Hypertension is one of the most common primary cardiometabolic diseases and is a major contributor to cardiac mortality and morbidity. Furthermore, cardiac risk factors such as obesity and sedentary lifestyle are often seen in hypertensive patients. Regular exercise acts against these risk factors and improves the overall health of an individual. High-intensity interval training appears to do so in a more efficient way. We used a systematic literature review (SLR) approach to provide an overview of the present literature highlighting the cardiovascular advantages of HIIT in hypertensive individuals. We reviewed 4004 articles from reputable journals published between 2013 and August 14, 2023, focusing on 7 selected papers for in-depth analysis. This systematic review revealed the protective effects of HIIT against cardiac complications in hypertension. All the reviewed articles showed a decrease in blood pressure and many other risk variables of cardiovascular diseases. However, guidelines for this exercise are needed for maximum benefits. Therefore, further research on HIIT is necessary to fully harness its potential.

The study of angular correlations of heavy-flavor particles in hadronic collisions can provide crucial insight into the heavy-quark production, showering and hadronization processes. The comparison with model predictions allows us to discriminate among different approaches for heavy-quark production and hadronization, as well as different treatments of the underlying event employed by the models to reproduce correlation observables. In ultra-relativistic heavy-ion collisions, where a deconfined state of matter, the quark-gluon plasma (QGP), is created, heavy-flavor correlations can shed light on the modification of the heavy-quark fragmentation due to interaction of charm and beauty quarks with the QGP constituents, as well as characterize their energy loss processes while traversing the medium. Insight into possible emergence of collective-like mechanisms in smaller systems, resembling those observed in heavy-ion collisions, can also be obtained by performing correlation studies in high-multiplicity proton-proton and proton-nucleus collisions. In this review, the most recent and relevant measurements of heavy-flavor correlations performed in all collision systems at the LHC and RHIC will be presented, and the new understandings that they provide will be discussed.

The Ames/quantitative structure-activity relationship (QSAR) International Challenge Projects held during 2014–2017 and 2020–2022, evaluated the performance of various predictive models. Despite the significant insights gained, the rules allowing participants to select prediction targets introduced ambiguity in model performance evaluation. This reanalysis identified the highest-performing prediction model, assuming a 100% coverage rate (COV) for all prediction target compounds and an estimated performance variation due to changes in COV. All models from both projects were evaluated using balance accuracy (BA), Matthews correlation coefficient (MCC), F1 Score (F1), and the first principal component (PC1). After normalizing the COV, a correlation analysis with these indicators was conducted, and the evaluation index for all prediction models in terms of the COV was estimated. In total, 109 models, the highest estimated BA (76.9) at 100% COV was MMI-VOTE1, reported by Meiji Pharmaceutical University (MPU). The best models for MCC, F1, and PC1 were all MMI-STK1, also reported by MPU. All models reported by MPU ranked in the top four. MMI-STK1 was estimated to have F1 scores of 59.2, 61.5, and 63.1 at COV levels of 90%, 60%, and 30%, respectively. These findings highlight the current state and potential of the Ames prediction technology.

Accurate determination of protein localization, levels, or protein-protein interactions is pivotal for the study of their function, and in situ protein labeling via homologous recombination has emerged as a critical tool in many organisms. While this approach has been refined in various model fungi, the study of protein function in most plant pathogens has predominantly relied on ex-situ or overexpression manipulations. To dissect the molecular mechanisms of development and infection for Verticillium dahliae, a formidable plant pathogen responsible for vascular wilt diseases, we have established a robust, homologous recombination-based in situ protein labeling strategy in this organism. Utilizing Agrobacterium tumefaciens-mediated transformation (ATMT), this methodology facilitates the precise tagging of specific proteins at their C-termini with epitopes, such as GFP and Flag, within the native context of V. dahliae. We demonstrate the efficacy of our approach through the in situ labeling of VdCf2 and VdDMM2, followed by subsequent confirmation via subcellular localization and protein-level analyses. Our findings confirm the applicability of homologous recombination for in situ protein labeling in V. dahliae and suggest its potential utility across a broad spectrum of filamentous fungi. This labeling method stands to significantly advance the field of functional genomics in plant pathogenic fungi, offering a versatile and powerful tool for the elucidation of protein function.

Based on the multiple coordination framework of “promising government-effective market-ordered society”, this paper takes 68 cases of adding elevators to old buildings as samples, and selects six conditional variables: approval optimization, financial subsidies, financing innovation, technological innovation, capable people leading and neighborhood committee guidance. Using Crisp-Set Qualitative Comparative Analysis (csQCA), this paper discusses the combination of conditions that affect the success or failure. It is found that: approval optimization and neighborhood committee guidance are sufficient conditions for the success; successful cases can be divided into three types: “political and social dual-drive type”, “market and social dual-drive type” and “ternary co-drive type”; lack of approval optimization, lack of financing innovation, and the existence of capable people leading are necessary conditions for the failure. The failure cases can be divided into “government and market double failure type” and “market failure type”.

Background and Objective: Intimate relationships hold significant importance during emerging adulthood. This study aimed to investigate the critical determinants of perceived well-being in friendship relationships during emerging adulthood.Method: Using a quantitative approach, a sample of 726 undergraduate students from the Ferdowsi University of Mashhad were selected through convenience sampling. They completed the Interpersonal Behaviors Questionnaire (IBQ), the Compassionate and self-image goals scale (CSIGS), the Basic Need Satisfaction in Relationships Scale (BNS-RS), the Interpersonal Needs Questionnaire (INQ-10), Friendship Self-Regulation Questionnaire (SRQ-F), Interpersonal Behaviors Questionnaire-Self (IBQ-self), State Level Subjective Vitality Scale (SVS-SL), the Perceived Relationship Quality Component (PRQC), and the Basic Empathy Scale (BES). Data analysis was conducted using Partial Least Squares Structural Equation Modeling (PLS-SEM).Results: The results indicated that the critical determinants in predicting perceived well-being in friendship relationships were, in order, goals in friendship relationships, friendship self-regulation, perceived support of basic psychological needs by friends, satisfied basic psychological needs, frustrated psychological needs, and supporting the basic psychological needs of friends.Conclusion: The findings demonstrate that self-determination theory (SDT) provides a coherent framework for explaining perceived well-being in friendships.

An all-dielectric metasurface composed of orthogonal-slit silicon disks is proposed in this study. By modifying the unit structure of the metasurface with the bound states in the continuum (BIC) theory, a sharp Fano resonance can be generated. The resonance properties of the metasurface are investigated by analyzing the effects of the structural parameters on the resonance using the eigenmode analysis method. The Q factor and the resonance wavelength can be adjusted by varying the slit width, the disk thickness, and the disk radius. The electromagnetic characteristics and mechanism of the toroidal dipole-BIC (TD-BIC) are explored in depth through an analysis of the multipole expansion of the scattered power, along with the electromagnetic field and the current distribution at resonance. This research provides a novel approach for excitation of a strong TD-BIC resonance and proposes potential applications in optical switches, high-sensitivity optical sensors, and related areas.

: This article reports on polymer (PLLA, poly(L-lactic acid)) nanosheets incorporated with Fe-ion nanoparticles, aiming at using the latter nanoparticles as source to release Fe ions to facilitate burn wound healing when such nanosheets are applied on skin as biomedical tissue. Laser ablation in liquid phase was used to produce Fe-containing nanoparticles that after incorporation into PLLA nanosheets would release Fe ions when in immersed in water. Such nanoparticles prepared in chloroform are shown by XPS to be based on iron chloride and oxide phases. After incorporation into PLLA nanosheets, the ion –release test demonstrated that Fe ions could be released successfully into water at pH 7.4, which implies that such polymer nanosheets show promise for biomedical applications as potential patches for healing burn wounds. Incorporation with two different metal ions (Fe and Zn) is shown to be efficient and both types of ions were demonstrated to be released simultaneously and with comparable release rates.

Uncontrolled chronic inflammation results in cardiovascular disease and early death. In this review, we studied the impact of rheumatoid arthritis on the cardiovascular system, including the early and accelerated development of atherosclerosis, and its clinical manifestations, focusing on the inflammatory mechanisms leading to arterial wall damage, rapid atherosclerotic plaque formation, and thrombosis. Furthermore, the influence of medications used to treat rheumatoid arthritis on the cardiovascular system. The influence of chronic inflammation and medicaments on traditional cardiovascular risk factors is not the main subject of this review. We found that uncontrolled chronic inflammation and some medications directly impact all stages of atherosclerosis. In conclusion, reducing inflammation and maintaining long-term remission in rheumatoid arthritis may pre-vent early atherosclerosis. We believe that this review will encourage a better interdisciplinary approach for these patients and further research in this field.

This paper aims to stress the nexus between sustainable development, economic freedom and local participatory democracy in 21 European smart cities. The development of smart cities is strongly correlated with technological advancements and improved access to pub-lic services for all residents. Furthermore, smart cities are characterized by efficient man-agement of social, economic and environmental resources and a strong partnership be-tween the public and private sectors. The paper aims to map the dynamics of local partic-ipatory democracy in European smart cities and to identify several relevant predictors of local participatory democracy. The sample is represented by 21 European capitals (20 EU countries plus UK), which are included in the Smart City Index (SCI). Using the quantita-tive design based on both statistical regressions and structural equations modelling (SEM), the paper shows positive statistical correlation between economic factors, sustainable de-velopment, political culture, education and the level of local participatory democracy. Be-sides the exogenous variables, the study emphasized the main priority areas, which might be seen as urgent issues for local governments. The conclusion of the paper underlines the fact that economic freedom, sustainable development, upper secondary education, afford-able housing and an increased level of citizens’ engagement could predict further evolu-tions of the local participatory democracy in 21 European capitals.

This study examined the status of Education for Sustainable Development (ESD) practices and the understanding of Sustainable Development (SD) among Saudi kindergarten teachers in a specific governorate. Two hundred twenty-seven kindergarten teachers participated, and data was collected through a questionnaire. The results indicated that most kindergarten teachers (89.9%) were unaware of SD. The overall status of ESD practices among the participating teachers was weak, with an average score of 2.60 out of 4. Among the different dimensions, values (2.74), competencies (2.69), and practice (2.65) obtained relatively higher scores, while the content dimension (2.49) received the lowest score. Significant differences were found in the mean scores of ESD practices based on teachers’ qualifications and the type of school. However, no differences were observed based on experience. The lack of awareness regarding SD emerged as the primary barrier to implementing ESD in kindergarten institutions. Expanding teacher training was identified as the most crucial step in promoting ESD in kindergartens. The findings highlight the importance of raising awareness among Saudi kindergarten teachers about SD, providing professional development opportunities to enhance ESD implementation in classrooms, and creating teaching materials aligned with ESD principles.

Forest education is pivotal for achieving the Sustainable Development Goals and promoting sustainable forest management in the face of global challenges. However, existing programs struggle to keep up with rapidly changing crises and uncertainties that contribute to deforestation and forest degradation. To address these challenges, integrating innovative approaches into forest education is crucial. This paper demonstrates the transformative use of a role-playing game as an innovative teaching method for integrated forest management. The game provides students with practical experience and a comprehensive understanding of landscape approaches, using the Congo Basin as a case study. Our research focuses on sustainable forest governance, stakeholder roles, and valuing natural assets and ecosystem services, supporting the transformation of economic, political, and social/cultural relationships at various scales. We highlight the potential of innovative forest education to foster sustainability, trigger critical thinking, resolve conflicts, and prevent costly forest losses.

Abstract: Background. The newer wireless portable scanners seem to permit a quicker bedside ultrasound (US) assessment, shortening the transfer times of the portable US unit and without the hindering of connection cables. However, no substantial evidence is currently available regarding of the clinical effectiveness of such new generation devices. Objective. The aim of the current study was to evaluate the efficacy of a wireless US system with respect to a high-end US unit in a cohort of consecutive respiratory patients. Materials and Methods. This prospective observational study included a total of 72 respiratory patients admitted in the department of Internal Medicine. The US examination were independently performed by two experienced blinded examiners with a high-end Esaote MyLab-Twice scanner and a wireless double-head linear and convex probe OTE-L/C501CD. The findings resulting from the high-end US assessment and the wireless US examination were then compared each other. All the patients had a confirmation chest CT scan. Results. The high-end US machine identified 64 positive cases for pleuro-pulmonary alterations, in comparison to which the wireless US unit resulted in 13 false negative results. The respective overall sensitivity and specificity for the portable wireless US unit were of 79.69% and 100.00%, respectively. The resolution of the portable wireless US device was judged as good in 22 (31%) cases, affected by minor diagnostic limitations in 26 (36%) cases and affected by major diagnostic limitations in 24 (33%). The main diagnostic strength of the wireless probe was in the detection of pleural effusion (sensitivity 100%). The diagnostic sensitivity of the wireless probe in assessing abnormalities of the pleural line (67%), pulmonary subpleural consolidations (65%), pleural lesions (33%) and pericardial effusion (0%) was reduced. Conclusions. The newer wireless US probes may have clinical roles for the detection and management of pleural effusion when used by experienced examiners. However, sensitivity in detecting other pleuro-pulmonary pathologies is not comparable to high-end ultrasound machines.

Dubermatinib (DMB, TP-0903), a benzenesulfonamide, is an inhibitor of the tyrosine kinase AXL, which is a member of the TAM family, and can prevent GAS6-mediated activation of AXL in cancer cells. Patients with previously treated chronic lymphocytic leukemia are being studied in phase I/II clinical trials to determine its antineoplastic potential (CLL). In the current work, the reactive intermediates of DMB were studied using liquid chromatography-mass spectrometry (LC-MS). Human liver microsomes (HLMs) were exposed to dimethylbenzene in a laboratory setting, and the resulting metabolites were collected through protein precipitation. Intense reactivity toward nucleophilic macromolecules was seen in the metabolites of the piperazine and pyrimidine rings in DMB, iminium and 2,5-quinone-imine, respectively. To assess the toxicities of the possibly reactive metabolites, DMB was incubated with HLMs in the presence of 1.0 mM KCN and 1.0 mM glutathione. The DMB metabolites found by LC-MS/MS were seven in vitro phase I metabolites, three cyano adducts, and two GSH conjugates. Phase I in vitro metabolic reactions included N-demethylation, hydroxylation, and dechlorination. The in vitro metabolism of DMB and the metabolites it produces have not been studied before.

Background. In the last decade, it was concluded that glaucomatous optic neuropathy is part of the neurodegenerative diseases in which destructive neuronal lesions are located not only in the structure of the retina, but they are also present at the level of the central visual and nervous pathways. Patients with Primitive Open Angle Glaucoma may have experienced changes such as sensorineural hearing loss as well as balance changes. The purpose of this study is to evaluate the degree of involvement of the auditory system in patients with glaucoma, the structural changes in the optic nerve and, to establish correlation between the hearing loss and structural changes in the optic nerve. The subjects included in the study are grouped as follows: a group of patients with glaucoma that will be compared to a group of patients without glaucoma only as well as identi-fy-ing the evolution of structural changes in optic nerve to patients with glaucoma and to normal patients. Material and methods. It is a prospective, cross-sectional study on 32 eyes of 16 subjects with Primitive Open Angle Glaucoma in a study group and 24 eyes of 12 healthy subjects in con-trol group with a mean age of 62 years in both groups. Both groups underwent ophthalmo-logical, audiological and radio imaging evaluation: Pure-tone audiometry (PTA) were recorded, oph-thalmologic evaluations according to a standardized protocol and MRI cerebral examination was performed. Results: In the Study group patients, compared to the Control group, the average lev-els of the left PTA, the cup/disc (C/D) area in both eyes, the C/D ratio in both eyes are in-creased. The mean level of Retinal nerve fiber layer (RNFL) mean thickness was slightly lower in patients with glaucoma. Multivariate analysis demonstrates that gender can be a good predictor of C/D area, gender and age can be good predictors of PTA both eyes and C/D ratio in the right eye, and gender, age and background can be good predictors of disc area in the left eye. Conclu-sions: Pa-tients with Primitive Open Angle Glaucoma show changes in audiometry test in correla-tion with ophthalmological parameters demonstrating that the auditory system can be affected in Primitive Open Angle Glaucoma. This study emphasizes the problem of interdisciplinarity in medicine with the aim of ensuring the quality of life of patients with glaucoma. A good collabora-tion between ophthalmologist and otolaryngologist will be very useful for these patients.

Migraine is a debilitating neurovascular disorder characterized by recurrent headache attacks of moderate to severe intensity. Calcitonin gene-related peptide (GGRP), which is abundantly expressed in trigeminal ganglion (TG) neurons, plays a crucial role in migraine pathogenesis. Cortical spreading depolarization (CSD), the biological correlate of migraine aura, activates the trigeminovascular system. In the present study, we investigated CGRP mRNA expression in TG neurons in a CSD-based mouse migraine model. Our in situ hybridization analysis showed that CGRP mRNA expression was observed in smaller neuronal populations. CSD did not significantly change the density of CGRP mRNA-synthesizing neurons in the ipsilateral TG. However, the cell sizes of CGRP mRNA-synthesizing TG neurons were significantly larger in the 48 h and 72 h post-CSD groups than in the control group. The proportions of CGRP mRNA-synthesizing TG neurons bearing cell diameters less than 14 μm became significantly less at several time points after CSD. In contrast, we found significantly greater proportions of CGRP mRNA-synthesizing TG neurons bearing cell diameters of 14–18 μm at 24 h, 48, and 72 h post-CSD. We deduce that the CSD-induced upward cell size shift in CGRP mRNA-synthesizing TG neurons might be causative of greater disease activity and/or less responsiveness to CGRP-based therapy.

Metal-organic frameworks (MOFs), composed of metal nodes and inorganic linkers are promising for a wide range of applications due to their unique periodic frameworks that can be flexibly tuned. Understanding of the structure-activity relationships can facilitate the development and application of MOFs nanomaterials. Transmission electron microscopy (TEM) is a one-of-a-kind technique capable of characterizing MOFs microstructures at the atomic scale. Besides, in-situ TEM set-ups make it possible to direct visualize the microstructural evolution of MOFs in real time, which enables monitoring transitions of MOFs during growth as well as under working conditions. However, MOFs are so sensitive to the high-energy electron beam which makes TEM-based characterizing methods challenging. In this review, we first introduce the main damage mechanisms for MOFs under electron beam irradiation and two strategies to minimize the damages: low-dose TEM and cryo-TEM. Then, we discuss the techniques combined with the two strategies to analyze the MOFs’ microstructure, including three-dimensional electron diffraction, direct detection electron counting camera, and iDPC-STEM. Groundbreaking milestones and research advances with respect to static characterization of MOFs structures are highlighted. In-situ TEM studies are exemplary reviewed to provide insights into MOFs dynamics induced by various stimuli. Additionally, perspectives on promising techniques that may further facilitate the MOFs study using TEM are analyzed.

Antarctic krill protein-iron complex and peptide-iron complex were obtained to investigate their iron bioavailability, expression of iron-regulated genes, and in vivo antioxidant capacity. Results indicated that Antarctic krill peptide-iron complex increased significantly the hemoglobin (Hb), serum iron (SI) and iron content in the liver and spleen in iron-deficiency anemia (IDA) mice (P < 0.05) compared with those of Antarctic krill protein-iron complex. Despite the gene expressions of divalent metal transporter 1(DMT1), transferrin (Tf) and transferrin receptor (TfR) could be better regulated by both Antarctic krill peptide-iron complex and protein-iron complex, the relative iron bioavailability of the Antarctic krill peptide-iron complex group (152.53±21.05%) was significantly higher than that of the protein-iron complex group (112.75±9.60%) (P<0.05). Moreover, Antarctic krill peptide-iron complex could enhance the antioxidant enzyme activities of superoxidase dismutase (SOD) and glutathione peroxidase (GSH-Px), reduce the malondialdehyde (MDA) level in IDA mice compared with the protein-iron complex, reducing the cell damage caused by IDA. Therefore, these results demonstrated that Antarctic krill peptide-iron complex could be used as a highly efficient and multifunctional iron supplement.

Background Community health workers (CHWs) drawn from the general population are an important human resource in health care systems, preventing non-communicable diseases (NCDs) and contributing to an increase in healthy life expectancy in Japan. Thus, we have developed the COmmunity health workers perceptual and behavioral Competency Scale for preventing Non-communicable diseases (COCS-N) to measure CHWs’ competence in preventing NCDs. The purpose of this study is to examine individual and community factors affecting CHWs’ COCS-N scores. Methods Municipal public health nurses and other public health professionals are responsible for training and supporting CHWs in Japan. Therefore, the existence of CHWs and their willingness to participate in the study were confirmed with the municipalities, who were asked to distribute the self-administered questionnaire to CHWs where consent was obtained (N = 6,480). Variables used included demographic characteristics, COCS-N scores, and individual- and community-related factors. Logistic regression analysis was used to assess associations between variables. Results A total of 3,120 people completed the questionnaire, a valid response rate of 48.1%. The respondents’ mean age was 67.0 years (standard deviation = 9.0), and 88.0% were female. Comparison of the high- and low- competence groups in terms of NCD prevention based on COCS-N scores identified 13 factors associated with significant differences, including years spent working as a CHW (p < 0.001), subjective sense of health (p = 0.005), European Health Literacy Survey Questionnaire (HLS-EU-Q47) scores (p < 0.001), and community commitment scale (CCS) scores (p < 0.001). Logistic regression analysis revealed that HLS-EU-Q47 scores (odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.02–1.03) were a significant individual factor, while CCS scores (OR: 1.14, 95% CI: 1.11–1.16) were a significant community factor. Conclusions We found that the COCS-N score was associated with the individual factors overall health literacy (HL), perceptions of HL, and subjective sense of health, and with the community factor CCS scores. These results suggest that strengthening individual factors such as HL and subjective sense of health, and community factors such as sense of community is an effective strategy for increasing CHWs’ competence in preventing NCDs.

We report the isolation of two novel degrading bacterial strains active against the potential environmental pollutant acetamino-phen/paracetamol. Streptomyces Chrestomyceticus (RS2) and Streptomyces Flavofuscus (M33) collected from El-Natrun Valley, Egypt, water, sediment, and sand samples were taxonomically characterized via conidiophores morphologic characterization under Trans-mission Electron Microscope (TEM). Genotypic identification, done based on their 16S rRNA gene sequence analysis followed by BLAST alignment and deposited on the NCBI as 2 novel strains. The phylogenetic tree was constructed using an appropriate software. Acetaminophen degradation-products chemical structure was identified by GC/LC MS. The biological antimicrobial activity of some selected acetaminophen degradation-products extracts and derived compounds was examined against panel of test micro-organisms and found to be have high anti-microbial effect. In addition, in silico cheminformatics Swiss ADMET evaluation of these selected deg-radation extract for gastric absorption, distribution, hepatic metabolism, renal excretion as well as distribution to CNS and finally not mutagenic/teratogenic or genotoxic virtually. In vitro cytotoxic activity of these selected bio-degradation products was performed against HepG2 and MCF7 cancer cell lines, revealing that M33 and RS2 extract effect on acetaminophen/paracetamol bio-degradation products are potentially safe with higher IC50 on HepG2 and MCF7, in comparison to acetaminophen/paracetamol with IC50 of 108.5 μg/ml. Moreover, the in vivo acute oral single dose toxicity experiment was conducted, being compared with acetamino-phen/paracetamol to confirm that the bio-degradation products have lower toxicity than acetaminophen in vivo and in silico.

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.

This article develops a duality principle and a related convex dual formulation suitable for a large class of models in physics and engineering. The results are based on standard tools of functional analysis, calculus of variations and duality theory. In particular, we develop applications to a model in non-linear elasticity.

This study was aimed to highlight the trends of antibiotic resistance (AR) prevalence in two annualities, 2021 and 2022, for a major bacterial pathogen, Staphylococcus aureus, that causes mastitis infections necessitating antibiotic therapy in milk producing animals. Fiftyfour isolates, 27 for each year, were obtained from routine tests for the identification of clinical mastitis agents carried out in the author institution for four provinces of Abruzzo and Molise regions, Italy. These were analyzed for phenotypic resistance to eight antibiotics used in human therapy suggested for testing by the European guidelines and for the presence of 14 transferable AR genes by qPCR tests developed in this study. The prevalence of AR genes was lower than reported in studies carried out in other countries, except for blaZ detected in 59.2% 2021 isolates and in 48.1 % 2022 isolates. However, some iso-lates with blaZ were not resistant to cefoxitin. One methicillin resistant (MRSA) strain, carrying the mecA gene, was isolated in 2022 and two multidrug resistant (MDR) isolates were identified in 2021. Other AR genes occurring were aph3’-III (two 2021 isolates), ant6-Ia (one 2021 isolate), ermB (one 2022 isolate), ermC/T (two 2021 isolates) and mph (one 2022 isolate). An interview to the veterinarians who conferred the samples indicated a good management of antibiotic therapies in farms that could explain why AR prevalence was stable in the time inter-val considered, thus underlining the effectiveness of controlled antibiotic usage in containing the AR threat.

This paper estimates the effect of trust in government on rural residents’ contributions in China’s rural pension program using the Propensity Score Matching (PSM) method. We construct an analytical framework for rural residents' decision-making in pension program and provide analysis using data from China Family Panel Studies (CFPS) and 25 provincial Departments of the Human Resources and Social Security (DOHRSS) in China. Our analysis shows that rural residents’ trust in government will influence their contributions to the pension programs by affecting their expected return of the investments. Our results suggest that the government should improve rural residents’ trust in government in order to develop a successful and sustainable rural pension program.

The calculation of the exact value of the square root of 2 is requested. In order to obtain its infinite value, A new concept is proposed where the accumulations of the infinitely many of finity is indicated by the change in direction which means that there is a jump from finity to infinity .The meaningless for an infinite number with a decimal point is indicated by this jump because any decimal number only have meanings within a finite range values and there is only an infinite integer quantity that can not be operated by algorithms like operations of multiplication，division,addition, and subtraction . The final result of the change in direction is two quantity where the second quantity and the first quantity extend in parallel line and never intersect and the second quantity represent the size of the first quantity. The first quantity is the infinitely great that can't be talked about anything outside of it and can compress any quantities outside of it to nothing and it is the exact value of the square root of 2 .

Acute kidney injury (AKI) is a complication that can occur after cardiac surgery and requires ongoing research in light of the exponential expansion of technological advancements and knowledge in medicine. In this study, we aim to evaluate the outcomes of treated electives of emergency aortic disease with high serum creatinine levels (SCr). Methods: The cohort includes 183 patients, all of whom have an aortic disease and whose SCr levels were checked upon admission on the first day in the intensive care unit (ICU) and upon discharge from the hospital. We examined the correlation of SCr levels with in-hospital mortality and immediate mortality at least six months after discharge as well as with cross-clamp time and bypass time.Results: A high SCr level upon admission is a significant predictive factor of n-hospital mortality (p = 0.001) but not immediate mortality (p = 0.409). A statistically significant correlation was also observed between elevated SCr level on the first day of ICU and aortic disease (p = 0.041) but not immediate mortality (p = 0.119). We observed a significant correlation between aortic disease and in-hospital mortality (p < 0.001), but no correlation was found between high SCr level on the first day of ICU and immediate mortality (p = 0.119). The cross-clamp time is statistically significant correlated with elevated SCr level (p = 0.013) and in-hospital mortality (p = 0.001) but not immediate mortality (p = 0.847). Furthermore, the bypass time is negatively correlated with a high SCr level on the first day of ICU (p = 0.090), in-hospital mortality (p = 0.410), and immediate mortality (p = 0.625). We also found that aortic disease is not correlated with elevated creatinine levels at ICU discharge (p = 0.152) or long-term mortality (p = 0.106). Conclusions: Although this study only included a small portion of the elaborate aspects of surgical and medical management developed around cardiac patients who received invasive treatment, the conclusions reached are nevertheless clearly relevant, as evidenced by the significantly correlations uncovered. In order to manage AKI after AAS and improve the outcome, the SCr level could be used as a marker for renoprotective strategy. Moving forward, these results serve as a first step in motivating us to expand the range of our research, collect newly relevant data, and use it to benefit patients.

Background: Sexualized substance use (SSU) is the practice of psychotropic substance usage, before or during sexual intercourse in order to increase sexual pleasure and arousal. It has a strong association with sexually transmitted infections (STIs). The present study aimed to assess the knowledge gaps regarding SSUs among the community health mobilizers by interviewing them regarding their knowledge, attitudes, and practices through qualitative approach. Methodology: In-depth interviews (IDIs) were conducted with a total of nineteen community health mobilizers engaged in counselling of sexualized substance users. A semi-structured open-ended questionnaire with socio-demographic information and probes related to SSU was administered. Informed consent was taken from each participant prior to data collection. Results: Gender-wise distribution indicated that 47% of the community mobilizers are men, followed by transgender persons (32%), and women (21%). Responses of participants highlighted that alcohol consumption was the most observed form of SSU. The findings indicated that drug administration through injection was most common, followed by sniffing and swallowing. Sources of drug pro-curement enlisted by participants included peddlers, peer groups, sexual parties, medical and liquor stores. Only 63% of participants had fair knowledge about STIs such as HIV, viral hepatitis, syphilis, and gonorrhoea. All were familiar with the administration of naloxone injections and the locations of nearby hospitals where patients could be transported in the event of an overdose. Conclusions: The in-depth interviews among the study participants reflected substantial know-ledge gaps related to various areas associated with SSU, which highlights the need for periodic workshops and training for upgradation of existing knowledge and practices among community health mobilizers. This will help to broaden their knowledge of different types of SSUs, the latest substances of abuse, the diseases caused by high-risk sexual practices, and additional health and psychological issues associated with SSUs, which would ultimately help in better counseling and management of sexualized substance users. It may also play a crucial role in the strengthening of capacity-building systems and engagements at the community level. This study may be used as formative research by researchers and policy makers to develop study protocols for multi-centric community-based studies among community health mobilizers and sexualized substance users across the country for further validation and exploration.

Noisy data is always encountered in real applications, such as bioinformatics, neuroimage and remote sensing. Existing methods mainly consider linear or generalized linear errors-in-variables regression, while relatively little attention is paid for the multivariate response case, and how to evaluate the estimation performance under perturbed covariates is still an open question. In this paper, we consider the information-theoretic limitations of estimating a low-rank matrix in the multi-response errors-in-variables regression model. By application of the information theory and statistical techniques on concentration inequalities, the minimax lower bound is provided in terms of the squared Frobenius loss, which recaptures the rate provided under the clean covariate assumption in previous literatures. Hence our result further indicates that though under the more realistic errors-in-variables situation, no more samples are required so as to achieve a rate-optimal estimation.

Endotoxins are toxic substances that widely exist in the environment and can enter the intestine with food and other substances. Intestinal epithelial cells are protected by a mucus layer that contains MUC2 as its main structural component. However, a detailed understanding of the mechanisms involved in the function of the mucus barrier in endotoxin penetration is lacking. Here, we established the most suitable proportion of Caco-2/HT-29 co-culture cells as a powerful tool to evaluate the intestinal mucus layer. Our findings significantly advance current knowledge as focal adhesion and ECM-receptor interaction were identified as the two most significantly implicated pathways in MUC2 small interfering RNA (siRNA)-transfected Caco-2/HT-29 co-culture cells after 24 h of LPS stimulation. When the mucus layer was not intact, LPS was found to damage the tight junctions of Caco-2/HT29 co-cultured cells. Furthermore, LPS was demonstrated to inhibit the integrin-mediated focal adhesion structure and damage the matrix network structure of the extracellular and actin microfilament skeletons. Ultimately, LPS inhibited the interactive communication between the extracellular matrix and the cytoskeleton for 24 h in the siMUC2 group compared with the LPS(+) and LPS(-) groups. Overall, we recognized the potential of MUC2 as a tool for barrier function in several intestinal bacterial diseases.

The presented results of simulations take into account the optical parameters of the selected sea region (from literature data on the southern Baltic Sea) and two optically extreme types of crude oil (from historical data) which exist in the form of a highly diluted oil-in-water emulsion (10 ppm). The spectral index was analyzed based on the results of modelling the radiance reflectance distribution for almost an entire hemisphere of the sky (zenith angle from 0 to 80o). The spectral index was selected and is universal for all optically different types of oil (wavelengths 650 and 412 nm). The possibility of detecting pollution in the conditions of the wavy sea surface (as a result of wind of up to 10 m/s) was studied. It has been also shown that if the viewing direction is close to a direction perpendicular to the sea surface, observations aimed at determining the spectral index are less effective than observation under the zenith angle of incidence of sunlight for all azimuths excluding the direction of sunlight specular reflection.

With this article, impact of effluent mixed water with the quality of the Mansagar Lake has been established by evaluating the physico-chemical parameters and the heavy-metal contents experimentally. The process of calculating water quality and the metal pollution quality indices is also explained in brief with respect to selected sample locations and varied environmental conditions (Pre- and Post-Monsoon season). Distribution trends of Pearson‘s correlation factor have also been discussed to establish their relation among the physico-chemical parameters and the heavy-metal contents for varied environmental conditions. In the end, detailed discussion on observations made during this study and useful recommendations are also elaborated in details. With this article, we intend to present a document for better understanding of the water quality of this lake in view of futuristic management strategies to be adopted to maintain it heritage values.

The deep neural network - BERT model (Bidirectional Encoder Representations from Transformers) and the stocks cumulative abnormal return is used in this article to analyze the sentiment of financial texts. The proposed approach, unlike those used so far, does not require the creation of dictionaries, takes into account the broad context of words and their meaning in financial texts, eliminates the problem of ambiguity of words in various contexts, does not require manual labelling of data and is free from the subjective assessment of the researcher. The sentiment of financial texts in the meaning presented in this paper is directly related to the market reaction to the information contained in these texts. For texts belonging to one of the two classes (positive or negative) with the highest probability the BERT model gives the results of predictions with a precision level of 62.38% for the positive class and 55% for the negative class. The results at this level can be used in event study, market efficiency research, investment strategy development or support of investment analysts using fundamental analysis.

Since HIV was first identified, and in a relatively short period of time, AIDS has become one of the most devastating infectious diseases of the 21st century. Classical antiretroviral therapies were a major step forward in disease treatment options, significantly improving the survival rates of HIV-infected individuals. Even though these therapies have greatly improved HIV clinical outcomes, antiretrovirals (ARV) feature biopharmaceutic and pharmacokinetic problems such as poor aqueous solubility, short half-life and poor penetration into HIV reservoir sites, which contribute to the sub-optimal efficacy of these regimens. To overcome some of these issues, novel nanotechnology-based strategies for ARV delivery towards HIV viral reservoirs have been proposed. The current review focus on the benefits of using lipid-based nanocarriers for tuning the physicochemical properties of ARVs to overcome biological barriers upon administration. Furthermore, a correlation of these properties and the potential therapeutic outcomes has been established. Biotechnological advancements using lipid nanocarriers for RNA interference delivery for the treatment of HIV infections were also discussed.

Theories of reading comprehension emphasize decoding and listening comprehension as two essential components. The current study aimed to investigate how Chinese character decoding and context-driven auditory semantic integration contribute to reading comprehension in Chinese middle school students. Seventy-five middle school students were tested. Context-driven auditory semantic integration was assessed with speech-in-noise tests in which the fundamental frequency (F0) contours of spoken sentences were either kept natural or acoustically flattened with the latter requiring a higher degree of contextual information. Statistical modelling with hierarchical regression was conducted to examine the contributions of Chinese character decoding and context-driven auditory semantic integration to reading comprehension. Performance on Chinese character decoding and auditory semantic integration scores with the flattened (but not natural) F0 sentences significantly predicted reading comprehension. Furthermore, the contributions of these two factors to reading comprehension were better fitted with an additive model instead of a multiplicative model. These findings indicate that reading comprehension in middle schoolers is associated with not only character decoding but also the listening ability to make better use of the sentential context for semantic integration in a severely degraded speech-in-noise condition. The results add to our better understanding of the multi-faceted reading comprehension in children. Future research could further address the age-dependent development and maturation of reading skills by examining and controlling other important cognitive variables, and apply neuroimaging techniques such as functional magmatic resonance imaging to reveal the neural substrates for the contribution of auditory semantic integration and the observed additive model to reading comprehension.

Authors such as Schnoebelen (2012: 12) suggest that in some languages (cf. Navajo) certain dependent clauses are frequently used independently to “mark emotional evaluation and background information”. Evans (2007) uses the term insubordination to refer to this phenomenon. Our study focuses on a particular insubordinate construction introduced by the sequence ni que in Spanish, as in the example [¡Una carta cada día!] Ni que yo fuese Umbral. (CORPES 100), used as an independent clause with a sociopragmatic meaning which is different from that of its subordinate counterpart (cf. No escribiría una carta cada día ni que yo fuese Umbral). Our research questions ask about the potential for ni que to be used as a discourse marker fulfilling an expressive function when it introduces this type of construction, and the derived hypothesis is then oriented to test whether Schnoebelen's (2012) observation about insubordinate constructions applies also to this Spanish construction. In order to test this hypothesis, we performed a functional-discourse analysis of more than 2000 concordances (and their extended contexts) in Mark Davies' Corpus del Español and the Real Academia CORPES XXI. Our findings show that the insubordinate construction differs in function and meaning from its subordinate counterpart, the former fulfilling a stronger emotive function, often combined with other discourse-pragmatic functions, such as evaluation or the organization of discourse.

Temporary pavilions play an important role as experimental fields for architects, designers and engineers, apart from providing exhibition spaces. Novel structural and formal solutions applied in pavilions also can give them unusual appearance that attracts eyesight of spectators. In this article authors explore the possibility of combination of structural novelty, visual attractiveness and low-cost by a design and construction of a temporary pavilion. For that purpose, an innovative structural system and design approach was applied, i.e. membrane structure designed in Rhino and Grasshopper environments with the use of Kiwi!3D IsoGeometric analysis tool. The designed pavilion, named Obverse/Reverse, was built in Opole, Poland, for the occasion of World Architecture Day in July 2019. Design and construction was performed by the authors in cooperation with students’ organisation Humanisation of Urban Environment from the Faculty of Architecture Wroclaw University of Science and Technology. The Rresultant pavilion proved the possibility of obtaining a low-budgets but visually attractive architectural solution with the adaption of parametrical design tools and some scientific background with innovative structural systems.

A new approach to fabricate TiNi surfaces combining the advantages of both monolithic and porous materials for implants is used in this work. New materials were obtained by depositing a porous TiNi powder onto monolithic TiNi plates followed by sintering at 1200°C. Then, further modification of the material surface with a high-current-pulsed electron beam (HCPEB) was carried out. Three materials obtained (one after sintering and two after subsequent beam treatment by 20 and 30 pulses, respectively) were studied by XRD, SEM, EDX, EIS methods, profilometry and OCP measurements. Structural and compositional changes caused by HCPEB treatment were investigated. Surface properties of the samples during their storage in saline for 10 days were studied and a model experiment with cell growth (MCF-7) was carried out for the sample unmodified with electron beam to detect cell appearance on different surface locations.

An extension of the models used to generate fractal traffic flows is presented by means of the formulation of a model that considers the use of one-dimensional chaotic maps. Based on the disaggregation of the temporal series generated by the model, a valid explanation of behavior of the values of Hurst exponent is proposed and the feasibility of their control from the parameters of the proposed model is shown.

Background: The t (2; 5) chromosomal rearrangement and resulting nucleophosmin (NPM1) -ALK fusion was first observed in 1994 in anaplastic large cell lymphoma (ALCL), a T-cell lymphoma responsive to cyclophosphamide, abriblastine, vincristine and prednisone in approximately 80% of cases; refractory cases usually respond favorably to brentuximab-vedotin. These treatments are regarded as a bridge to allogeneic hematopoietic stem cell transplantation (allo-SCT). Nowadays, transplant procedures and monitoring of chemotherapy patients proceed very slowly because the SARS-CoV-2 pandemic has heavily clogged the hospitals in all countries. Results: A 40-year-old Caucasian woman was first seen at our clinical center in June 2020. She had ALCL ALK +, a history of failure to two previous therapeutic lines and was in complete remission after 12 courses of Brentuximab, still pending allo-SCT after two failed donor selection. Facing of a new therapeutic failure, we requested the Italian drug regulatory agency, and obtained the authorization, to administer 250 mg twice a day of Crizotinib, a drug incomprehensibly not registered for ALCL ALK +. Conclusions: The response to Crizotinib was optimal, since no adverse event occurred, and CT-PET persisted negative; this drug has proved to be a valid bridge to allo-SCT

RAS oncogenes are amongst the most commonly mutated proteins in human cancers. They regulate a wide range of effector pathways that control cell proliferation, survival, differentiation, migration and metabolic status. Including aberrations in these pathways, RAS dependent signaling is altered in more than half of human cancers. Targeting mutant RAS proteins and their downstream oncogenic signaling pathways has been elusive. However, recent results comprising detailed molecular studies, large scale omics studies and computational modeling have painted a new and more comprehensive portrait of RAS signaling that helps us to understand the intricacies of RAS, how its physiological and pathophysiological functions are regulated, and how we can target them. Here, we review these efforts particularly trying to relate the detailed mechanistic studies with global functional studies. We highlight the importance of computational modeling and data integration to derive an actionable understanding of RAS signaling that will allow us to design new mechanism based therapies for RAS mutated cancers.

In the energy-momentum density expressions for a relativistic perfect fluid with a bulk motion, one comes across a couple of pressure-dependent terms, which though well known, are to an extent, lacking in their conceptual basis and the ensuing physical interpretation. In the expression for the energy density, the rest mass density along with the kinetic energy density of the fluid constituents due to their random motion, which contributes to the pressure as well, are already included. However, in a fluid with a bulk motion, there are, in addition, a couple of explicit, pressure-dependent terms in the energy-momentum densities, whose presence to an extent, is shrouded in mystery, especially from a physical perspective. We show here that one such pressure-dependent term appearing in the energy density, represents the work done by the fluid pressure against the Lorentz contraction during transition from the rest frame of the fluid to another frame in which the fluid has a bulk motion. This applies equally to the electromagnetic energy density of electrically charged systems in motion and explains in a natural manner an apparently paradoxical result that the field energy of a charged capacitor system decreases with an increase in the system velocity. The momentum density includes another pressure-dependent term, that represents an energy flow across the system, due to the opposite signs of work being done by pressure on two opposite sides of the moving fluid. From Maxwell's stress tensor we demonstrate that in the expression for electromagnetic momentum of an electric charged particle, it is the presence of a similar pressure term, arising from electrical self-repulsion forces in the charged sphere, that yields a natural explanation for the famous, more than a century old, 4/3 factor in the electromagnetic mass.

Breast cancer is the leading cause of cancer deaths worldwide in women. This aggressive tumour can be categorized into two main groups: in situ and infiltrative, with the latter being the most common malignant lesions. The current use of Magnetic Resonance Imaging (MRI) was shown to provide highest sensitivity in the detection and discrimination between benign vs. malignant lesions, when interpreted by expert radiologists. In this article, we present the prototype of a Computer-Aided Detection/Diagnosis (CAD) system that could provide valuable assistance to the radiologist for the discrimination between in situ and infiltrating tumours. The system consists of two main processing levels: 1) Localization of possibly tumoral regions of interest (ROIs) through an iterative procedure based on intensity values (ROI Hunter) followed by a deep-feature extraction and classification method for false-positive rejection; 2) Characterization of the selected ROIs and discrimination between in situ and invasive tumour, consisting of Radiomics feature extraction and classification through a machine-learning algorithm. The CAD system was developed and evaluated using a DCE-MRI image database, containing at least one confirmed mass per image, as diagnosed by an expert radiologist. When evaluating the accuracy of the ROI Hunter procedure with respect to the radiologist-drawn boundaries, sensitivity to mass detection was found to be 75%. The AUC of the ROC curve for discrimination between in situ and infiltrative tumors was 0.70.

We argue that the problem of time is not a crucial issue inherent in the quantum picture of the universe evolution. On the minisuperspace model example with the massless scalar field, we demonstrate four approaches to the description of quantum evolution, which give similar results explicitly. The relevance of these approaches to building a quantum theory of gravity is discussed.

Single nucleotide polymorphisms (SNP) are associated with diseases and drug response variabilities in humans. Elucidating the damaging and disease-associated SNPs using wet-laboratory approaches can be challenging and resource-demanding due to the large number of SNPs in the human genome. Due to the growth in the field of computational biology and bioinformatics, algorithms have been developed to help screen and filter out the most deleterious SNPs that are worth considering for wet-laboratory studies. Here we review the existing in-silico based methods used to predict and characterize the effects of SNPs on protein structure and function. This cutting-edge approach will facilitate the search for novel therapeutics, help understand the etiology of diseases and fast-track the personalized medicine agenda.

A significant part of the literature on innovative practice in medicine relates to seizing opportunities and curbing harms for patients in desperate situations. Unfortunately, the term innovation has multiple meanings and a rich rhetorical flourish that adds confusion and misunderstanding to an already difficult debate. This paper aims to enhance the current definition of innovative practice for medicine. First, we replace the term innovation with the more literal of new non-validated practice. To identify this meaning, we analyse the traditional research ethics’ distinction between research, validated practice, and innovation in the Belmont Report. Second, we propose the following explicit definition of new non-validated practice: the first or recent use of diagnostic, therapeutic or preventive interventions that introduce a significant change, with an insufficient level of evidence of safety or efficacy for regular healthcare, and with the main aim to benefit individual patients. This definition is a promising conceptual tool to inform empirical research, ethicists, and the harmonization of its regulation and legislation (e.g. right-to-try laws).

This paper presents findings of a study on continuous feed-in management and continuous synthetic inertia contribution with wind turbines. A realistic case study, based on real measurements, is outlined. A wind turbine feeds into a weak feeder, such that its power has to be adapted to the permissible loading of this feeder. At the same time the wind turbine is to provide inertia to the grid by applying the previously published variable inertia constant controller. It is discussed that optimal grid utilisation and simultaneous inertia contribution are mandatory for the frequency control in power systems that are heavily penetrated with renewable energies. The study shows that continuous feed-in management can be combined well with continuous inertia provision. There are hardly any negative consequences for the wind turbine. The benefits for the grid are convincing, both in terms of increased system utilisation and in terms of provided inertia. It is concluded that wind turbines can enhance angular stability in a power system to a larger extent than conventional power plants.

Three kinds of hydrophobic groups grafted starches of maleic anhydride grafted starch (MAH-g-starch), lactic acid grafted starch (LA-g-starch), and methyl acrylate grafted starch (MA-g-starch) were prepared by in-situ solid phase polymerization. The results of Fourier transform infrared spectroscopy (FT-IR) and X-ray photoelectron spectroscopy (XPS) were confirmed successful grafting. The grafting ratios of MAH-g-starch, LA-g-starch and MA-g-starch were 6.50%, 12.45%, and 0.57%, respectively. Influenced by the grafting ratio, LA-g-starch had the best hydrophobic properties and the largest molecular weight, and those for MA-g-starch was the worst. The surfaces of grafted starches were covered with graft polymer, with obvious surface roughness and bond degree of MAH-g-starch and LA-g-starch. The crystalline structure of grafted starches showed some damage, with LA-g-starch exhibiting the greatest decrease in crystallinity, and less of a change for MA-g-starch. Overall, the grafting reaction improved thermoplasticity, with LA-g-starch the most improved, followed by MAH-g-starch, and then MA-g-starch.

This is a theoretical and empirical article. In the first part, an original definition of the cross-border market for cultural services has been developed, based on classic market definitions. The structure and conditions of functioning for this market have also been presented. The next part of the article discusses the supply side of the cross-border market of cultural services for the two twin towns: Cieszyn (Poland) and Český Těšín (Czech Republic). Next, based on the surveys conducted, the participation of residents of both towns in the most important cultural events organised by cultural institutions on both sides of the border was examined.

This paper reports on the production and mechanical properties of Ti6Al4V micro-lattice structures, with strut thickness nearing the single-track width of the laser-based powder bed fusion (LPBF) system used. Besides providing new information on the mechanical properties and manufacturability of such thin-strut lattices, this paper also reports on the in-situ deformation imaging of micro-lattice structures with 6 unit cells in every direction. LPBF lattices are of interest for medical implants, due to the possibility of creating structures with an elastic modulus close to that of the bones and small pore sizes which allow effective osseointegration. In this work four different cubes were produced by laser powder bed fusion and subsequently analyzed using microCT, compression testing and one selected lattice was subjected to in-situ microCT imaging during compression. The in-situ imaging was performed at 4 steps during yielding. The results indicate that mechanical performance (elastic modulus and strength) correlate well with actual density and that this performance is remarkably good, despite the high roughness and irregularity of the struts at this scale. In-situ yielding is visually illustrated.

The past decade has witnessed enormous progress, which has seen the noncoding RNAs (ncRNAs) turn from the so called dark matter RNA to critical functional molecules, influencing most physiological processes in development and disease contexts. Many ncRNAs interact with each other and are part of networks that influence the cell transcriptome and proteome and consequently the outcome of biological processes. The regulatory circuits controlled by ncRNAs have become increasingly more relevant in cancer. Further understanding of these complex network interactions and how ncRNAs are regulated, is paving the way for the identification of better therapeutic strategies in cancer.

Collision avoidance is an important feature in advanced driver-assistance systems, aiming at providing correct, timely and reliable warnings before an imminent collision (objects, vehicles, pedestrians, etc.). A co-simulation framework is proposed in this paper to address the design and evaluation of collision avoidances in a cyber-physical system. The co-simulation framework is supported on the interaction between SCANeR and Matlab/Simulink. From the best of authors’ knowledge, two main contributions are reported in this paper. Firstly, the modelling and simulation of virtual on-chip LIDAR sensors in a cyber-physical system (CPS) considering traffic scenarios is presented. The CPS is designed and implemented in SCANeR. Secondly, an obstacle recognition library with three specific Artificial Intelligence-based methods is also designed based on sensory information database provided by SCANeR. Three methods for collision avoidance detection are considered, i.e.; a multi-layer perceptron neural network, a self-organization map and a support vector machine. Finally, a comparison among these methods for detecting obstacles before different weather conditions is done with very promising results in terms of accuracy. The best results are achieved using the multi-layer perceptron in sunny and fog conditions, the support vector machine in rainy and self-organized map in snowy conditions.

In the study of relativistic jets one of the key open questions is their interaction with the environment on the microscopic level. Here, we study the initial evolution of both electron–proton (e^- - p⁺) and electron–positron (e^±) relativistic jets containing helical magnetic fields, focusing on their interaction with an ambient plasma. We have performed simulations of "global" jets containing helical magnetic fields in order to examine how helical magnetic fields affect kinetic instabilities such as the Weibel instability, the kinetic Kelvin-Helmholtz instability (kKHI) and the Mushroom instability (MI). In our initial simulation study these kinetic instabilities are suppressed and new types of instabilities can grow. In the e^- - p⁺ jet simulation recollimation-like instability occurs and jet electrons are strongly perturbed. In the e^± jet simulation a recollimation-like instability occurs at early times followed by a kinetic instability and the general structure is similar to a simulation without helical magnetic field. Simulations using much larger systems are required in order to thoroughly follow the evolution of global jets containing helical magnetic fields.

Dengue virus is a global health problem most prevalent in tropical and subtropical regions. However, after the approval of two vaccines, Dengvaxia, TV003/TV005 of Takeda, for its prevention, problems were reported, like enhanced risks of infection or less efficiency of protection. Since then, more struggles have been in demand for the development of better vaccines. Here, we conducted a new design through an in-silico strategy. Initially, epitopes were chosen based on their antigenicity, immunogenicity, and binding affinity with MHC molecule, while excluded with allergenicity, toxicity and potential risk of antibody dependent enhancement. Subsequently, a core antigen was constructed with selected epitopes and linked with distinct adjuvant proteins to achieve three candidate vaccines, PSDV-1~3. PSDV-2 was chosen for further validation based on their advantage in physicochemical and structural properties. With a panel of simulations, this artificial protein showed tight binding with pattern recognition receptors, good stability, robust immune induction, and ultimately was confirmed as a high quality vaccine candidate. The plasmid for its recombinant expression was then designed accordingly. With our new design, one more choice was obtained for the effective protection from Dengue virus. Further experimental validations are still require to confirm it protection capacity and safety.

Simple Summary: Breast cancer is the most common invasive cancer among women. Triple-negative breast cancer (TNBC) accounts for 15–20% of newly diagnosed breast cancers and has the worst prognosis. However, TNBC patients are not a homogeneous group, and there are differences in the course of the disease as well as in response to treatment. For this reason, differentiation of subtypes of this tumor is important for optimal therapeutic decision and risk prediction. The presented study focuses on the expression of the androgen receptor (AR) and the infiltration of T-lymphocytes in the tumor stroma (TILs) of TNBC patients. Correlation of these tested biomarkers with standard prognostic factors. Defining new prognostic factors for 3-year overall survival (OS). Abstract: Background: Analysis of the practical benefit of testing the expression of AR and the TILs in patients with TNBC and their correlation with standard prognostic factors. Methods: The study group consisted of 86 female patients treated for TNBC. T-lymphocyte infiltration was examined in H+E staining. AR expression, CD8 and CD4 T-lymphocytes were evaluated in immunohistochemistry. Results: Significantly negative correlation was found between AR expression and the CD8 T-lymphocyte infiltration levels. A significant negative correlation was found between the AR expression and G and Ki 67, and a positive correlation between the TILs levels and G and Ki 67. Patients with AR expression and low TILs levels had the highest percentage of diagnosed distant metastases and 3-years OS. Patients with high TILs no distant metastases or deaths were diagnosed. The level of TILs turned out to be a significant independent prognostic factor. Conclusions: Based on the assessment of AR expression and TILs infiltration, the group of highest and lowest risk was determined. The prognostic factor of known parameters such as TNM and a new factor - TILs was confirmed. On the other hand, parameters such as G and Ki 67 and the tested factor - AR had no effect on the prognosis.

The aim of this article is to present the course of the COVID-19 pandemic in Poland in 2020-2022, the formation of ad hoc health and anti-crisis policies, an assessment of crisis management and the perceived impact of the pandemic and anti-crisis measures.The paper draws on literature, official reports on the pandemic, data from Eurostat and other information from state institutions and public organisations.Particular attention was paid to the analysis and evaluation of the objectives, instruments and effects of the policies pursued by the state in a coordinated manner, i.e. the anti-pandemic policy and the anti-crisis policy. The anti-pandemic policy in Poland has failed to protect the country from significant personal losses and negative impacts on the health of the population and demographic processes.The anti-crisis policy of the state carried out with the mobilisation of businesses and disciplined society, in the form of anti-crisis shields supplemented and adjusted on an ongoing basis, allowed Poland to avoid a deep crisis and economic recession. Attention was drawn to the need to coordinate the management of health and economic crises nationally and internationally, and to the need to have a medium-term anti-crisis state strategy and a system for the early detection of crisis symptoms.

Cured-in-place pipe (CIPP) lining is a widely adopted method for pipeline renewal, offering advantages such as rapid installation and cost-effectiveness. However, concerns regarding the environmental impacts of volatile organic compound (VOC) emissions during the installation process have raised issues regarding the CIPP method. The literature review conducted in this paper indicated the need for stringent monitoring and management practices to mitigate adverse effects, emphasizing the importance of safe installation protocols. This paper presents the initial results of a case study focusing on VOC emissions, specifically investigating non-styrene polyester resins and water curing. To capture emissions from CIPP activities, the methodology involved air sampling using various equipment, including photoionization detectors (PID), summa canisters, passive worker sampler sorbent tubes, and method 13 cartridges. The preliminary findings indicate that non-styrene polyester resins do not exceed the exposure limits set out by the OSHA and USEPA. The future phases of this project will explore different resins and curing methods.

The study looks at how joining live video chats with native English speakers on TikTok helps people who are learning English feel more ready to talk in English and less nervous about it. This study looks at EFL students who join TikTok live sessions. The researcher wants to understand how confident and nervous the students feel when they communicate. He uses qualitative research methods to do this. The study shows that using TikTok in a fun and calming way could help people learn a new language and reduce feelings of worry. This is helpful for teachers and language experts who want to use social media to help people learn languages.

This study investigates the transformative impact of ChatGPT, a cutting-edge AI language model developed by OpenAI, on the financial sector. We explore ChatGPT's applications in financial analysis, focusing on its ability to perform tasks traditionally handled by human analysts. By creating a set of multi-step and advanced reasoning financial tasks, and establishing several task-specific evaluation metrics, our experimental results demonstrate that ChatGPT-4o can effectively perform both basic and some complex financial analysis tasks comparable to those executed by humans. However, our empirical evaluation reveals limitations in its performance on complex tasks that require comprehensive understanding and critical thinking. The study highlights the necessity for meticulous task formulation and robust evaluation to achieve consistent functionality. While ChatGPT enhances efficiency in financial analysis, its integration with human expertise remains crucial for effective decision-making. This study contributes to the understanding of AI's role in finance and provides insights into its potential and constraints, guiding future integration of AI technologies in financial practices.

During the development of new medicines mutually exclusive specificity appears to be required but hitherto is most often included at the late clinical trial stage. Here, I describe the use of Hedgehog signalling in Drosophila as a model to represent a mutually exclusive relationship within the context and report the identification of CG43658, a putative Rho guanine nucleotide exchange factor and orthologue of the Charcot-Marie-Tooth disease associated gene ARHGEF10. Furthermore, a Computer that is able to consider the whole and describe the sum of everything in it absolutely in unambiguous terms is a useful tool. Here I describe such a computer with a suggestion for an application to examine any component in the context where a medicine is sought. Taken, together I would like to propose this method as a fundamental necessity and improvement upon current existing methods related not only to Hedgehog signalling but plausibly to life science research and the search for medicines in general.

Oilseed plants of the Brassicaceae plant family are cultivated for food, feed and industrial purposes on large-scale in Europe. This review gives an overview of current market-oriented applications of new genomic techniques (NGTs) in relevant Brassicaceae oilseed crops based on a literature survey. In this respect, changes in oil quality, yield, growth and resistance to biotic and abiotic stress are goals in oilseed rape (B. napus) and camelina (C. sativa). Environmental risk assessment scenarios are developed for specific NGT applications in Brassicaceae oilseed crops with either a changed oil composition or with fitness related traits. In case of a changed oil composition an increase or decrease of polyunsaturated fatty acids (PUFA) demonstrates risks for health and survival of pollinators. In case of fitness related traits other risks were identified, i. e. an increased risk of spread and persistence of NGT plants. Furthermore, there are indications for potential disturbance of interactions with the environment, involving signalling pathways and reaction to stress conditions. It is shown that for a comprehensive risk assessment the technological potential of NGTs, the plants’ biology and the scale of releases have to be considered in combination. Therefore, the release of NGT plants into the environment for agricultural purposes will require risk assessment and monitoring of single traits as well as of combinatorial and long-term cumulative effects. In addition, risk management should develop concepts and measures to control and potentially restrict the scale of releases. This is especially relevant for NGT Brassicaceae in Europe which is a centre of diversity of this plant family.

The object of study is a transversely bent triangular plate made of orthotropic material fixed along the edges of the plate under the action of a uniformly distributed load. Fourth-order differential equilibrium equations with variable orthotropy parameters were used. The equations were approximated by finite differences for a grid of scalene triangles. This type of mesh accurately describes the boundary contour of the triangular-shaped plates. The boundary conditions for the mesh consider the orthotropy of the plate material. Seven standard finite-difference equations have been developed considering the boundary conditions along the three edges of the plate and the presence of three angles of an irregularly shaped triangle. A finite difference matrix is obtained. The matrix structure makes calculating a triangular plate at different base angles possible. The boundary conditions were varied in the form of rigid or hinged support of triangular plates. The calculation method considers the orthotropic parameters of the material in two mutually perpendicular planes. The adaptation of the numerical method to the calculation of orthotropic plates of arbitrary shape is described. Relationships are given for determining the rigidity characteristics of orthotropic materials. An algorithm for simple engineering calculation of triangular orthotropic plates is proposed, which makes it possible to perform accurate calculations in variant design.

We prove a quasi-pseudometric version of the strong Ekeland principle proved by P. Georgiev and T. Suzuki.

The chemical reaction of ion-adsorption type rare earth during in-situ leaching process is accompanied by ion migration and charge movement, making the leaching process electrochemical in nature. The chemical reaction rate plays an important role in the leaching rate of rare earth elements. In this work, electrochemical impedance spectroscopy (EIS) was used to reveal characteristics of electrical resistance alteration and leaching rate of rare earth elements during in-situ leaching. The equivalent circuit model of the leaching process was established, and two critical parameters of solution resistance Rs and charge transfer resistance Rt were analyzed to reflect the electrochemical characteristics. According to the characteristics of electrical resistance alteration, the leaching process was divided into four stages: wetting, reaction, equilibrium, and top water stage. The resistance parameters Rs and Rt decreased first and then increased during the leaching process. The maximum value of Rs was 1330Ω∙cm2 at the end of the top water stage, and the minimum value was 135Ω∙cm2 at the beginning of the equilibrium stage. The maximum value of Rt was 8310Ω∙cm2 at the beginning of the leaching stage, and the minimum value was 21Ω∙cm2 at the end of the reaction stage. Rs and Rt were negatively correlated with the pore size and chemical reaction rate during leaching. With increasing of pore size and reaction rate , the resistance parameter decrease. This study provide a new idea for intelligent monitoring of rare earth ore.

Pharmaceutical aerosols play a key role in the treatment of lung disorders, but also systemic diseases, due to their ability to target specific areas of the respiratory system (RS). This article focuses on identifying and clarifying the influence of various factors involved in the generation of aerosol micro- and nanoparticles on their regional distribution and deposition in the RS. Attention is given to the importance of process parameters during aerosolization of liquids or powders and the role of aerosol flow dynamics in RS. The interaction of deposited particles with the fluid environment of the lung is also pointed out as an important step in the mass transfer of the drug to the RS surface. The analysis presented highlights the technical aspects of preparing the precursors to ensure that the properties of the aerosol are suitable for a given therapeutic target. Analyzing existing technical limitations, several potential strategies for enhancing the efficiency of targeted therapeutic delivery to or through the respiratory system are identified and presented, including the use of smart inhaling devices incorporating AI algorithms.

In order to reveal the frost heaving mechanism of void water behind the lining of high-speed railway tunnels in cold regions，the voids were first classified according to the positional relationship between voids and waterproof panels，and then the water supply and discharge conditions of different types of voids were investigated，then the influence of the excretion conditions on the frost heave force was experimentally studied. Based on these conditions，circular wedge-shaped and flying saucer-shaped void freezing models were established to analyze the evolution process of accumulated water frost heave. Then，according to the relative position of the excretion channel and the void，the excretion coefficient was introduced，and the calculation method of the frost heaving force of the voided water was proposed，and the influencing factors and laws of the frost-heave force were revealed. The results are shown as follows: 1) The blockage of the excretion channel will lead to the generation of frost heaving force; 2) The freezing and thawing process of the water within the cavity develops from the thinnest part of the void edge to the thicker part，and the process of frost heave-thaw，water replenishment-re-freeze heave of the water within the cavity leads to greater and greater frost heave force; 3) The frost-heaving force of the water within cavity is controlled by the void height and the position of the excretion channel. The larger the cavity height is or the closer the excretion channel is to the bottom surface of the void，the greater the frost-heave force is.

Artificial intelligence (AI)-based conversational models, such as ChatGPT, Microsoft Bing, and Google Bard, emerged as valuable sources of health information for the lay individuals. However, the accuracy of information provided by these AI models remains a significant concern. This pilot study aimed to test a new tool referred to as “CLEAR”, designed to assess the quality of health information delivered by AI-based models. Tool development involved a literature review on health information quality, followed by initial establishment of the CLEAR tool comprising five items that aimed to assess the following: completeness of content in response to the prompt, lack of false information, evidence support, appropriateness, and relevance of the generated content. Each item was scored on a 5-point Likert scale from excellent to poor. Content validity was checked by expert review of the initial items. Pilot testing involved 32 healthcare professionals using the CLEAR tool to assess content on eight different health topics deliberately designed with varying qualities. The internal consistency was checked using the Cronbach α. Feedback through the pilot test resulted in language modifications to improve the clarity of the items. The final CLEAR tool was used to assess health information quality generated through four different AI-based models in five different, yet common health topics. The AI models were ChatGPT 3.5, ChatGPT 4, Bing, and Bard, and the content generated was scored by two independent raters with Cohen κ to assess the inter-rater agreement. The final five CLEAR items were: (1) Is the content sufficient? (2) Is the content accurate? (3) Is the content evidence-based? (4) Is the content clear, concise, and easy to understand? and (5) Is the content free from irrelevant information? Pilot testing using the eight different health topics revealed an acceptable internal consistency with a Cronbach α range of 0.669–0.981. The use of the final CLEAR tool yielded the following average scores: Bing (mean=24.4±0.42), ChatGPT-4 (mean=23.6±0.96), Bard (mean=21.2±1.79), and ChatGPT-3.5 (mean=20.6±5.20). The inter-rater agreement revealed the following Cohen κ values: for ChatGPT-3.5 (κ=0.875, P<.001), ChatGPT-4 (κ=0.780, P<.001), Bing (κ=0.348, P=.037), and Bard (κ=.749, P<.001). The CLEAR tool is a brief yet helpful tool that can aid to standardize testing of the quality of health information generated by the AI-based conversational models. Future studies are recommended to validate the utility of the CLEAR tool to assess the quality of the AI-generated health-related content using a larger sample across various complex health topics.

The radiation stability of polymer test objects fabricated by direct laser writing is studied. The two groups of 6 cubes (50×50×50 μm3) were printed on a common silicon substrate. 6 cubes were irradiated with X-rays in the synchrotron radiation beam (12 keV, 1010 photons/mm2/s), the other 6 kept non-irradiated for the reference. In each group, the fabrication parameters (laser power and slicing step) were uniformly varied from cube to cube. Each irradiated cube was exposed with the dose of 1013 X-ray photons. The calibration of this dose in the radiological units (Gy) was carried out using the tissue-equivalent thermoluminescent detectors (TLD-800). The corresponding exposition dose was estimated as 30 kGy for each cube. The radiation effects were evaluated by Raman spectroscopy and by morphological changes observed with the raster electron microscope. The primary radiation effect appears in the essential increase of the polymerization degree with consuming carbon-carbon double bonds in favor of the polymer cross-linking. Only one cube of 6 has changed the size and shape due to this effect, while the others retained the initial shape. Morphological changes are connected with the improper fabrication parameters (laser power and slicing step). Properly fabricated objects withstand the X-rays of the synchrotron radiation beam.

The rising prevalence of autism internationally has been accompanied with an increased appreciation of the poorer mental health experienced by people with this condition and also of their family care-givers. In particular higher incidences of anxiety and depression are reported in high income nations and these conditions are likely to be under-recognised and under-reported in lower resourced regions or countries. Mainstream mental health services seem to be ill-equipped to respond adequately to the needs of autistic persons and their care-givers. This scoping review of 30 recently published literature reviews covering over 1,000 journal articles, summarises the insights and strategies that have been shown to promote the mental health and emotional wellbeing of autistic persons. In particular, a focus on family-centred, community-based supports is needed that aim to enhance social communication, extend social connections and promote an individual’s self-esteem, self-determination and social motivation. These low-cost interventions are especially pertinent in low resourced settings but they can be used internationally to prevent mental illness and assist in the treatment of anxiety and depression in autistic persons and their family carers. The priority is to focus on primary care responses with cross-sectoral working rather than investing in high-cost psychiatric provision.

Zinc, being a part of many proteins and enzymes, plays an important role in the vital processes of the body. Racemic α-lipoic acid (LA) has a wide range of biological activities: antioxidant, antidiabetic, anticancer, and it is also used in diseases such as Parkinson's and Alzheimer's. Nowadays, the synthesis and structural studies of new zinc complexes with biologically active compounds are of great importance for drug discovery. This work shows the studies carried out on the synthesis, structure, identification, also biological activity using in silico methods of a complex compound based on LA and zinc. A complex compound of zinc with LA (ZnLA) was synthesized in the presence of LA and zinc acetate in ethanol. The identification of ZnLA by (FT-IR, XRD and TGA-DTA), also DFT calculations at the B3LYP/def2-TZVPP level of theory was performed. The molecular docking investigation involved docking ZnLA with two different protein receptors such us Glycogen phosphorylase (2GPA) and Kv potassium channel beta subunit (1ZSX) using CB-Dock 2 server and Auto-Dock Vina program to determine the mechanism of action and biological activity. This study reveals potential ligand-protein interactions at the atomic level and suggests that the treatment of diabetes (non-insulin dependent) with ZnLA.

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.

Abstract: rainfall is the main driver of soil erosion. With the daily rainfall, riverine flow discharge and sediment load in the upper Lianjiang River watershed from 1990 to 2020, extreme rainfall events were defined by the 95th percentile method and minimum event interval time (MIT), change trends and mutations of yearly rainfall, riverine flow discharge and sediment load were identified using the Mann-Kendall test, then the optimum lag response time and antecedent rainfall were investigated with the multiple linear regression. The results showed that (1) the sediment changed significantly and abruptly in 1995 due to the expansion of the garden land. (2) Compared with ordinary rainfall, extreme rainfall events explained more variations of riverine flow and sediment with a higher degree, and had a more significant effect on the lag time of runoff and sediment. (3) Garden land expansion in extreme rainfall scenarios resulted in longer lag times for runoff and sediment and decreased demand for antecedent rainfall with more pre-event time. Therefore, taking the rainfall event as a breakthrough, analyzing the antecedent rainfall and the lag response of riverine flow discharge and sediment load is conducive to revealing the response mechanism of riverine flow discharge and sediment load and improving the simulation accuracy of riverine flow and sediment under extreme rainfall condition, thus help for the soil erosion control under extreme rainfall.

In recent, Chae found that, at weak gravitational acceleration g_N≲10⁻⁹ms⁻², the observed orbit of the wide binary stars is not accordant with current theory of binary star. Here, we present, this finding should be an observational evidence for that Newtonian theory of orbit perturbation is still valid in galactic scale.

With the rapid increase in diabetes worldwide, the number of patients with diabetic kidney disease (DKD), a complication of diabetes mellitus, is also on the rise. DKD is a major cause of chronic kidney disease progressing to end-stage renal failure; however, current medical treatments for DKD do not achieve satisfactory outcomes. Molecular hydrogen (H2) is an antioxidant that selectively reduces hydroxyl radicals, a reactive oxygen species with a very potent oxidative capacity. H2 was recently shown to exert not only antioxidant, but also anti-inflammatory, cell lethality-regulating, and signal transduction-regulating effects, and is now being applied clinically. Many factors contribute to the onset and progression of DKD, with mitochondrial dysfunction, oxidative stress, and inflammation being strongly implicated. Recent preclinical and clinical trials reported that substances with antioxidant properties may slow the progression of DKD. Therefore, we conducted a literature review on animal models and human clinical trials in which H2 showed efficacy against various renal diseases. This literature review and our previous findings collectively suggest that H2 exerts therapeutic effects in patients with DKD by improving mitochondrial function. Future large-scale clinical studies are needed to confirm these findings.

Transmembrane carriers of the Slc11 family catalyze proton (H+)-dependent uptake of divalent metal-ions (Me2+) such as manganese and iron - vital elements coveted during infection. Slc11 mechanism of high affinity Me2+ cell import is selective and conserved between prokaryotic (MntH) and eukaryotic (Nramp) homologs, though processes coupling the use of the proton motive force to Me2+ uptake evolved repeatedly. Adding bacterial piracy of Nramp genes spread in distinct environmental niches suggests selective gain of function that may benefit opportunistic pathogens. To better understand Slc11 evolution Alphafold (AF2)/Colabfold (CF) 3D predictions for bacterial sequences from sister clades of eukaryotic descent (MCb and MCg) were compared using both native and mutant templates. AF2/CF model an array of native MCb intermediates spanning the transition from outward open (OO) to inward open (IO) carrier. In silico mutagenesis targeting i) a set of (evolutionary coupled) sites that may define Slc11 function (putative synapomorphy), and ii) residues from networked communities evolving during MCb transition, indicate Slc11 synapomorphy primarily instructs Me2+-selective conformation switch which unlocks carrier inner gate, and contributes to Me2+ binding site occlusion and outer gate locking. Inner gate opening apparently proceeds from interaction between transmembrane helix (h) h5, h8 and h1a. MCg1 xenologs revealed marked differences in carrier shape and plasticity, owing partly to altered intramolecular H+-network. Yet, targeting Slc11 synapomorphy also converted MCg1 IO models to OO state, apparently mobilizing the same residues to control gates. But MCg1 response to mutagenesis differed, extensive divergence within this clade correlating with MCb-like modeling properties. Notably, MCg1 divergent epistasis marks emergence of the genus Bordetella-Achromobacter. Slc11 synapomorphy localizes to the 3D areas that deviate least among MCb and MCg1 models (either IO or OO) implying it constitutes a 3D network of residues articulating Me2+-selective carrier conformation switch which is maintained in fast evolving clades at the cost of divergent epistatic interactions impacting carrier shape and dynamics.

In recent times, the process control network (PCN) of oil and gas installation has been subjected to amorphous cyber-attacks which include Denial-of-Service (DoS), Distributed-Denial-of-Service (DDoS), Man-in-the-Middle (MitM) attacks, and this may have been caused majorly by the integration of open network to Operation Technology (OT) as a result of low-cost network expansion. The connection of the OT to the internet for firmware updates, third-party support, or vendor interventions, has exposed the industry to attacks. The inability to detect these unpredictable cyber-attacks exposes the PCN and a successful attack can lead to devastating effects. This paper reviews the different forms of cyber-attacks in PCN of oil and gas installations and proposes the use of machine learning algorithms to monitor data exchanges between the sensors, controllers, processes, and the final control elements on the network so as to detect anomalies in such data exchanges. Python 3.0 Libraries, Deep-Learning Toolkit, MATLAB, and Allen Bradley RSLogic 5000 PLC Emulator software were used in the simulation of process control. The outcome of the experiments shows the reliability and functionality of the different machine-learning algorithms in detecting these anomalies with significant precise attack detections identified using a coarse tree algorithm.

Glioblastoma multiforme (GBM) is a highly heterogeneous brain tumor with limited treatment options and a poor prognosis. Cancer stem cells (CSCs) have emerged as a critical factor in GBM resistance and management, contributing to tumor growth, heterogeneity, and immunosuppression. The transcription factor FOXM1 has been identified as a key player in the progression, spread, and therapy resistance of various cancers, including GBM. In this study, researchers conducted structure-based in silico screening to identify natural compounds that could target the DNA-binding domain (DBD) of the FOXM1 protein. Through molecular docking analyses, identified Silybin B as a potential inhibitor of FOXM1, exhibiting strong interaction with the protein. MD simulations were performed to validate the binding stability of the FOXM1-Silybin B complex. The study provides valuable insights into the potential of Silybin B as a FOXM1 inhibitor and its ability to induce senescence in GBM stem cells. These findings contribute to the development of structure-based design strategies for FOXM1 inhibitors and innovative therapeutic approaches for the treatment of Glioblastoma.

The economical load dispatch problem is a critical concern in thermal power systems to ensure cost-effective operation. This paper conducts a comparative analysis between the Social Spider Algorithm (SSA) and Particle Swarm Optimization (PSO) for economical load dispatch in a 6-unit thermal power system with the integration of 11,000 plug-in electric vehicles (PEVs). Both SSA and PSO are population-based optimization techniques designed to minimize the overall fuel cost while satisfying the load demand by determining the optimal power output of each unit. SSA emulates the social behavior of spiders, while PSO simulates the collective intelligence of a swarm of particles. Performance evaluation of the algorithms considers power system data, such as unit fuel costs, minimum and maximum loads, and total load demand. The objective is to minimize fuel cost while meeting the load demand. Comparative analysis of SSA and PSO includes convergence speed, solution quality, and computational efficiency. Experimental results indicate that SSA outperforms PSO in achieving a more optimal and economical load dispatch solution for the 6-unit thermal power system. SSA demonstrates faster convergence and provides superior-quality solutions compared to PSO. This paper contributes to the field by highlighting SSA's effectiveness in achieving cost-efficient operation of thermal power systems. The findings suggest that SSA holds promise as an optimization technique for similar power system optimization problems, enhancing overall operational efficiency and reducing costs for thermal power plants.

(1) Background: Acute myocardial infarction in pregnancy (pAMI) is a rare event, often caused by non-classical factors rather than atherosclerosis. The management of pAMI poses unique chal-lenges as it requires considering both maternal and fetal well-being.; (2) Methods: We present the case of a 36-week pregnant woman who presented with antero-lateral ST elevation myocardial infarction (STEMI) complicated by cardiogenic shock. To ensure comprehensive decision-making, an emergency Pregnancy Heart Team meeting was convened, comprising interventional cardi-ologists, gynecologists, and anesthesiologists. The team prioritized interventional treatment for pAMI and opted for primary percutaneous coronary intervention (PCI) due to the unstable ma-ternal condition.; (3) Results: The patient underwent primary PCI as the chosen intervention for pAMI. A rapid response gynecology team closely monitored the procedure and was prepared to intervene in case of irreversible hemodynamic compromise leading to cardiac arrest. A caesarean section was deemed necessary if cardiac activity was not restored within 4 minutes.; (4) Conclusions: Managing pAMI requires a multidisciplinary approach that balances the maternal and fetal well-being. In this particular case, the Pregnancy Heart Team decided to prioritize interventional treatment with primary PCI due to the unstable maternal condition. The presence of a closely monitored gynecology team ensured prompt action in case of complications.

The integration of spray drying and agglomeration offers significant advantages, such us continuous production with lower energy consumption. However, it is a knife-edge process with a narrow operating window and limited degrees of freedom that decide between successful agglomeration and fluidized bed blockage due to excessive moisture. In this contribution, factors influencing the spray-through agglomeration process of skim milk powder as a model system were investigated via a design of experiments. Three in-line monitoring methods were applied and tested to observe the most important parameters in the agglomeration process: product moisture and particle size distribution. Regarding the moisture content, a capacitive moisture sensor was calibrated with linear regression and a near-infrared sensor with partial least squares regression. Near-infrared spectroscopy was found to be the suitable method for determining moisture content, while the capacitive moisture sensor mainly provides information on the bulk density, the filling level or fluidization state in the fluidized bed. Additionally, particle size distribution data was extracted from the spectral data using in-line data of a spatial filter velocimetry probe in the fluidized bed. This opens the potential to monitor both parameters in real-time with a single non-invasive sensor.

Oral and parenteral delivery of first-line anticonvulsant Valproic cid (VA) are associated with serious adverse effects, high hepatic metabolism, high clearance, and low bioavailability in brain. GastroPlus program was used to predict in vivo performance of immediate (IR) and sustained release (SR) products in human. HSPiP software predicted excipients with maximum possible miscibility of the drug. Based on GastroPlus and HSPiP program, various excipients were screened for experimental solubility study and prepared cationic nanoemulsions and respective gels for nasal to brain delivery. These were characterised for size, size distribution, polydispersity index, zeta potential, morphology, pH, % transmittance, drug content, and viscosity. In vitro drug release, ex vivo permeation profile (goat nasal mucosa), and penetration studies were conducted. Result showed that in-vivo oral drug dissolution and absorption were predicted as 98.6 mg and 18.8 mg, respectively from both tablets (IR and SR) at 8 h using GastroPlus. The drug access to the portal vein was relatively predicted high in IR (115 mg) as compared to SR (82.6 mg). Plasma drug concentration-time profile predicted was in good agreement with published reports. The program predicted duodenum and jejunum as the prime site of drug absorption and no effect of nanonization on Tmax for sustained release formulation. Hansen parameters suggested suitable selection of excipients. The program recommended for nasal to brain delivery of the drug using cationic mucoadhesive product. The optimized stable CVE6 was associated with optimal size (113 nm), low PDI (0.26), high zeta potential (+34.7 mV), high transmittance (97.8%), and high strength (0.7 %w/w). In vitro release and ex vivo permeation of CVE6 were found to be substantially high as compared to anionic AVE6 and respective gels. Penetration study executed high fluorescence intensity with CVE6 and CVE6-gel as compared to suspension and ANE6 which may be attributed to electrostatic interaction between mucosal membrane and nanoglobules. Thus, cationic nanoemulsion and respective mucoadhesive gel are promising strategy for delivery of VA to brain through intransal administration for the treatment of seizure and convulsion.

This study aims at better understanding the damage and fracture kinetics in flax fibres elements at both the unitary and bundle scales using an experimental setup allowing optical observation at high recording rate in the course of tensile loading. Defects issues from flax unitary fibre extraction are quantitated using polarized light microscopy. Tensile loading is conducted according to a particular setup adapted to fibres of 10 to 20 µm in diameter and 10 mm in length. Optical recording using high speed camera is performed during loading up to the failure at acquisition speed ranging from 108,000 to 270,000 frames per second. Crack initiation in polymer layers of fibre elements, propagation as well as damage mechanisms are captured. The results show different failure scenarios depending on the fibre element nature. In particular, fractured fibres underline either a fully transverse failure propagation or a combination of transverse and longitudinal cracking with different balances. Image recordings with high time resolution down to 3.7 μs suggest unstable system and transverse crack speed higher than 4 m/s and a slower propagation for longitudinal crack deviation.

This paper investigates the classical but yet intriguing question of modeling orthotropic RC floor systems endowed with lightening elements, by means of a uniform orthotropic slab, in order to describe accurately the building response under seismic loads. The simplified method, commonly adopted by engineers, based on the equivalence between the transverse stiffness of the RC elements of the real floor and those of the orthotropic slab is presented. A case study in which this simplified method is used is also provided. Then, an advanced finite elements (FE) based method to determine the elastic properties of the equivalent homogenized orthotropic slab is proposed. Based on the results obtained from the application of this method to a case study, a discussion on the adequacy of the simplified method is also provided.

Developing new energy is critical to China's green and low-carbon development. And the New Energy Demonstration City Policy (NEDCP) is a vital innovation policy that inspires the development of new energy. Is the NEDCP facilitating green and low-carbon development, if so, how? Employing unbalanced panel data from 2003 to 2017, the impact of NEDCP on green and low-carbon development was studied by using the "difference in difference" (DID) model. We find that this policy can take significantly role. After various robustness tests, our results are still valid. According to the heterogeneity analysis, non-resource and non-old industrial base cities have a greater positive impact from this policy. The mechanism analysis denotes that the positive policy effect works through upgrading the industrial structure and stimulating urban innovation. The substantial empirical evidence presented in this article supports the continued promotion and implementation of new energy demonstration cities.

Low pasture biomass production and fodder scarcity are among the major challenges affecting productivity of dairy cattle farms in Sri Lanka. As a potential solution to this, two Napier hybrid cultivars CO-5 and Sampoorna were recently introduced and a field experiment was conducted to evaluate their growth, dry matter production and nutritional composition during May to September 2020. Plant measurements and samples were collected at five harvest intervals (4, 6, 8, 10 and 12 weeks after planting), with the plant samples subjected to biomass and nutritional assessments. The number of tillers and leaf length differed (P=0.01) between the two cultivars at 4 weeks harvesting interval (HI) whilst number of leaves differed at 12 HI respectively. Dry matter yield increased (P=0.16) almost linearly whilst crude protein declined exponentially with CO-5 greater than Sampoorna (P=0.057; 9.3% vs 8.7%), with increasing harvesting intervals respectively. In-vitro Organic Matter Digestibility and In-vitro Metabolizable Energy contents were similar across weeks 4, 6 and 8 but then decreased. This study demonstrates that higher dry matter yields (12.54 t/ha) can be obtained by harvesting both cultivars at 12 HI, but from a nutritional perspective harvesting at 6 HI during Yala season of the year would be optimum for farmers.

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.

Purpose: Hearing assistive technology (HAT) has been shown to be a viable solution to the speech-in-noise perception (SPIN) issue in children with autism spectrum disorder (ASD); however, little is known about its efficacy in tonal language speakers. This study compared sentence-level SPIN performance between Chinese children with ASD and neurotypical (NT) children and evaluated HAT use in improving SPIN performance and easing SPIN difficulty. Methods: Children with ASD (n=26) and NT children (n=19) aged 6-12 performed two adaptive tests in steady-state noise and three fixed-level tests in quiet and steady-state noise with and without using HAT. Speech recognition thresholds (SRT) and accuracy rates were assessed using adaptive and fixed-level tests, respectively. Parents or teachers of the ASD group completed a questionnaire regarding children’s listening difficulty under six circumstances before and after a ten-day trial period of HAT use. Results: Although the two groups of children had comparable SRTs, the ASD group showed a significantly lower SPIN accuracy rate than the NT group. Also, a significant impact of noise was found in the ASD group’s accuracy rate, but not in the NT group’s. There was a general improvement in the ASD group’s SPIN performance with HAT and a decrease in their listening difficulty ratings across all conditions after the device trial. Conclusion: The findings indicated inadequate SPIN in the ASD group using a relatively sensitive measure to gauge SPIN performance among children. The markedly increased accuracy rate in noise during HAT-on sessions for the ASD group confirmed the feasibility of HAT for improving SPIN performance in controlled laboratory settings, and the reduced post-use ratings of listening difficulty further confirmed the benefits of HAT use in daily scenarios.

Abstract This essay presents a real-world demonstration of the evidence-based science communication process, showing how it can be used to create scientific data visualizations for public audiences. Visualizing research data can be an important science communication tool. Maximizing its effectiveness has the potential to benefit millions of viewers. As with many forms of science communication, creators of such data visualizations typically rely on their own judgments and the views of the scientists providing the data to inform their science communication decision-making. But that leaves out a critical stakeholder in the communications pipeline: the intended audience. Here, we show the practical steps that our team - the Advanced Visualization Lab at the University of Illinois at Urbana-Champaign - has taken to shift towards more evidence-based practice to enhance our science communication impact. We do this using concrete examples from our work on two scientific documentary films, one on the theme of ‘solar superstorms’ and the other focusing on the black hole at the center of the Milky Way galaxy. We used audience research with each of these films to inform our strategies and designs. We describe how such research evidence informed our understanding of ‘what works and why’ with cinematic-style data visualizations for the public. We close the essay with our key ‘take home’ messages from this evidence-based science communication process.

High-grade gliomas are the most common and aggressive adult primary brain tumors with a median survival of only 12-15 months. Current standard therapy consists of maximal safe surgical resection followed by DNA-damaging agents, such as irradiation and chemotherapy that can delay but not prevent inevitable recurrence. Some have interpreted glioma recurrence as evidence of glioma stem cells which persist in a relatively quiescent state after irradiation and chemotherapy, before the ultimate cell cycle re-entry and glioma recurrence. Conversely, latent cancer cells with a therapy-induced senescent phenotype have been shown to escape senescence, giving rise to more aggressive stem-like tumor cells than those present in the original tumor. Therefore, approaches are needed to either eliminate or keep these glioma-initiating cells in a senescent state for a longer time to prolong survival. In our current study, we demonstrate that the radiation-induced cell cycle inhibitor P21 can provide a powerful route to induce cell death in short-term explants of PDXs derived from three molecularly diverse human gliomas. Additionally, cells not killed by P21 overexpression were maintained in a stable senescent state for longer than control cells. Collectively, these data suggest that P21 activation may provide an attractive therapeutic target to improve therapeutic outcomes.

The present study was aimed at revealing the influence of the mechanical stress induced by water molecules adsorption on the composition of crystalline phases in the ZrO2–3mol%Y2O3-nanoparticles. Three basic methods have been used to determine the phase transition: neutron diffraction, Raman microspectroscopic scanning, and X-ray diffraction. The fact of phase-structural β → α transformation and the simultaneous presence of two polymorphic structural modifications (β is the phase of the tetragonal syngony and α of monoclinic syngony in nanosized particles (9nm)) under normal physical conditions was established by these methods. Satisfactory consistency was achieved between the results obtained using different techniques.

Recent developments in mid-infrared (MIR) spectroscopic ellipsometry enabled by quantum cascade lasers (QCLs) resulted in a drastic improvement in signal-to-noise ratio compared to conventional thermal emitter based instrumentation. Thus, it was possible to reduce the acquisition time for high-resolution broadband ellipsometric spectra from multiple hours to less than 1 second. This opens up new possibilities for real-time in-situ ellipsometry in polymer processing. To highlight these evolving capabilities we demonstrate the benefits of a QCL based MIR ellipsometer by investigating single and multilayered polymer films. The molecular structure and reorientation of a 2.5m thin biaxially oriented polyethylene terephtalate film is monitored during a stretching process lasting 24.5 s to illustrate the perspective of ellipsometric measurements in dynamic processes. In addition, a polyethylene/ethylene vinyl alcohol/polyethylene multilayer film is investigated at continuously varying angle of incidence ( 0∘ – 50∘) in 17.2 s, highlighting an unprecedented sample throughput for the technique of varying angle spectroscopic ellipsometry in the MIR spectral range. The obtained results underline the superior spectral and temporal resolution of QCL ellipsometry and qualify this technique as suitable method for advanced in-situ monitoring in polymer processing.

When you type” Iodine” in google scholar, you will end up with 2,200,000 articles that are titled with anything regarding iodine, except “what is it”. Here in this short note review, a summary of iodine that includes its origin, structure, types, sources, uses, concentration, toxicity, and iodine intake and how to measure it, was collected and infused in a nutshell.

For the better part of a century researchers across disciplines have sought to explain the crystallography of the elemental transition metals: hexagonal close packed, body centered cubic, and face centered cubic in a form similar to that used to rationalize the structure of organic molecules and inorganic complexes. Pauling himself tried with limited success to address the origins of transition metal stability. These early investigators were handicapped, however, by incomplete knowledge regarding the structure of metallic charge density. Here we exploit modern approaches to charge analysis to first comprehensively describe transition metal charge density. Then, we use topological partitioning and quantum mechanically rigorous treatments of kinetic energy to account for the structure of the density as arising from the interactions between metallic tetrahedra. We argue that the crystallography of the early transition metals results from charge transfer from the so called “octahedral” to “tetrahedral holes” while the face centered cubic structure of the late transition metals is a consequence of antibonding interactions that increase octahedral hole kinetic energy.

Testing in animals is mandatory in drug testing and the gold standard for evaluation of toxicity. This situation is expected to change in the future because the 3Rs principle, which stands for replacement, reduction and refinement of the use of animals in science, is reinforced by many countries. On the other hand, technologies for alternatives to animals experiments have increased. The necessity to develop and use of alternatives is influenced by the complexity of the research topic and also by the fact, to which extent the currently used animal models can mimic human physiology and/or exposure. Rodent lung morphology and physiology differs markedly for that of humans and inhalation exposure of the animals are challenging. In vitro and in silico methods can assess important aspects of the in vivo action, namely particle deposition, dissolution, action at and permeation across the respiratory barrier and pharmacokinetics. Out of the numerous homemade in vitro and in silico models some are available commercially or open access. This review discusses limitations of animal models and exposure systems and proposes a panel of in vitro and in silico techniques that, in the future, may replace animal experimentation in inhalation testing.

Cellular redox state is highly dynamic and delicately balanced between constant production of reactive oxygen species (ROS), and neutralization by endogenous antioxidants, such as glutathione. Physiologic ROS levels can function as signal transduction messengers, while high levels of ROS can react with and damage various molecules eliciting cellular toxicity. The redox state is reflective of the cell’s metabolic status and can inform on regulated cell-state transitions or various pathologies including aging and cancer. Therefore, methods that enable reliable, quantitative readout of the cellular redox state are imperative for scientists from multiple fields. Liquid-chromatography mass-spectrometry (LC-MS) based methods to detect small molecules that reflect the redox balance in the cell such as glutathione, NADH and NADPH, have been developed and applied successfully, but because redox metabolites are very labile, these methods are not easily standardized or consolidated. Here we report a robust LC-MS method for the simultaneous detection of several redox-reactive metabolites that is compatible with parallel global metabolic profiling in mammalian cells. We performed a comprehensive comparison between three commercial hydrophilic interaction chromatography (HILIC) columns, and we describe the application of our method in mammalian cells and tissues. The presented method is easily applicable and will enable the study of ROS function and oxidative stress in mammalian cells by researchers from various fields.

This paper contains a concise overview of the deployment of scattered solar power plants in Poland, mainly from the perspective of their communication networks, and how the recent development of the Polish 4G networks has a very positive impact for the performance of the whole monitoring system (production control and video-surveillance), with a special emphasis on video-analytics, due to its higher bandwidth demand. All the information will be shown from the point of view of the solar photovoltaics developer I+D Energías, and therefore it constitutes a real user’s experience.

This work is concerned with the existence and uniqueness of boundary value problems defined on semi-infinite intervals. These kinds of problems seldom admit exactly known solutions and, therefore, the theoretical information on their well-posedness is essential before attempting to derive an approximate solution by analytical or numerical means. Our utmost contribution in this context is the definition of a numerical test for investigating the existence and uniqueness of solutions of boundary problems defined on semi-infinite intervals. The main result is given by a theorem relating the existence and uniqueness question to the number of real zeros of a function implicitly defined within the formulation of the iterative transformation method. As a consequence, we can investigate the existence and uniqueness of solutions by studying the behaviour of that function. Within such a context the numerical test is illustrated by two examples where we find meaningful numerical results.

To better understand the genes with altered expression caused by infection with the novel coronavirus strain SARS-CoV-2 causing COVID-19 infectious disease, a tensor decomposition (TD)-based unsupervised feature extraction (FE) approach was applied to a gene expression profile dataset of the mouse liver and spleen with experimental infection of mouse hepatitis virus, which is regarded as a suitable model of human coronavirus infection. TD-based unsupervised FE selected 134 altered genes, which were enriched in protein-protein interactions with orf1ab, polyprotein, and 3C-like protease that are well known to play critical roles in coronavirus infection, suggesting that these 134 genes can represent the coronavirus infectious process. We then selected compounds targeting the expression of the 134 selected genes based on a public domain database. The identified drug compounds were mainly related to known antiviral drugs, several of which were also included in those previously screened with an in silico method to identify candidate drugs for treating COVID-19.

This work studies a novel low voltage (<60 V) hybrid system that supports engine boosting and downsizing in addition to start-stop, regenerative braking, and constrained torque assist/regeneration. The hybrid power split supercharger (PSS) shares a 9 kW motor between supercharging the engine or providing hybrid functionalities through a planetary gear set, a brake and a bypass valve. The PSS operation is limited to only one of the parallel hybrid or boosting modes at a time, necessitating a highly optimized decision making algorithm to select the device mode and power split ratio. In this work an adaptive equivalent consumption minimization strategy (A-ECMS) is developed for energy management of the PSS. The A-ECMS effectiveness is compared against a dynamic programming (DP) solution with full drive cycle preview through hardware-in-the-loop experiments on an engine dynamometer testbed. The experiments show that the PSS with A-ECMS reduces a vehicle fuel consumption by 18.4% over standard FTP75 cycle compared to a baseline turbocharged engine, while global optimal DP solution decreases the fuel consumption by 22.8% compared to baseline.

Downregulated microRNA-142-3p signaling contributes to the pathogenesis of endometriosis [1] [2], an invasive disease where the lining of the uterus grows at ectopic locations, by yet incompletely understood mechanisms. Using bioinformatics and in vitro assays, this study identifies cytoskeletal regulation and integrin signaling as two relevant categories of miR-142-3p targets. qPCR revealed that miR-142-3p upregulation in St-T1b cells downregulates ROCK2, CFL2, RAC1, WASL and ITGAV. qPCR and Western-blotting showed miR-142-3p effect on WASL and ITGAV was significant also in primary endometriotic stroma cells. Luciferase reporter assays in ST-T1b cells then confirmed direct regulation of ITGAV and WASL. On the functional side, miR-142-3p upregulation significantly reduced ST-T1b cell size, the size of vinculin plaques, migration through fibronectin-coated transwell filters and the ability of ST-T1b and primary endometriotic stroma cells to contract collagen I gels. These results suggest that miR-142-3p has a strong mechanoregulatory effect on endometrial stroma cells and its external administration reduces the invasive endometrial phenotype. Within the limits of an in vitro investigation, our study provides new mechanistic insights into the pathogenesis of endometriosis and provides a perspective for the development of miR-142-3p based drugs for inhibiting invasive growth of endometriotic cells.

We study the center of energy (CE) before and after the separation of superposed wave from a moving medium (MM). It is assumed that two out-of-phase mechanical transverse waves propagating from the opposite directions on a medium moving at non-relativistic speeds are superposed and the superposed portion (SP) is separated from the MM at that moment. We consider the CE of the SP before and after the separation from the MM. The location of CE (LCE) of the SP seems to be at the center of it at the moment of superposition. The SP rotates due to the separation from the MM since the velocity of each portion symmetric with respect to the center of the SP is equal in magnitude and opposite in direction. The magnitudes of velocities of the symmetric portions become different as soon as the SP begins to rotate with the separation from the MM. Then the energies of their symmetric portions are not the same, so the LCE of the SP is not at the center of it. As a result, the LCE of it looks different before and after the separation from the MM. We must find a solution to keep the LCE of the SP constant. We propose that two out-of-phase mechanical transverse waves (MTWs) propagating from the opposite directions on a MM originally have hidden difference in relativistic energy and it suddenly appears within the range observable in Newtonian mechanics when the SP starts rotating. This means that the point of view of hidden difference in relativistic energy is necessary to keep the LCE constant.