and 50 normal women from the admixed Venezuelan population. No differences were observed in the genetic polymorphisms rs2275913 and rs763780. A significant decrease (P&lt;0.001) was observed in RPL patients compared to controls in the IL-17+ cell populations CD3+, CD8+, CD56+, and CD4CD25 FoxP3, but not in the CD4IL17+ cells. The response upon cell priming was significantly decreased (P&lt;0.001) in all subpopulations of RPL as compared to controls. It is concluded that despite the increase in IL-17A in the serum of patients, the number of circulating IL-17 cells and the lymphocyte response to stimulation was significantly decreased (p&lt;0.001). No differences in the genetic polymorphism compared to controls suggest that biological factors influence IL-17 levels in RPL patients, which must be carefully studied.

Acoustic emissions (AE) are produced by elastic waves generated by damage in solid materials. AE sensors have been widely used in several fields as a promising tool to analyze damage mechanisms such as cracking, dislocation movement, etc. However, accurately determining the location of damage in solids in a non-destructive manner is still challenging. In this paper, we propose a crack wave arrival time determination algorithm that can identify crack waves with low SNR(signal-to-noise ratios) generated in rocks. The basic idea comes from that the variances of the crack wave and noise have different characteristics depending on the size of the moving window. The results can be used to accurately determine the crack source location. The source location is determined by observing where the variance in the crack wave velocities of the true and imaginary crack location reach a minimum. By performing a pencil lead break test using rock samples, it was confirmed that the proposed method could successfully find wave arrival time and crack localization. The results using the proposed algorithm to detect crack wave source localization suggest use for evaluating and real-time monitoring of damage in tunnels or other underground facilities.

Dielectric barrier discharge (DBD) plasma has several applications in different fields. One of these fundamental applications is medical usages, where various methods are employed to improve the plasma treatment process. The combination of different gases is one of the important strategies to improve the performance of plasma in treatment. In this paper, the optimized plasma parameters for one-dimensional radiofrequency discharge produced at low pressures in a helium gas combination is studied. In this research, the optimal combination of H₂O and He is identified to attain the highest amount of reactive oxygen species (ROS). Considered mixture are 5,10,15 and 20 precent of H₂O for one dimensional helium gas discharge. The results show that the parameters of the output plasma are highly dependent on the composition of the input gases. It is found that the greatest concentrations of H+, He+, Hes (excited helium), and OH/ densities are observed when the H₂O percentage is 10%. Moreover, the density distributions of various species and the temperatures of electrons are numerically calculated during the electrical discharge process. These findings provide useful knowledge on how to optimize plasma parameters for biomedical applications, which may lead to improved treatment results in several therapeutic areas.

The BET family of proteins is characterized by the presence of two tandem bromodomains and an extra-terminal domain. The mammalian BET family of proteins comprises Brd2, Brd3, Brd4, and Brdt, which are encoded by paralogous genes that may have been generated by repeated duplication of an ancestral gene during evolution. Bromodomains that can specifically bind acetylated lysine residues in histones serve as chromatin-targeting modules that decipher the histone acetylation code. BET proteins play a crucial role in regulating gene transcription through epigenetic interactions between bromodomains and acetylated histones during cellular proliferation and differentiation processes. On the other hand, BET proteins have been reported to mediate latent viral infection in host cells and be involved in oncogenesis. Human BRD4 is involved in multiple processes of the DNA virus life cycle, including viral replication, genome maintenance, and gene transcription through interaction with viral proteins. Aberrant BRD4 expression contributes to carcinogenesis by mediating hyperacetylation of the chromatin containing the cell proliferation-promoting genes. BET bromodomain blockade using small-molecule inhibitors gives rise to selective repression of the transcriptional network driven by c-Myc. These inhibitors are expected to be potential therapeutic drugs for a wide range of cancers. This review presents an overview of the basic roles of BET proteins and highlights the pathological functions of BET and the recent developments in cancer therapy targeting BET proteins in animal models.

Enveloped viruses represent a significant category of pathogens that cause serious diseases in animals. These viruses express envelope glycoproteins that are singularly important during infection of host cells by mediating fusion between the viral envelope and host cell membranes. Despite low homology at protein levels, three classes of viral fusion proteins have, as of yet, been identified based on structural similarities. Their incorporation into viral particles is dependent upon their proper sub-cellular localization after being expressed and folded properly in the endoplasmic reticulum (ER). However, viral protein expression can cause stress in the ER, and host cells respond to alleviate the ER stress in the form of the unfolded protein response (UPR); the effects of which have been observed potentiating or inhibiting viral infection. One important arm of UPR is to elevate the capacity of the ER-associated protein degradation (ERAD) pathway, which is comprised of host quality control machinery that ensures proper protein folding. In this review, we provide relevant details regarding viral envelope glycoproteins, UPR, ERAD, and their interactions in host cells.

Human serum albumin (HSA) corona formation at polymer microparticles of a spheroidal shape was studied using dynamic light scattering and laser Doppler velocimetry (LDV). Physicochemical characteristics of the albumin comprising, the zeta potential and the isoelectric point were determined as a function of pH for various ionic strengths. Analogous characteristics of the polymer particles were carried out. The adsorption of albumin on the particles was monitored by electrophoretic mobility measurements (LDV). The stability of the HSA functionalized particle suspensions under various pHs and their electrokinetic properties were determined. The deposition kinetics of the particles on mica, silica and gold sensors were determined in situ by optical microscopy, AFM and by the quartz microbalance (QCM) under diffusion and flow conditions. The obtained results were interpreted in terms of the coarse-grained random sequential adsorption model that allowed to estimate the range of applicability of QCM for determining deposition kinetics of virus and bacteria at abiotic surfaces.

In bacteria, enzymes usually comprise of enzymatic domains only. In eukaryotes/mammals, and here particularly in context of signal transduction, proteins with enzymatic functions contain additional modules promoting interactions with cooperating signaling proteins. Often such protein-protein interaction domains, such as SH2- and SH3-domains, help to localize the enzymatic function (e.g. kinase, phosphatase) to another protein, cellular compartment, or membrane nanodomain. In such cases, the interaction domain(s) serve(s) the enzymatic function. However, there are molecular situations in which an interaction domain fulfills its task completely independent of the protein´s enzymatic function and in this review, we call such function the adapter function of an enzyme. Though many stories can be told, we will concentrate on several proteins playing crucial roles in cells of the immune system, such as BTK, PI3K, and SHIP1, as well as in cancer cells, such as proteins of the RAS/ERK MAPK pathway. We will also discuss how these adaptor functions of enzymes determine or even undermine the efficacy of targeted therapy compounds, such as ATP-competitive kinase inhibitors, thereby highlighting the need to develop pharmacological approaches, such as PROTACs, that eliminate the entire protein. We also review how genetic kock-out and knock-in approaches can be leveraged to identify adaptor functions of signaling proteins.

Silencing of the fragile X mental retardation 1 (FMR1) gene and consequently lack of synthesis of FMR protein (FMRP) are associated with fragile X syndrome, which is one of the most prevalent inherited intellectual disabilities. FMRP is a multifunctional protein involved in many cellular functions in nearly all subcellular compartments under normal conditions and under conditions of cellular stress in both neuronal and non-neuronal cell types. This is achieved through its trafficking signals, nuclear localization signal (NLS), nuclear export signal (NES), and nucleolar localization signal (NoLS), as well as its RNA and protein binding domains, and is modulated by various post-translational modifications such as phosphorylation, ubiquitination, sumoylation, and methylation. This review summarizes recent advances in understanding the interaction networks of FMRP with a special focus on FMRP stress-related functions, including stress granule formation, mitochondrion and endoplasmic reticulum plasticity, ribosome biogenesis, cell cycle control, and DNA damage response.

The social fear conditioning (SFC) paradigm, which is an animal model of social anxiety disorder, has been extensively used to investigate the cellular and molecular mechanisms underlying the psychopathology of this disorder. Studies using the SFC paradigm have suggested that the lateral septum plays a pivotal role in regulating social fear. While several lines of evidence have indicated the involvement of various neuronal mechanisms within the LS in modulating social fear, the role played by LS astrocytes in the tripartite synapses in regulating social fear expression is not yet fully understood. Over the years, astrocytes have emerged as key players in regulating synaptic transmission and a plethora of animal behaviors. Given their dynamic morphological and molecular response to various stimuli, studying astrocyte morphology remains an excellent tool for understanding their role in brain function and disease. By applying immunofluorescent-immunohistochemical methods, here we describe a protocol to characterize changes in the morphology of astrocytes in response to social fear acquisition using confocal microscopy.

Anaerobic digestion is a biological process that transforms high-strength organic effluents into biogas with multiple benefits. However, concurrent with organics' biological transformation, a liquid phase with a high solid content is also derived from this process. Valorizing this fraction is not an easy task if an agronomic application cannot be considered as a suitable option. The thermal valorization of this fraction allows for energy extraction, but also gives rise to additional capital investment and increases the energy demand of the global process. In addition, the thermal treatment of digestate has to deal with a mineralized material. The changes in organic matter due to anaerobic stabilization were studied in the present manuscript, by evaluating the thermal behavior of samples, activation energy and organic transformation using FTIR spectroscopy. Digested samples of a mixture composed of manure and glycerin (5% v/v) were studied. The stabilization caused a dramatic decrease in aliphatic compounds, greatly increasing the mineral content of the sample. Thermal valorization of digestates must consider the lower energy content and more complex structure of these materials, with higher content of lignin and protein-type compounds.

Cotton fiber is the leading natural textile material, and fiber elongation plays an essential role in the formation of cotton yield and quality. Although a wealth of components in the molecular network controlling cotton fiber elongation have been reported, a lot of players still need to be functionally dissected to understand the regulatory mechanism of fiber elongation comprehensively. In the present study, an R2R3-MYB transcription factor gene, GhMYB201, was characterized and functionally verified via CRISPR/Cas9 mediated gene editing. GhMYB201 was homologous to Arabidopsis AtMYB60, and both coding genes (GhMYB201At and Dt) were preferentially expressed in elongating cotton fibers. Knocking-out of GhMYB201 significantly reduced the rate and duration of fiber elongation, resulting in shorter and coarser mature fibers. It was found that GhMYB201 could bind and activate the transcription of cell wall loosening genes (GhRDLs), and also β-ketoacyl-CoA synthase (GhKCSs) genes to enhance very-long-chain fatty acid (VLCFA) levels in elongating fibers. Taken together, our data demonstrated that the transcription factor GhMYB201s play essential roles in promoting fiber elongation via activating genes related to cell wall loosening and VLCFA biosynthesis.

This study focuses on the potential medicinal properties of Campsis radicans L. extracts and its aim is to investigate the antioxidant and antiproliferative effects of these extracts on the human colon adenocarcinoma cell line (HT-29). Cytotoxic activity in the HT-29 cell line was evaluated, and the 3-dimensional structures of phenolic compounds were obtained using the GC-MS method. Docking simulations were performed with AutoDock Vina, targeting proteins that are crucial in the apoptotic pathway (Bax, Bcl-2, and Caspase-3). Drug similarities and ADMET estimates of the phenolic compounds were obtained from databases. The highest antioxidant activity of Campsis radicans L. plant was observed in ethanol and water extracts, with notable inhibition capacities. While the total phenolic content was highest in ethanol, water, and ether extracts respectively the total flavonoid content was highest in ethanol, then ether, and water extracts. Certain elements were undetectable in mineral determination, and others exceeded the toxic doses for plants. The water extract exhibited dose-dependent cytotoxic activity in the HT-29 cell line, with an IC50 value of 4.47 mg/mL. Molecular docking results revealed the binding of phenolic molecules to the active sites of apoptotic pathway proteins. The findings suggest that Campsis radicans L. plant possesses cytotoxic properties, significant phenolic and flavonoid content, and a high antioxidant capacity. These properties make it a potential candidate for treatment use, emphasizing its potential therapeutic value in the HT-29 cell line. Further research and exploration on the identified phenolic compounds could contribute to the development of novel therapeutic agents.

Plant growth-promoting rhizobacteria (PGPR) are beneficial bacteria that play a crucial role in sustainable agriculture by enhancing plant growth through various mechanisms. This review examines the contributions of PGPR in improving nutrient availability, producing phytohormones, providing biocontrol against pathogens, and enhancing abiotic stress tolerance. By reducing the necessity for chemical fertilizers and pesticides, PGPR mitigate environmental impacts, enhance soil health, and support long-term agricultural productivity. However, challenges such as inconsistent performance across various soils, regulatory barriers, and limited farmer awareness hinder their widespread adoption. Recent advancements in nano-encapsulation technology, genetic engineering, and bioinformatics present promising solutions for overcoming these obstacles and enhancing PGPR efficacy. The incorporation of PGPR into biofertilizers, biopesticides, and integrated pest management (IPM) strategies offers a sustainable resolution to global agricultural challenges. This review addresses the current state of PGPR research, applications, and future directions for optimizing their use in promoting sustainable agriculture.

The interaction forces and mechanical properties of the interaction between melittin (Mel) and lipopolysaccharide (LPS) are considered a crucial driving force for Mel in killing Gram−negative bacteria (GNB). However, how their interaction forces are performed at the single−molecule level and the dissociation kinetic characteristics of the Mel/LPS complex remain poorly understood. In this study, the single−molecule level interaction forces between Mel and LPSs from E. coil K−12, O55:B5, O111:B4, and O128:B12 were explored using atomic force microscopy (AFM) based single−molecule force spectroscopy (SMFS). Further, the AFM−based dynamic force spectroscopy (DFS) and advanced analytical model were employed to investigate the kinetic characteristics of the Mel/LPSs complex dissociation. The results indicated that Mel could interact with both rough (R)−form LPS (E. coli K−12) and smooth (S)−form LPSs (E. coli O55:B5, O111:B4, O128:B12), and the S−form LPSs showed a more robust interaction with Mel than R−form LPS, and a slight difference existed in the interaction forces between Mel and diverse S−form LPSs. The Mel interacts with S−form LPSs showed greater specific and non−specific interaction forces than R−form LPS (p &lt; 0.05), as determined by AFM−based SMFS. However, there was no significant difference in the specific and non−specific interaction forces among the three S−form LPSs (p &gt; 0.05), indicating the variability of O−antigen could not affect the interaction between Mel and LPSs. The DFS result showed that the Mel/S−form LPSs complexes had a lower dissociation rate constant (koff), a shorter energy barrier width (xβ), a longer bond lifetime (τoff), and a higher height of the energy barrier (∆G), demonstrating that Mel could interact with S−form LPSs to form more stable complexes. In conclusion, this study promotes our knowledge of the interaction micromechanics and kinetics characteristics between Mel and LPS at the single−molecule level. Moreover, it can help us design and evaluate new anti−GNB drugs.

Liver fibrosis, a consequence of chronic liver damage or inflammation, is characterized by the excessive buildup of extracellular matrix components. This progressive condition significantly raises the risk of severe liver diseases like cirrhosis and hepatocellular carcinoma. The lack of approved therapeutics underscores the urgent need for novel anti-fibrotic drugs. Hepatic stellate cells (HSCs), key players in fibrogenesis, are promising targets for drug discovery. This study investigated the anti-fibrotic potential of Citrus hystrix DC. (KL) and its bioactive compound, β-citronellol (β-CIT), in a human HSC cell line (LX-2). Cells exposed to TGF-β1 to induce fibrogenesis were co-treated with crude KL extract and β-CIT. Gene expression was analyzed by Real-Time qRT-PCR to assess fibrosis-associated genes (ACTA2, COL1A1, TIMP1, SMAD2). The releasing of matrix metalloproteinase 9 (MMP-9) was measured by ELISA. Proteomic analysis and molecular docking identified potential signaling proteins and modeled protein-ligand interactions. Results showed that both crude KL extract and β-CIT suppressed HSC activation genes and MMP-9 levels. The MAPK signaling pathway emerged as a potential target of β-CIT. This study demonstrates the ability of KL extract and β-CIT to inhibit HSC activation during TGF-β1-induced fibrogenesis, suggesting a promising role of β-CIT in anti-hepatic fibrosis therapies.

Transition-metal-free synthesis of 4-pyrones via TfOH-promoted nucleophilic addition/cyclization of diynones and water has been developed. This transformation is simple, atom economical and environmentally benign, providing rapid and efficient access to substituted 4-pyrones.

Background: G6PD is a rate-limiting enzyme of the pentose phosphate pathway. The loss of G6PD activity in red blood cells exposes to the risk of acute haemolytic anaemia under oxidative stress, induced by infections, some medications, or fava beans. More than 200 single missense mutations are known in the G6PD gene. This study reports a 41-year-old woman coming from Basilicata region (Italy) that carried out the G6PD status in our hospital for prenatal investiga-tions. Methods: DNA was extracted from peripheral blood sample and genotyped for common-est G6PD pathogenic variants (PVs). Positive results obtained by Restriction Fragment Length Polymorphism (RFLP), as per practice in our laboratory, are then re-confirmed in Sanger se-quencing. Results: RFLP analysis highlighted a variant compatible with G6PD Cassano variant. Confirmatory testing by Sanger unexpectedly identified a novel variant: c.1357G>A, p.(Val453Met) (NM_001360016.2). In silico models predicted a deleterious effect of this variant at the protein level. The novel G6PD variant was named "G6PD Potenza", on the basis of the pa-tient's regional origin. Conclusion: This case describes a novel G6PD variant. It also highlights how the Sanger sequencing technique still represents an indispensable confirmatory standard method for variants that could be miss-interpreted by using of “first-level” approached, as the RFLP. We stress that the evaluation of clinical manifestations in G6PD deficient patients is of primary importance for the classification of each new G6PD mutation, in agreement with the new WHO guidelines.

Carotid atherosclerotic lesions are a major cause of cerebrovascular disease (CVD). Identification and quantification of carotid plaques are important for categorizing the vulnerability of plaques for rupture and assessing the impact of treatments. The irregularity of plaque surface is associated with previous plaque rupture and plays an important role in the risk of stroke. Thus, the aim of this study is to develop and validate novel vulnerability biomarkers from three-dimensional ultrasound (3DUS) images by analyzing the surface morphological characterization of carotid plaque using fractal geometry features. 3D box-counting and 3D blanket are the two types of 3D fractal dimension that were employed to describe the smoothness of plaques. This fractal dimension analysis tool was used to evaluate the effect of atorvastatin using 3DUS carotid images, which were acquired from 6 patients treated with atorvastatin with 80 mg daily and 5 patients with placebo. The Student's T Test results showed that those two fractal features were effective for detecting the statin-related changes in carotid atherosclerosis with p<0.0068 and p<0.015 respectively, suggesting that 3D fractal dimension measurements can be used effectively to analyze the surface characteristics of carotid plaques, especially for evaluating the impact of the treatment.

This article develops a multi-perspective view on motivations and methods for tobamovirus purification through the ages, and presents a novel efficient, easy-to-use approach that can be well-adapted to different species of native and functionalized virions. We survey the various driving forces prompting researchers to enrich tobamoviruses: from the search for the causative agents of mosaic diseases in plants to their increasing recognition as versatile nanocarriers in biomedical and engineering applications. Best practice and also rarely applied options for the serial processing steps required for successful isolation of tobamoviruses are then reviewed. Adaptations for distinct particle species, pitfalls and 'forgotten' or underrepresented technologies are considered as well. The article is topped off with our own development of a method for virion preparation, rooted in historical protocols. It combines selective re-solubilization of polyethylene glycol (PEG) virion raw precipitates with density step gradient centrifugation in biocompatible iodixanol formulations, yielding ready-to-use particle suspensions. This newly established protocol and some considerations for perhaps worthwile further developments could serve as putative stepping stones towards preparation procedures appropriate for routine practical uses of the multivalent soft-matter nanorods.

The process of oxygenic photosynthesis is primarily driven by two multiprotein complexes known as photosystem II (PSII) and photosystem I (PSI). PSII facilitates the light–induced reactions of water–splitting and plastoquinone reduction, while PSI functions as the light–driven plastocyanin-ferredoxin oxidoreductase. In contrast to the highly conserved structure of PSII among all oxygen–evolving photosynthetic organisms, the structures of PSI exhibit remarkable variations, especially for photosynthetic organisms that grow in special environments. In this review, we make a concise overview of the recent investigations of PSI from photosynthetic microorganisms including prokaryotic cyanobacteria and eukaryotic algae from the perspective of structural biology. All known PSI complexes contain a highly conserved heterodimeric core; however, their pigment compositions and peripheral light-harvesting proteins are substantially flexible. This structural plasticity of PSI reveals the dynamic adaptation to environmental changes for photosynthetic organisms.

Gestational trophoblastic diseases (GTDs) encompass a spectrum of conditions characterized by abnormal trophoblastic cell growth, ranging from benign molar pregnancies to malignant trophoblastic neoplasms. This systematic review explores the molecular underpinnings of GTDs, focusing on genetic and epigenetic factors that influence disease progression and clinical outcomes. Based on 65 studies identified through systematic search and selection criteria, key findings include dysregulations in tumor suppressor genes such as p53, aberrant apoptotic pathways involving BCL-2, and altered expression of growth factor receptors and microRNAs. These molecular alterations not only differentiate molar pregnancies from normal placental development but also contribute to their clinical behavior, from benign moles to potentially malignant forms. The review synthesizes insights from immunohistochemical studies and molecular analyses to provide a comprehensive understanding of GTD pathogenesis and implications for personalized care strategies.

Type-1 Diabetes Mellitus (T1D) onset and development is closely linked with imbalance of gut microbiome, while supplementation with probiotics may result in positive alterations in gut microbiome composition. In the present study, the effect of a dietary intervention including free or immobilized cells of the presumptive probiotic Pediococcus acidilactici ORE5 on Corinthian currants, a food with beneficial impact in the condition of diabetes, was investigated. Male Wistar rats were studied which were divided into 4 groups: healthy animals, which received the free (H_FP) or the immobilized cells (H_IPC), and diabetic animals, which received the free (D_FP) or the immobilized cells (D_IPC), for 4 weeks (109 cfu/day, in all groups). At the end of the dietary intervention, D_IPC group exerted lower concentration of the inflammatory cytokine IL-1b compared to D_FP. Consumption of immobilized on Corinthian currants P. acidilactici ORE5 cells by diabetic animals led to increased loads of fecal lactobacilli and lower levels of Enterobacteriaceae, coliforms, and E. coli, while Actinobacteria phylum, Akkermansia, and Bifidobacterium genera abundances were increased, and fecal lactic acid was elevated. Overall, the results of the present research demonstrated that functional ingredients can ameliorate gut dysbiosis present in T1D and could be used to design dietary patterns aiming at T1D management. However, well-designed clinical trials are necessary, in order to confirm the beneficial effects in humans.

A lead zirconate titanate [PZT;Pb(Zr_0.52Ti_0.48)O₃] layer embedded infrared (IR) detector decorated with wavelength-selective plasmonic crystals has been investigated for high-performance non-dispersive infrared (NDIR) spectroscopy. A plasmonic IR detector with an enhanced IR absorption band has been designed based on numerical simulations, fabricated by conventional microfabrication techniques, and characterized with a broadly tunable quantum cascade laser. The enhanced responsivity of the plasmonic IR detector at specific wavelength band has improved the performance of NDIR spectroscopy and pushed the limit of detection (LOD) by an order of magnitude. In this paper, a 13 fold enhancement in the LOD of a methane gas sensing using NDIR spectroscopy is demonstrated with the plasmonic IR detector.

Many fundamental molecular techniques (PCR, Microarray, Southern and northern hybridization, siRNA, CRISPR/Cas9 etc.) developed so far shows errors. I wish to highlight these molecular techniques are developed on basis of Watson-Crick DNA model, ignoring the concept of parallel stranded DNA. Through this opinion article, I wish to highlight specificity and accuracy of these molecular techniques can be enhanced by considering both parallel and anti parallel hybridization of DNA. Hopefully my views will also solve issue of irreproducibility in life science research.

The development of a rapid, sensitive, specific method for detecting foodborne pathogens is paramount in supplying safe food to enhance public health safety. Despite the significant improvement in pathogen detection methods, key issues are still associated with rapid methods, such as distinguishing living cells from dead, pathogenic potential or health risk of the analyte at the time of consumption, detection limit, and sample-to-result. The mammalian cell-based assays analyze pathogens' interaction with the host cells and are responsive to only live pathogens or active toxins. In this study, a human embryonic kidney (HEK293) cell line expressing Toll-Like Receptor 5 (TLR-5) and chromogenic reporter system (HEK dual hTLR5) was used for the detection of viable Salmonella in a 96-well tissue culture plate. This cell line responds to low concentrations of TLR5 agonist flagellin. Stimulation of TLR5 ligand activates nuclear factor-kB (NF-κB) - linked alkaline phosphatase (AP-1) signaling cascade inducing the production of secreted embryonic alkaline phosphatase (SEAP). With the addition of a ρ-nitrophenyl phosphate as a substrate, a colored end product representing a positive signal is quantified. The assay's specificity was validated with the top 20 Salmonella enterica serovars and 19 non-Salmonella spp. The performance of the assay was also validated with spiked food samples. The total detection time (sample-to-result), including shortened pre-enrichment (4 h) and selective enrichment (4 h) steps with artificially inoculated outbreak-implicated food samples (chicken, peanut kernel, peanut butter, black pepper, mayonnaise, and peach) was 15 h when inoculated at 1–100 CFU/25 g sample. These results show the potential of HEK-DualTM hTLR5 cell-based functional biosensors for rapid screening of Salmonella.

Recurrent pregnancy loss (RPL) affects around 2 % of women of reproductive age. Primary RPL is defined by ≥2 pregnancy losses and no normal birth delivery. In secondary RPL, the losses are after a normal pregnancy and delivery. Most cases have no clear aetiology, although primary cases are the most complex. Several gene polymorphisms have been associated with RPL. Some polymorphisms are increased in women of Asian or Caucasian race. In admixed RPL populations, the information on possible genetic links is scarce and contradictory. The study aimed to assess the frequency of two SNP in different enzymes involved in medical conditions observed during pregnancy. Microsomal epoxy hydrolase (mEPH) is involved in detoxifying xenobiotics. It is present in ovaries, and it is hormonally regulated. The endothelial nitric oxide synthase forms nitric oxide from arginine and is involved in vascular tone. Two SNPs, rs1051740 and rs1799983, were assessed. The study included 26 controls and 63 primary RPL patients. Significant differences were observed in the frequencies of both SNP (p<0.05). The frequency of mutated alleles was higher in patients. Double mutated homozygotes were encountered only in RLP patients (p<0.05). Genetic polymorphisms rs1051740 and rs1799983 may be involved in primary RPL in the Venezuelan admix population. Genetic studies could provide crucial information on the aetiology of primary RPL.

The African continent has the highest prevalence of hypertension globally, with South Africa reporting the highest prevalence in Southern Africa. While the influence of genetic variability in the pathogenesis of hypertension is well described internationally, limited reports are available for African populations. This study aimed to assess the association of genetic variants and essential hypertension in a cohort of two ethnic South African population groups. Two hundred and seventy-seven hypertensive and one hundred and seventy-six normotensive individuals were genotyped for 79 variants. Genotyping was performed using the Illumina GoldenGate Assay and allele-specific polymerase chain reaction. The association of variants was assessed using the Fisher Exact test under the additive and allelic genetic models, while multivariate logistic regression was used to predict the development of hypertension. Five variants (CYP11B2 rs179998, AGT rs5051 and rs699, AGTR1 rs5186 and ACE rs4646994) were significantly associated with essential hypertension in the cohort under study. Furthermore, AGTR1 rs5186 and AGT rs699 were identified as risk factors for the development of hypertension in both ethnic groups. In two ethnic South African populations an association was observed between Renin-Angiotensin-Aldosterone System (RAAS) related genes and the development of hypertension.

Global warming and the associated increasing frequency of heatwaves are on the rise leading to numerous health complications. Diabetic patients are more vulnerable to heat exposure than healthy individuals, owing to their impaired sweating ability, however, little is known about how heat exposure may impact the function of skin cells, commonly keratinocytes. Our recent report provided the first proof-of-concept revealing that the metabolic composition of sweat EVs is associated with metabolic changes in healthy individuals and type 2 diabetes patients. Given this and the shared cellular proprieties of eccrine sweat glands with keratinocytes, we questioned whether the metabolic changes in sweat EVs may mirror the responses of keratinocytes upon heat exposure. To this, we exposed HaCat, which were maintained in low (mimicking healthy condition) and high glucose (mimicking diabetes condition) to acute (90 min), chronic (48 h), and repetitive heat exposure at 40 ⁰C. Through conducting a set of experiments including a targeted metabolomics approach, Greiss assay, western blotting analysis, and electron microscopy studies. The data demonstrate that heat exposure results in substantial changes of metabolite levels belonging to amino acids, pyrimidine metabolism, and glycolysis pathways in high glucose maintained HaCat cells when compared to those noted in low glucose condition. Exploring the molecular mechanisms through which heat exposure may impact the metabolic composition in keratinocytes, our discoveries highlight nitric oxide (NO) as a novel biomarker that the level is correlated with heat duration and frequency. Furthermore, data reveal that the HSP-70 protein levels and mitochondrial morphology are consequently altered. This study provides evidence of shared metabolic alterations in keratinocytes and sweat EVs collected from clinical study and proposes, for the first time, NO as a novel biomarker for monitoring changes in health and diabetes upon heat exposure.

The p53 tumor suppressor protein is an activator of transcription. Diverse stress factors lead to various sets of posttranslational modifications of p53 what results in different sets of upregulat-ed genes. We noticed that actinomycin D and nutlin-3a (A+N) synergize in inducing activating phosphorylations of p53 and upregulation of selected p53-target genes. Here we found that one of these genes is DUSP13, which codes for poorly-studied, dual-specificity phosphatase having at least two isoforms, one expressed in testis and the other in skeletal muscles. In cancer cells ex-posed to A+N, DUSP13 is expressed from an alternative promoter in intron, what results in ex-pression of isoform named TMDP-L1. The luciferase reporter tests demonstrated that this pro-moter is activated by both endogenous and ectopically expressed p53. We showed for the first time that mRNA expressed from this promoter actually produces the protein, which can be de-tected by Western blotting in all examined cancer cell lines with wild-type p53 exposed to A+N. In some cell lines it is also induced by clinically relevant camptothecin or by nutlin-3a acting alone. This isoform, fused with green fluorescent protein localizes in perinuclear region of cells. Thus, TMDP-L1 isoform may be an important element of p53-regulated stress response system.

. Protein cysteine S-glycosylation is a relatively rare and less well characterized post-translational modification (PTM). Creating reliable model proteins that carry this modification is challenging. The lack of available model or natural S-glycosylated proteins significantly hampers the development of MS-based methodologies for detecting protein cysteine S-glycosylation in real-world proteomic studies. There is also limited MS-sequencing data describing easier to create synthetic S-glycopeptides. Here, we present the results of an in-depth manual analysis of automatically annotated CID/HCD spectra for model S-glucopeptides. The CID spectra show a long series of y/b-fragment ions with retained S-glucosylation, regardless of the dominant m/z signals corresponding to neutral loss of 1,2-anhydroglucose from the precursor ions. In addition, the spectra show signals manifesting glucosyl transfer from the cysteine position onto Lys, Arg side chains, and a peptide N-terminus. Other spectral evidence indicates that the N-glucosylated initial products of transfer are converted into N-furanosylated (i.e., glycated) structures due to Amadori rearrangement. We discuss the peculiar transfer of the glucose oxocarbenium ion (Glc+) to positively charged guanidinium residue (ArgH+) and propose a mechanism for the gas-phase Amadori rearrangement involving a hydride ion shift.

Chronic kidney disease patients treated by hemodialysis present a high cardio-vascular morbidity and mortality. There is an imperative need for novel biomarkers in identifying and to offer possible therapeutically intervention in these patients. We performed a prospective observational cohort study on 77 patients in the period October 2021 – October 2023. We measured serum plasma levels of Interleukin 1-Beta, Galectin 3, human suppression of tumorigenicity factor 2, bone morphogenetic protein 2 and fibroblastic growth factor 23 at the inclusion. We evaluated the correlations of these biomarkers with cardiac function and structure evaluated by echocardiography. Mean age was 61.02 (±11.81) years, 45 (56.2%) males and with a dialysis vintage of 4.95 (2.4-7.8) years. Median ejection fraction was 51 (43-54 %) and more than two thirds of the patients presented valvular calcifications. Overall mortality was 22%. Interleukin 1-Beta correlated positively with ejection fraction and global longitudinal strain and negatively with left atrium diameter and left ventricle tele systolic diameter. Galectin 3 values negatively correlated with aortic valve fibrosis and mitral valve calcifications and human suppression tumorigenity factor 2 negatively correlated with mitral valve calcifications. Some of these novel biomarkers could be used to better asses the cardio-vascular disease in patients on maintenance hemodialysis.

Currently, SARS-CoV-2 has evolved into various variants, including the numerous highly mutated Omicron sub-lineages, significantly increasing immune evasion ability. The development raises concerns about possibly diminished effectiveness of available vaccines and antibody-based therapeutics. Here, we describe those representative categories of broadly neutralizing antibodies (bnAbs) that retain prominent effectiveness against emerging variants including Omicron sub-lineages. The molecular characteristics, epitope conservation, and resistance mechanisms of these antibodies are further detailed, aiming to offer suggestion or direction for the development of therapeutic antibodies, and facilitate the vaccine design with broad-spectrum potential.

Darier disease (DD) is an autosomal dominant disorder due to mutation of ATP2A2 gene causing an isolated skin manifestation based on keratinocyte disconnection and apoptosis. Systemic manifestations of DD have not been demonstrated so far although a high incidence of neuropsychiatric syndromes suggest an involvement of central nervous system. A Novel ATP2A2 Gene Mutation c.118G>A, causing keratinocyte and cardiomyocyte disconnection in Darier disease, is reported. Their common pathologic pathway, still unreported, was documented by both skin and left ventricular endomyocardial biopsy because of cardiac dilatation and dysfunction appeared several decades after skin manifestations.Keratinocyte disconnection was paralleled by cardiomyocyte separation at lateral junction. Cardiomyocyte separation was associated to cell disarray, sarcoplasmic reticulum dilatation and increased myocyte apoptosis. Clinically, hyperkeratotic skin papules were associated to chest pain, severe muscle exhaustion and ventricular arrhythmias that improved following administration of aminophylline, a phosphodiesterase inhibitor enhancing SERCA2 protein phosphorylation.Specific mutations of ATP2A2 gene may cause cardiac involvement in patients with DD. Cardiac pathologic changes are similar to those documented in the skin including cardiomyocyte disconnection that promotes precordial pain and cardiac arrhythmias. Phosphodiesterase inhibitors, enhancing SERCA2 protein phosphorylation may substantially attenuate the symptoms.

Nose mask is a fomite and its usage was mandatory during the COVID-19 outbreak. Its effectiveness has been established; however, as a fomite, it can harbor opportunistic respiratory pathogens such as Streptococcus spp., which could complicate COVID-19 infections. This study profiled Streptococcus species resident on nose masks obtained from consenting participants. Phenotypic assays and 16S rRNA sequencing were used to identify Streptococcus spp. resident on the interior and exterior of 100 nose masks analyzed. Antibiotic resistance (AMR) was determined with disc diffusion and broth microdilution assays. AMR and virulence makers were profiled with primer-specific PCR amplification. 23% of the analyzed samples had Streptococcus isolates. The isolates were highly resistant to the antimicrobials, including conventional, last-resort antibiotics, disinfectants and antiseptics. All the isolates are multidrug resistant with 80-100% levels of AMR to the 16 antibiotics tested with a Multiple-Antibiotic Resistance index greater than 0.2, indicative of potential pathogens. The isolates harbored tetB, ermB, pbp2B, pbp2b1 (resistance) and lytA, lytA1, ply1, cbpA, lytA, pavA (virulence) markers, which might constitute a serious public health risk. Overall, the study emphasizes the need to assess mask usage and the risks associated with opportunistic pathogens that are resident on frequently used nose masks in the COVID-19 era.

Diesel is consistently a very popular fuel for internal combustion engines. Its consumption in the European Union has been rising over recent years, as has the number of engines increasingly sensitive to fuel contamination. One of the most important parameters affecting diesel quality is water content. Although its exceedances of the standard’s permissible amount are not common, they carry the risk of serious damage to expensive, modern fuel injection systems. Current methods of measuring water content require both specialised personnel and equipment, as well as transporting the sample to a suitable laboratory. The research presented in this paper was aimed at verifying whether it would be possible to test the moisture content of diesel using impedance spectroscopy. Once refined, such measurement method could be used in situ. Analysing the properties of diesel is challenging, mainly because many types of the fuel are sold, the chemical composition of which is always a well-guarded manufacturer’s secret. The experimental results obtained on many types of commercially available diesel show that it is possible to use impedance spectroscopy to estimate the water content of different types of diesel fuel. The measurement accuracy achieved makes it possible to detect approaching or exceeding the permissible water content.

Salinity stress emerges as an important menace to global food security, particularly affecting susceptible crops such as common bean plants (Phaseolus vulgaris L.). The disruption of ion balances caused by salt stress withing plants cells reduces water and nutrient absorption, and hampers growth and productivity. Sacchorhiza polyschides, a brown macroalga rich in essential elements, and macrominerals, has drawn attention as a natural biostimulant, being a potential remedy to bolster crop resilience against salt stress. This study delves into the effect of water extracts of Sacchorhiza polyschides (SPE) across varying concentrations (1%, 2%, and 5%) in common bean plants under salt stress (68.4 mM NaCl) conditions. Two different methods of application were used: by spraying the aerial part of the plant or by irrigation together with the watering solution. The effects of both systems of application were studied on the aerial parts of the plants. SPE exhibited significant enhancements in morphological parameters, chlorophyll content, carbon-nitrogen activities, and antioxidant enzymatic system activities, alongside increasing osmolyte accumulation, compared to salt-stressed plants without biostimulation. Moreover, SPE reduced reactive oxygen species (ROS) levels caused by salt stress, mitigating lipid peroxidation. The concentrations of 2% and 5% SPE applied by spraying showed the most significant results in most of the parameters analyzed. By shedding light on the underlying science behind this biostimulant effect, this research underscores the potential of SPE to enhance crop resilience and augment food production in salt-challenged environments.

The wealth of data obtained during the past 20 years using Laser-Induced Breakdown Spectroscopy (LIBS) indicates that the technique is very promising to detect small chemical contents of alloying elements. The potential of LIBS was looked more seriously during the past two decades or so as more data were obtained on Aluminum and steel to study the phenomena in the condition of local thermodynamic equilibrium and time-delay between a Q-switch laser and an intensified CCD camera. Since the past decade, some data on compounds were also shown to be useful in determining small concentrations of harmful elements. This manuscript is intended to show that the technique of LIBS performance is very promising in fields such as micro-machining, in alloying element analysis, surface cleaning and environmental applications even with lightweight spectrometers having a relatively low resolution, which can potentially be air-borne.

Biohydrogen is a versatile energy carrier for the generation of electric energy from renewable sources. Hydrogenases can be used in enzymatic fuel cells to oxidize dihydrogen. The rate of electron transfer (ET) at the anodic side between the [NiFe]-hydrogenase enzyme distal iron-sulfur cluster and the electrode surface can be described by the Marcus equation. All parameters for the Marcus equation are accessible from DFT calculations. The distal cubane FeS-cluster has a three cysteine and one histidine coordination [Fe₄S₄](His)(Cys)₃ first ligation sphere. The reorganization energy (inner- and outer-sphere) is almost unchanged upon a histidine-to-cysteine substitution. Differences in rates of electron transfer between the wild-type enzyme and the all-cysteine mutant can be rationalized by a diminished electronic coupling between the donor and acceptor molecules in the [Fe₄S₄](Cys)₄ case. The fast and efficient electron transfer from the distal iron-sulfur cluster is realized by a fine-tuned protein environment which facilitates the flow of electrons. This study enables the design and control of electron transfer rates and pathways by protein engineering.

Due to its intriguing applications across a wide range of industries, nanotechnology is generating a lot of interest globally. Titanium dioxide (TiO2) nanoparticles are one type of nanoparticle (NP) that is commonly utilised in everyday use and can be produced using a variety of physical, chemical, and environmentally friendly techniques. Green synthesis is an economical, environmentally benign, and non-toxic method of synthesising NPs. Under normal circumstances, the application of TiO2 greatly enhanced the plants' shoot length, leaf area, and root dry weight. These growth-promoting factors coincided with elevated proline, soluble sugar, and chlorophyll B levels as well as improved antioxidant enzyme activity. Thus, higher levels of proline and other metabolites played a role in osmo-protection, while increased antioxidant enzyme activities helped to explain the observed decrease in hydrogen peroxide and malondialdehyde contents. Taken together, these factors significantly improved plant growth under salinity. TiO2 nanoparticles have demonstrated efficacy in treating contaminated water and have been shown to positively impact plant physiology, particularly in response to abiotic stresses. However, the reaction to these nanoparticles varies depending on characteristics such as metal species, type, size, shape, dose, duration of exposure, and other variables. One of the most popular nanomaterials in customer goods, agricultural, and energy industries is TiO2 NPs. Therefore, harm to ecosystems and living things will unavoidably result from high demand and widespread usage. Gaining more knowledge about the toxicity of TiO2 NP to living things could help with risk assessments and safe handling procedures for these nanoparticles. The synthesis of titanium oxide, its many uses, the toxicity of titanium dioxide nanoparticles, and their mode of toxicity are all summarised in this paper.

Plant-microbe interactions play a crucial role in shaping plant health and survival. In recent years, the role of extracellular vesicles (EVs) in mediating intercellular communication between plants and microbes has emerged as an intriguing area of research. EVs, serve as important carriers of bioactive molecules and genetic information, facilitating communication between cells and even between different organisms. Pathogenic bacteria leverage extracellular vesicles (EVs) to amplify their virulence, exploiting their cargo rich in toxins and virulence factors. Conversely, beneficial microbes initiate EV secretion to stimulate plant immune responses and nurture symbiotic relationships. The transfer of EV-packed small RNAs (sRNAs) has been demonstrated to facilitate the modulation of immune responses. Furthermore, harnessing the potential of EVs holds promise for the development of innovative diagnostic tools and sustainable crop protection strategies. This review highlights the biogenesis and functions of EVs in bacteria, and their importance in plant defense and paves the way for future research in this exciting field.

This work discusses laboratory measurements of atomic and diatomic molecular species in laser-plasma generated in gases. Noticeable self-absorption of the Balmer series hydrogen alpha line occurs for electron densities of the order of one tenth of standard ambient temperature and pressure density. Emission spectra of selected diatomic molecules in air or specific gaseous mixtures at or near atmospheric pressure reveal minimal plasma re-absorption. Abel inversion of the plasma in selected gases and gas mixtures confirm expansion dynamics that unravel regions of atomic and molecular species of different electron temperature and density. Time resolved spectroscopy diagnoses self-absorption of hydrogen alpha and hydrogen beta lines in ultra-high pure hydrogen gas. Radiation from a Nd:YAG laser device induces micro-plasma for pulse widths in the range of 6 ns to 14 ns, energies in the range of 100 mJ to 800 mJ, and for peak irradiance of the order 1 to 10 TW/cm². Atomic line profiles yield electron density and temperature from fitting of line profiles to wavelength and sensitivity corrected spectral radiance data. Analysis of measured diatomic emission data yields excitation temperature of primarily molecular recombination spectra. Applications of the laboratory experiments extend to investigations of stellar astrophysics white dwarf spectra.

Aluminium alloys are used for fabrication of fuel clad of research grade nuclear reactors as well as of several types of core components of high flux research reactors. In order to carry out design and safety analysis of these components, their mechanical and fracture properties are required by the designer. In this work, experiments have been conducted on tensile specimens machined from an aluminium alloy block to evaluate the material stress-strain curve. For evaluation of fracture properties, experiments have been conducted on disc shaped compact tension specimens in order to determine the fracture toughness of aluminium alloy. From crystal plasticity based finite element analysis and experimental data, a material damage parameter for prediction of crack initiation has been evaluated. The variation of the parameter for various values of initial a/W ratios of the disc-shaped CT specimens have been studied. It was observed that the damage parameter is independent of crack geometry and hence, it qualifies as transferable material property which can be used to predict crack initiation in a component of this material subjected to different kinds of loading conditions. In addition, the JR curves of the disc-shaped CT specimens have also been evaluated from experiments. The material damage parameter has also been used to study the crack initiation in single crystal fracture specimens with two different orientations. It was observed that the [111] orientation is more susceptible to crack initiation and propagation compared to the [100] orientation as the damage parameter is high in the ligament of the specimen ahead of the crack-tip for the same level of load. The results of the experiments and the material damage parameter shall be helpful for integrity analysis of fuel clad of research reactors as well as components of high flux research reactors.

Sepsis still remains one of the most difficult conditions to diagnose as it presents unspecific clinical signs and symptoms, which makes early detection crucial. Our study aimed to enhance the accuracy of sepsis diagnosis by integrating multimodal monitoring technologies with traditional diagnostic methods. The research involved 121 newborns, comprising 39 cases of late-onset sepsis, 35 cases of early-onset sepsis, and 47 control subjects. Biosignals including pulse oximetry (PO), near-infrared spectroscopy (NIRS), and skin temperature (ST) were continuously monitored and an algorithm was developed using Python for identifying early signs of sepsis. The model demonstrated the ability to detect sepsis 6 to 48 hours in advance with an accuracy rate of 87.67% ± 7.42%. Sensitivity and specificity were recorded at 76% and 90%, respectively, with NIRS and ST having the most significant impact on predictive accuracy. Despite the promising results, limitations such as sample size, data variability, and potential biases were noted. The findings highlight the critical role of non-invasive biosensing methods in conjunction with traditional biomarkers and cultures, offering a robust framework for early sepsis detection and improved neonatal care. Further studies are recommended to validate these results across diverse clinical settings.

Background : Newly generated cardiomyocytes (NGC) concur to recovery of human myocarditis. However, Methods: We retrospectively assessed NGC in 213 consecutive patients with endomyocardial biopsy denoting acute myocarditis, with normal coronaries and valves. Tissue samples were processed for histology (H&E), immunohistochemistry for the evaluation of inflammatory infiltrates, immunostaining for alpha-sarcomeric-actin, junctional connexin-43, Ki-67, phosphorylated STAT3 (p-STAT3) and Western Blot (WB) for HMGB1. Frozen samples were analyzed with polymerase chain reaction (PCR) for cardiotropic viruses. Controls included 20 normal surgical biopsies. Results: NGCs were defined as small myocytes (diameter < 10 µm) with nuclear positivity to Ki-67 and p-STAT3, positive immunostaining for cytoplasmic α-sarcomeric actin and connexin 43. Their number/mm2 in relation with age and pathway of integration were evaluated. NGCs crossed the membrane and grew integrated within the empty necrotic myocytes. NGC mean diameter was 6.6 ± 3.34 vs 22.5 ± 3.11 µm adult cells; their number, in comparable LVEF, was 86.3 ± 10.3/mm2 in patients between 10 and 40 years; 50.4 ±13.8/mm2 in those between 41 and 60; 15.1 ± 5.7/ mm2 in those between 61 and 80; control NGC mean diameter was 0.2± 0.2/mm2. PCR was positive for viral genomes in 16% of cases; NGCs were not statistically different in viral and non-viral myocarditis. WB analysis revealed a higher expression of HMGB1 in myocarditis compared to myocardial controls. Conclusions: NGCs are constantly recognizable in acute human myocarditis. Their number declines with age. Their integration within necrotic myocytes consents preservation of cardiac structure and function.

Ti-Al based alloys, particularly TiAl and Ti3Al two-phase alloys, have garnered significant attention as potential replacements for various high-temperature structural materials due to their exceptional properties, including low density, oxidation resistance, and high strength at elevated temperatures. Despite these advantages, experimental studies on the microstructure evolution of Ti-Al based alloys under complex conditions remain challenging to observe and characterize. This review article examines the current research on molecular dynamics (MD) simulations of Ti-Al based alloys, focusing on two-phase Ti-Al alloys, Ti-Al amorphous alloys, Ti-Al composite materials, and the welding and multi-layer/film applications of Ti-Al alloys. The review highlights the unique capabilities of MD simulations in predicting the behavior of Ti-Al based alloys and addresses existing scientific challenges. Furthermore, the article discusses future research directions and development prospects in this field.

Several studies with kaempferol (KP) and linearolactone (LL) have shown antiparasitic activities. However, the toxicity of treat-ments with both active principles is unknown. Therefore, this study aimed to evaluate the toxicological effects of treatments with KP and LL on the amoebic liver abscess (ALA) model in M. auratus administered intraperitoneally (i.p.). For this, ALA in-duction was carried out in male hamsters with 1.5 x105 E. histolytica trophozoites inoculated in the left hepatic lobe. The lesion evolved for four days and the i.p. of the treatments with KP (5 mg/kg body weight/day) and LL (10 mg/kg body weight/day) was carried out for four consecutive days. For histopathological evaluation, NMR studies, paraclinical analysis, and necropsy were performed. The results revealed that the inhibition of ALA by KP and LL were similar to that metronidazole (MTZ). Biochemical parameters revealed hepatic and renal alterations in all treatment groups, mainly for KP (AST and BUN). The lesions found in the organs were those that are directly linked to the pathology. In conclusion, KP and LL decrease ALA development but have few toxicological effects. Both compounds combined with MTZ could be therapeutic alternatives for amoebiasis caused by E. histolytica.

This work discusses diatomic molecular spectroscopy of laser-induced plasma and analysis of data records, specifically signatures of cyanide, CN. Line strength data from various databases are compared for simulation of the CN, B2Σ+⟶X2Σ+, Δv=0 sequence. Of interest are recent predictions using an astrophysical database, i.e., ExoMol, a laser-induced fluorescence database, i.e., LIFBASE, and a program for simulating rotational, vibrational and electronic spectra, i.e., PGOPHER. Cyanide spectra that are predicted from these databases are compared with line strength data that are in use by the author for the last three decades in the analysis of laser-plasma emission spectra. Comparisons with experimental laser-plasma records are communicated as well, and for spectral resolutions of 33 and 110 picometer. The accuracy of the CN line strength data is better than one picometer. Laboratory experiments utilize 308-nm, 35-picosecond bursts within an overall 1-nanosecond pulse-width, and 1064-nm, 6-ns pulse-width radiation. Experimental results are compared with predictions. Differences of the databases are elaborated for equilibrium of rotational and vibrational modes and at an internal, molecular temperature of the order of 8,000 Kelvin. Applications of accurate CN data include for example combustion diagnosis, chemistry, and supersonic and hypersonic expansion diagnosis. The cyanide molecule is also of interest in the study of astrophysical phenomena.