Background: Contrast-induced acute kidney injury (CIAKI) is a common complication in hospital-acquired renal conditions, yet its pathogenesis remains unclear and effective treatments are limited. Intermedin (IMD), a peptide related to the calcitonin gene, exhibits vasodilatory and endothelial barrier-stabilizing effects via the calcitonin receptor-like receptor (CLR). However, the potential of IMD in mitigating CIAKI has not been thoroughly investigated. Aims: This study aimed to delineate the protective role of IMD in CIAKI through both in vitro and in vivo models, with a particular focus on elucidating the underlying mechanisms, specifically the cAMP/Rac1 signaling pathway. Methods: Human umbilical vein endothelial cells (HUVECs) were treated with iohexol to simulate kidney injury in vitro. The protective effects of IMD were evaluated using the CCK8 assay, flow cytometry, ELISA, and western blotting. A CIAKI rat model was developed to assess renal peritubular capillary endothelial cell injury and renal function using a range of techniques, including histopathology, immunohistochemistry, immunofluorescence, western blotting, and transmission electron microscopy. Results: In vitro, IMD significantly enhanced HUVEC viability and mitigated iohexol-induced toxicity by preserving intercellular adhesion junctions and activating the cAMP/Rac1 pathway. The protective effects of IMD were attenuated by Rac1 inhibition. In vivo, CIAKI caused considerable damage to peritubular capillary endothelial cell junctions, leading to impaired renal function. IMD treatment markedly improved renal function, an effect that was abolished by Rac1 inhibition. Conclusion: IMD protects against renal injury in CIAKI by activating the cAMP/Rac1 pathway, thereby preserving the integrity of peritubular capillary endothelial cells and mitigating acute renal injury induced by contrast media. These findings underscore the therapeutic potential of IMD in CIAKI and emphasize the critical role of the cAMP/Rac1 pathway in renal protection.

In recent years, due to the detrimental impact of traditional gas-liquid refrigerants on the environment, the pursuit of solid-state refrigeration technology based on elastocaloric effect, as a promising sustainable alternative, has been promoted. However, the traditional trial-and-error method is inefficient and difficult to meet the material application requirements. In this work, machine learning (ML) was employed to accelerate the development of NiTi-based shape memory alloy (SMA) with excellent elastocaloric effect. By means of active learning, we identified 9 novel NiTi-based SMAs in four iterations, the phase transformation-induced entropy change (ΔS) of which are as high as over 90 J/kg·K-1. Moreover, the model exhibits good interpretability, allowing us to understand the relevance between the target and features from the aspect of mechanism.

Based on the electron-deficient property of picric acid (PA), two neutral Ir(III) complexes 1 and 2 modified with the electron-rich carbazolyl groups were synthesized and characterized. Both 1 and 2 exhibit aggregation-induced phosphorescence emission (AIPE) properties in THF/H2O. Among them, 2 is extremely sensitive for detecting PA with a limit of detection of 0.15 μM in THF/H2O. Furthermore, the selectivity for PA is significantly higher compared to other analytes, enabling efficient detection of PA in four common water samples. The density functional theory calculations and the spectroscopic results confirm that the sensing mechanism is photo-induced electron transfer.

Soil-borne Trichoderma spp. have been extensively studied for their biocontrol activities against pathogens and growth promotion ability with plants. However, the beneficial effect of Trichoderma on inducing resistance against insect herbivores has been considered only recently. Among diverse Trichoderma species, consistent with previous reports, we showed that root colonization by T. virens triggered induced systemic resistance (ISR) to leaf-infecting fungal pathogens. Whether T. virens induces ISR to insect pests has not been tested before. In this study, we investigated whether T. virens affects jasmonic acid (JA) biosynthesis and defense against fall armyworm (FAW) and western corn rootworm (WCR). Unexpectedly, the results showed that T. virens colonization of maize seedlings grown in autoclaved soil suppressed wound-induced production of JA, resulting in reduced resistance to FAW. Similarly, the bacterial endophyte Pseudomonas chlororaphis 30-84 suppressed systemic resistance to FAW due to reduced JA. Further comparative analyses of the systemic effects of these endophytes when applied into sterile or non-sterile field soil showed that both T. virens and P. chlororaphis 30-84 triggered ISR against hemibiotrophic fungal pathogen Colletotrichum graminicola in both soil conditions, but only suppressed resistance to FAW in sterile soil. In contrast to the effect on FAW defense, T. virens colonization of maize roots suppressed WCR larvae survival and weight gain. This is the first report suggesting the potential role of T. virens as a biocontrol agent against WCR.

This study concerns calculation and comparison of Fe, Co, Ni and Cu deposition rates in tungsten codeposition process based on electrodeposition of numerous tungsten alloys. 8 different tungsten alloys containing from 2 to 5 metals were electrodeposited in constant conditions in order to compare exact reduction rates. Calculated rates enabled control of the alloy composition precise enough to obtain a high-entropy WFeCoNiCu alloy with well-balanced composition. Introduction of copper to form the quinternary alloy was found to catalyze the whole process, increasing deposition rates of all components of the high-entropy alloy.

Background: Proteins targeted by the Ubiquitin Proteasome System (UPS) are identified for degradation by the proteasome, which has been implicated in the development of neuro-degenerative diseases. Major histocompatibility complex (MHC) molecules present peptides broken down by the proteasome and are involved in neuronal plasticity, regulating synapse number and axon regeneration in the central or peripheral nervous system during develop-ment and in brain diseases. The mechanisms governing these effects are mostly unknown, but evidence from different compartments of the cerebral cortex indicates the presence of im-mune-like MHC receptors in the central nervous system. Methods: We have used human induced pluripotent stem cells (iPSC) differentiated to neural stem cells and then to motor neurons as a developmental model to better understand the structure of the proteasome in developing motor neurons. We perform a proteomic analysis of starting human skin fibroblasts, their matching iPSC, differentiated neural stem cells and motor neurons that highlighted significant differences in the constitutive proteasome and immunoproteasome subunits during development towards motor neurons from iPSC. Results: Proteomic analysis showed that the catalytic proteasome subunits expressed in fi-broblasts differ to those in neural stem cells and motor neurons. Western blot analysis con-firmed the proteomic data, particularly the decreased expression of Beta5i (PSMB8) subunit immunoproteasome. Conclusion: The constitutive proteasome subunits are upregulated in iPSC from HFF and the immunoproteasome subunit beta 5i expression is higher in MN than NSC suggesting a im-munoproteasome phenotype in MN. The immunoproteasome may have implications on motor neuron development and neurodevelopmental diseases that warrants further investi-gation.

Background: no reports have examined the profile of drug-induced dysphagia in detail. The goal of this study was to investigate if there are any differences in the profiles of drug-induced dysphagia. Methods: This study used the Japanese Adverse Drug Event Report (JADER) database. Further, reported odds ratios (RORs) were used to analyze data on adverse drug events from 2004 to 2021. The top ten drugs with the most drug-induced dysphagia occurrences were used as target drugs. The association between RORs and drug-induced dysphagia caused by the target drugs was evaluated, and the age distribution and time of onset of drug-induced dysphagia for each drug were compared. RORs were the primary endpoint. Moreover, age and time of onset of drug-induced dysphagia were secondary outcomes. Results: In total, 756,965 reports were analyzed. All the target drugs were associated with drug-induced dysphagia. Among them, cevimeline was a novel finding, as no dysphagia was observed during the clinical trial. For most drugs, the onset of drug-induced dysphagia was occurring within approximately 25 days of administration. However, even after long-term use, paroxetine and milnacipran were associated with drug-induced dysphagia. Conclusion: The onset profile of drug-induced dysphagia may differ from one drug to the next.

Most of the current methods for stabilizing electric arc furnace (EAF) slag are time-consuming and cannot be completely stabilized. In view of this, this study aimed to apply microbial‑induced calcium carbonate precipitation (MICP) technology in the stabilization of EAF reducing slag, and this was to be achieved by using the reaction between carbonate ions and free calcium oxide (f-CaO) in reducing slag to form a more stable calcium carbonate to achieve the purpose of stabilization. The test results showed that, when the EAF reducing slag aggregates (ERSAs) were immersed in Bacillus pasteurii bacteria solution or water, the f-CaO contained in it would react such that stabilization was achieved. The titration test results showed that the f-CaO content of the ERSAs immersed in the bacterial solution and water decreased. The expansion test results of the ERSAs that were subjected to hydration showed that the seven-day expansion of ERSAs after biomineralization could meet the Taiwan regulation requirement of a less than 0.5% expansion rate. The thermogravimetric analysis showed that both the experimental group and the control group might contain calcium carbonate compounds. The results of the X-ray diffraction analysis showed that the CaCO3 content in the ERSAs that were immersed in the bacterial solution was significantly higher than those that were immersed in water. Moreover, the compressive strength test results of concrete prepared with ERSAs showed that the compressive strength of the control group concrete began to decline after 28 days. In contrast, the experimental group concrete had a good stabilization effect, and there was no decline in compressive strength until the age of 180 days. At the age of 240 days, the surface cracks of the experimental group were particularly small, while the surface of the control group showed obvious cracks. These results confirmed that a mineralization reaction with B. pasteurii bacteria could be used as a stabilization technology for ERSAs.

We report the use of four-layer graphene (4LG) as a highly reliable transparent conductive electrode (TCE) for polymer-dispersed liquid crystal (PDLC)-based smart window devices. The adhesion between 4LG and the substrate was successfully improved through a water-induced interface-cleaning (WIIC) process. We compared the performance of a device with a WIIC-processed 4LG electrode with that of devices with a conventional Indium tin oxide (ITO) electrode and a 4LG electrode without a WIIC. With the application of the WIIC process, the PDLC smart window with a 4LG electrode exhibited reduced turn-on voltage and haze compared to 4LG without the WIIC process and characteristics comparable to those of the ITO electrode. Based on our observations, we conclude that 4LG with WIIC is a promising TCE for flexible smart windows.

The microstructure of oil pipeline steels is polycrystalline due to the presence of a complex grain boundary (GB) network in them. The performance of them when exposed to stresses in corrosive environments is largely dictated by the interplay between the hydrogen (H) diffusion, the dislocation slip, and their interactions with the GBs. However, the slip-GB interaction in the presence of H and the subsequent cracking along the GBs remains not fully understood up to date. It is challenging to simultaneously resolve the collective dislocation motions away from the GBs together with the H diffusion near the atomically structured GBs using single-scale techniques. To address this challenge, taking bcc iron as a model material, here we present a a concurrent atomistic-continuum (CAC) computational analysis of the interaction between dislocation slip and a H-charged GB. With the large number of dislocations-mediated plastic flow away from the GB together with the atomistic structure evolution at the GB being simultaneously retained, several main findings from our simulations are: (i) the large number of dislocation-mediated pileup-induced internal stress nearby the H-charged GB can be as high as 3GPa; (ii) the more dislocations accumulated nearby the GB, the slower H diffusion ahead of the slip-GB intersection; (iii) H atoms diffuse fast behind the pileup tip, get trapped within the GB, and diffuse slow ahead of the pileup tip; (iv) the local stresses nearby the pileup tip exhibits a strong heterogeneity along the dislocation line direction. This differs from the common wisdom in many existing 2D theories/models. The buildup of such a high local stress heterogeneity leads to inhomogeneous H diffusion within the GB plane. The CAC simulation-predicted local H diffusivity, Dpileup−tip, and local stresses, σ, nearby the GB are then correlated with each other and consolidated into a mechanics model by considering the dislocation pileup as an Eshelby inclusion. These findings will provide researchers with opportunities to: (a) characterize the coupled dynamics between plasticity, H diffusion, and crack initiation underlying the hydrogen-induced cracking (HIC); (b) develop mechanism-based constitutive rules to be used in diffusion-plasticity coupling models for understanding the interplay between mechanical and mass transport in materials at the continuum level; and (c) connect the atomistic deformation physics of polycrystalline materials with their overall performance in aqueous environments, which is currently difficult to achieve in laboratory experiments.

Typically, a diesel generator on the merchant ship, composed of a wound rotor synchronous generator and a four-stroke diesel engine, supplies electrical power to various loads. Recently, shaft generators for merchant vessels are increasingly replacing diesel generators to reduce CO2 emissions through fuel efficiency improvement. In particular, permanent magnet generators replace induction generators due to their high-efficiency characteristics at light loads. The surface-mounted permanent magnet can be a suitable rotor topology due to the relatively short constant power range. This generator can also operate as a motor according to the propulsion mode, so minimizing the harmonics of the induced voltage and the torque ripple is necessary. This paper proposes an alternative NdFeB magnet pole topology combined with the modular step-skewed rotor. The step-skewed rotor affects to reduce higher-order harmonics, and the modular pole reduces the permanent magnet assembly process and harmonics in voltage and torque. A 2-D finite element method is used to evaluate the harmonics of induced voltage and torque pulsation for the proposed topology. The topology shows harmonic minimization effect by comparing the characteristics of three flatted-bottom magnets. Compared to the tapered bread-loaf magnet, voltage harmonics to the 100th component are almost the same, and the torque ripple is reduced by more than 12% at the same residual flux density. The analysis method is verified by comparing test and analysis results for prototype machines with similar specifications.

For the replacement of lost contractile elements in the treatment of coronary heart disease, the most promising approaches to obtain cardiomyocytes by cardiac differentiation of pluripotent cells. The aim of this work is to develop a technology for the formation of a functional layer of cardiomyocytes differentiated from iPSCs, capable of generating rhythmic activity and synchronous contractions. To accelerate cardiomyocyte maturation, the renal subcapsular transplantation model was used in SCID mice. After explantation, the formation of cardiomyocyte contractile apparatus was assessed by fluorescence and electron microscopy, and calcium ion oscillation in the cytoplasm was assessed by visualization of the fluorescent calcium binding dye Fluo-8. It was shown that human iPSC-derived cardiomyocyte cell layers transplanted (for up to 6 weeks) under SCID mouse kidney fibrous capsules begin to form an ordered contractile apparatus and retain functional activity and the ability to oscillate calcium ion fluxes after explantation from the body.

This interdisciplinary work communicates identification and quantification of elements responsible for the bioactive potency of leaves from pointed gourd, trichosanthes dioica,using laser induced breakdown spectroscopy (LIBS). Calibration-free LIBS determines the presence of various trace and major elements, their concentrations, and ratios in which they are present in the leaves. The presence of specific elemental ratios of magnesium/sodium and magnesium/potassium could be promising for managing diabetes mellitus. Variable doses of 500, 750, 1000, and 1250 mg per kg body weight of aqueous extract from trichosanthes dioica leaves are administered. A dose of 1000 mg per kg body weight is found to be the most effective. Based on encouraging results, the extract could be harvested to serve as anti-diabetic medication for diabetes and associated symptoms.

Mandibular advancement devices (MAD) are an effective alternative treatment to CPAP. However, different maneuvers have been performed during the performance of drug sleep-induced endoscopy (DISE) to mimic the effect of MAD. Using the Selector Avance Mandibular (SAM) device, we aimed to identify MAD candidates during DISE using a titratable, reproducible, and measurable maneuver. This DISE-SAM protocol may help to find the relationship between the severity of the respiratory disorder and the degree of response, and to determine the advancement required to improve the collapsibility of the upper airway. Explorations were performed in 161 patients (132 males; 29 females) with a mean age of 46.81 (SD = 11.42) years, a BMI of 27.90 (SD = 4.19) kg/m2 and a mean AHI of 26.51 (SD = 21.23). Results showed no relationship between severity and MAD recommendation. Also, there was a weak positive relationship between the advancement required to obtain a response and the disease severity. Using the DISE-SAM protocol, the response and the range of mandibular protrusion were assessed, avoiding the inter-examiner bias of the jaw thrust maneuver. We suggest prescribing MAD as a single, alternative, or multiple treatment approaches following the SAM recommendations in a personalized design.

Centromeres, the chromosomal loci where spindle fibers attach during cell division to segregate chromosomes, are typically found within satellite arrays in plants and animals. Satellite arrays have been difficult to analyze because they comprise megabases of tandem head-to-tail highly repeated DNA sequences. Much evidence suggests that centromeres are epigenetically defined by the location of nucleosomes containing the centromere-specific histone H3 variant cenH3, independently of the DNA sequences where they are located; however, the reason that cenH3 nucleosomes are generally found on rapidly evolving satellite arrays has remained unclear. Recently, long read sequencing technology has clarified the structures of satellite arrays and sparked rethinking of how they evolve, while new experiments and analyses have helped bring both understanding and further speculation about the role these highly repeated sequences play in centromere identification.

The induced draft (ID) fan is important auxiliary equipment in the thermal power plant. It is of great significance to monitor the operation of the ID fan for safe and efficient production. In this paper, an adaptive warning model is proposed to detect early faults of ID fans. First, a non-parametric monitoring model is constructed to describe the normal operation states with the multivariate state estimation technique (MSET). Then, an early warning approach is presented to identify abnormal behaviors based on the results of the MSET model. As the performance of the MSET model is heavily influenced by the normal operation data in the historic memory matrix, an adaptive strategy is proposed by using the samples with a high data quality index (DQI) to manage the memory matrix and update the model. The proposed method is applied to a 300 MW coal-fired power plant for early fault detection, and it is compared with the model without an update. Results show that the proposed method can detect the fault earlier and more accurately.

Amorphous silicon (α-Si) film present an inexpensive and promising material for optoelectronic and nanophotonic applications. Its basic optical and optoelectronic properties are known to be improved via phase transition from amorphous to polycrystalline phase. Infrared femtosecond laser radiation can be considered as a promising nondestructive and facile way to drive uniform in-depth and lateral crystallization of α-Si films that are typically opaque in UV-visible spectral range. However, so far only a few studies reported on utilization of near-IR radiation for laser-induced crystallization of α-Si providing no information regarding optical properties of the resultant polycrystalline Si films. The present work demonstrates efficient and gentle single-pass crystallization of α-Si films induced by their direct irradiation with near-IR femtosecond laser pulses coming at sub-MHz repetition rate. Comprehensive analysis of morphology and composition of laser-annealed films by atomic-force microscopy, optical, micro-Raman and energy-dispersive X-ray spectroscopy, as well as numerical modeling of optical spectra, confirmed efficient crystallization of α-Si and high-quality of the obtained films. Moreover, we highlight localized laser-driven crystallization of α-Si as a promising way for optical information encryption, anti-counterfeiting and fabrication of micro-optical elements.

The study of neurodegenerative diseases using pluripotent stem cells requires new methods to assess neurodevelopment and neurodegeneration of specific neuronal subtypes. The cholinergic system, characterized by its use of the neurotransmitter acetylcholine, is one of the first to degenerate in Alzheimer’s disease and is also affected in frontotemporal dementia. We developed a differentiation protocol to generate basal forebrain cholinergic neurons (BFCNs) from induced pluripotent stem cells (iPSCs) aided by the use of small molecule inhibitors and growth factors. Ten iPSC lines were successfully differentiated into BFCNs using this protocol. The neuronal cultures were characterised through RNA and protein expression, and functional analysis of neurons was confirmed by whole-cell patch clamp. We have developed a reliable protocol using only small molecule inhibitors and growth factors, while avoiding transfection or cell sorting methods, to achieve a BFCN culture that expresses the characteristic markers of cholinergic neurons.

Meteorites represent the recoverable portions of asteroids occurring between Mars and Jupiter within the solar system that reach the surface of the Earth. Meteorites are rare extraterrestrial objects studied extensively to improve understanding of planetary evolution. In this work, calibration-free laser-induced breakdown spectroscopy (CF-LIBS) evaluates quantitative elemental and molecular analysis of the Dergaon meteorite, an H 4-5 chondrite fall sample, Assam, India. Spectral signatures of H, N, O, Na, Mg, Al, Si, P, K, Ca, Ti, Cr, Mn, Fe, Co, Ni, Ir, are measured. Along with the atomic emission, this work reports as well molecular emission from FeO molecules. The concentration of the measured elements obtained using CF-LIBS are in close agreement with earlier reports. The elements H, N and O and their concentrations are estimated using CF-LIBS for the first time. This study applies laser spectroscopy to establish presence of Ni, Cr, Co, and Ir in meteorites. Elemental analysis forms the basis for establishment of potential molecular composition of the Dergaon meteorite. Moreover, the elemental analysis approach bodes well for in-situ analyses of extraterrestrial objects including applications in planetary rover missions.

Fast neutron (FN) radiation mediated mutagenesis is a unique approach among the several induced mutagenesis methods being used in plant science in terms of impacted mutations. The FN mutagenesis usually creates deletions from a few bases to several million bases (Mb). A library of random deletion generated using FN mutagenesis lines can provide indispensable resources for the reverse genetic approaches. In this review, information from several efforts made using FN mutagenesis has been compiled to understand the type of induced mutations, frequency, and genetic stability. Concerns regarding the utilization of FN mutagenesis technique for a plant with different level of ploidy and genome complexity are discussed. We have highlighted the utility of next-generation sequencing techniques which can be efficiently utilized for the characterization of mutant lines as well as for the mapping of causal mutations. Pros and cons of Mut-map, MutChromSeq, exon capture, whole genome sequencing, MutRen-Seq, and different tilling approaches can be used for the detection of FN-induced mutation has also been discussed. Genomic resources developed using the FN mutagenesis have been catalogued wooing to meaningful utilization of the available resources. The information provided here will be helpful for the efficient exploration for the crop improvement programs and for better understanding of genetic regulations.

In this work, the parameters of plasma (electron temperature (T_e), electron density n_e, plasma frequency (f_p) , Debye length (λ_D) and Debye number (N_D)) have been studied by using the spectrometer that collect the spectrum of Laser produce Cadmium telluride plasma at different energies. The results of electron temperature for CdTe range 0.93-1.18 eV also the electron density 5 × 10¹⁰ – 3.8 × 10¹¹ cm^-3 have been measured under vacuum reaching 2.5 × 10^-2 mbar .Optical properties of CdTe were determined through the optical transmission method using ultraviolet visible spectrophotometer within the range 190 – 1100 nm.

This work reports measurements of calcified gallstone elemental compositions using laser-induced optical emission spectroscopy. The experimental results support the importance of the magnesium concentration in gallstone growth. Granular stones reveal an increased magnesium concentration at the periphery of the granules, suggesting the inhibition of further growth. Non-granular gallstones reveal lower overall magnesium concentrations but with higher values near the center.

Initial attempts to develop monoclonal antibodies as therapeutics to resolve influenza infections focused mainly on searching for antibodies with the potential to neutralise the virus in vitro with classical haemagglutination inhibition and micro-neutralisation assays. This led to the identification of many antibodies that bind to the head domain of haemagglutinin (HA) which generally have potent neutralisation capabilities that block viral entry or viral membrane fusion. However, this class of antibodies has a narrow breadth of protection in that they are usually strain specific. This led to the emphasis on stalk targeting antibodies which are able to bind a broad range of viral targets that span across different influenza subtypes. Recently, a third class of antibodies targeting the vestigial esterase (VE) domain have been characterised. In this review, we describe the key features of neutralising VE targeting antibodies and compare them with head and stalk class antibodies.

Background: Regular moderate-vigorous intensity exercise is recommended for adults as it can improve longevity and reduce health risks associated with a sedentary lifestyle. However, there are barriers to achieving intense exercise that may be addressed using virtual reality (VR) as a tool to promote exercise intensity and adherence, particularly through visual feedback and competition. The purpose of this work is to compare visual feedback and competition within fully-immersive VR to enhance exercise intensity and user experience of exercise for young adults; and to describe and compare visual attention during each of the conditions. Methods: Young adults (21- 34 years old) bicycled in three 5-minute VR conditions (visual feedback, self-competition and competition against others). Exercise intensity (cycling cadence and % of maximum heart rate) and visual attention (derived from a wearable eye tracking sensor) were measured continuously. User experience was measured by an intrinsic motivation questionnaire, perceived effort and participant preference. A repeated measures ANOVA with paired t-test post-hoc tests was conducted to detect differences between conditions. Results: Participants exercised at a higher intensity and had higher intrinsic motivation in the two competitive conditions compared to visual feedback. Further, participants preferred the competitive conditions and only reached a vigorous exercise intensity during self-competition. Visual exploration was higher in visual feedback compared to self-competition. Conclusion: For young adults bicycling in VR, competition promoted higher exercise intensity and motivation compared to visual feedback.

Understanding and preventing the “great obstetrical syndromes” has been the focus of pregnancy research for decades. The combined global impact from these syndromes on maternal and perinatal morbidity and mortality is compounded by increased long-term risk of adverse health effects following pregnancy. Accumulating evidence indicates that conditions such as pre-eclampsia, fetal growth restriction, spontaneous preterm labour, and stillbirth, are syndromes with etiologic heterogeneity that share common pathophysiologic pathways involving placental dysfunction. Recently, the importance of the interaction between fetal and maternal genomes has been extended to include the epigenetic impact of pre-existing maternal pathophysiology on placental development and highlights the importance of nutritional and environmental factors in altered placentation. Validated first-trimester screening algorithms for preeclampsia can identify high-risk women and prophylactic treatment with low-dose aspirin can be initiated. High-risk women can be monitored during the second trimester using clinical assessment, ultrasound, and biochemical markers, that are able to predict complications prior to the development of clinical signs and symptoms. The integration of lifestyle interventions, pregnancy screening, and medical management represents a conceptual advance in pregnancy care. This approach has the potential to significantly reduce pregnancy complications, maternal and perinatal morbidity and mortality, adverse health outcomes later in life, and health-care costs.

Despite significant prevention efforts, the numbers of physically inactive individuals, chronic illnesses, exhaustion syndromes and sick leaves are increasing. A still unresolved problem with exercise promotion is the low participation of sedentary persons. This collective term covers heterogeneous subgroups. Their engagement with movement campaigns and resistance to change are influenced by numerous factors. Our aim was to analyse survey data on health, performance, lifestyle habits and the approachability to physical activity campaigns obtained from the Germany-wide ActIv survey. From 2,888 study participants aged 50-60 years, 668 persons were categorised into the subgroups "never-athletes", "sports-dropouts", "always-athletes" and "sports-beginners". Large and significant group differences were found for BMI, assessment of quality of life, health and fitness, risk factors and health problems. 42.5% of "never-athletes" and 32.5% of "sports-dropouts" did not state any barriers to sport. There are substantial disparities between the non-athlete groups in terms of their motivation to exercise. In contrast, there are comparatively minor differences in motivation between "sports-dropouts" and "sports-beginners", whose health and fitness are the primary motivators for sport. Our analyses suggest that (i) negative health and performance trends cannot be compensated by appeals for voluntary participation in exercise programmes and (ii) powerful incentive systems are required.

Objective: The objective of our study was to explore the potential benefits of combining moderate alcohol consumption with regular vigorous physical activity on HDL-cholesterol levels and its potential positive impact on cardiovascular health. Material and method: The study comprised two groups: group A (102 patients) who consumed 1 gram of alcohol per day, specifically red wine, and increased their exercise levels in addition to their standard medical treatment, and group B (108 patients) who adhered only to their standard medical treatment. The patients were monitored for a year, during which various clinical parameters were observed. Results:Our study showed that moderate alcohol consumption, particularly red wine, along with increased physical activity levels, was associated with enhancements in exercise tolerance and elevated levels of HDL-cholesterol. Our findings suggest the efficacy of the intervention in improving lipid profiles, with the group that consumed alcohol as part of their treatment scheme, generally experiencing more pronounced positive effects. Statistically significant differences between groups in terms of angina evolution, AMI recurrence, or arrhythmias evolution were not found. However, there were important differences in terms of EF improvement and quality of life, with the alcohol consuming group displaying greater improvements in both aspects. Conclusions:In conclusion, our study emphasizes the potential benefits of combining moderate alcohol consumption, specifically red wine, with increased physical activity levels for improving exercise tolerance and enhancing HDL-cholesterol levels. However, further research and clinical trials are essential to fully understand the mechanisms and optimize the integration of these lifestyle elements for improved cardiovascular health outcomes.

Objective: The objective of our study was to explore the potential benefits of combining moderate alcohol consumption with regular vigorous physical activity on HDL-cholesterol levels and its potential positive impact on cardiovascular health. Material and method: The study comprised two groups: group A (102 patients) who consumed 1 gram of alcohol per day, specifically red wine, and increased their exercise levels in addition to their standard medical treatment, and group B (108 patients) who adhered only to their standard medical treatment. The patients were monitored for a year, during which various clinical parameters were observed. Results:Our study showed that moderate alcohol consumption, particularly red wine, along with increased physical activity levels, was associated with enhancements in exercise tolerance and elevated levels of HDL-cholesterol. Our findings suggest the efficacy of the intervention in improving lipid profiles, with the group that consumed alcohol as part of their treatment scheme, generally experiencing more pronounced positive effects. Statistically significant differences between groups in terms of angina evolution, AMI recurrence, or arrhythmias evolution were not found. However, there were important differences in terms of EF improvement and quality of life, with the alcohol consuming group displaying greater improvements in both aspects. Conclusions:In conclusion, our study emphasizes the potential benefits of combining moderate alcohol consumption, specifically red wine, with increased physical activity levels for improving exercise tolerance and enhancing HDL-cholesterol levels. However, further research and clinical trials are essential to fully understand the mechanisms and optimize the integration of these lifestyle elements for improved cardiovascular health outcomes.

This study explores the intriguing relationship between personality traits, self-rated fitness (SRF), and physical activity (PA) variables among German university students (N = 4,244), and sheds light on the impact of personality on adherence to PA guidelines. Employing an online cross-sectional study, the short-form of the Big Five Inventory-2 assessed five domains of personality traits (Extraversion, Negative Emotionality, Agreeableness, Conscientiousness, and Open-Mindedness). PA, including sitting time, was assessed using the International Physical Activity Questionnaire (short-form). SRF and muscle-strengthening activities (MSA) were assessed with one item each. Multiple linear and logistic regression analyses examined associations of individual personality trait domains and all domains combined with SFR, PA variables, and adherence to PA guidelines, controlling for sociodemographic, behavioral, and (mental) health covariates. Most reliably, Extraversion and Conscientiousness revealed positive associations with PA variables, while Negative Emotionality yielded inverse relationships with PA variables. For instance, each unit increase in Extraversion corresponded to additional 17 minutes weekly MSA. Contrary, daily sitting time was unrelated to personality. Of note, high Open-Mindedness was associated with lower odds for adhering to current PA guidelines. The findings have implications for developing targeted interventions that promote a physically active lifestyle and support students' well-being and academic success.

Judo is a popular Japanese martial art and an Olympic sport. Recently, an increasing interest has been observed in the application of judo as a multicomponent exercise, with a growing body of evidence showing that multicomponent exercise improves physical and cognitive performance in older adults. Therefore, this review highlights the benefits of judo training in preventing physical and cognitive decline in older adults. Specifically, first, this review outlines the basic characteristics of judo (philosophy, match, and training). Next, previous studies investigating the effects of judo training on physical and cognitive aspects of older adults are reviewed. Thereafter, the brain mechanisms underlying the effects of judo training in improving physical and cognitive performance are discussed. Throughout this review, judo training demonstrated some positive effects on physical (gait and balance, among others) and cognitive (memory and executive function) function in older adults. These positive effects are attributed to a variety of changes in the brain (e.g., increased neurotrophic factor expression and increased cerebral blood flow, among others), that affect different brain regions and networks both functionally and structurally. From these findings, this review concludes that judo training can be an effective way to maintain and prevent physical and cognitive decline in older adults.

There are evidences of shared biological mechanisms between obesity and hypertension during childhood in the adulthood, and loads of research literatures have proven that, it will cost the economies and health of nations profoundly if neglected. The Prevention and early diagnosis of cardiovascular risk factors such as overweight and hypertension is an essential strategy for control, effective treatment and prevention of its’ complications. The aim of the study is to assess the effect of school based Exercise and Life style Motivation Intervention (SEAL-MI) on adolescent's cardiovascular risk factors and academic performance. An experimental study was conducted among 1005 adolescents - 520 and 485 adolescents were randomly selected for control and study group, respectively. Demographic details and the data related to dietary habits, physical activity and sleep quality were collected by a structured interview questionnaire. The study group adolescents were given the SEAL-MI for six months which includes a school based rope exercise for 45 minutes per day for 5 days a week and a motivation intervention related to dietary habits, physical activity and sleep. Post-test 1 and 2 were done after 3 and 6 months of intervention. The prevalence of overweight among adolescents was 28.73% and prehypertension was 9.26%. Among overweight adolescents, the prevalence of prehypertension was found to be very high (32.25%). In post intervention, there was a significant reduction in weight, BP (p=0.000) and improvement in dietary habits, physical activity, sleep (p=0.000) and academic performance. A significant positive correlation was found between BMI and SBP (p=0.000) and BMI and academic performance (p=0.003). The linear regression analyses revealed that the gender (ß: 0.47, 95% CI: 0.39, 0.81), age (ß: 0.39, 95% CI: 0.17, 0.46), family income (ß: 0.2, 95% CI: 0.41, 0.5), residence (ß: 0.19, 95% CI: 0.01, 0.27) and type of family (ß: 0.25, 95% CI: 0.39, 0.02) had the strongest correlate with the BMI of the adolescents. Also, Mother’s education Mother’s education (ß: 0.35, 95% CI: 0.18, 0.59) had the strongest correlate with the SBP of the adolescents. In contrast, the DBP was negatively persuaded by age (ß: -0.36, 95% CI: 1.54, 0.29) and gender (ß: -0.26, 95% CI: 1.34, 0.12) of the adolescents. Regular practice of rope exercise and lifestyle modification such as diet, physical activity and sleep quality among adolescents prevent and control childhood CVD risk factors like overweight, hypertension. The SEAL-MI may lead to age appropriate development of adolescents and improves their academic performance and quality of life. Giving importance to the adolescents from urban habitat, from affluent nuclear family and catching them young will bring significant change in the disease burden.

Athletes living with and beyond cancer can continue to train and, in some cases, compete during treatment. Following cancer treatment, athletes can return to competitive sport but need to learn to adapt their physical strength and training to lingering effects of cancer. It is critical for oncology healthcare providers to use the principles of assess, refer and advise to exercise oncology programs that are appropriate for the individual. Managing side effects of treatment is key to being able to train during and immediately following cancer treatment. Keen attention to fatigue is important at any point in the cancer spectrum to avoid overtraining and optimize the effects of training.

Pervasive and wide-ranging cognitive deficits are a core feature of schizophrenia and an important determinant of long-term functional outcome. The lack of sufficiently effective treatments for cognitive impairment associated with schizophrenia (CIAS) represents a major unmet need and a central roadblock towards recovery. This is partly due to the current therapeutic focus on clinical symptoms, and the relative neglect of cognitive impairments despite their functionally disabling effects. Furthermore, effective treatment is impeded by our limited knowledge of the complex pathophysiology, which gives rise to perturbed information processing. Here, we review mechanisms and effectiveness of available pharmacological and non-pharmacological treatments for CIAS. Current evidence indicates, that while techniques which broadly enhance neural plasticity show the greatest therapeutic potential, effect sizes are at best moderate. Among other reasons, this is due to a considerable heterogeneity of responses to individual interventions. Furthermore, we discuss how recent conceptual advances in operationalizing cognitive impairments based on cognitive neuroscience have the potential to address these issues and facilitate the development of novel treatment strategies for CIAS. This includes more clearly elucidating pathophysiological mechanisms in both humans and animal models, identifying new treatment targets as well as establishing biomarkers for a better prediction of treatment responses.

Abstract: This article provides a brief review of the ontogeny of chondrocytes and the pathophysiology of osteoarthritis (OA), and details how physical exercise improves the health of osteoarthritic joints and enhances the potential of mesenchymal stem cells for successful transplantation therapy. In response to exercise chondrocytes increase their production of glycosaminoglycans, bone morphogenic proteins and antiinflammatory cytokines and decrease their production of proinflammatory cytokines and matrix degrading metalloproteinases. These changes are associated with improvements in cartilage organization and reductions in cartilage degeneration. Studies in humans indicate that exercise increases peripheral blood recruitment of bone marrow-derived mesenchymal stem cells (BM-MSC) and upregulates BM-MSC expression of osteogenic and chondrogenic genes, osteogenic micro-RNAs, and osteogenic growth factors. Rodent experiments are uniform in demonstrating that exercise enhances the osteogenic potential of BM-MSC while diminishing their adipogenic potential, and that exercise done after stem cell implantation may benefit stem cell transplant viability. Physical exercise also exerts a beneficial effect on the skeletal system by decreasing immune cell production of osteoclastogenic cytokines interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and interferon (INF)-γ while increasing their production anti-osteoclastogenic cytokines IL-10 and transforming growth factor (TGF)-β. In conclusion, physical exercise done both by stem cell donors and recipients may improve the outcome of mesenchymal stem cell transplantation.

Epigenetic changes are a hallmark of short- and long-term transcriptional regulation, and hence instrumental in the control of cellular identity and plasticity. Epigenetic mechanisms leading to changes in chromatin structure, accessibility for recruitment of transcriptional complexes, and interaction of enhancers and promoters all contribute to acute and chronic adaptations of cells, tissues and organs to internal and external perturbations. Similarly, the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is activated by stimuli that alter the cellular energetic demand, and subsequently controls complex transcriptional networks responsible for cellular plasticity. It thus is of no surprise that PGC-1α is under the control of epigenetic mechanisms, and constitutes a mediator of epigenetic changes in various tissues and contexts. In this review, we summarize the current knowledge of the link between epigenetics and PGC-1α in health and disease.

Magnetorheological elastomers (MREs) are in demand in the field of high-tech micro- and nano-industries such as biomedical applications and soft robotics due to their exquisite magneto-sensitive response. Among various MRE applications, programmable actuators are emerging as promising soft robots because of their combined advantages of excellent flexibility and precise controllability in a magnetic system. Here, we present the development of a magnetically programmable soft magnetic microarray actuators through field-induced injection molding using MREs, which consist of styrene-ethylene/butylene styrene (SEBS) elastomer and carbonyl iron powder (CIP). The ratio of the CIP/SEBS matrix is designed to maximize the CIP fraction based on a critical solids loading. Further, as part of the design of the magnetization distribution in micropillar arrays, the magnetorheological response of the molten composites is analyzed using the static and dynamic viscosity results for both the on- and off- magnetic states, which reflect the particle dipole interaction and subsequent particle alignment during field-induced injection molding process. To develop high aspect ratio soft magnetic microarray, X-ray lithography is applied to prepare the sacrificial molds with a height-to-width ratio of 10. The alignment of CIP is designed to achieve a parallel magnetic direction along the micropillar columns, and consequently, the micropillar arrays successfully achieve the uniform and large bending actuation of up to approximately 81˚ with an applied magnetic field. This study suggests that the injection molding process offers a promising manufacturing approach to build a programmable soft magnetic microarray actuator.

Pinosylvin and its methylated derivatives, pinosylvin monomethyl ether (PME) and dihydropinosylvin monomethyl ether (DPME), are representative phytoalexins found in Pinus species. Both PME and DPME have strong nematicidal activity against pine wood nematodes (PWNs). In this study, we investigated the resistance of Pinus densiflora to PWN after trunk injection or soil drenching with a fungal elicitor prepared from Penicillium chrysogenum. Fungal elicitor treatment by soil drenching resulted in increased accumulation of PME and DPME in the needles of the plants. When the pine trees without fungal elicitor pretreatment were inoculated with PWNs, 67.9% died after five months, but only 33.3% died among the plants pretreated with the fungal elicitor. Injection of the fungal elicitor into the trunks of P. densiflora trees also strongly increased the synthesis of PMEs. The concentration of PME in the leaves of P. densiflora reached a maximum (155.4 µg/g DW) after 4 weeks of fungal elicitor injection. The second injection of the elicitor after the first injection of the fungal elicitor also increased the accumulation of PME. To investigate PWN resistance in P. densiflora after two months of trunk injection of elicitor, the downward movement of PWNs from the top of branches to the bottom was monitored after PWNs were inoculated on the holes of the upper internodal segments of branches. The number and mobility of PWNs that moved from the bottom of branches were highly reduced in fungal elicitor-injected pine plants. This result suggests an eco-friendly approach for eliciting-induced PWN resistance in PWN-susceptible P. densiflora via fungal elicitor treatment.

Background and objective: Iliopsoas abscess (IPA) is a rare condition with varied symptomology and etiology. Less than one-third of patients with IPA present on the emergency department (ED) admission with the traditional triad of fever, back pain, and restricted hip motion (or limp), leading to delays in diagnosis and management. This case report aims to bring awareness among healthcare professionals regarding the atypical presentation and introduce a potential differential diagnosis when evaluating patients with fever and back pain. The intention is to provide insights into the signs and symptoms that may indicate the presence of an iliopsoas abscess and prompt additional investigations. Case report: Here, we describe a case of primary iliopsoas abscess associated with drug-induced acute liver failure in our ED. The patient complained of pain in the left lumbar region and fatigue that started two weeks before this presentation, claiming that, during the previous night, the pain suddenly worsened. She had a fever, pain at palpation in the right hypochondriac and left lumbar regions, accompanied by fever and vomiting, jaundiced skin, and sclera at the examination in ED. On abdominal ultrasonography, the diagnosis of acute cholangitis was suspected. The laboratory test shows leukocytosis with neutrophilia, thrombocytosis, hepatocytolysis syndrome, and hyperbilirubinemia with the predominance of indirect bilirubin. We performed then abdominal and pelvic computed tomography, which confirmed the diagnosis of cholelithiasis observed with the diameter of the bile duct within normal limits but also showed an abscess-like collection fused to the interfibrillar level of the left iliopsoas muscle; a diagnosis we most likely would have been missed. After that, the patient was hospitalized in the General Surgery Department, and surgery drainage of the abscess was performed. The patient's evolution was excellent; she was discharged after 11 days. Conclusions: The case presented here exemplifies how iliopsoas abscess, a rare cause of back pain, can quickly go unrecognized, especially in the emergency department. Our experiences will raise awareness among doctors in emergency departments about this uncommon but essential diagnosis. With advancements in diagnostic tools and techniques, we aspire that more cases of iliopsoas abscess will be accurately diagnosed.

The ability to control the temperature distribution T(t,r) and the rate of temperature change Rt,r inside glasses is important for their microstructuring. The lattice temperature is considered at time t, exceeding the electron-phonon thermalization time, and at a distance r from the center of the model spherical heating zone. In order to describe thermal excitations, the heat capacity of glasses must be considered as a function of time due to its long-term relaxation. A method for analytical calculation of T(t,r) and R(t,r) for glasses with dynamic heat capacity cdyn(t) is proposed. It is shown that during laser microstructuring the local cooling rate -R(t,r) significantly depends on the time dispersion of cdyn(t). It has been established that at the periphery of the model heating zone of the laser beam focus, the local cooling rate can reach more than 1011 K/s. Strong cooling rate gradients were found at the periphery of the heating zone, affecting the microstructure of the material. This effect is significantly enhanced by the time dispersion of cdyn(t). The effect associated with this time dispersion is significant even well above the glass transition temperature Tg, since even short relaxation times of the dynamic heat capacity cdyn(t) are significant.

When developing bone implants Young's modulus is one of the primary characteristics of the material that should be considered. The study focuses on the possibility of regulating the modulus of the alloy Ti-50.8 at % Ni by varying its initial structure as well as aging-induced microstructure in a wide range. Microstructure observations were performed using TEM and SEM observations. The calorimetric studies of martensitic transformations were carried out using "Mettler Toledo 822e". Tensile tests were performed in a test temperature range of ‒196≤T≤+100°C using an «IN-STRON 5966». The grain/subgrain size of B2-austenite strongly affects the modulus magnitude. This effect is ambiguous for a material with a grain size of 0.13–3 µm and depends on the test temperature. The effectiveness of aging on the modulus reduction depends on the initial structure: it is most pronounced in an alloy with a relatively coarse grain size of 9 µm and brings a decrease by 3.8 times at a temperature of 37°C. Bone-like elastic modulus (10–30 GPa) at a human body temperature of 37°C is realized in an aged fine-grained NiTi alloy. An ultrafine-grained sub-structure exhibits he same values of Young's modulus in the temperature range from -100°С to 25°С.

This study presents a novel approach to analyzing the present value of total profit for non-participating and participating insurance policies in order to determine the optimal profitability of non-participating and participating insurance policies based on applying the approach used in operations research to the field of finance. As such, a comprehensive insurance product evaluation model was developed using both mathematical models and numerical analysis to evaluate the demand for non-participating and participating life insurance policies in response to changes in interest rates. The findings indicate that non-participating life insurance policies offer greater solvency for insurance companies compared to participating policies. The study also highlights the significance of spontaneous and induced demand in determining the total profit of both types of policies. The study concludes that life insurance companies should focus on generating spontaneous consumer demand, reducing induced demand, and implementing the optimal pricing strategy to achieve maximum profits.

Embryoid bodies (EBs) are multicellular three-dimensional (3D) aggregates generated from induced pluripotent stem cells (iPSCs) in suspension and serve as useful biological sources for many downstream applications. Imaging of live EBs has been hampered mainly due to the inherent limitations of the imaging techniques applied to date. This study aimed to image human iPSC (hiPSC) derived EBs to obtain their 3D volume, determining size, morphology, and cell viability from day 7 to 14 using Light Sheet Fluorescence Microscopy (LSFM). Furthermore, chromosomal stability was assessed using Multicolor fluorescence in situ hybridization (M-FISH) from day 8 to 14. EB volume increased from day 7 to 13 which, decreased at day 14. From day 7 to 11, the EBs mainly appeared spherical and morphed into an ellipsoidal shape by day 13. All EBs showed varied external morphologies and larger cavities at day 14. The EB karyotype was diploid 46XY at day 8 and exhibited a low level of aneuploidy from day 10 to 14. This study shows that an increase in cell death affects the morphology and chromosomal stability in EBs derived from hiPSC. We demonstrate that the combination of LSFM and M-FISH helps characterize EBs that will assist future stem cell therapies.

Proteomic analysis revealed the preservation of many proteins in the “Heslington brain” (which is at least 2,600-year-old brain tissue uncovered within the skull excavated in 2008 from a pit in Heslington, Yorkshire, England). Five of these proteins (“main proteins”), heavy, medium, and light neurofilament proteins (NFH, NFM, and NFL), glial fibrillary acidic protein (GFAP), and myelin basic (MBP) protein are engaged in the formation non-amyloid protein aggregates, such as intermediate filaments and myelin sheath. We used a wide spectrum of bioinformatics tools to evaluate the prevalence of functional disorder in several related sets of proteins, such as “main proteins” and their 44 interactors, as well as all other protein identified in the Heslington brain. These analyses revealed that all five “main proteins”, half of their interactors and almost one third of the Heslington brain proteins are expected to be mostly disordered. Furthermore, most of the remaining proteins are expected to contain sizable disordered regions. This is in contrary the expected substantial (if not complete) elimination of the disordered proteins from the Heslington brain. Therefore, it seems that the intrinsic disorder of NFH, NFM, NFL, GFAP, and MBP, their interactors and many other proteins might play a crucial role in preserving the Heslington brain by forming tightly folded brain protein aggregates, in which different parts are glued together via the disorder-to-order transitions.

Calcareous sand deposits are widely distributed along the shoreline in ropical and subtropical regions. Microbially induced calcite precipitation treatment (MICP) is a relatively new method to improve the stiffness and strength of the soil. Little is known about the small-strain shear modulus and damping ratio of MICP-treated calcareous sand, which are two crucial parameters for the prediction of the dynamic behavior of soil. A series of resonant column tests are performed to investigate the dynamic performance of MICP-treated calcareous sand, with special attention paid to the influence of treatment duration and confining stress on the stiffness and damping characteristics. The relationship between the initial dynamic shear modulus and unconfined compressive strength is analyzed. Additionally, the empirical equations of the reference shear strain between treatment duration and confining stress are given. The G/G0 of MICP-cemented calcareous sand presents a higher strain sensitivity than that of untreated sand, and its attenuation pattern can be described by Hardin-Drnevich model. The σc has an apparent effect on the degradation characteristics of the dynamic shear modulus of MICP-treated calcareous sand with a low cementation level, however, its effect decreases with the increasing treatment duration. The relationship between the reference shear strain and the treatment duration and confining stress can be described by a power and a linear formula, respectively.

Age-related macular degeneration is a progressive retinal disease that is associated with factors such as oxidative stress, decreased phagocytic activity, and inflammation. In this study, we evaluated the protective effects of SIG-1451, a non-steroidal anti-inflammatory drug developed for treating atopic dermatitis and known to inhibit toll-like receptor 4, on light-induced photoreceptor degeneration. SIG-1451 was intraperitoneally injected into rats once a day before exposure to 1000 lx light for 24 h; one day later, optical coherence tomography showed a decrease in retinal thickness, and electroretinogram (ERG) amplitude was also found to have decreased 3 d after light exposure. Moreover, SIG-1451 protected against this decrease in retinal thickness and increase in ERG am-plitude. One day after light exposure, upregulation of inflammatory response-related genes was observed, and SIG-1451 was found to inhibit this upregulation. Iba-1, a microglial marker, was suppressed in SIG-1451-injected rats. To investigate the molecular mechanism underlying these effects, we used lipopolysaccharide (LPS)-stimulated rat immortalised Müller cells. The upregu-lation of C-C motif chemokine 2　by LPS stimulation was significantly inhibited by SIG-1451 treatment, and western blot analysis revealed a decrease in phosphorylated I-κB levels. These results indicate that SIG-1451 protects photoreceptor cells by attenuating light damage progression through inhibiting inflammatory responses.

The connection of two phenomena - non-conservative friction forces and dissipation-induced instability can lead to many interesting engineering problems. The paper studies general material-dependent damping influence on dynamical instability of disc brake systems leading to brake squeal. The effect of general damping is demonstrated on a minimal and complex model of a disc brake. A complex system including material-dependent damping is defined in the commercial finite element software. The finite element model validated by experimental data on the brake-disc test bench is used to compute the influence of a pad and a disc damping variations on system stability by complex eigenvalue analysis. Analyzes show a significant sensitivity of the experimentally verified unstable mode of the system to the ratio of the damping between the disc and the friction material components.

NASA’s ICESat-2space-borne photon-counting lidar mission is providing global elevation measurements that will provide significant benefits to a variety of bio-geoscience research applications. Given the novelty of elevation and the derived data products from the ICESat-2 mission, the research community needs software tools that can facilitate photon-level analyses to support product validation and development new analysis methods. Here, we describe PhotonLabeler, a free graphic user interface (GUI) for manual labeling and visualization of ICESat-2 Geolocated Photon data (ATL03). Developed in MATLAB, the GUI facilitates the reading and display of ATL03 Hierarchical Data Format (HDF) files, the manual labeling of individual photons into target classes of choice using a number of point selections tools and enables eventual saving of labeled data in ASCII format. Other capabilities include saving and loading of labeling sessions to manage labeling tasks over time. We expect labeled data generated using the application to serve two main purposes. First, serve as ground truth for validating various products from ICESat-2 mission, especially for study sites around the world that do not have existing reference datasets such as airborne lidar. Second, serve as training and validation data in the development of new algorithms for generating various ICESat-2 data products. We demonstrate the first use case through a validation case study for the land and vegetation product (ATL08), which provides canopy and terrain height estimates, over two sites. For the first site, located in northwestern Zambia, we used ICESat-2 ATL03 data acquired at night and for our second site in Texas, US, we used ATL03 data acquired during the day. The PhotonLabeler application is freely available as a compiled MATLAB binary to enable free access and utilization by interested researchers.

This study measures the noise levels in a baseball stadium and analyzes baseball fans’ attitude of effect of recreational noise exposure on their hearing. In the baseball stadium, noise levels were measured in four seating sections using a sound level meter during the games. The LAeq average of the 16 measures produced 91.7 dBA, showing a significantly high noise level in the red and navy sections. As a function of frequency by LZeq analysis, the noise levels were significantly higher in low frequencies than other frequencies. For the survey sample, 688 randomly selected participants completed a 16-question survey on their noise exposure during the game and on the potential risk of hearing loss. Despite the very high noise levels, 70% of the respondents preferred sitting in either the red or the navy section to be closer to the cheerleaders and to obtain a good view. Most respondents reported that they did not consider wearing earplugs, and one-third experienced hearing muffled speech after the game. We conclude that the noise levels in baseball stadiums are high enough to cause hearing damage and/or tinnitus later, but expect these results to improve public education regarding safe noise exposure during popular sports activities.

Cancer stem cells (CSCs) have been identified in many cancer types. This study identified and characterized CSCs in head and neck metastatic malignant melanoma (HNmMM) to regional lymph nodes using induced pluripotent stem cell (iPSC) markers. Immunohistochemical (IHC) staining performed on 20 HNmMM tissue samples demonstrated expression of iPSC markers OCT4, SOX2, KLF4 and c-MYC in all samples while NANOG was expressed at low levels in two samples. Immunofluorescence (IF) staining demonstrated an OCT4+/SOX2+/KLF4+/c-MYC+ CSC subpopulation within the tumor nests (TNs) and another within the peritumoral stroma (PTS) of HNmMM tissues. IF also showed expression of NANOG by some OCT4+/SOX2+/KLF4+/c-MYC+ cells within the TNs in an HNmMM tissue sample that expressed NANOG on IHC staining. In situ hybridization (n=6) and reverse-transcription quantitative polymerase chain reaction (n=5) on the HNmMM samples confirmed expression of all five iPSC markers. Western blotting of four primary cell lines derived from four of the 20 HNmMM tissue samples showed expression of SOX2, KLF4, and c-MYC but not OCT4 and NANOG, and three of these cell lines formed tumorspheres in vitro. We demonstrate the presence of two putative CSC subpopulations within HNmMM, which may be a novel therapeutic target in the treatment of this aggressive cancer.

We report the development of an extrinsic self-healing coating system that shows no fluorescence from the intact coating, yellowish fluorescence in cracked regions, and greenish fluorescence in healed regions, thus allowing the separate monitoring of cracking and healing of coatings. This fluorescence monitoring self-healing system consisted of a top coating, an epoxy matrix resin containing mixed dye-loaded in single microcapsule. The dye-loaded microcapsules consisted of a poly(urea-formaldehyde) shell encapsulating a healing agent containing MAT-PDMS and styrene, a photo-initiator and a mixture of two dyes, one that fluoresces only in the solid state (DCM) and a second that fluoresces dramatically increased in the solid than solution state (4-TPAE). A mixture of the healing agent, photo-initiator and the two dyes was yellow due to fluorescence from DCM. On UV curing of this mixture, however, the color changed from yellow to green and the fluorescence intensity increased due to fluorescence from 4-TPAE in the solid state. When a self-healing coating embedded with microcapsules containing the DCM/4-TPAE dye mixture was scratched, the damaged region exhibited a yellowish color that changed to green after healing. Thus, the self-healing system reported here allows the separate monitoring of cracking and healing based on changes in fluorescence color.

Reduced autonomic responses have been reported in horses of advanced age, predisposing them to compromised well-being. Maintained physical exertion tends to preserve autonomic function in geriatric horses. However, the impact of structured exercise regimens on autonomic modulation in geriatric horses has yet to be elucidated. A study was conducted to compare the autonomic modulation in geriatric horses with different activity levels: living sedentarily (SEL), retaining unstructured activities (RAT) and practising a structured exercise regimen (SER). The study observed heart rate variability (HRV) and found that the minimum and mean heart rate decreased in SER horses at 10–12 weeks, with no changes in SEL or RAT horses over the study period. Beat-to-beat (RR) intervals showed no differences in SEL horses, temporal fluctuation at 8–10 weeks in RAT horses and an increase at 10–12 weeks in SER horses. HRV was higher in SER than in RAT horses, as well as in SER horses to a lesser extent. Geriatric horses engaging in a structured exercise regimen demonstrated better autonomic regulation, reflecting lower stress than those retaining unstructured activities or living sedentarily. These results carry welfare implications for developing health management in geriatric horses.

This narrative review examines the crucial role of physical activity in managing long COVID, characterized by persistent symptoms such as fatigue, breathlessness, and cognitive impairments following SARS-CoV-2 infection. The methodology involved a comprehensive literature search across PubMed, EBSCO (EDS), and Google Scholar, selecting peer-reviewed articles from December 2019 focusing on long-term COVID physical activity interventions. The review highlights that tailored exercise programs, adjusted to individual health status and abilities, significantly alleviate symptoms and enhance psychological well-being. Key findings emphasize the importance of personalized exercise prescriptions due to the variability in patient responses and the need for a multidisciplinary approach in developing and monitoring interventions. Despite promising outcomes, the review identifies research gaps, including the need for long-term studies, randomized controlled trials, and deeper mechanistic insights. It suggests that standardized reporting, templates like CERT, and integrating digital health tools are essential for optimizing interventions. Overall, the review advocates including personalized physical activity programs in standard care for long COVID to improve patient outcomes and quality of life.

Background/Objectives: This study looks at how a kinematic chain exercise regimen that targets the lower, core, and upper body affects university shot put participants' shoulder muscle strength and throwing efficiency. This study fills an apparent research void on shot put training approaches by presenting a comprehensive kinematic chain workout program. It was anticipated that this method would improve performance the most, considering the complex biomechanical require-ments of the sport. Methodology: Athletes, seventy in age (19.87 ± 1.31 years), were assigned into two groups at random: experimental (n = 35) and control (n = 35). While the control group carried on with their usual training, the experimental group participated in an 8-week kinematic chain training program, pre- and post-training evaluations were carried out to evaluate shot put throwing ability, shoulder muscle strength, and participant satisfaction with the exercise regimen. Results: demonstrated that, when compared to the control group, the athletes in the kinematic chain program had a significantly improved throwing distance (p = 0.01) and shoulder muscle strength (p = 0.01). Furthermore, there was a significant difference (p = 0.005) in the athletes' satisfaction levels with the workout program among those in the experimental group. This implies that a kinematic chain-focused strategy improves performance and emphasizes the significance this type of training is for shot put athlete performance. Conclusion: As an improvement forward in sports science, the study's finding promotes the inclusion of kinematic chain workouts in shot put training programs and calls for more research on kinematic chain-based approaches in a variety of sports.

Background: Depression, a multifaceted mental health condition, necessitates a multidimensional approach to treatment. This study aimed to elucidate the potential efficacy of various mitochondrial interventions, ranging from pharmacological treatments to lifestyle modifications, in alleviating depressive symptoms and enhancing overall mental well-being and assess the diverse range of mitochondrial assessments for managing depression by synthesizing findings from selected studies. Methods: A systematic compilation of studies, employing observational, interventional, and animal-based designs, was undertaken to elucidate the intricate relationship between mitochondrial function and depression as well as depressive signs and symptoms. The PRISMA guidelines were employed for conducting this review and a specific set of selection criterion were formulated by a team of reviewers for selection of relevant papers. Results: The synthesized results from the 21 selected papers highlighted the potential of these interventions to target diverse aspects of depression. Hyperbaric oxygen therapy and psychotherapy demonstrated significant reductions in depression and anxiety scores, with hyperbaric oxygen therapy particularly effective in improving nerve function and daily living activities. Whole-body cryotherapy displayed substantial improvements in depressive symptoms and quality of life. Frequent sauna bathing exhibited a lower risk of depressive symptoms in males. Dietary patterns, including Paleolithic and Mediterranean diets, showcased potential protective effects against depression, anxiety, and stress. The ketogenic diet revealed promise in ameliorating depression and psychosis symptoms alongside positive metabolic changes. Fasting interventions, though challenging, were associated with lower anxiety and depression levels without increased fatigue. Bright white light therapy enhanced remission rates and reduced depression scores in bipolar depression. Probiotic supplementation exhibited potential in reducing depression scores and improving metabolic markers, although further investigation is warranted. Conclusion: The diverse array of interventions explored in this study underlines the multifaceted nature of depression treatment. While these findings offer hope for more personalized and effective approaches, it is imperative to consider the variability in study designs, sample sizes, and methodologies among the selected papers. The mechanisms underlying the observed effects remain partially understood, emphasizing the need for continued mechanistic research. This study sets the stage for future investigations and clinical practices, showcasing the potential of various interventions in mitigating the challenges posed by depression and paving the way for more effective treatment strategies.

The worldwide prevalence of type 2 diabetes (T2D) and prediabetes is rapidly increasing, particularly in children, adolescents, and young adults. Oxidative stress (OxS) has emerged as a likely initiating factor in T2D. The role of natural antioxidant products in combating T2D is best evaluated in the context of the complex physiological processes that modulate T2D-OxS such as glycemic control and exercise. The role of natural antioxidant compounds such as vitamin E in T2D must likewise be considered beyond their roles as inhibitors of OxS. In addition to antioxidant properties, vitamin E vitamers (tocopherols and tocotrienols) also exhibit distinct abilities to regulate cellular signal transduction pathways important to T2D progression. Most research on the role of vitamin E in T2D or prediabetes has been limited to tocopherols (Ts) but emerging trials with tocotrienols (T3s) show promise. Minimizing factors that induce chronic damaging OxS and maximizing natural antioxidant protective factors may provide a means of preventing or slowing T2D progression. This “optimal redox” (OptRedox) approach also provides a framework in which to discuss the potential benefits of natural antioxidant factors such as antioxidant products. Since early, effective intervention is critical, the OptRedox strategy would be optimally effective if implemented in the pediatric population.

Back pain is a common symptom that affects all age groups across the globe, when left untreated may eventually lead to disability. A convenient sample selection method was used in this study due to the global Covid-19 pandemic lockdown which was effective in Turkey during the investigation period. Thus, virtual data collection and health education including some health risks were employed. A total population of two hundred adult women was involved in the study but one hundred and twenty-one responses were collected. Findings show that, for socio-demographic characteristics, the pain was found highest in women between the ages of 41-50 and obese/overweight individuals. Although, there was no significant difference recorded in the marital status category. Moreover, statistical mean differences were detected between the scales for ODI (4.18) and BPFS (6.09). Also, p<0.05, paired sample t-test was 0.001 ODI and 0.001 BPFS after the training exercise. This suggests that exercise training is inversely correlated with pain severity which implies that training has a significant influence on pain intensity. Thus, it could be concluded that there is a relationship between the training exercise and ODI/BPFS.

1) Background: A population-based cross-sectional study was conducted to understand how green cover and accessibility of common public open spaces in compact urban areas affect physical activeness of resident. 2) Methods: A total of 554 residents completed a structured questionnaire on quality-of-life, physical activity level, and healthy eating practice. 3) Results: The sampled population lived with green cover averaged 10.11 ± 7.95% (ranged 1.56–9.88), whereas majority (90%) of the residents performed physical activities at medium and high levels. Metabolic Equivalent of Task (MET)-minutes/week was associated with the green cover percentage (Pearson r = 0.092; p < 0.05). Irrespective of age and physical activity level, active residents commonly used public open spaces within district for performing exercise, especially parks and promenade were mostly used by older residents while sports facilities by the younger groups. 4) Conclusions: Current findings suggested promotion of exercise could be achieved by the design or redesign of built environment to include more parks accessible to the residents with the increase of vegetation.

Harmful algal blooms are a serious problem for humanity, so the development of tools and methods for their timely detection is an urgent task. The use of optical methods often allows scientists to solve problems of remote and automated monitoring. Temperature spectra of fluorescence can be used as distinctive features of algae, and the fluorescence parameters obtained from them can be used for identification. The paper presents a description of the fluorescence parameters of Alexandrium catenella, and shows their stability during cumulative cultivation. In addition, the cytometric properties of the culture and its pigment composition were studied. In addition, the article compares all the studied properties of this microalga with the alga Prorocentrum cordatum. We demonstrated clear differences in their fluorescence parameters, which makes it possible to distinguish these microalgae by optical methods, for example, during their dominant blooms.

Recent advancements in vascular organoid (VO) and vessel-on-chip (VoC) technologies have revolutionized our approach to studying cardiovascular diseases (CVDs), offering unprecedented insights through more physiologically relevant models. VOs generated from human pluripotent stem cells exhibit remarkable self-organization capabilities, forming complex three-dimensional structures that closely mimic human blood vessel architecture and function, while VoCs engineered with groundbreaking microfluidic systems that meticulously recreate the physical and functional attributes of blood vessels. These innovative constructs serve as powerful tools for investigating vascular development, disease progression, and therapeutic efficacy. By enabling the creation of patient-specific VOs and VoCs, they pave the way for personalized medicine approaches, allowing researchers to delve into genetic variations, intricate cellular interactions, and dynamic processes with exceptional resolution. The synergy between VOs and VoCs with cutting-edge technologies such as single-cell sequencing and high-resolution imaging has further amplified their potential, unveiling novel mechanisms underlying CVDs and identifying promising therapeutic targets. Herein, we summarize different types of VOs and VoCs and present an extensive overview on the generation and applications of VOs and VoCs in CVDs. We will also highlight clinical and translational challenges and future perspectives around VOs and VoCs.

This study aims to demonstrate the possibility of incorporating a natural antioxidant biomolecule, into polymeric porous scaffolds. To this end, Poly-L-Lactic Acid (PLLA) scaffolds were produced using the Thermally Induced Phase Separation (TIPS) technique and additivated with different amounts of Rosmarinic Acid (RA). The scaffolds, with a diameter of 4 mm and a thickness of 2 mm, were characterized with a multi-analytical approach. Specifically, Scanning Electron Mi-croscopy analyses demonstrated the presence of an interconnected porous network, character-ized by a layer of RA at the level of the pore’s surfaces. Moreover, the presence of RA biomole-cules increased the hydrophilic nature of the sample, as evidenced by the decrease in contact angle with water from 128° to 76°. This approach is cost-effective, and it could be customized with different biomolecules, offering the possibility of producing porous polymeric structures con-taining antioxidant molecules. These scaffolds meet the requirements of tissue engineering and could be offered a potential solution to reduce inflammation associated with scaffold implantation thus improving tissue regeneration.

Globally, habitat fragmentation has increased the proximity between wildlife, humans, and emerging predators such as free-ranging dogs. In these fragmented landscapes, encounters between primates and dogs are escalating, with primates often falling victim to dog attacks while navigating patchy landscapes and fragmented forests. We aim to investigate how these primates deal with the simultaneous threats posed by humans and predators, specifically focusing on the adaptive strategies of Central Himalayan Langur (CHL) in the landscape of fear. To address this, we conducted a behavioral study on the CHL in an agro-forest landscape, studying them for a total of 3912 hours over two consecutive years. Our results indicate that, compared to their most common resting behavior, CHL allocate more time to feeding and locomotion, and less time to socializing in the presence of humans and predatory dogs. Additionally, they exhibit increased feeding and locomotion and reduced social behavior in agro-forest or open habitats. These behavioral patterns reflect adaptive responses to the landscape of fear, where the presence of predators significantly influences their behavior and resource utilization. This study suggests measures to promote coexistence between humans and wildlife through the integration of effective management strategies that incorporate both ecological and social dimensions of human-wildlife interactions.

To maintain an optimal body content of phosphorus throughout postnatal life, variable phosphate absorption from food must be finely matched with urinary excretion. This amazing feat is accomplished through synchronised phosphate transport by myriads of ciliated cells lining the renal proximal tubules. These respond in real time to changes in the phosphate and composition of the renal filtrate, and to hormonal instructions. How they do this has stimulated decades of research. New analytical techniques, coupled with incredible advances in computer technology, have opened new avenues for investigation at a sub-cellular level. There has been a surge of research into different aspects of the process. These have verified long held beliefs and are also dramatically extending our vision of the intense, integrated, intracellular activity which mediates phosphate absorption. Already, some have indicated new approaches for pharmacological intervention to regulate phosphate in common conditions, including chronic renal failure and osteoporosis, as well as rare inherited biochemical disorders. It is a rapidly evolving field. The aim here is to provide an overview of our current knowledge, to show where it is leading, and where there are uncertainties. Hopefully this will raise questions and stimulate new ideas for further research.

Wild-type p53 cancer therapy-induced senescent cells frequently engulf and degrade neighboring ones inside a massive vacuole in their cytoplasm. After clearance of the internalized cell, the vacuole persists, seemingly empty, for several hours. Despite large vacuoles being associated with cell death, this process is known to confer a survival advantage to cancer engulfing cells, leading to therapy resistance and tumor relapse. Previous attempts to resolve the vacuolar structure and visualize their content using dyes were unsatisfying for lack of known targets and ineffective dye penetration and/or retain. Here, we overcame this problem by applying optical diffraction tomography and Raman spectroscopy to MCF7 doxorubicin-induced engulfing cells. We demonstrated a real ability of cell tomography and Raman to phenotype complex microstructures, such as cell-in-cells and vacuoles, and detect chemical species in extremely low concentrations within live cells in a completely label-free fashion. We show that vacuoles had a density indistinguishable to the medium, but were not empty, instead contained diluted cell-derived macromolecules, and we could discern vacuoles from medium and cells using their Raman fingerprint. Our approach is useful for the non-invasive investigation of senescent engulfing (and other peculiar) cells in unperturbed conditions, crucial for a better understanding of complex biological processes.

Adult stem cells (ASCs) can be cultured with difficulty from most tissues, often requiring chemical or transgenic modification to achieve adequate quantities. We show here that mouse primary fibroblasts grown in suspension change from the elongated and flattened morphology observed under standard adherent culture conditions generating rounded cells with large nuclei and scant cytoplasm expressing the mesenchymal stem cell (MSC) marker (Sca1; Ly6A) within 24hrs. Based on this initial observation, we describe here a suspension culture method that, irrespective of the lineage used, mouse fibroblast, primary human somatic cells (fibroblasts, hepatocytes and keratinocytes), is capable of generating a high yield of cells in spheroid form which display expression of ASCs surface markers, circumventing the anoikis which often occurs at this stage. Moreover, mouse fibroblasts-derived spheroids can be differentiated into adipogenic and osteogenic lineages. Analysis of single cell RNA sequence data identified 8 distinct cell clusters with one in particular comprising approximately 10% of the cells showing high levels of proliferative capacity expressing high levels of genes related to MSCs and self-renewal as well as extracellular matrix (ECM). We believe the rapid, high-yield generation of proliferative, multi-potent ASC-like cells by the process we term suspension-induced stem cell transition (SIST) could have significant implications for regenerative medicine.

Large-area nanostructuring of glasses using intense laser beam remains a difficult task due to the extreme non-linear absorption of the laser energy by the material. Precise optimization of the process parameters is essential for fabricating nanostructures with large area coverage. In this study, we report the findings on creating high spatial frequency LIPSS (HSFL) on borosilicate glass through direct laser writing, using a femtosecond laser with a wavelength λ = 800 nm, pulse duration τ = 35 fs, and repetition frequency frep = 1 kHz. The orientation of the HSFL was found to be parallel to the electric field vector. We measured the single pulse ablation threshold (Fth=3.87±0.26 J/cm2) and incubation factor (S=0.68±0.03) of Borosilicate glasses for precise control for large area surface structuring. Single-spot experiments indicate that uniform LIPSS formation is limited by melt formation inside the irradiated area for higher fluence and a larger number of irradiated laser pulses. The orientation of the scan axis with the laser beam polarization is found to be significantly influencing the uniformity of the large area processing. We found that the orientation of the scan axis with the laser beam polarization significantly affects the uniformity of large-area processing, with redeposition and melt formation being higher when the scan axis is perpendicular to the laser beam polarization. Large-area processing of the borosilicate glass surface is done by line-by-line scanning over the surface with a scan orientation parallel to the laser beam polarization. The optical characterization reveals that the transmittance and reflectance of the borosilicate glass decreased significantly after processing. Also, the wettability of the surface has been changed from hydrophilic to super hydrophilic after processing. These chemical contamination-free and uniformly distributed structures have potential applications in optics, microfluidics, photovoltaics, and biomaterials.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, with septic cardiomyopathy being a common and severe complication. Despite its significant clinical impact, the molecular mechanisms underlying sepsis-induced cardiomyopathy (SICM) remain incompletely understood. In this study, we performed a comparative analysis of whole transcriptome profiles in two widely used mouse models of septic cardiomyopathy, the cecal ligation and puncture (CLP) model and the lipopolysaccharide (LPS) model. Our aim was to identify key genes and pathways involved in the development of septic cardiomyopathy and to evaluate the similarities and differences between the two models. Our findings suggested that 1) both methods can induce septic heart dysfunction within 24 hours; 2) distinct whole transcriptome expression profiles are revealed; 3) potentially different pathways are involved in causing heart failure in sepsis. The comprehensive comparison provides valuable insights into the molecular basis of septic cardiomyopathy and contributes to the ongoing search for effective treatment strategies, triggered by different factors for SICM.

Despite extensive research, the links between the accumulation of glycosaminoglycans (GAGs) and the clinical features seen in patients suffering from various forms of Mucopolysaccharidoses (MPSs) have yet to be further elucidated. This is particularly true for the neuropathology of these disorders, even though the neurological symptoms are currently incurable, even in the cases where a dis-ease-specific therapeutic approach does exist. One of the best ways to get insights on the molecular mechanisms driving that pathogenesis is the analysis of patient-derived cells. Yet, not every pa-tient-derived cell holds potential to recapitulate relevant disease features. For the neurodegenerative forms of these diseases in particular, it is challenging to grow neuronal cultures that accurately represent them because of the obvious inability to access live neurons. This scenario changed sig-nificantly since Yamanaka et al. published their protocol for induction of pluripotent stem cells (SC) from adult human fibroblasts. From then on, a series of differentiation protocols to generate neurons from induced pluripotent stem cells (iPSC) was developed and extensively used for disease mod-eling. Currently, human iPSC and iPSC-derived cell models have been generated for several MPS and numerous lessons were learnt from their analysis. Here we review most of those studies, not only listing the currently available MPS iPSC lines and their derived models, but also summarizing how they were generated and the major information different groups have gathered from their analysis. Finally, and taking into account that iPSC generation is a laborious/expensive protocol that holds significant limitations, we also comment on a tempting alternative to establish MPS pa-tient-derived neuronal cells in a much more expedite way by taking advantage of the existence of a population of multipotent SC in human dental pulp, to establish mixed neuronal and glial cultures.

Contrast-induced acute kidney injury (CI-AKI) is a serious complication after angiographic examinations in cardiology. Diagnosis may be delayed based on standard serum creatinine, and subclinical forms of kidney damage may not be detected at all. In our study we investigate the clinical use in these directions of a “damage” type biomarker - Neutrophil Gelatinase-Associated Lipocalin (NGAL). Among patients with a high-risk profile undergoing scheduled coronary angiography and/or angioplasty, plasmsa NGAL was determined at baseline, at 4 and 24 hours after contrast administration. In the CI-AKI group, NGAL increased significantly at the 4th hour (132.33±72.83 ng/ml versus 111.48±65.06 ng/ml, p=0.006) and at the 24th hour (212 .93±276.61 ng/ml, p=0.008). In patients with subclinical CI-AKI, NGAL also increased significantly at the 4th hour (128.18±99 ng/ml, p=0.002) and reached levels close to those in patients with CI-AKI. Unlike new biomarker, however, serum creatinine did not change significantly in this group. The diagnostic power of NGAL is extremely good - AUC 0.847 (95% CI: 0.677-1.000; p=0.001) in CI-AKI and AUC 0.731 (95% CI: 0.539 – 0.924; p=0.024) in subclinical CI-AKI. NGAL may be a reliable biomarker for early diagnosis of clinical and subclinical forms of renal injury after contrast angiographic studies.

This work communicates line strength data and associated scripts for computation and spectroscopic fitting of selected transitions of the diatomic molecules AlO, C2, CN, OH, N2+, NO, and TiO. For ease of use, the scripts for data analysis are designed for inclusion in various software packages or program languages. The accuracy of the data is of the order of less than one picometer, suitable for analysis of laser-induced fluorescence and laser-plasma spectra. Selected results demonstrate the applicability of the program for data analysis in laser-induced optical breakdown spectroscopy primarily at The University of Tennessee Space Institute, Center for Laser Applications. Representative spectra are calculated and referenced to measured data records.

This review summarizes current understanding of the interaction between circadian rhythms of gene expression and epigenetic clocks characterized by the specific profile of DNA methylation in CpG-islands which mirror the chronological age of individual cells and the entire organism. Basic mechanisms of regulation for circadian genes CLOCK- BMAL1 as well as downstream clock-controlled genes (ССG) are also discussed here. It has been shown that circadian rhythms operate by finely tuned regulation of transcription and rely on various epigenetic mechanisms including activation of enhancers / suppressors, acetylation / deacetylation of histones and other proteins as well as DNA methylation. Overall, up to 20% of all genes expressed by the cell are subject to expression oscillations associated with circadian rhythms. Also included in the review is a brief list of genes involved in the regulation of circadian rhythms, along with genes important for metabolic control, aging, and oncogenesis. Knocking out some of them (for example, Sirt1) accelerates the aging process, while overexpression of Sirt1, on the contrary, protects against age-related changes. Circadian regulators control a number of genes that activate the cell cycle (Wee1, c-Myc, p20, p21, and Cyclin D1) and regulate histone modification and DNA methylation. Approaches for determining the epigenetic age from methylation profiles across CpG islands in individual cells are described. DNA methylation, which characterizes the function of the epigenetic clock, appears to link together such key biological processes as regeneration and functioning of stem cells, aging and malignant transformation. Finally, main features of adult stem cell aging in stem cell niches and current possibilities for modulating the epigenetic clock as part of antiaging therapy are discussed.

Here, I introduce a concept called autonomous selection to refer to a source of selection that is part of the individuals upon which it acts. The concept is motivated by a set of phenomena with the following characteristics: Natural selection shaped a variant (e.g., gene, epigenetic mark, or combination thereof) to act in a manner that reduces the frequency of one or more heritable traits of the individual in which it is located if those traits are detrimental to individual or group fitness. Phenomena with these characteristics are peculiar to traditional evolutionary theory but have been identified rather frequently in recent decades. They are also relevant to adaptive evolution: By reducing the frequency of a trait detrimental to fitness, the variant accelerates the evolution of adaptations, which allows its holders to adapt better to constantly changing environments. The variant is shaped by (natural) selection, but also does (autonomous) selection. Several phenomena with these characteristics have been invoked by proponents of the extended evolutionary synthesis (EES). The concept of autonomous selection helps resolve some of the controversy surrounding the EES: EES proponents call attention to the incompleteness of contemporary theory, emphasizing individuals’ processes that influence which adaptations those individuals evolve. I argue for the special importance of individuals’ processes that do not just influence those individuals’ adaptations, but also accelerate the adaptive evolution of those individuals. All known phenomena that fit this description are examples of autonomous selection. Other phenomena raised by EES proponents do not meet this threshold.

An experimental study is carried out in a cavitation tunnel on a propeller operating downstream of a non-uniform wake. The goal of this work is to establish quantitative correlations between the near pressure field and the cavitation pattern that takes place on the propeller blades. The pressure field is measured at the walls of the test section and in the near wake of the propeller, and is combined with quantitative high-speed image recording of the cavitation pattern. Through simple harmonic analysis of the pressure data and image processing techniques that allow to retrieve the cavitation extension and volume, we discuss the potential sources that generate the pressure fluctuations. Time correlations are unambiguously established between pressure peak fluctuations and cavitation collapse events, based upon the Rayleigh collapse time. Finally, we design a model to predict the cavitation-induced pressure fluctuations from the derivation of the cavitation volume acceleration. This simple model demonstrates a remarkable agreement with the actual pressure field.

Fucoidans, known for their diverse biological properties such as anti-inflammatory, antiviral, antitumor, and immune-stimulatory effects, have recently gained attention for their potential benefits in exercise endurance, muscle mass, and anti-fatigue. However, the mechanisms by which fucoidans enhance exercise performance are still unclear. To investigate these effects, we administered 400 mg/kg/day of fucoidan extract derived from Undaria pinnatifida to sixty-four C57BL/6J mice over ten weeks. We evaluated changes in running activity, mitochondrial-related gene expression in skeletal muscle, and alterations in the intestinal microbiome. Our results showed that fucoidan supplementation significantly increased daily running distance and muscle mass by 25.5% and 10.4%, respectively, in mice on a standard chow diet, and with more modest effects observed in those on a high-fat diet (HFD). Additionally, fucoidan supplementation led to a significant increase in beneficial gut bacteria, including Bacteroides/Prevotella, Akkermansia muciniphila, and Lactobacillus, along with a notable reduction in the Firmicutes/Bacteroidetes ratio, indicating improved gut microbiome health. Mechanistically, fucoidan supplementation upregulated the mRNA expression of key genes related to mitochondrial biogenesis and oxidative capacity, such as COX4, MYH1, PGC-1α, PPAR-γ, and IGF1, in both standard chow and HFD-fed mice. Our findings suggest that fucoidan supplementation enhances exercise performance, improves muscle function, and positively modulates the gut microbiome in mice, regardless of diet. These effects may be attributed to fucoidans' potential prebiotic role, promoting the abundance of beneficial gut bacteria and contributing to enhanced exercise performance, increased muscle strength, and improved recovery.

The responses of inflammatory cytokines and brain-derived neurotrophic factor (BDNF) to a high-intensity interval training (HIIT) session were compared between 7 postmenopausal (57±2 y) and 8 premenopausal females (44±3 y) during the luteal phase of their menstrual cycle, when estrogen and progesterone are highest, and. HIIT consisted of 10 x 1 min running intervals (90% maximum heart rate) separated by 1 min recovery intervals. Blood samples were collected at baseline (fasted), pre-exercise (postprandial), and 0, 30 and 90 min post-HIIT and analyzed for interleukin (IL-6) and 10 (IL-10), tumour necrosis factor-alpha (TNF-α) and BDNF. IL-6 significantly increased from pre-exercise to 0 min post-HIIT in postmenopausal (+40%, p=0.01) but 30 min post-HIIT in premenopausal females (+60%, p=0.02). IL-6 remained elevated at 90 min post-HIIT in premenopausal (+104%, p=0.05) and to a higher degree in postmenopausal (+385%, p&lt;0.001). IL-10 showed no response. TNF-α increased from pre- to 0 min post-HIIT (+10%, p=0.05), then decreased to below pre-exercise at 30 min (-10%, p=0.02) and 90 min (-5%, p=0.04) in both groups. BDNF increased immediate post-HIIT in premenopausal (+60%, p&lt;0.001) but not postmenopausal females. The differences in IL-6 and BDNF response to HIIT between pre and postmenopausal females provide evidence of the role of female reproductive hormones in the regulation of these exercise-induced responses.

ABSTRACTBackground: Crohn's disease (CD) is a chronic inflammatory bowel disorder with limited treatment options. Mitochondrial dysfunction has been implicated in CD pathogenesis, and mitochondrial-based interventions have emerged as a potential therapeutic avenue. This systematic review aimed to assess the efficacy of mitochondrial-based interventions in the management of CD.Methods: A systematic search of multiple databases was conducted to identify relevant studies in accordance with the PRISMA protocol. Inclusion criteria encompassed studies investigating mitochondrial-targeted interventions in CD patients. Methodological quality and risk of bias assessments were performed. Data synthesis involved both quantitative meta-analysis and qualitative narrative synthesis.Results: A total of 23 studies were included in this review, comprising randomized controlled trials, observational studies, and case reports. Mitochondrial-based interventions encompassed nutraceuticals, probiotics, exercise, and dietary modifications. However, the overall quality of evidence was moderate, primarily due to methodological limitations in some studies.Conclusion: This systematic review suggests that mitochondrial-based interventions hold promise as adjunctive therapies for CD management. They appear to contribute to clinical remission and amelioration of disease activity. Nevertheless, the moderate quality of evidence underscores the need for further well-designed clinical trials to substantiate these findings and delineate optimal intervention strategies.

Course-based Undergraduate Research Experiences (CUREs) in high-enrollment, introductory classes are a 37 potentially transformative approach to retaining more students in STEM majors. We developed and piloted a CURE 38 in the introductory biology courses at the University of Washington. This CURE focuses on analyzing experimental 39 evolution of antibiotic resistance in Escherichia coli and generates data on two topics relevant to clinical practice: 40 compensatory mutations and cross-drug effects. By studying mutations in central cellular machinery that confer drug 41 resistance, students not only gain insight into fundamental cellular phenomena, but also recognize the molecular 42 basis of a medically important form of evolutionary change, connecting genetics, microbiology, and evolution.

Background: Low-level physical activity (PA) among Chronic Low Back Pain (cLBP) is associated with various biopsychosocial factors. This research aimed to study the predictors of PA behavior among cLBP patients. Methods: In the present study 300 eligible patients with cLBP who referred to comprehensive health service centers in the Shahid Beheshti University of Medical Sciences (SBUMS) in Tehran, Iran were random selected.To diagnose the predictors of PA behavior, all the Theory of Reasoned Action (TRA) constructs were examined as risk factors to see if they influence on the probability of PA behavior occurrence and were interpreted through odds ratio (OR). SPSS version 19 was used to analyze the data. Results: Totally 280 cLBP patients with mean age of 57.07 ±13.09 years old participated in the study. This study showed that motivation to comply significant predictor the cLBP patients for subjective norm OR (%95CI): 2.095(0.116-2.792), p-value<0.001), intention was significant predictor for perform the PA behavior OR (%95CI): 1.431(0.138-1.538), p-value <0.001), behavior beliefs could predictor for attitude OR (%95CI): 1.276(0.106-1.355), p-value= 0.002). attitude, normative beliefs, subjective norm ,and evaluation outcome behavior could predictors the cLBP patients for intention to perform the PA behavior OR (%95CI): 1.188(0.032-1.312), p-value<0.001)., OR (%95CI): 1.158(0.076-2.208), p-value=0.003) ., OR (%95CI): 1.104(0.076-1.128), p-value<0.001) ., OR (%95CI): 0.814(0.301-1.440), p-value=0.007). Conclusions: This study showed that the cLBP patients who were normative beliefs and evaluation regarding PA behavior could effect on the intention to engage in greater PA than those via other constructs (attitude and subjective norm). This study showed that the cLBP patients who were normative beliefs and evaluation regarding PA behavior could effect on the intention to engage in greater PA than those via other constructs (attitude and subjective norm). This study showed that the cLBP patients who were normative beliefs and evaluation regarding PA behavior could effect on the intention to engage in greater PA than those via other constructs (attitude and subjective norm).

A large body of evidence reports about the positive effects of physical activity in pathophysiological conditions associated with aging. Physical exercise, alone or in combination with other medical therapies, unquestionably causes reduction of symptoms in chronic non-transmissible diseases often leading to significant amelioration or complete healing. The molecular basis of this exciting outcome, however, remain largely obscure. Epigenetics, exploring at the interface between environmental signals and the remodelling of chromatin structure, promises to shed light on this intriguing matter possibly contributing to the identification of novel therapeutic targets. In this review, we shall focalize on the role of sirtuins (Sirts) a class III histone deacetylases (HDACs) which function has been frequently associated, often with a controversial role, to the pathogenesis of aging-associated pathophysiological conditions including cancer, cardiovascular, muscular, neurodegenerative, bones and respiratory diseases. Numerous studies, in fact, demonstrate that Sirt-dependent pathways are activated upon physical and cognitive exercises linking mitochondrial function, DNA structure remodelling and gene expression regulation to designed medical therapies leading to tangible beneficial outcomes. However, in similar conditions, other studies assign to sirtuins a negative pathophysiological role. In spite of this controversial effect, it is doubtless that studying sirtuins in chronic diseases might lead to an unprecedented improvement of life quality in the elderly.

Drilling and blasting is the conventional method used for rock fragmentation in open pit mining. Blast-induced damage can reduce the level of stability of benches and pit slopes. To develop an optimal blast design, an adequate knowledge of the rock properties and in-situ fractures is needed. Fractures are generally the paths of least resistance for explosive energy and can affect the intensity of blast-induced damage. Discrete Fracture Networks (DFN) are 3D representations of joint systems used for estimating the distribution of in-situ fractures in a rock mass. The combined finite/discrete element method (FDEM) can be used to simulate the complex rock breakage process during a blast. The objective of this paper is to develop a methodology for assessing the influence of in-situ joints on the post-blast fracturing and the associated wall damage in 2D bench blasts scenarios. First, a simple one-blasthole scenario is analyzed with the FDEM software Irazu 2D and calibrated based on a laboratory-scale blasting experiment available from previous literature. Secondly, more complex scenarios consisting of one-blasthole models at the bench-scale were simulated. A bench blast without DFN (base case) and one with DFN, were numerically simulated. The model with DFN demonstrated that the growth path and intensity of blast-induced fractures were governed by pre-existing fractures which led to smaller wall damage area. The damage intensity for the base case scenario is about 42% higher than for the blast model with DFN included, which highlights the significance of in-situ fractures in the resulting blast damage intensity. The methodology for developing the DFN-included blasting simulation provides a more realistic modeling process for blast-induced wall damage assessment. This results in a better characterization of the blast damage zone and can lead to improved slope stability analyses.

Corticosteroids are extensively used in medicine for their powerful anti-inflammatory and immunosuppressive effects. However, their psychiatric side effects—such as mood disturbances, anxiety, and psychosis—are significant yet often underappreciated. This review provides a comprehensive exploration of corticosteroid-induced psychiatric disorders, with a focus on their underlying mechanisms and clinical implications. We examine how corticosteroids influence the Hypothalamic-Pituitary-Adrenal (HPA) axis, leading to dysregulation of stress responses and alterations in neurotransmitter levels, particularly dopamine, serotonin, and glutamate. These changes are linked to structural abnormalities in key brain areas such as the hippocampus and amygdala, which are implicated in mood and anxiety disorders, psychosis, and conditions like post-traumatic stress disorder (PTSD) and eating disorders. This review highlights the need for healthcare providers to be vigilant in recognizing and managing corticosteroid-induced psychiatric symptoms, especially in vulnerable populations with pre-existing mental health conditions. The complex relationship between corticosteroid type, dose, duration, and mental health outcomes is explored, emphasizing the importance of personalized treatment approaches to mitigate psychiatric risks. Given the widespread use of corticosteroids, there is an urgent need for more focused research on their psychiatric side effects. This review underscores the importance of patient education and careful monitoring to ensure optimal therapeutic outcomes while minimizing mental health risks associated with corticosteroid therapy.

Smith-Magenis syndrome is a complex neurobehavioral genetic disorder. The spectrum of SMS phenotype is broad but commonly includes craniofacial, neurobehavioral, and otolaryngologic features. While the etiology of SMS is commonly attributed to one copy interstitial deletion in the 17p11.2 region (90-95% of cases), variants identified by sequence analysis in RAI1 have also been reported in 5-10% of cases. The phenotypic spectrum of patients with RAI1 sequence alterations is not clear. In this study, we report a 9-year-old male with global cognitive and psychomotor developmental delay, musculoskeletal and cardiovascular abnormalities, and dysmorphic craniofacial features. Whole genome quad analysis of the proband, unaffected parent, and unaffected brother identified a novel de novo RAI1:c.2736delC variant. This is the first report of this variant in the literature. This report also highlights the details of the genome analysis and this patient's phenotypic spectrum.

Background: Acute kidney injury (AKI) and contrast-induced nephropathy (CIN) are common complications following percutaneous coronary intervention (PCI) or coronary angiography (CAG), presenting significant clinical challenges. Machine learning (ML) models offer promise for improving patient outcomes through early detection and intervention strategies. Methods: A comprehensive literature search following PRISMA guidelines was conducted in PubMed, Scopus, and Embase from inception to June 11, 2024. Study characteristics, ML Models, performance metrics (AUC, accuracy, sensitivity, specificity, precision), and risk of bias assessment using the PROBAST tool were extracted. Statistical analysis used a random-effects model to pool AUC values, with heterogeneity assessed via the I² statistic. Results: From 431 initial studies, 14 met the inclusion criteria. Gradient Boosting Machine (GBM) and Support Vector Machine (SVM) models showed the highest pooled AUCs of 0.87 (95% CI: 0.82-0.92) and 0.85 (95% CI: 0.80-0.90), respectively, with low heterogeneity (I² < 30%). Random Forest (RF) had a similar AUC of 0.85 (95% CI: 0.78-0.92) but significant heterogeneity (I² > 90%). Multilayer Perceptron (MLP) and XGBoost models had moderate pooled AUCs of 0.79 (95% CI: 0.74-0.84) with high heterogeneity. RF showed strong accuracy (0.83, 95% CI: 0.70-0.96), while SVM had balanced sensitivity (0.69, 95% CI: 0.63-0.75) and specificity (0.73, 95% CI: 0.60-0.86). Age, serum creatinine, left ventricular ejection fraction, and hemoglobin consistently influenced model efficacy. Conclusions: GBM and SVM models, with robust AUCs and low heterogeneity, are effective in predicting AKI and CIN post-PCI/CAG. RF, MLP, and XGBoost, despite competitive AUCs, showed considerable heterogeneity, emphasizing the need for further validation.

Thrombosis is the pathological clot formation under abnormal hemodynamic conditions, which can result in vascular obstruction, causing ischemic strokes and myocardial infarction. Thrombus growth under moderate to low shear (<1000 s^-1) relies on platelet activation and coagulation. Thrombosis at elevated high shear rates (>10,000 s-1) is predominantly driven by unactivated platelet binding and aggregating mediated by von Willebrand factor (VWF), while platelet activation and coagulation are secondary in supporting and reinforcing the thrombus. Given the molecular and cellular level information it can access, multiscale computational modelling informed by biology can provide new pathphysiological mechanisms that are otherwise not accessible experimentally, holding promise for novel first-principle-based therapeutics. In this review, we summarize the key aspects of platelet biorheology and mechanobiology, focusing on the molecular and cellular scale events and how they build up to thrombosis through platelet adhesion and aggregation in the presence or absence of platelet activation. In particular, we highlight recent advancements in multiscale modeling of platelet biorheology and mechanobiology and how they can lead to better prediction and quantification of thrombus formation, exemplifying the exciting paradigm of digital medicine.

The theory of heavy ion double charge exchange (DCE) reactions proceeding by effective rank–2 isotensor interactions is presented. Virtual pion–nucleon charge exchange interactions are investigated as the source for induced isotensor interactions, giving rise to the Majorana DCE (MDCE) reaction mechanism. MDCE is of a generic character, proceeding through pairs of complementary (π±,π∓) reactions in the projectile and target nucleus. The dynamics of the elementary processes is discussed where the excitation of pion–nucleon resonances are of central importance. Investigations of initial and final state ion–ion interactions show that these effects are acting as vertex renormalizations. In closure approximation, well justified by the finite pion mass, the second order transition matrix elements reduce to pion potentials and effective two–body isotensor DCE interactions, giving rise also to two–body correlations in either of the participating nuclei. Connections to neutrinoless Majorana double beta decay (MDBD) are elucidated at various levels of dynamics, from the underlying fundamental electro–weak and QCD scales to the physical scales of nuclear MDBD and MDCE physics. It is pointed out that heavy ion MDCE reactions may also proceed by competing electro–weak charge exchange processes, leading to lepton MDCE by electrons, positrons, and neutrinos.

The statistical analysis of impact of the top 50 solar flares of X-class (1997-2023) on the global seismic activity, as well as on the earthquake preparation zones located in illuminated part of the globe and in the area of 5000 km radius around the subsolar point was carried out. It is shown by a method of epoch superposition that for all cases the increase of seismicity is observed, especially in the region around the subsolar point (up to 38%) during 10 days after the solar flare in comparison with preceding 10 days. The case study of aftershock sequence of strong M=9.1 earthquake (Su-matra-Andaman Islands, 26.12.2004) after the solar flare of X7.2 class (20.01.2005) demonstrated that the number of aftershocks with magnitude M≥2.5 increases more than 20 times after the solar flare with a delay of 7 days. For the case of the Darfield earthquake (M=7.1, 04.09.2010, New Zealand) it was shown that strong solar flares of class X and M probably triggered two strong aftershocks (M>6) with the same delay of 6 days on the Port Hills fault, which is the most sensitive to external electromagnetic impact from point of view of the fault electrical conductivity and orientation. Based on the obtained results the possible application of natural electromagnetic triggering of earthquakes is discussed for a short-term earthquake prediction using confidently recorded strong external electromagnetic triggering impacts on the specific earthquake preparation zones, as well as ionospheric perturbations due to aerosol emission from the earthquake sources recorded by satellites.

A recent study revealed a persistent presence of the PP-Spike recombinant protein in 50% of individuals who received ModRNA injections, contrasting with unvaccinated controls, whether SARSCoV-2 infected or not, up to 187 days post-injection. The implications of these findings are discussed in the context of PP-Spike recombinant protein-induced hyperimmune/inflammatory reactions and thrombotic vasculitis as mechanisms to elucidate the serious side effects, long-term organ complications, and excess deaths observed after administering Covid ModRNA products. These results underscore the urgent need for a comprehensive reassessment of the risk-benefit profile of ModRNA injections, including an immediate halt in their use for any person, and a renewed emphasis on understanding and addressing their long-term effects on human health

Earthquakes often entail alterations in the groundwater flow regime, in the phreatic level, in the surge and loss of springs, and discharge in brooks and springs. As for the latter, there are diverse feasible mechanisms, so there is a variety of theoretical approaches to elucidate the post-earthquake effects on spring discharge. This study adopts a conceptual approach, primarily presenting various methods for estimating water released by earthquakes by calculating discharge surpluses in springs. This study delves into refined techniques rooted in groundwater hydraulics, displaying applications of analytical and simulation methodologies to quantify seismic-induced groundwater discharge in springs. Investigating springs as natural indicators, this research applies mathematical precipitation-runoff models, specifically the CREC model, for simulating hydrographs in post-earthquake scenarios. We apply analytical procedures or mathematical simulation techniques employed in groundwater hydraulics for natural aquifer recharge calculations. Firstly, we briefly describe the methods based on the analysis of depletion curves of hydrographs in spring discharge. Additionally, certain mathematical rainfall-runoff models utilized in simulating hydrographs of karstic springs, along with derived analytical approximations, are adapted for this scenario. These hydraulic calculations involve the depletion coefficient and hydrodynamic volumes of aquifers, parameters that reveal certain aspects of the relation between groundwater and earthquakes, such as: a) Acknowledging faults as the primary geological structures in transmitting pore pressures due to earthquakes. b) Clarifying mechanisms of permeability enhancement during earthquakes. c) Highlighting the substantial volumes in motion within the Earth's interior, which, for instance, could constitute a significant source for the origin of mineral deposits. The findings highlight diverse features of the complex interplay between hydrogeological and tectonic processes at challenging spatial and temporal scales.

Background: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease of unknown origin, with a median survival time of ~3 years after diagnosis without anti-fibrotic therapy. It is characterized by progressive fibrosis indicated by increased collagen deposition and high numbers of fibroblasts in the lung. It was demonstrated that CCL18 induces collagen and αSMA synthesis in fibroblasts. We aimed to identify the CCL18 receptor responsible for its pro-fibrotic activities. Methods: We used a random phage display library to screen for potential CCL18-binding peptides, demonstrated its expression in human lungs and fibroblast lines by PCR and immunostaining and verified its function in cell lines. Results: We identified CCR6 (CD196) as a CCL18 receptor and found its expression in fibrotic lung tissue and on lung fibroblast lines derived from fibrotic lungs but it is almost absent in control lines and tissue. CCL18 induces receptor-internalization in a CCR6-overexpressing cell line. CCR6 blockade in primary human lung fibroblasts reduces CCL18-induced FGF2 release as well as collagen-1 and αSMA expression. Knock-down of CCR6 in a mouse fibroblast cell line abolishes the induction of collagen and -smooth muscle actin expression. Conclusion: Our data indicate that CCL18 triggers pro-fibrotic processes via CCR6, highlighting its role in fibrogenesis.

Nonlinear properties of zinc germanium diphosphide (ZGP) crystals enable their ap-plications in powerful mid-IR optical parametric oscillators and second-harmonic generators. This paper summarizes mechanisms of the laser induced damage (LID) in high-purity ZGP crystals under periodically pulsed nanosecond irradiation by a Ho3+:YAG laser at 2.1 μm. The ZGP samples were manufactured by “LOC” Ent., Tomsk, Russia, or Harbin Institute of Technology, China. The impact of processing techniques and the post-growing methods for polishing and anti-reflection coating on the LID threshold are discussed. The importance of the defect structure of the crystal lattice and the parameters of transparent coatings for increasing the LID threshold is discussed. The impact of the test laser parameters on the LID threshold is analyzed. The transient area near the LID threshold obtained using digital holography is ana-lyzed. Influence of the pre-damage processes on the optical parametric oscillations is reported. Prospects for improving ZGP crystals to further increase the LID threshold are discussed.

Drug-induced pruritus triggers a desire to scratch, thereby diminishing one’s quality of life. Certain instances of this phenomenon follow complex mechanisms of action that diverge from histamine-mediated pathways, known contributors to pruritus. However, investigations into the relationship between drugs and pruritus are limited. In this study, data mining techniques were employed to comprehensively analyze the characteristics of drugs linked to pruritus, using the FDA Adverse Event Reporting System(FAERS) Data maintained in the United States. Reports linked to pruritus demonstrated noteworthy differences in gender, age, and weight when compared with non-pruritus cases. Among the leading candidates for drugs prompting pruritus were ophthalmic drugs, systemic antibacterials, contrast media, dermatological antifungals, and dermatological preparations. Principal component analysis showed that the second principal component served as an indicator for distinguishing between onsets at mucous membranes or the skin surface. Additionally, the third principal component functioned as an indicator for categorizing administration methods as either invasive or noninvasive. Furthermore, a hierarchical cluster analysis conducted on these obtained principal components revealed the potential for classifying drugs based on the site of pruritus onset and the method of drug administration. These findings contribute to the development of targeted prevention and treatment strategies for avoiding pruritus in clinical practice.

The time-resolved CIDNP method can provide information about degenerate exchange reactions (DEE) involving short-lived radicals. In the temperature range from 8 to 65°C, the DEE reactions of the guanosine-5’-monophosphate anion GMP(-H)- with the neutral radical GMP(-H)•, of the N-acetyl tyrosine anion NacTyrO- with a neutral radical NacTyrO• and of the tyrosine anion TyrO- with a neutral radical TyrO• were studied. In all the studied cases, the radicals were formed in the reaction of quenching triplet 2,2’-dipyridyl. The reorganization energies were obtained from Arrhenius plots. The rate constant of the reductive electron-transfer reaction in pair GMP(-H)•/TyrO- was determined at T = 25°C. Rate constants of GMP(-H)• radical reduction reactions with TyrO- and NacTyrO- anions calculated by the Marcus cross relation differ from the experimental ones by two orders of magnitude. The rate constants of several other electron transfer reactions involving GMP(-H)-/•, NacTyrO-/•, and TyrO-/• pairs calculated by cross relation agree well with the experimental values. The rate of nuclear paramagnetic relaxation was found for the 3,5 and β-protons TyrO• and NacTyrO•, the 8-proton GMP(-H)• the 3,4-protons DPH• at each temperature. In all cases, the dependences of the rate of nuclear paramagnetic relaxation on temperature are described by the Arrhenius dependence.

Volumetric modification of transparent materials by femtosecond laser pulses is successfully used in a wide range of practical applications. The level of modification is determined by the locally absorbed energy density, which depends on numerous factors. In this work, it is shown experimentally and theoretically that, in a certain range of laser pulse energies, the peak of absorption of laser radiation for doughnut-shaped (DS) pulses is several times higher than for Gaussian ones. This makes the DS pulses very attractive for material modification and direct laser writing applications. Details of the interaction of laser pulses of Gaussian and doughnut shapes with fused silica obtained by numerical simulations are presented for different pulse energies and compared with the experimentally obtained data. The effect of absorbed energy delocalization with increasing laser pulse energy is demonstrated for both beam shapes while, at relatively low pulse energies, the DS beam geometry provides a stronger local absorption compared to Gaussian one. Implications of a DS pulse action on post-irradiation material evolution are discussed based on thermoelastoplastic modeling.

Abstract: The trend of fasting until noon (omission or delayed breakfast) is increasingly prevalent in modern society. This eating pattern triggers discordance between endogenous circadian clock rhythms and the feeding/fasting cycle and is associated with an increased incidence of obesity and T2D. Although the underlying mechanism of this association is not well understood, growing evidence suggests that fasting until noon, also known as an “extended postabsorptive state,” has the potential to cause a deleterious effect on clock gene expression and disrupted regulation of body weight, postprandial and overall glycemia, skeletal muscle protein synthesis, appetite and may also lead to lower energy expenditure. This manuscript overviews the clock gene-controlled glucose metabolism during the active and resting phases. The consequences of postponing until noon the transition from postabsorptive to fed state on glucose metabolism, weight control, and energy expenditure. Finally, we will discuss the metabolic advantage of shifting more energy, carbohydrates (CH), and proteins to the early hours of the day.

Genetic sensorineural hearing loss and Meniere disease have been associated with rare variations in the coding and non-coding region of the human genome. Most of these variants are classified as likely pathogenic or variants of unknown significance and require functional validation in cellular or animal models. Given the difficulties to obtain human samples and the raising concerns about animal experimentation, human induced pluripotent stem cells emerge as cellular models to investigate the interaction of genetic and environmental factors in the pathogenesis of inner ear disorders. The generation of human sensory epithelia and neuron-like cells carrying the variants of interest may facilitate a better understanding of their role during differentiation. These cellular models will allow us to explore new strategies for restoring hearing and vestibular sensory epithelia as well as neurons. This review summarizes the use of human induced pluripotent stem cells in sensorineural hearing loss and Meniere disease and proposes some strategies for its application in clinical practice.

Background: Both natural immunity and vaccine-induced immunity to COVID-19 may be useful to reduce the mortality/morbidity of this disease, but still a lot of controversy exists. Aims: This narrative review analyzes the literature about: a) the duration of natural immunity; b) cellular immunity; c) cross-reactivity; d) the duration of post-vaccination immune protection; e) the probability of reinfection and its clinical manifestations in the recovered patients; f) comparisons between vaccinated and unvaccinated in the possible reinfections; g) the role of hybrid immunity; h) the effectiveness of natural and vaccine-induced immunity against Omicron variant; i) comparative incidence of adverse effects after vaccination in recovered individuals vs. COVID-19-naïve subjects. Material and Methods: through multiple search engines we investigated COVID-19 literature related to the aims of the review, published since April 2020 through July 2022, including also the previous articles pertinent to the investigated topics. Results: nearly 900 studies were collected and 238 pertinent articles were included. It was highlighted that the vast majority of individuals after COVID-19 develop a natural immunity both of cell-mediated and humoral type, which is effective over time and provides protection against both reinfection and serious illness. Vaccine-induced immunity was shown to decay faster than natural immunity. In general, the severity of the symptoms of reinfection is significantly lower than in the primary infection, with a lower degree of hospitalizations (0.06%) and an extremely low mortality. Conclusions: this narrative review regarding a vast number of articles highlighted the valuable protection induced by the natural immunity after COVID-19, which seems comparable or superior to the one induced by anti-SARS-CoV-2 vaccination. Vaccination of the unvaccinated COVID-19-recovered subjects may not be indicated. Further research is needed in order to: a) measure the durability of immunity over time; b) evaluate both the impacts of Omicron-5 on vaccinated and healed subjects and of hybrid immunity.

Plasmodium falciparum dihydroorotate dehydrogenase (PfDODH) is one of the enzymes currently explored in the treatment of malaria. Although there is currently no clinically approved drug targeting PfDODH, many of the compounds in clinical trials have [1, 2, 4,] triazolo [1, 5-a] pyrimidin-7-amine backbone structure. This study sought to design new compounds from the fragments of known experimental inhibitors of PfDODH. Nine experimental compounds retrieved from Drug Bank online were downloaded and broken into fragments using Schrodinger power shell; the fragments were recombined to generate new ligand structures using BREED algorithm. The new compounds were docked with PfDODH crystal structure, after which the compounds were filtered with extensive drug-likeness and toxicity parameters. A 2D-QSAR model was built using the multiple linear regression method and externally validated. The compounds electronic behaviours were studied using DFT calculations. Structural investigation of the six designed compounds, which had lower binding energies than the standard inhibitors, showed that five of them had [1, 2, 4,] triazolo [1, 5-a] pyrimidin-7-amine moieties and interacted with essential residues at the PfDODH binding site. In addition to their drug-like and pharmacokinetic properties, they also showed minimal toxicities. The externally validated 2D-QSAR model with R² and Q² values of 0.6852 and 0.6691, confirmed the inhibitory prowess of these compounds against PfDODH. The DFT calculations showed regions of the molecules prone to electrophilic and nucleophilic attack. The current study thus provides insight into the development of a new set of potent PfDODH inhibitors.

Introduction: Wound healing is a multifaceted biological process, and diabetic wounds add more complexity to it. In diabetic wounds, the combination of chloroform fractions of Achyranthes aspera L. (A.aspera) leaves with β-Glucans has not been investigated. The additive effect of these two (A.aspera + β-Glucans) would benefit the inflammatory phase of diabetic wounds, as improper treatment will lead to chronic injuries. Therefore, the goal of this research work was to assess the in-vivo wound healing and anti-inflammatory effects of a combination of chloroform fractions of A.aspera leaves and β-Glucans in a variety of wound models in STZ-induced diabetic rats. Methods: Preliminary phytochemical analyses of A.aspera were conducted to identify various phytoconstituents in the test extract. Acute and sub-acute dermal toxicity tests of A.aspera were carried out on mice and rats, respectively, to see whether there were any abnormalities. Excision and incision wound models, cotton pellet-induced granuloma models, rat paw edema and burn wounds were used to test wound healing and anti-inflammatory actions. To induce diabetes, streptozotocin (STZ) was administered intraperitoneally at a dosage of 65 mg/kg (i.p.). A.aspera (10% w/w) and β-Glucans (2% w/w) ointments were tested separately and in combination for wound healing activities. Silver sulfadiazine (1 % w/w) ointment was used to treat the positive control groups. Excision wound model rats that had been treated with basic ointment were used as negative controls, as were incision wound model rats that had not been treated. A.aspera (400 mg/kg, po) and β-Glucans (30 mg/kg, po) were tested separately and in combination for anti-inflammatory efficacy. Positive control groups were given indomethacin (10 mg/kg, po) for cotton pellet-induced granuloma and rat paw oedema models. Negative controls for both anti-inflammatory activity models were provided 2% Tween 80. The groups were made up of six rats, and the treatments were given topically and orally to assess wound healing and anti-inflammatory effects. The levels of hydroxyproline and hexosamine and the antioxidant enzymes (SOD and CAT) in the granulation tissue were measured in excision wound model. Healed excision wound skin was examined histopathologically. Results: The A.aspera and β-Glucans combination resulted in a significant percentage of wound contraction and a shorter epithelialization time (P<0.01). The combination was found to be the most effective, with the highest percentage of edema reduction (55 %; p<0.01). The combination also exhibited favourable hydroxylamine, hexosamine and anti-oxidant profiles supported by histopathology data. Conclusion: This research showed that the immunomodulatory effect of β-Glucans had significantly enhanced the wound healing, anti-inflammatory, and anti-oxidant potential of A.aspera in diabetic wounds.

Keywords: Chemical Intolerance, Drug Intolerance, Food Intolerance, QEESI, BREESI, Multiple Chemical Sensitivity, Toxicant-induced Loss of Tolerance, Prevalence

Immunotherapy has gained great momentum with chimeric antigen receptor T cell (CAR-T) therapy, in which patient’s T lymphocytes are genetically manipulated to recognize tumor-specific antigens increasing tumor elimination efficiency. In the last years, CAR-T cell immunotherapy for hematological malignancies achieved a great response rate on patients and is a very promising therapy for several other malignancies. Each new CAR design requires a preclinical proof-of-concept experiment using immunodeficient mouse models. The absence of a functional immune system in these mice makes them simple and suitable to be mathematically modeled. In this work, we developed a three population mathematical model to describe tumor response to CAR-T cell immunotherapy in immunodeficient mouse models, encompassing interactions between a non-solid tumor and CAR-T cells (effector and long-term memory). We account for several phenomena, such as tumor-induced immunosuppression, memory pool formation, and conversion of memory into effector CAR-T cells in the presence of new tumor cells. Individual donor and tumor specificities were considered as uncertainties in the model parameters. Our model is able to reproduce several CAR-T cell immunotherapy scenarios, with different CAR receptors and tumor targets reported in the literature. We found that therapy effectiveness mostly depends on some specific parameters such as the differentiation of effector to memory CAR-T cells, CAR-T cytotoxic capacity, tumor growth rate, and tumor-induced immunosuppression. In summary, our model can contribute to reduce and optimize the number of in vivo experiments with in silico tests to select specific scenarios that could be tested in experimental research. Such in silico laboratory was made available in a Shiny R-based platform called CARTmath. It is an open-source, easy to run simulator, available at github.com/tmglncc/CARTmath or directly on the webpage cartmath.lncc.br, containing this manuscript results as examples and documentation. The developed model, together with the CARTmath platform, provides potential use for assessing different CAR-T cell immunotherapy protocols and associated efficacy, becoming an accessory towards in silico trials.

Recently, several research groups have reported on anomalous enhancement of the self-field critical currents, Ic(sf,T), at low temperatures in superconductor/Dirac-cone material/superconductor (S/DCM/S) junctions. Some papers attributed the enhancement to the low-energy Andreev bound states arising from winding of the electronic wave function around DCM. In this paper, Ic(sf,T) in S/DCM/S junctions have been analyzed by two approaches: modified Ambegaokar-Baratoff and ballistic Titov-Beenakker models. It is shown that the ballistic model is an inadequate tool to analyze experimental data from S/DCM/S junctions. The primary mechanism for limiting superconducting current in S/DCM/S junctions is different from the conventional view that the latter is the maximum value within the order parameter phase variation. Thus, there is a need to develop a new model for self-field critical currents in S/DCM/S systems.