Cardiac development is a complex developmental process that results in the formation of the four-chambered organ from a single linear heart tube. In the early stages of development, the linear heart tube is composed of only two tissue layers, an external myocardium that is internally lined by the endocardium. Subsequently, the proepicardium emerges at the septum transversum and soon thereafter proepicardial cells will migrate into the naked myocardium, leading to the formation of the embryonic epicardium. As cardiac development proceeds, epicardial-derived cells migrate into the subepicardial space and subsequently invade the developing ventricular chambers leading to the contribution of distinct cardiovascular cell types such as the cardiac fibroskeleton and different components of coronary vasculature. At present, the molecular mechanisms that regulate the transitional process from the proepicardium to the embryonic myocardium are largely unexplored. In this study we have implemented an ex vivo proepicardium/septum transversum (PE/ST)-embryonic myocardium explant model and we demonstrated that miR-223, but not miR-195, is capable of modulating PE/ST migration, a process that seems to be mediated by Slug expression. Thus, our study demonstrates for the first time the implication of distinct microRNAs in the PE/ST to embryonic myocardium transition in chicken embryonic hearts.

The use of hydrogen fuel cells as a mobile source of electricity might prove to be a keystone in future decarbonization of heavy duty road and marine transport. Due to complex interplay of various physicochemical processes in the fuel cells, further development of these devices will rely on concerted effort of researchers from various fields, e.g. chemistry, physics, electric and mechanical engineering. This results in knowledge gaps which are filled by the information, dispersed in wide range of literature, but rarely covered in a short and condensed form. To address this issue and with the aim of providing a concise and simple explanation of fuel cell operation, we propose a simple educational model of the most relevant processes in the fuel cell, aimed at proper description of causal relations. The derivation of model equations provides an intuitive understanding of electric potentials acting on protons on the microscopic level and relates this knowledge to the common terminology in fuel cell research community, such as catalyst electric overpotential and internal membrane resistance. The results of the model fit well with experimental data, indicating that a simple description, provided in the paper, is sufficient for intuitive understanding of fuel cell operation.

Microstructured surfaces are renowned for their unique properties, such as waterproofing and low adhesion, making them highly applicable in the biomedical field. These surfaces play a crucial role in influencing cell response by mimicking the native microenvironment of biological tissues. In this study, we engineered a series of biomimetic micropatterned surfaces using polydimethylsiloxane (PDMS) to explore their effects on primary breast cancer cell lines, contrasting these effects with those observed on conventional flat surfaces. The surface topography was varied to direct cells’ attachment, growth, and morphology. Our findings elucidate that surface-free energy is not merely a background factor but plays a decisive role in cell dynamics, strongly correlating with the spreading behaviour of breast cancer cells. Notably, on micropillar surfaces with high surface-free energy, an increase in the population of cancer cells was observed. Conversely, surfaces characterised by lower surface-free energies noted a reduction in cell viability. Moreover, the structural parameters, such as the gaps and diameters of the pillars, were found to critically influence cellular dispersion and adherence, underscoring the importance of the microstructures’ topography in biomedical applications. These insights pave the way for designing advanced microstructured surfaces tailored to specific cellular responses, opening new avenues for targeted cancer therapies and tissue engineering.

Heart failure (HF) is a life-threatening disorder and is treated by drug therapies and surgical interventions such as heart transplantation and left ventricular assist device (LVAD). However, these treatments can lack effectiveness in the long term and are associated with issues such as donor shortage in heart transplantation, and infection, stroke, or gastrointestinal bleeding in LVADs. Therefore, alternative therapeutic strategies are still needed. In this respect, stem cell therapy has been introduced for the treatment of HF and numerous preclinical and clinical studies using various types of stem cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have been shown to improve cardiac function and attenuate left ventricular remodeling. IPSCs, which have a capacity of unlimited proliferation and differentiation to cardiomyocytes, are a promising cell source for myocardial regeneration therapy. This review discusses the current status of cardiac regenerative therapy using iPSCs.

Abstract: The venom-containing barb attached to their ‘whip-like’ tail provides stingrays a defensive mechanism for evading predators such as sharks. From human encounters, dermal stingray envenomation is characterized by intense pain often followed by tissue necrosis occurring over several days to several weeks. The bioactive components in stingray venoms (SRV’s) and their molecular targets and mechanisms that mediate these complex responses are not well understood. Given the utility of venom-derived proteins from other venomous species for biomedical and pharmaceutical applications, we set out to characterize the bioactivity of SRV from three local species that belong to the Dasyatoidea ‘whiptail’ superfamily. Multiple cell-based assays were used to quantify and compare the in vitro effects of these SRV’s on different cell lines. All three SRV’s demonstrated concentration-dependent growth inhibitory effects on three different human cell lines tested. In contrast, a mouse fibrosarcoma cell line was markedly resistant to all three SRV’s, indicating the molecular target(s) for mediating the SRV effects are not expressed on these cells. The multifunctional SRV responses were characterized by an acute disruption of cell adhesion leading to apoptosis. These findings aim to guide future investigations of identified SRV proteins and their molecular targets for potential use in biomedical applications.

Viral infection can regulate the cell cycle, thereby promoting viral replication. Hijacking and altering the cell cycle are important for the virus to establish and maintain latent infection. Previously, Spodoptera exigua multiple nucleopolyhedrovirus (SeMNPV) latently infected P8-Se301-C1 cells, which grew more slowly than Se301 cells and interfered with homologous SeMNNPV superinfection, were established. However, the effects of latent and superinfection with baculoviruses on cell cycle progression remain unknown. In this study, the cell cycle profiles of P8-Se301-C1 cells, and SeMNPV or Autographa californica mutiple nucleopolyhedrovirus (AcMNPV) infected P8-Se301-C1 cells were characterized by flow cytometry. The results showed that replication-related genes MCM4, PCNA, and BAF were down-regulated (p < 0.05) in P8-Se301-C1 cells and the S phase of P8-Se301-C1 cells was longer than that of Se301 cells. P8-Se301-C1 cells infected with SeMNPV did not arrest in G2/M phase and or affect the expression of Cyclin B and cyclin-dependent kinase 1 (CDK1). Furthermore, when P8-Se301-C1 cells were infected with SeMNPV after synchronized treatment with hydroxyurea and nocodazole, light microscopy and qRT-PCR analysis showed that compared with unsynchronized cells and S and G2/M phase cells, SeMNPV-infected P8-Se301-C1 cells in G1 phase induced G2/M phase arrest, and the amount of virus adsorption and intracellular viral DNA replication were significantly increased (p < 0.05). In addition, the BV production and the OB containing cells were both increased at 120 h post-infection (p < 0.05). The expression of Cyclin B and CDK1 was significantly down-regulated at 48 h post infection (p < 0.05). Finally, arrest of SeMNPV-infected G1 phase cells in the G2/M phase increased BV production (p < 0.05) and the number of OB containing cells. In conclusion, G1 phase infection and G2/M arrest are favorable to SeMNPV proliferation in P8-Se301-C1 cells, thereby alleviating the homologous superinfection exclusion. The results contribute to a better understanding of the relationship between baculoviruses and insect cell cycle progression regulation.

(1) Background: P-cadherin (CDH3) is a transmembrane protein that plays a crucial role in maintaining the structural integrity of epithelial tissue and homeostasis. Its role in carcinogenesis remains a subject of debate, as its behavior can vary depending on the molecular context and the specific tumor cell model under study. In this study, we explored the role of P-cadherin in head and neck squamous cell carcinoma (HNSCC) and the mechanism underlying its function. (2) Methods: We analyzed P-cadherin expression in HNSCC patients using The Cancer Genome Atlas (TCGA) database. For in vitro functional analysis, we conducted proliferation, migration, invasion, and western blot assays after either suppressing or overexpressing P-cadherin. For in vivo functional analysis, we utilized mouse xenograft models. (3) Results: P-cadherin was significantly overex-pressed in tumor samples compared to normal samples in the TCGA-HNSCC cohort. P-cadherin knockdown resulted in decreased proliferation, migration, and invasion compared to control cells, while P-cadherin overexpression increased cell proliferation and migration in HNSCC cells. We discovered that c-Met functioned as an upstream regulator of P-cadherin. Surprisingly, we found that P-cadherin knockdown increased the phosphorylation of c-Met and STAT3. Combining P-cadherin siRNA with the c-Met inhibitor SU11274 resulted in a more effective reduction in HNSCC cell growth, both in vitro and in vivo, compared to either treatment alone. (4) Conclusions: Our study uncovered a previously unknown aspect of P-cadherin-mediated c-Met regulation. The enhanced activation of c-Met/STAT3 following P-cadherin inhibition could be responsible for the survival of resistant tumor cells. Therefore, dual inhibition of P-cadherin and c-Met may be a potentially effective approach for treating HNSCC.

The precise differentiation of renal cell tumours (RCTs) is sometimes hard to achieve using standard imaging and histopathological methods. This study investigated 43 cell renal cell car-cinomas (ccRCC), 15 papillary renal cell carcinomas (pRCC), 20 chromophobe renal cell carcino-mas (chRCC), and 18 renal oncocytomas (RO), stained with anti-mitochondria antibody (Thermo Scientific) by immunohistochemistry and immunofluorescence, and assessed by electron micros-copy, in order to define mitochondria distribution pattern (coarse scanty, moderate granular and diffuse granular). Thus, the majority of males had coarse granular staining in the tumours, while females were almost equally distributed among groups (p=0.005). An average patient age, tumour side and dimension, and tumour stage were similar in all staining pattern groups. However, pathohistological tumour types had significantly different expression patterns, with the lower amount of staining detected in majority of ccRCC, moderate expression in all chRCC, and diffuse expression in all RO, pRCC and two cases of ccRCC (p<0.001) presented with higher nuclear grade (p=0.005). Moreover, with increased distribution of mitochondria, the intensity of staining was higher (p<0.001). Here we present a strategy that utilizes mitochondria detection to differentiate RO from chRCC, as well as to distinguish other frequent RCTs, such as ccRCC and pRCC.

The neural-crest derived enteric nervous system (ENS) is the intrinsic nervous system of the gastrointestinal (GI) tract and controls all gut functions, including motility. Lack of ENS neurons causes various ENS disorders such as Hirschsprung Disease. One treatment option for ENS dis-orders includes the activation of resident stem cells to regenerate ENS neurons. Regeneration in the ENS has mainly been studied in mammalian species using surgical or chemically-induced injury methods. These mammalian studies showed a variety of regenerative responses with generally limited regeneration of ENS neurons, but (partial) regrowth and functional recovery of nerve fibers. Several aspects might contribute to the variety in regenerative responses, including observation time after injury, species, and gut region targeted. Zebrafish have recently emerged as a promising model system to study ENS regeneration as larvae possess the ability to generate new neurons after ablation. As the next steps in ENS regeneration research, we need a detailed under-standing of how regeneration is regulated on a cellular and molecular level both in animal models with high and low regenerative capacity. Understanding the regulatory programs necessary for robust ENS regeneration will pave the way for using neural regeneration as a therapeutic approach to treating ENS disorders.

The modern paradigm of studying the processes of carcinogenesis and vital activity of tumor tissues implies increased attention to constituents of tumor microenvironment (TME) and their interactions. These interactions between the cells in TME can be mediated via protein junctions of different types. Connexins (Cnxs) are one of the major contributors to intercellular communication. They form gap junctions responsible for the transfer of ions, metabolites, peptides, miRNA, etc. between neighboring tumor cells as well as between tumor and stromal cells. Cnx hemichannels mediate purinergic signaling and bidirectional molecular transport with the extracellular environment. Additionally, Cnxs were reported to localize in tumor-derived exosomes and facilitate the release of their cargo. A large body of evidence implies that the role of connexins in cancer is multifaceted. Pro- or anti-tumorigenic properties of connexins are determined by their abundance, localization and functionality as well as channel assembly and non-channel functions. In this review we have summarized the data on the Cnxs contribution in TME and to the cancer initiation and progression.

Oral cancer cells (TYS) and the signalling pathways involved in metastasis, in response to cancer-associated fibroblasts (CAFs, COM) and normal oral mucosal fibroblasts (MM1) was studied. Metastatic cell behaviour was observed by cell-scatter, 3D-collagen gel migration and 3D-spheroid invasion assays. Akt, MAPK, EGFR, TGFβRii and CXCR4 inhibitors were used to identify the signalling pathways involved. Signalling pathway protein expression and activation were assessed by SDS-PAGE and Western Blotting. COM-CM (conditioned medium) and MM1-CM stimulated cancer cell scattering, which was blocked only by the Akt inhibitor. COM-CM induced scattered cancer cells showed higher levels of Akt phosphorylation than the negative control and MM1-CM. Migration and invasion of TYS cells into the collagen gels from the spheroids was stimulated by CM from both sources, compared to the negative control. COM cells stimulated TYS, cancer cell invasion into the collagen more than MM1 and the control. Akt and EGFR inhibitors effectively blocked CM and COM cell-induced invasion. Akt-silenced cancer cells were not stimulated to migrate and invade by fibroblast-CM and did not survive addition of the EGFR inhibitor. This suggests that CAFs stimulate oral cancer cell migration and invasion in an Akt- dependent manner. EGFR and Akt are potential therapy targets in metastatic oral cancer.

Human Cytomegalovirus (HCMV) infection is a serious complication in hematopoietic stem cell transplant (HSCT) recipients due to virus-induced myelosuppression and impairment of stem cell engraftment. Despite the clear clinical link between myelosuppression and HCMV infection, little is known about the mechanism(s) by which the virus inhibits normal hematopoiesis because of the strict species specificity and the lack of surrogate animal models. In this study, we developed a novel humanized mouse model system that recapitulates the HCMV-mediated engraftment failure after hematopoietic cell transplantation. We observed significant alterations in the hematopoietic populations in peripheral lymphoid tissues following engraftment of a subset of HCMV+ CD34+ HPCs within the transplant suggesting that a small proportion of HCMV-infected CD34+ HPCs can profoundly affect HPC differentiation in the bone marrow microenvironment. This model will be instrumental to gain insight into the fundamental mechanisms of HCMV myelosuppression after HSCT and provides a platform to assess novel treatment strategies.

The stromal vascular cell fraction (SVF) of visceral and subcutaneous adipose tissue (VAT and SAT) has increasingly come into focus in stem cell research, since these compartments represent a rich source of multipotent adipose-derived stem cells (ASCs). ASCs exhibit a self- renewal potential and differentiation capacity. Our aim was to study the different expression of embryonic stem cell markers NANOG, SOX2 and OCT3/4 and to evaluate if there exists a hierarchal role in this network in ASCs derived from both SAT and VAT. ASCs were isolated from SAT and VAT biopsies of 72 consenting patients (23 men, 47 women; age 45 ± 10; BMI between 25 and 30 range) undergoing elective open-abdominal surgery. Sphere-forming capability was evaluated by plating cells in low adhesion plastic. Stem cell markers CD90 and CD105 were analyzed by flow cytometry and stem cell transcription factors NANOG, SOX2 and OCT3/4 were detected by immunoblotting and Real-Time PCR. NANOG, SOX2 and OCT3/4 interplay was explored by gene silencing. ASCs from VAT and SAT confirmed their mesenchymal stem cell (MSC) phenotype expressing the specific MSC markers CD90, CD105, NANOG, SOX2 and OCT3/4. NANOG silencing induced a significant OCT 3/4 (70% ± 0.05) and SOX2 (75% ± 0.03) down-regulation whereas SOX2 silencing did not affect NANOG gene expression. Adipose tissue is an important source of MSC, and siRNA experiments endorse a hierarchical role of NANOG in the complex transcription network that regulates pluripotency and plasticity.

Small-cell lung cancer (SCLC) is a cancer with poor prognosis. For relapsed extensive-stage (ES) SCLC, second-line treatment options are scarce. Topotecan was the only approved treatment in this setting until 2020. Since topotecan induces significant toxicities, alternative off-label regimens are being used. This study evaluated real-world efficacy and safety of Paclitaxel Gemcitabine chemotherapy in patients with relapsed ES-SCLC. We retrospectively reviewed data from all consecutive patients with relapsed ES-SCLC who received Paclitaxel Gemcitabine chemotherapy from september 2008 to january 2022 in two centers. Patient characteristics (n=188) were: PS≥2: 24.5%; brain metastasis: 42%; platinum-sensitive disease: 41%. Patients received Paclitaxel Gemcitabine as second- (77%) third (18%) or fourth (6%) line of therapy. Median progression-free and overall survival were 2.1 (95CI 1.8–2.4) and 3.8 (95CI 3.3–4.8) months in the overall population, respectively, with 17% response rate (RR) and 28% disease-control rate. PS, history of brain radiation, platinum-sensitive disease, liver, and adrenal gland metastasis were associated with longer survival in univariate analysis. PS was the only prognostic factor in multivariate analysis, with 21% RR and 4.1 months median DOR in PS 0-1 patients. Paclitaxel Gemcitabine chemotherapy may represent a treatment option in PS0-1 relapsed SCLC.

Though early-stage colorectal cancer has a high 5-year survival rate of 65-92% depending on the specific stage, this probability drops to 13% after the cancer metastasizes. Frontline treatments for colorectal cancer such as chemotherapy and radiation often produce dose-limiting toxicities in patients and acquired resistance in cancer cells. Additional targeted treatments are needed to improve patient outcomes and quality of life. Immunotherapy involves treatment with peptides, cells, antibodies, viruses, or small molecules to engage or train the immune system to kill cancer cells. Preclinical and clinical investigations of immunotherapy for treatment of colorectal cancer including immune checkpoint blockade, adoptive cell therapy, monoclonal antibodies, oncolytic viruses, anti-cancer vaccines, and immune system modulators have been promising, but demonstrate limitations for patients with proficient mismatch repair enzymes. In this review, we discuss preclinical and clinical studies investigating immunotherapy for treatment of colorectal cancer and predictive biomarkers for response to these treatments. We also consider open questions including optimal combination treatments to maximize efficacy, minimize toxicity, and prevent acquired resistance and approaches to sensitize mismatch repair proficient patients to immunotherapy.

Background: Developing an efficient and standardized method to isolate and characterize adipose-derived stem cells (ASCs) from the stromal vascular fraction (SVF) of the adipose tissue for clinical application represents one of the major challenges in cell therapy and tissue engineering. Methods: In this study, we proposed an innovative, non-enzymatic protocol to collect clinically useful ASCs within freshly isolated SVF from adipose tissue by centrifugation of the infranatant portion of lipoaspirate and to determine the characteristic cytofluorimetric pattern, prior to in vitro culture. Results: The SVF yielded a mean of 73,32 \pm\ 10,89% cell viability evaluated with CALCEINA-FITC, i.e. cell-permeant dye. The ASCs were positive for PC7-labeled mAb anti-CD34 and negative for both PE-labeled mAb anti-CD31 and APC-labeled mAb anti-CD45. The frequency of ASCs estimated according to the panel of cell surface markers used was 51,06%\ \pm 5,26% versus the unstained ASCs subpopulation that was 0,74%\pm0,84% (P<0.0001). The ASCs events/\muL were 1602,13/\muL \pm 731,87/\muL. Conclusion: Our findings suggested that ASCs found in freshly isolated adipose SVF obtained by centrifugation of lipoaspirate can be immunophenotypically identified with a basic panel of cell surface markers. These findings aimed to provide standardization and contribute to reducing the inconsistency on reported cell surface antigens of ASC derived from the existing literature.

Hard tissue apposition along the root canal walls is a slow, normally occurring physiological aging process. In response to tooth wear, local deposition of hard tissue may also occur in the pulp at a slow pace. Sometimes, the rate of hard tissue deposition acceleration may seem to be uncontrolled after dental trauma, autotransplantation, and orthodontic therapy, leading to rapid partial or total obliteration of the root canal space. This situation is called calcific metamorphosis (CM) or pulp canal obliteration (PCO). Although the incidence of pulpal necrosis in these teeth is believed to be infrequent, conventional endodontic therapy in severely calcified canals poses extreme difficulties and a higher risk for procedural accidents. This article aims to review the available approaches for the predictable negotiation of calcified canals and to introduce the buckling resistance activation test (BRAT) technique.

Study design: Technical note. Objectives: To present a novel technique of treatment for patient with basilar invagination. Background : Basilar invagination (BI) is considered a congenital condition and can compress the cervicomedullary junction, causing neurologic deficit. Severe neurological deficit due to BI should be treated surgically. However, there is controversy regarding whether an anterior or posterior approach should be used. Anterior approach is optimal for decompression of cervicomedullary junction, but this approach has high complication rates. Posterior reduction has a high risk of occipital screws backout and/or instrument failure. Materials and Methods : A 15-year-old boy with severe myelopathy was referred to our hospital. He had neck pain, muscle weakness of bilateral upper limbs, gait disturbance appeared 3 months before he visited our hospital, he drops a cup several times recently. In the examination, he had hyperreflexia of upper and lower limbs and muscle weakness of bilateral arms (MMT 4), hypoesthesis was observed bilaterally below elbow and both legs. He also had clumsiness of bilateral hands, mild urinary and bowel incontinence, and spastic gait. His 10 second grip and release test was 16 in both hands. His grip power was 20 kg in right and 17 kg in left. Radiograms showed severe BI and spinal cord was severely compressed with odontoid process.. Results : The patinet underwent posterior surgery with C-arm free technique. All screws including occipital screws were inserted adequate position under navigation guidance. Reduction was achieved with skull rotation and distraction. A follow-up at one year we have these results : Manual muscle testing results and sensory function tests showed almost full recovery, bilateral arms (MMT 5) ,walking smoothly. Cervical Japanese orthopedic association score of the patient has improved from 9/17 to 16/17. Post-operative images showed an excellent spinal cord decompression, and no major or severe complications has occured . Conclusions/Level of Evidence : Basilar invagination with Klippel-Feil syndrome is relatively rare condition. Posterior approach and occipito-cervical fixation for BI treatment with navigation technique is a safe method to treat severe myelopaty with reducible odontoid. This novel navigation technique provides an excellent results for a patient with BI. Level V.

Cavitation bubbles are commonly existing in shipbuilding engineering, ocean engineering, mechanical engineering, chemical industry, and aerospace. Asymmetric deformation of bubble occurs near the boundary, and the non-spherical cavitation bubbles have strong destructive effects, inducing high amplitude loading at the nearby boundary. The purpose of this paper is to investigate the laser-induced of cavitation bubble, non-spherical collapse behavior near the boundary. In this study, experimental data such as bubble pulsation process and bubble surface velocity distribution were obtained by high-speed camera technique and full-field velocity calculation. The results show that the bubble appeared non-spherical collapse shapes, near different boundaries, with near-hemispherical, near-ellipsoidal, near-cone and near-pea shapes, and the bubble surface velocity distribution is not uniform. When bubble near the free surface or rigid boundary, the smaller the stand-off r is, the more obvious the repulsive effect of the free surface and the attractive effect of the rigid boundary are. As the stand-off r decreases, the larger the Bjerknes force and the bubble surface velocity difference, the more pronounced the non-spherical shape.

Band structure calculations using the spin-polarized relativistic Korringa-Kohn-Rostoker (SPRKKR) band structure method have been performed to determine the intrinsic magnetic properties (magnetic moments, magneto-crystalline anisotropy -MAE and Curie temperatures) of the Fe5-x-yCoxMySiB2 (M = Re, W) alloys. The general gradient approximation for ex-change-correlation potential and the atomic sphere approximation (GGA ASA) have been em-ployed. Previous studies showed that the Co doping is turning the in-plane into axial anisotropy for a certain doping range, whilst the 5d doping enables a strong spin-orbit coupling of Fe-3d and M-5d states which is needed to enhance the MAE. The theoretical calculations aim to find the dependence of the anisotropy constant K1 for combined Co and M doping, building a two-dimensional (2D) map of K1 for 0 ≤ x ≤ 2 and 0 ≤ y ≤ 1. Similar theoretical 2D maps for magnetization and Curie temperature vs. Co and M content (M = W and Re) have been built, allowing to select alloy compositions with enhanced values of uniaxial anisotropy, magnetization and Curie temperature. Magnetic properties of Fe4.1W0.9SiB2 alloy that meets the selection criteria for axial anisotropy K1 > 0.2 meV/f.u., Curie temperature Tc > 800 K determined by mean field approach and magnetization µ0Ms > 1 T are discussed.

This research investigates the utilization of human driving models in autonomous vehicles, particularly in scenarios with minimal or no interactions with other vehicles. Human driving models provide valuable insights into driver behavior and play a crucial role in shaping the behavior of autonomous vehicles, enhancing their performance and user experience. The primary focus of the study is the creation of a planning model for autonomous vehicles when navigating roundabouts in the absence of traffic. This model seeks to emulate human driving behavior, ensuring predictability, safety, optimization of traffic flow, and adaptation to various roundabout geometries. To achieve this, the research introduces a trajectory model that takes into account geometric attributes and speed variations within roundabouts. The model is calibrated using empirical data and generalizes parameters through statistical regression methodologies. This model is referred to as "MRoundabout" and is evaluated for its consistency in generating plans that closely mimic human driving behavior within roundabouts. While the study presents a promising approach, it acknowledges limitations related to the model's reliance on geometric attributes and its inability to account for external factors like weather conditions. This research underscores the importance of bridging the gap between theoretical research and practical application, with the aim of enhancing safety and the overall user experience in real-world driving scenarios.

This article presents the possibilities of using ferrite absorption material for shielding rooms with medical devices in order to additionally protect them against the limits of the electric component of the E field, which are up to 61 V/m. These values may appear in connection with the currently launched 5G system operating in the high-band frequency range, i.e. 28 GHz and 38 GHz, and may cause negative effects on the operation of medical devices. The possibilities of using ferrite absorption material for shielding rooms with medical devices were determined based on the results of measurements of the electrical properties of the ferrite material performed using two methods: the reflection method and the free space method. In the article, the complex electrical permittivity and complex magnetic permeability were determined for a ferrite plate based on measurements of the reflection coefficient and the transmission (attenuation) coefficient. The presented calculation and measurement results were used to show the properties of the ferrite material in the frequency range from 15 GHz to 45 GHz and to show the possibility of using it for shielding rooms as a material absorbing electromagnetic waves in this frequency range.

Rollover prevention of partially-filled tank trucks is an industry teaser, with the core challenge being real-time perception and observation of the liquid state inside the tank. In order realize re-liable observation of sloshing liquid, this article firstly proposes a sloshing modeling method based on multi-degree-of-freedom pendulum model, and derives the double mass trammel pendulum model (DMTP, 2DOF) accordingly, which accurately reflects the sloshing dynamics under more pervasive working conditions. Secondly, a free surface fluctuation sensor is designed based on magnetostriction, capable of measuring the inclination and height of the liquid level inside tanks filled with hazardous chemical. Finally, the unscented Kalman filter (UKF) is utilized to synthesize the information of the two, establishing a credible real-time observation of the sloshing liquid. Verified through vehicle-fluid coupled co-simulation, under condition of con-secutive double lane change, observation error of the proposed method is only 25.9% that of the open-loop calculation, providing a secure guarantee for the observation of the state variables of the single pendulum model (SP) used for most kinds of anti-rollover controller.

In recent years, there has been a notable rise in the incidence of breast cancer among young patients, who exhibit worse survival outcomes and distinct characteristics compared to the intermediate and elder patients. Therefore, it’s imperative to identify identify the specific features unique to young patients, which could offer insights into potential therapeutic strategies and improving survival outcomes. In our study, we performed an integrative analysis of bulk transcriptional and genomic data from extensive clinical cohorts to identify prognostic factors. Additionally, we analyzed the single-cell transcriptional data and conducted in vitro experiments. Our work confirmed that young patients exhibited higher grading, worse disease-free survival (DFS), a higher frequency of mutations in TP53 and BRCA1, a lower frequency of mutations in PIK3CA, and upregulation of eight metabolic pathways. Notably, galactose metabolism pathway showed upregulation in young patients and was associated with worse DFS. Further analysis and experiments indicated that galactose metabolism pathway may regulate the stemness of cancer cells and ultimately contribute to worse survival outcomes. In summary, our finding identified distinct clinicopathological, transcriptional, and genomics features and revealed a correlation between galactose metabolism pathway, stemness, and poor disease-free survival of breast cancer in young patients.

Roller milling of sorghum and quinoa seeds into flour fractions (course, middle, and fine) was investigated, chemically analysed and applied in the baking of gluten-free sourdough bread. Gap settings were adjusted to 0, 5, 8 and 10 for quinoa and 3, 5, and 7 for sorghum. The fine fractions reached values of up to about 41% (gap 8) for quinoa and around 20% for sorghum (gap 5). SEM pictographs illustrated clear separation of each fraction with chemical analysis showing high contents of protein, TDF (total dietary fibre) and IDF (insoluble dietary fibre) in the course fraction. Up to 77% starch content was obtained in the fine fraction with significant amounts of SDF (soluble dietary fibre) which has good health benefits. Increasing the dough moisture up to 90% helped in decreasing the bread crumb firmness, while low Avrami parameters and RVA pasting behaviour indicated slow bread staling rate for both sourdough breads.

Various vestibuloplasty techniques have been reported to increase the attached mucosa (AM) and vestibular depth around dental implants. However, these surgical methods have disadvantages, such as limitations in manipulation, necessity of suturing, postoperative discomfort, swelling, and pain. This study aimed to evaluate the efficacy of laser-assisted periosteal fenestration (LA-PF) in treating a patient with a shallow vestibule and insufficient AM around dental implants. The LA-PF technique was performed using an Er:YAG laser. First, a partial-thickness apically positioned flap (APF) was performed. Horizontal periosteal fenestration was performed using an Er:YAG laser to expose the bones. Periosteal suturing was not required. After 12 months, sufficient AM and deepened vestibule were obtained and maintained. Thus, the LA-PF technique may be a simple and predictable treatment modality for vestibuloplasty around dental implants.

Coffee is not only a delicious beverage but also an important dietary source of natural antioxidants. We live in an oxidative world where it is impossible to avoid pollution, stress, food additives, radiation, and other sources of oxidants that eventually lead to severe health disorders. Fortunately, there are chemicals in our diet that counteract the hazards posed by the reactive species that trigger oxidative stress. They are usually referred to as antioxidants; some of them can be versatile compounds that exert such a role in various ways. This review summarizes, from a chemical point of view, the antioxidant effects of relevant molecules found in coffee. Their ways of action and trends in activity are analyzed, considering the data gathered so far from both theory and experiments. The influence of the media and pH in aqueous solution, and structure-activity relationships are discussed. The protective role of the explored compounds is examined. A particular section is devoted to derivatives of some coffee components, and another one to their bioactivity. The data used in the analysis come from theoretical anc computational protocols, which have been proven to be very usefull in this context. Hopefully, the information provided here will promote further investigations into the amazing chemistry contained in our morning cup.

Coffee is not only a delicious beverage but also an important dietary source of natural antioxidants. We live in an oxidative world where it is impossible to avoid pollution, stress, food additives, radiation, and other sources of oxidants that eventually lead to severe health disorders. Fortunately, there are chemicals in our diet that counteract the hazards posed by the reactive species that trigger oxidative stress. They are usually referred to as antioxidants; some of them can be versatile compounds that exert such a role in various ways. This review summarizes, from a chemical point of view, the antioxidant effects of relevant molecules found in coffee. Their ways of action and trends in activity are analyzed, considering the data gathered so far from both theory and experiments. The influence of the media and pH in aqueous solution, and structure-activity relationships are discussed. The protective role of the explored compounds is examined. A particular section is devoted to derivatives of some coffee components, and another one to their bioactivity. Hopefully, the information provided here will promote further investigations into the amazing chemistry contained in our morning cup.

This work aimed to develop an easy-to-use smartphone-based electrochemical biosensor to quickly assess coffee blend's total polyphenol (Phs) content at industrial and individual level. The device is based on a commercial carbon-based screen-printed electrode (SPE) modified with multi-walled carbon nanotubes (CNTs) and gold nanoparticles (GNPs). At the same time, the biotransducer, Laccase from Trametes versicolor, TvLac, was immobilized on the sensor surface by using glutaraldehyde (GA) as cross-linking agent. The platform was electrochemically characterized to ascertain the influence of the SPE surface modification on its performance. The working electrode (WE) surface morphology characterization was obtained by scanning electron microscopy (SEM) and Fourier-transform infrared (FT-IR) imaging. All the measurements were carried out with a micro-potentiostat Sensit Smart by PalmSens connected to a smartphone. The developed biosensor provided a sensitivity of 0.12 μA/μM, a linear response ranging from 5 to 70 μM, and a lower detection limit (LOD) of 2.99 μM. Afterwards, the biosensor was tested for quantifying the total Phs content in coffee blends, evaluating the influence of both the variety and the roasting degree. The smartphone-based electrochemical biosensor performance has been validated though the Folin-Ciocâlteu standard method.

The free energy principle (FEP) is a mathematical and scientific principle that describes the relationship between the physical behavior of a dynamical system and the interpretation of such behavior as carrying out inference. It blurs the boundary between the ontological mode of the system of interest and the epistemological significance it acquires through its dynamic interaction with the environment. New materialism (or neo-materialism), despite lacking a single definition, refers to a range of emerging perspectives that attempt to dismantle the long-held divisions between ontology, epistemology, and even ethics, with the aim of achieving a comprehensive transformation of naturalized thinking. In this context, new materialism provides powerful tools to reframe some of the conceptual foundations of the FEP. This paper is the first in a series that aims to systematically construct a neo-materialistic perspective for the FEP, exploring its wide-ranging implications. It serves as an introduction to the series, arguing for the justification of deploying new materialism to reframe the FEP and introducing some essential concepts to be utilized in developing a neo-materialistic account of the FEP.

Diets that restrict the amount of carbohydrates positively affect markers related to metabolic syndrome (MS). However, completely carbohydrate-free diets have been studied in lesser extent, being their effect on biochemical and morphometric parameters in a rat model of MS the main objective of this study. MS was induced by a high-glucose diet for 20 weeks in male Wistar rats with a subsequent exposition to an essentially carbohydrate-free diet (CFD) for 20 weeks. Daily measurements of food consumption and monthly measurements of body weight were made. At week 40, glucose, insulin, lipid profile, ketone bodies, C-reactive protein (CRP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, creatinine, liver and muscle glycogen, and serum, hepatic, renal and pancreatic malondialdehyde (MDA) were assessed. Exposition to CFD showed decrease in caloric intake and body weight. Likewise, the group showed normalization in liver and serum MDA parameters, insulin, lipid profile, ALT, liver glycogen, and creatinine. The CFD decreased glucose concentration and the inflammatory state, also, increased the concentration of ketone bodies and urea. The change towards CFD reverses the metabolic alterations generated with MS except for glycemia and uremia, probably due to the high rate of gluconeogenesis generated by the high protein content in the diet.

In this work we report recent theoretical calculations of a superconducting island in a strong vortex confinement regime. The obtained results reveal the evolution of superconducting condensate as a function of electron mean-free path (l) with the evolution of an applied magnetic field H0. The results of this study provide an insight about the emergent superconducting properties under such conditions, using the Ginzburg-Landau numerical simulations where spatial variation of thickness d on island, omnipresent in these kind of structures grown on Si (111), is taken into account. These results offer a new route to tailor superconducting circuits by using the controlled bombardment, in order to explore the impact on vortex distribution, phase of order parameter, number of vortices, free energy and the first H1 and second critical field H2.

In this work, we report the electric energy storage properties of (1-x)Bi0.5(Na0.8K0.2)0.5TiO3-xBi0.2Sr0.7TiO3 (BNKT-BST; x = 0.15-0.50) relaxor ferroelectric ceramics enhanced via a domain engineering method. A rhombohedral–tetragonal phase, the formation of highly dynamic PNRs, and a dense microstructure are confirmed from XRD, Raman vibrational spectra, and microscopic investigations. The relative dielectric permittivity (2664 at 1 kHz) and loss factor (0.058) were gradually improved with BST (x=0.45). The incorporation of BST into BNKT can disturb the long-range ferroelectric order, lowering the dielectric maximum temperature Tm and inducing the formation of highly dynamic polar nano-regions. In addition, the Tm shifts toward high temperature with frequency and a diffuse phase transition, indicating relaxor ferroelectric characteristics of BNKT-BST ceramics, which is confirmed by the modified Curie Weiss law (γ=1.83). The rhombohedral–tetragonal phase, fine grain size, and lowered Tm with relaxor properties synergistically contribute to a high recoverable energy density Wrec of 0.81 J/cm3 and a high energy efficiency η of 86.95% at 90 kV/cm for x = 0.45.

A structural study of the 6√3 reconstruction conversion on 4H-SiC substrate surface in an Ar medium with a short sublimation annealing time into quasi-free epitaxial graphene by means of hydrogen intercalation between the upper layer of SiC and the adjacent reconstructed layer was carried out using the technique of reflection high-energy electron diffraction (RHEED) characterizing the surface of a crystalline material. A slight violation of the 6√3 reconstruction layer formation uniformity was found. The results of the study of the crystal structure of quasi-free graphene and single-layer graphene comprising a buffer layer formed on 4H-SiC in the traditional way in an Ar atmosphere without intercalation were compared.

Histone deacetylases (HDAC) represent promising epigenetic targets for several diseases including different cancer types. The HDAC inhibitors approved to date are pan-HDAC inhibitors and most show a poor selectivity profile, side effects and especially hydroxamic acid based inhibitors lack good pharmacokinetic profiles. Therefore, the development of isoform-selective non-hydroxamic acid HDAC inhibitors is a highly regarded field in medicinal chemistry. In this study, we analyzed different ligand-based and structure-based drug design techniques to predict the binding mode and inhibitory activity of recently developed alkylhydrazide HDAC inhibitors. Alkylhydrazides have recently attracted more attention as they have shown promising effects in various cancer cell lines. In this work, pharmacophore models and atom-based quantitative structure-activity relationship (QSAR) models were generated and evaluated. The binding mode of the studied compounds was determined using molecular docking as well as molecular dynamics simulations and compared with known crystal structures. Calculated free energies of binding were also considered to generate QSAR models. The models created show a good explanation of in vitro data and were used to develop novel HDAC3 inhibitors.

Heterojunctions based on metal halide perovskites (MHPs) are promising systems for photocatalytic hydrogen evolution reaction (HER). In this work, we coupled Cs3Bi2Br9 nanocrystals (NCs), obtained by wet ball milling synthesis, with g-C3N4 nanosheets (NSs) produced by thermal oxidation of bulk g-C3N4 in air. These methods are reproducible, inexpensive, and easy to scale up. Heterojunctions with different loadings of Cs3Bi2Br9 NCs were fully characterized and tested for HER. A relevant improvement of H2 production with respect to pristine carbon nitride was achieved at low NCs levels reaching values up to about 4600 µmol g-1 h-1. This work aims to provide insights on the synthesis of inexpensive and high performing heterojunctions using MHP for photocatalytic applications.

Many countries have implemented free early childhood education to solve the affordability and accessibility problems without considering the sustainability of policy; thus, they have to discontinue the policy. The city of Nanjing, China, is no exception. This case study adopted a mixed-methods approach to understanding how and why the policy was formulated, implemented, and failed in the city, using the “policy cycle” framework. Altogether 232 kindergarten principals and teaching/research staff were randomly sampled and surveyed, and 5 kindergarten principals and 5 teaching/researcher staff were interviewed. The results indicated that there were many obstacles to the policy’s sustainability, including the conflict of interest, the inefficient policy implementation, the insufficient funding, and more social inequality issues. And the policymakers made mistakes in the five domains of the policy cycle: the context of influence, the context of policy text production, the context of practice, the context of outcomes, and the context of political strategy. Finally, the lessons for a more sustainable policy decision process are discussed.

Transcription factors (TFs) are proteins that recognize specific DNA fragments in order to decode the genome and ensure its optimal functioning. TFs work at the local and global scales by specifying cell type, cell growth and death, cell migration, organization and timely tasks. We investigate the structure of DNA-binding motifs with the theory of finitely generated groups. The DNA ‘word’ in the binding domain -the motif- may be seen as the generator of a finitely generated group Fdna on four letters, the bases A, T, G and C. It is shown that, most of the time, the DNA-binding motifs have subgroup structure close to free groups of rank three or less, a property that we call ‘syntactical freedom’. Such a property is associated to the aperiodicity of the motif when it is seen as a substitution sequence. Examples are provided for the major families of TFs such as leucine zipper factors, zinc finger factors, homeo-domain factors, etc. We also discuss the exceptions to the existence of such a DNA syntactical rule and their functional role. This includes the TATA box in the promoter region of some genes, the single nucleotide markers (SNP) and the motifs of some genes of ubiquitous role in transcription and regulation.

Gastric emptying rate (GER) may impact diabetes and obesity in humans and could provide a method to reduce canine weight gain. Starch, the most common source of carbohydrates (CHOs) in pet food, is classified as rapidly or slowly digestible, or resistant to digestion. This study investigated starch source effects in commercial extruded dog foods on the GER of 11 healthy adult Siberian Huskies (5.63±0.72 years; mean±SEM). Test diets were classified as traditional, grain-free, whole-grain, and vegan. Dogs received each diet once, a glucose control twice, and acetaminophen (Ac) as a marker for GER in a randomized, partially-replicated, 6x6 Latin square design. Pre- and post-prandial blood samples were collected at 16 timepoints from -15 to 480 minutes. Serum Ac concentrations were assessed via standard spectrophotometric assays and fitted with a mathematical model to estimate parameters of GER. Data was analyzed using a repeated measures ANOVA, followed by a Tukey-Kramer post-hoc test when significant (p<0.05). More total emptying (p= 0.0430) occurred at faster rate (p=0.0668) in dogs fed the grain-free diet, which contained the lowest total starch (34.03 ± 0.23%) and highest resistant starch (0.52 ± 0.007%). This research may benefit future diet formulations to reduce the prevalence of canine weight gain.

Background: Ultrasonography’s usefulness in endometrial cancer (EC) diagnosis consists of its staging and predictive roles. Ultrasound-measured tumor-free distance from the tumor to the uterine serosa (uTFD) is a promising marker for this variable. The aim of the study was to determine the usefulness of this biomarker in locoregional staging, and thus in the prediction of lymph node metastasis (LNM). Methods: We conducted a single-institutional, prospective study on 116 consecutive patients with EC who underwent 2D transvaginal ultrasound examination. The uTFD marker was compared with the depth of ultrasound-measured myometrial invasion (uMI). Univariate and multivariate logit models were evaluated to assess the predictive power of the uTFD and uMI in regard to LNM. The reference standard was a final histopathology result. Survival was assessed by the Kaplan-Meyer method. Results: LNM was found in 17% of the patients (20/116). In the univariate analysis, uMI and uTFD were significant predictors of LNM. Accuracy was 70.7%, and NPV was 92.68% (OR 4.746, 95% CI 1.710-13.174) for uMI (p = 0.002), and 63.8%, and 89.02% (OR 0.842, 95% CI 0.736 – 0.963), respectively, for uTFD (p = 0.01). The cut-off value for uTFD in the prediction of LNM was 5.2 mm. The absence of LNM was associated more with biomarker values uMI &lt;1/2 and uTFD &gt;=5.2 mm than with the presence of metastases with uMI &gt;1/2 and uTFD values &lt;5.2 mm. In the multivariate analysis, the accuracy of the uMI-uTFD model was 74%, and NPV was 90.24% (p = NS). Neither uMI nor uTFD are surrogates for overall and recurrence-free survivals in endometrial cancer. Conclusions: Both uMI and uTFD, either alone or in combination, are valuable tools for gaining additional preoperative information on expected lymph node status. Negative lymph nodes status is better described by ultrasound biomarkers than a positive status. It is easier to use uTFD measurement as a biomarker of EC invasion than uMI, and the former still maintains a similar predictive value for lymph node metastases to the latter at diagnosis.

This article presents, for the first time, the kinetics and the general conversion features of a 3-initiator system (A/B/N), based on proposed mechanism of Mokbel et al, for both free radical polymerization (FRP) of acrylates and the free radical promoted cationic polymerization (CP) of epoxides using copper complex as the initiator. Higher FRP and CP conversion can be achieved by co-initiators concentration [B] and [N], via the dual function of (i) regeneration [A], and (ii) generation of extra radicals S' and S. The FRP and CP conversion is proportional to, respectively, the nonlinear and linear power of bI[A][B], where b and I are the absorption coefficient and the light intensity, respectively. System in air has lower conversion than in laminate due to the oxygen inhibition effects. For thick samples (with thickness z), there is an optimal concentration [A*] which is inverse proportional (bzI), in contrast with very thin sample, in which the conversion is an increasing function of [A] and [B]. The unique feature of dark polymerization in CP conversion enables the polymerization to continue in living mode, in contrasts with that of the radical-mediated pathway in most conventional FRP. The measured results of Mokbel et al are well analyzed and matching the predicted features of our modeling.

In this article, a technology for producing wire and rod solder from 52In-48Sn alloy has been developed and investigated in the conditions of small-scale production. The use of direct extrusion of wire and rods instead of the traditional technology for producing solder, which includes pressing, rolling and drawing, can significantly reduce the fleet of required equipment. Using only a melting furnace and a hydraulic press, solder wires and rods can be produced in various sizes. Shortening the production cycle allows you to quickly fulfill small orders and be competitive in sales. The article developed a mathematical model of direct extrusion, which allows you to calculate: extrusion ratio, extrusion speed and pressing force. The results of modeling the process of extrusion of wire ∅2.00 mm and rods ∅8.0 mm made of 52In-48Sn alloy are presented. The temperature of the solder and the tool is simulation in software QForm based on the finite element method. Experimental results of manufacturing ∅2.0 mm solder wire and ∅8.0 mm rods are presented. The microstructure of the direct extruded solder is a eutectic of phases γ and β. Energy-dispersive X-ray spectroscopy (EDS) mapping of the 52In-48Sn alloy showed that the solder obtained by direct extrusion has a uniform distribution of structural phases. The developed technology can be used in the manufacture of wires and rods from other low-melting alloys.

In this paper, we present and analyze a compact inner-wall grating slot microring resonator (IG-SMRR) with the footprint of less than 13 μm × 13 μm on the SOI platform for label-free sensing, which comprises a slot microring resonator (SMRR) and inner-wall grating (IG). Its detection range is significantly enhanced without the limitation of the free spectral region (FSR) owing to the combination of SMRR and IG. Structural parameters of IG and SMRR are investigated and optimized for favorable transmission properties. The simulation results shows that the IG-SMRR has an ultra-large quasi-FSR of 84.6 nm, and the concentration sensitivities of sodium chloride solutions and D-glucose solutions are up to 960.61 pm/% and 933.06 pm/%, respectively. The investigation on the combination of SMRR and IG is a valuable exploration of label-free sensing application for ultra-large detection range and ultra-high sensitivity in future.

High oxidative stress in cells due to inflammation process or excessive cell proliferation would produce oxidants or free radicals with biomarkers, one of which is malondialdehyde (MDA). Passion fruit seed’s contain high antioxidant and are expected to decrease the level of cholesterol and MDA. The objective is to identify the effect of passion fruit seed’s ethanol extract in Wistar rats that have been fed with atherogenic feed. The method was preclinical trial (post-test control group design) in rats, by administering passion fruit seed’s ethanol extract for 14 days. This study used 26 male rats aged two months, divided into 5 groups. The result showed significant difference in MDA level which was found in group that was given passion fruit seed extract 10mg/kg BW with positive control group that was given standard feed. Passion fruit seed’s extract showed significant difference in level of triglyceride, which was found in negative control group that was given atherogenic feed with group that was given passion fruit seed’s extract 5mg/kg BW (mean±standard deviation: 1.09±0.30 mg/dL vs 0.77±0.25mg/dL; p=0.048). This study showed that passion fruit seed’s ethanol extract had significant lowering effect in level of MDA, total cholesterol, and triglyceride for 14 days.

According to Copenhagen interpretation, a quantum particle can exist in a superposition of all possible states, out of which only one state is observed when it is measured. Interestingly, it has been observed that interaction with the quantum particle during measurement can also affect the outcome of the state. A scheme for interaction free measurement was proposed by Elitzur and Vaidman [Found. Phys. 23, 987 (1993)], where they used Mach Zehnder interferometer to detect whether a bomb is alive or dead. In 25 % of the cases they were able to detect that the bomb is alive without exploding it. Here, we demonstrate the above experiment using quantum computing, which can be realized in a quantum computer designing quantum circuits on it. We explicate all the cases, including whether the bomb is alive or dead by proposing new quantum circuits and executing those in QISKit as provided by IBM Quantum Experience platform and verify the obtained results.

Deep fat frying is not novel, but a classical antiquity culinary technique preferred chiefly for its swiftness, amenity, conferment of a crisp texture, attractive sensorial and organoleptic qualities and thus delectableness of the fries. Regrettably, repeated use of oils for deep frying impacts the storage life and nutritional suitability of fries. This concerted study investigated the effects of continuous deep fat frying on the physicochemical properties of ten brands of edible cooking oils: Fortune Butto, Roki, Tamu, Best Fry, Golden Fry, Mukwano, Sunny, Sunvita, Sunlite and Sunseed used in deep frying of potato chips in Kampala, Uganda. Three oil samples from local Irish chip fryers were also collected. The color value (CV) and the acidification of the oils as free fatty acid (FFA), peroxide value (POV), paraanisidine value (AnV) and iodine adsorption value (IV) before and between ten successive deep-fryings using potato chips were determined. The possible reuse of the oils was estimated from the frying round when a quality criterion surpassed national or CODEX specifications for the respective edible cooking oils. For fresh oils, the statistical parameter ranges were: CV (0.4R 3.4Y-7.7R 70Y), % FFA (0.0430-0.1508), POV (0.5951-6.6134 meqO₂/Kg), AnV (0.90-4.30) and IV (57.62-128.35gI₂/100g). By the tenth fry, the values were respectively 3.0R 23Y-20.4R 70Y, 0.2286-0.4817, 11.1138-15.7525 meqO₂/Kg, 10.31-22.16 and 53.66-126.03 gI₂/100g. Reuse of the oils for continuous frying of potatoes on the same day can be done only up to 7 times on average for hard oils and 6 times for soft oils.

As bakery products contribute considerably to the daily intake of the carcinogen acting substance acrylamide (AA), the aim of this study was to evaluate the impact of the cropping system (conventional vs. organic farming) on AA precursor levels of free asparagine (Asn) across different cultivars of the cereal species, namely winter wheat (Triticum aestivum), winter spelt (Triticum aestivum ssp. spelta) and winter rye (Secale cereale) with simultaneous consideration of gained grain yields and flour qualities. For this purpose, orthogonal field trials were established at two sites in Southwest Germany over two growing seasons (2006-2007 and 2007-2008). The results indicated a significant impact of the cropping system on free Asn contents. Across all species, free Asn contents in the flour were 26 % lower under organic compared to conventional farming. The impact of the cropping system on individual cultivars was obvious with a maximum reduction in free Asn contents of 50 % (e.g. for cultivars Ludwig, Privileg, Capo) if organically produced. For spelt, a significant impact of the cropping system was only found in 2008 with a reduction in free Asn of up to 25 % if organically produced. Across both cropping systems, cultivar Franckenkorn reached the lowest levels of free Asn. For rye, a significant impact of the cropping system was observed only in 2007 with 33 % higher Asn amounts in the conventional cropping system. Independent of the cropping system, rye reached the highest levels of free Asn followed by wheat and spelt. Across both cropping systems, species and cultivars, the amount of free Asn correlated with the AA content in heated flour with R2=0.63***. Furthermore, the results indicated that lower AA contents in bakery products can be achieved by proper selection of species (e.g. 66 % lower if rye is replaced by wheat) and cultivars. With an appropriate choice of the cultivar, a reduction of up to 65 % was possible within wheat, along with a reduction of 44 % within spelt and 12.5 % within rye. In summary, the results indicated that organically produced wheat especially offers the opportunity to significantly lower the AA potential of bread and bread rolls by the choice of raw materials low in free Asn.

Free vibration analysis of the porous functionally graded circular plates has been presented on the basis of classical plate theory. The three defined coupled equations of motion of the porous functionally graded circular/annular plate were decoupled to one differential equation of free transverse vibrations of plate. The one universal general solution was obtained as linear combination of the multiparametric special functions for the functionally graded circular and annular plates with even and uneven porosity distributions. The multiparametric frequency equations of functionally graded porous circular plate with diverse boundary conditions were obtained in the exact closed-form. The influences of the even and uneven distributions of porosity, power-law index, diverse boundary conditions and the negligibled effect of the coupling in-plane and transverse displacements on the dimensionless frequencies of the circular plate were comprehensively studied for the first time. The formulated boundary value problem, the exact method of solution and the numerical results for the perfect and imperfect functionally graded circular plates have not yet been reported.

Satellite remote sensing is a powerful tool to map flooded areas. In the last years, the availability of free satellite data sensibly increased in terms of type and frequency, allowing producing flood maps at low cost around the World. In this work, we propose a semi-automatic method for flood mapping, based only on free satellite images and open-source software. As case studies, we selected three flood events recently occurred in Spain and Italy. Multispectral satellite data acquired by MODIS, Proba-V, Landsat, Sentinel-2 and SAR data collected by Sentinel-1 were used to detect flooded areas using different methodologies (e.g., MNDWI; SAR backscattering variation; Supervised classification). Then, we improved and manually refined the automatic mapping using free ancillary data like DEM based water depth model and available ground truth data. For the areas affected by major floods, we also validated and compared the produced flood maps with official maps made by river authorities. We calculated flood detection performance (flood ratio) for the different datasets we used. The results show that it is necessary to take into account different factors for the choice of best satellite data, among these, the time of satellite pass with respect to the flood peak is the most important one. SAR data showed good results only for co-flood acquisitions, whereas multispectral images allowed detecting flooded areas also with the post-flood acquisition. With the support of ancillary data, it was possible to produce reliable geomorphological based flood maps in the study areas.

Clinical rehabilitation and sports performance analysis both require the objectification of movement. Kinovea^© is a free 2D motion analysis software that enables the establishment of kinematics parameters. This low-cost technology has been used in sports sciences, as well as clinical field and research work. Although it has been validated as a tool with which to assess time-related variables, this is not yet the case regarding angular and distance variables. The main objective of this study was to determine the validity and reliability of the Kinovea software in obtaining angular and distance data at different perspectives of 90°, 75°, 60° and 45°. For this purpose, a figure with 29 points was designed (in AutoCAD) and 24 frames analysed. Each frame was examined by three observers who each made two attempts. For each export data item, 20 angles and 20 distance variables were calculated, with intra- and inter-observer reliability also analysed. To evaluate Kinovea reliability and validity a multiple approach was applied involving the following analysis: -systematic error with a two-way ANOVA 2x4; -relative reliability with ICC and CV (95% confidence interval); -absolute reliability with Standard Error. The results thus obtained indicate that the Kinovea software is a valid and reliable tool that is able to measure accurately at distances up to 5 m from the object and at an angle range of 90°–45°. Nevertheless, for optimum results an angle of 90° is suggested.

It has been proposed that tumourigenicity was an intrinsic feature of embryonic/germ cell developmental axis as well as embryonic/germ cell-related genes play a crucial role in tumourigenicity. Our previous studies indicated that primordial germ cell (PGC)-like potential could be reactivated in tumourigenesis. In this study, 4T1, 168FARN and 67NR cells which originated from the same mouse breast cancer were studied and the results indicated that the acquisition of embryonic/germ cell-like state is essential for tumourigenicity. We further demonstrated that somatic to PGC-like transformation (SPLT) was activated in 4T1 cells and that inhibition of PGC-like cell formation by depleting pluripotency and/or PGC specification-related genes markedly repressed SPLT and the tumourigenicity. Collectively, our findings reveal that tumourigenicity is linked to the acquisition of PGC-like state through SPLT in 4T1 cells, provide new insight into deeper understanding the biological nature of tumours and novel therapeutical strategies for cancer targeting.

Background: Metastatic tumors to the oro-facial tissues are rare, with an incidence ranging between 1% and 8% of all oral malignant tumors. Generally reported with a peak of incidence in the 5th–7th decades, but possibly occurring at any age, metastases may represent the first sign of an occult cancer or manifest in patient with an already known history of a primary carcinoma, mostly from the lungs, kidney, prostate, and colon-rectum in males, or uterus, breast, lung, and ovary in females. In the oro-facial tissues the sites mostly involved are the oral mucosa, gingiva/jawbones, tongue, and the salivary glands. Methods: A systemic Review of the literature on the oro-facial metastases from Renal Cell Carcinoma has been conducted by searching the most used databases, also focusing the attention on the Clear Cell histological variant, representing the most frequent one. Results: Among the 160 analyzed studies, 211 cases of oral metastases of renal cancer were found (148 in males, 70.1%; 63 in females, 29.8%), with an average age of 59.8 years. In almost 40% of cases, metastasis represented the first clinical manifestation of the primary tumor and 122 were histologically diagnosed as ccRCCs (57.8%). The tongue was involved in most of the cases (26% - 55 cases), followed by mandible (18.9% - 40 cases), gingiva (18.4% - 39 cases), maxilla (10.9% - 23 cases), parotid gland (10.4% - 22 cases), buccal mucosa (5.2% - 11 cases), lips (3.3% - 7 cases), hard palate (2.8% - 6 cases), soft palate, masticatory space and submandibular gland (0.9% - 2 cases), lymph nodes, tonsil and oral floor (0.4% - 1 case). Among the 122 ccRCCs (84 were males, 68.8 %; 38 females, 31.1%), with an average age of 60.8 years and representing in 33.6% the first clinical manifestation, the tongue remained the most involved site (25.4% - 31 cases), followed by the gingiva (17.2% - 21 cases), parotid gland (13,1% - 16 cases), mandibular bone (12.2% - 15 cases), maxillary bone (11.4% - 14 cases), buccal mucosa and lips (4.9% - 6 cases), hard palate (4% - 5 cases), submandibular gland and soft palate (1.6% - 2 cases), lymph nodes, tonsil, oral floor and masticatory space (0.8%. 1 case). The clinical presentation in soft tissues was represented by a fast-growing exophytic mass, sometimes accompanied by pain. Instead inn bone appeared as radiolucent lesions, with ill-defined borders and cortical erosion. Conclusions: Our data focus the attention on the incidence of Renal cancer Metastases in the oro-facial tissues. Their early identification surely represents a diagnostic challenge, especially when the clinical work-up is limited to the cervico-facial region. Nevertheless, early diagnosis and recently introduced adjuvant therapies may represent the key for better outcomes. Therefore, general guidelines about clinical and radiological identification of oro-facial potentially malignant lesions should be part of the cultural background of any dentists.

Plant cells are omnipotent and breeding of new varieties can be achieved by protoplast fusion. Such fusions can be achieved by treatment with poly(ethylene glycol) or by applying an electric field. Microfluidic devices allow for controlled conditions and targeted manipulation of small batches of cells down to single cell analysis. To provide controlled conditions for protoplast fusions and achieve high reproducibility, we developed and characterized a microfluidic device to reliably trap few of Arabidopsis thaliana protoplasts and induced a cell fusion by controlled addition of poly(ethylene glycol) (PEG, with a molecular weight of 6000). Experiments were conducted to determine the survival rate of isolated protoplasts in our microfluidic system. Afterwards, PEG induced fusion was studied. Our results indicate that the following fusion parameters had significant impact on the fusion efficiency and duration: PEG concentration, osmolarity of solution, and flow velocity. PEG concentration below 10% led to only partial fusion. Osmolarity of the PEG fusion solution was found to strongly impact the fusion process; complete fusion of two source cells sufficiently took part in slightly hyper osmotic solutions, whereas iso-osmotic solutions led to only partial fusion at 20% PEG concentration. We observed accelerated fusion for higher fluid velocities. Up to this study, it was common sense that fusion is one directional, i.e. once two cells were fused into one cell they stay fused. Here, we present for the first time reversible fusion of protoplasts. Our microfluidic device paves the way to a deeper understanding on the kinetics and processes of cell fusion.

The increasing global demand for energy and the pressing challenge of environmental pollution necessitates a paradigm shift towards sustainable energy sources. Hydrogen, a viable renewable energy carrier, has the potential to substantially alleviate these concerns. This review offers a comprehensive exploration of the technologies imperative to the production and operation of fuel cell vehicles (FCVs), ranging from various fuel cell types, hydrogen storage methods, fueling station logistics, batteries in hydrogen vehicles, and the emerging influence of artificial intelligence and quantum computing. An analytical overview of global adoption patterns reveals significant geographical disparities, with the United States and South Korea at the forefront of FCV integration, primarily in the form of passenger cars, followed by buses and trucks. Asia emerges as the region with the highest proportion of FCVs. This paper also delves into the diverse challenges facing FCV implementation, shedding light on the essential role of continued investment in the evolution of sustainable transportation systems. Furthermore, it provides insights into the varying contributions of different companies in the field, demonstrating the collective effort required to advance this promising technology. The comprehensive exploration provided in this review aids in understanding the opportunities, challenges, and potential of hydrogen as an integral player in the future of sustainable transportation. The increasing need for energy carriers and the rise of environmental pollution have driven the exploration of renewable energy sources, with hydrogen being a promising option.

Our findings indicate that all five phytocannabinoids reduce HG-HL-induced -cell loss likely through reducing apoptosis and pyroptosis. The protective effects of CBD, THCV, CBC, and CBN were seen in the GSIS impairment by HG-HL. Although all five phytocannabinoids tested in this research demonstrated the capability to inhibit β-cell dedifferentiation induced by HG-HL, CBD seems to be more effective compared to the other phytocannabinoids, as indicated by the specific biomarker responses of β-cells and progenitor cells to CBD.

Production of biofuel from lignocellulosic biomass is relatively low due to the limited knowledge about natural cell wall loosening and cellulolytic processes in plants. Industrial separation of cellulose fiber mass from lignin, its saccharification and alcoholic fermentation is still cost-ineffective and environmental unfriendly. Assuming that the green transformation is inevitable and that the new sources of raw materials for biofuels are needed, we decided to study cell death - a natural process occurring in plants in a context of reducing the recalcitrance of lignocellulose for production of second generation bioethanol. “members of the enzyme families responsible for lysigenous aerenchyma formation were identified during the root hypoxia stress in Arabidopsis thaliana cell death mutants. The cell death regulatory genes, LESION SIMULATING DISEASE 1 (LSD1), PHYTOALEXIN DEFICIENT 4 (PAD4) and ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1) conditionally regulate the cell wall when suppressed in transgenic aspen. During four years of growth in the field the following effects were observed: lignin content was reduced, the cellulose fiber polymerization degree increased and the growth itself was unaffected. The wood of transgenic trees was more efficient as a substrate for saccharification, alcoholic fermentation and bioethanol production. The presented results may trigger the development of novel biotechnologies in the biofuel industry.

Djeya1 (RKLAFRYRRIKELYNSYR), is a very effective cell penetrating peptide (CPP) which mimics the α5 helix of the highly conserved Eya domain (ED) of eyes absent (Eya) proteins. The objective of this study was to bioengineer analogues of Djeya1 that, following effective translocation into planarian tissues, would reduce the ability of neoblasts (totipotent stem cells) and their progeny to regenerate the anterior pole in decapitated S. mediterranea. As a strategy to increase the propensity for helix formation, molecular bioengineering of Djeya1 was achieved by the mono-substitution of the helicogenic aminoisobutyric acid (Aib) at three species variable sites: 10,13,16. CD analyses indicted that Djeya1 is highly helical and that Aib-substitution had little influence on secondary structure. Aib-substituted Djeya1 analogues are highly efficient CPPs, devoid of influence upon cell viability or proliferation. All three peptides increase the migration of PC-3 cells which express high concentrations of Eya. Two peptides, [Aib13]Djeya1 and [Aib16]Djeya1, are bioportides which delay planarian head regeneration. As neoblast are the only cell population capable of division in planaria, these data indicate that bioportide technologies could be utilised to directly manipulate other stem cells in situ, thus negating any requirement for genetic manipulation.

Bacterial transformation is the essential tool for introducing foreign DNA into bacterial cells in a host of recombinant technology applications useful for biomanufacturing and drug production. Thus far, chemically competent cells remain an important enabling technology for bacterial transformation given its facile transformation approach. However, many parameters affect transformation efficiency, and there is relatively little documentation of their cross-interacting effect in the literature. This work explores the roles played by incubation time on ice, competent cell concentration, and plasmid-to-cell ratio on transformation efficiency in Escherichia coli DH5α. Results revealed that increases in incubation time improve transformation efficiency, but 2 minutes incubation still yield appreciable efficiency. On the other hand, low concentration competent cells (10⁶ CFU/mL) yielded significant improvement in transformation efficiency compared to high concentration competent cells (10⁸ CFU/mL). In terms of plasmid-to-cell ratio, higher ratio increases transformation efficiency. Overall, bacterial transformation is incompletely understood particularly in the area of cross-interacting parameters. Experiments reported here revealed the possibility of short duration transformation where lower competent cell concentration and higher plasmid-to-cell ratio could improve transformation.

The global context of research for new sustainable energy storage technologies makes it a very active sector with significant scientific and economic challenges. Indeed, due to the irregular development of renewable energies and the shutdown of traditional power facilities, it is difficult to maintain a stable balance in terms of supply and demand: energy storage can help in particular for substantial changes in the latter. Metal air batteries have a higher energy density and are safer than other available energy storage devices. Based on the existing and proven lead-acid battery technology, this paper proposed an open cell foam manufactured by the Excess Salt Replication process for use as an anode for lead-air battery cellsies with sulphuric acid as the electrolyte. This will save lead and reduce the battery weight. A 25% antimonial lead alloy was used to produce open cell foams with a cell diameter between 2 mm and 5 mm for the antimonial lead-air battery. Preliminary results of the effective electrical conductivity of self-discharged primary battery cells, measured experimentally, showed that all antimonial lead foam-air battery cellsies performed better than that made from the same dense non porous antimonial lead alloy. This is generally due to their important specific surface area where oxidation-reduction reactions took place. A correlation between the effective electrical conductivity and the cell diameter has been established and the highest conductivity was obtained with a cell diameter of 5mm. The feasibility of such an electrical system has been demonstrated.

Diabetes is a group of diseases characterized by loss of β cell mass and/or -function, resulting in hyperglycemia. Approx. 537 million people worldwide suffer from diabetes – a number which is expected to increase. Diabetes is primarily treated by exogenous insulin, which comes with the challenges of maintaining glycemic control to prevent ketoacidosis and severe complications. The need for a curative treatment has initiated the research in β cell regeneration. Several studies in mice have identified essential genes for β cell fate, which can be manipulated in other cells to induce generation of new β cells. Zebrafish, a regeneration-positive animal model, has shown several different sources of new β cells, including regeneration by self-replication, neogenesis by duct-associated progenitor cells, and transdifferentiation of other endocrine islet cells. The animal models used in this research area are either limited by their low regenerative ability (mice), or their small size and remoteness from humans (zebrafish). There is a need for new animal models of diabetes, in which the molecular pathways of endogenous regeneration can be studied. This study proposes the axolotl salamander (Ambystoma mexicanum) as a model for studying the regeneration of β cells. The axolotl has shown great regenerative capability, as they have proven capable of regenerating amputated limbs, and hearts with myocardial infarction, among other organs. This study aims to establish a diabetic axolotl model, investigate their regenerative ability in the pancreas, and examine the potential systemic effects of the induced disease. In a pilot study, five different protocols using STZ (streptozotocin) were tested, and the most optimal protocol was found. Furthermore, the glucose tolerance test was optimized to characterize the glycemic state of the animals. The effect of the treatment on blood glucose levels was measured to characterize the development and decline of the disease. The histological changes in the pancreas were examined. Moreover, the systemic effects of the STZ treatment were investigated in blood and urine. The study indicated that it is possible to induce diabetes in the axolotl, but variations between the animals should be minimized, or the sample size should be increased to conduct a satisfying experiment, as it was not possible to induce diabetes in all animals. Regeneration was not observed histologically, but a restoration of blood glucose levels was seen over the span of the experiment. Lastly, edema formation was observed in some of the STZ-treated animals, but the cause of edema remains undetermined.

A significant number of persons with coronavirus disease 2019 (COVID-19) experience persistent, recurrent, or new symptoms several months after the acute stage of severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection. This phenomenon, termed Post-Acute Sequelae of SARS-CoV-2 (PASC) or Long COVID, is associated with high viral titers during acute infection, a persistently hyperactivated immune system, tissue injury by NETosis-induced micro-thrombofibrosis (NETinjury), microbial translocation, complement deposition, fibrotic macrophages, the presence of auto-antibodies, and lymphopenic immune environments. Here, we review the current literature on the immunological imbalances that occur during PASC. Specifically, we focus on data supporting common immunopathogenesis and tissue injury mechanisms shared across this highly heterogenous disorder including NETosis, coagulopathy, and fibrosis. Mechanisms include changes in leukocyte subsets/functions, fibroblast activation, cytokine imbalances, lower cortisol, autoantibodies, co-pathogen reactivation, and residual immune activation driven by persistent viral antigens and/or microbial translocation. Taken together, we develop the premise that SARS-CoV-2 infection results in PASC as a consequence of acute and/or persistent single or multiple organ injury mediated by PASC determinants to include degree of host response (inflammation, NETinjury), residual viral antigen (persistent antigen) and exogenous factors (microbial translocation). Determinants of PASC may be amplified by co-morbidities, age, and sex. Keywords: long COVID, PASC, long haulers, NETosis, T cell, NK cell, DC, neutrophil,

Although the first cancer immunotherapy was given in the clinic more than a century ago, this line of treatment has remained more of a distant goal than a practical therapy due to limited understanding of the tumor microenvironment and the mechanisms at play within it, which lead to failures of numerous clinical trials. However, in the last two decades, the immune checkpoint inhibitors and chimeric antigen receptor-T cell therapies have revolutionized the treatment of cancer and provided proof-of-concept that immunotherapies are a viable option. So far, immunotherapies have majoritarily focused on utilizing T cells, however T cells are not autonomous but rather function as part of, and therefore are influenced by, a vast cast of other immune cells, including innate lymphoid cells (ILCs). Here, we summarize the role of ILCs, especially helper ILCs, in tumor development, progression and metastasis, as well as their potential to be used as immunotherapy for cancer. By reviewing the studies that used helper ILCs as adoptive cell therapy, we highlight the rationale behind considering these cells as novel adoptive cell therapy for cancer as well as identify open questions and areas for future research.

Cell migration is essential for physiological, pathological and biomedical processes such as, in embryogenesis, wound healing, immune response, cancer metastasis, tumour invasion and inflammation. In light of this, quantifying mechanical properties during the process of cell migration is of great interest in experimental sciences, yet few theoretical approaches in this direction have been studied. In this work, we propose a theoretical and computational approach based on the optimal control of geometric partial differential equations to estimate cell membrane forces associated with cell polarisation during migration. Specifically, cell membrane forces are inferred or estimated by fitting a mathematical model to a sequence of images, allowing us to capture dynamics of the cell migration. Our approach offers a robust and potentially accurate framework to compute geometric mechanical membrane forces associated with cell polarisation during migration and also yields geometric information of independent interest, we illustrate one such example that involves quantifying cell proliferation levels which are associated with cell division, cell fusion or cell death.

Cancer stem cells (CSCs) are a tumor cell subpopulation that drives tumor progression and metastasis, leading to poor overall survival of patients. In colorectal cancer (CRC), hyper-activation of Wnt/β-catenin signaling by mutation of both Adenomatous polyposis coli (APC) and K-Ras increases the size of the CSC population. We previously showed that the CPD0857 inactivates Wnt/β-catenin signaling by promoting ubiquitin-dependent proteasomal degradation of β-catenin and Ras proteins, thereby decreasing proliferation and increasing apoptosis of CRC lines. CPD0857 also decreased growth and invasiveness of CRC cells harboring mutant K-Ras resistant to EGFR mAb therapy. Here, we show that CPD0857 treatment decreases proliferation and increases neuronal differentiation of neural progenitor cells (NPCs). CDP0857 effectively reduced expression of CSC markers and suppressed self-renewal capacity. CPD0857 treatment also inhibited proliferation and expression of CSC markers in D-K-Ras MT cells carrying K-Ras, APC and PI3K mutations, indicating inhibition of PI3K/AKT signaling. Moreover, CPD0857-treated xenograft mice showed regression of tumor growth and decreased numbers of CSCs in tumors. We conclude that CPD0857 could serve as the basis of a drug development strategy targeting CSCs activated through Wnt/β-catenin-Ras MAPK-PI3K/AKT signaling in CRCs.

Acute chemical ablation of lateral line hair cells is an important tool to understand lateral line-mediated behaviors in free-swimming fish larvae and adults. However, lateral line-mediated behaviors have not been described in fish larvae prior to swim bladder inflation, possibly because single doses of ototoxin do not effectively silence lateral line function at early developmental stages. To determine if ototoxins can effectively silence the lateral line during early development, we repeatedly expose zebrafish larvae to the ototoxin neomycin during a 36-hour period from 3-4 days post-fertilization (dpf). We use simultaneous transgenic and vital dye labeling of hair cells to compare 6- hour and 12-hour repeated treatment timelines and neomycin concentrations between 0–400 µM in terms of larval survival, hair cell death, regeneration, and functional recovery. Following exposure to neomycin, we find that the emergence of newly functional hair cells outpaces cellular regeneration, likely due to the maturation of ototoxin-resistant hair cells that survive treatment. Furthermore, hair cells of 4 dpf larvae exhibit faster recovery compared to 3 dpf larvae. Our data suggest that the rapid functional maturation of ototoxin-resistant hair cells limits the effectiveness of chemical-based methods to disrupt lateral line function. Furthermore, we show that repeated neomycin treatments can continually ablate lateral line hair cells between 3–4 dpf in larval zebrafish.

Electrochemical-mechanical interactions, in particular pressure-induced ones, have been identified to be a cause for lithium-plating in lithium-ion cells. Mechanically-induced porosity inhomogeneities in the separator layers due to electrode expansion during charging especially lead to cell internal balancing currents and can cause localized plating. To identify cell-format and cell-material dependent mechanical weak spots, a layer-resolved mechanical simulation of different cell types and cell-material combinations is presented in this work. The simulation results show distinctive layer strain patterns for different cell-types that coincide with localized lithium-plating found in post-mortem cells. Additionally, the effects of cell bracing in battery modules is investigated and a method to mitigate the increased layer strain due to bracing counterforces is proposed that also increases cell energy density for hardcase-type automotive cells.

Understanding the biology underlying the mechanisms and pathways regulating pancreatic β-cell development is necessary to understand the pathology of diabetes mellitus (DM), which is characterized by the progressive reduction in insulin producing β-cell mass. Pluripotent stem cells (PSCs) can potentially offer an unlimited supply of functional β-cells for cellular therapy and disease modeling of DM. Homeobox protein NKX6.1 is a transcription factor (TF) that plays a critical role in pancreatic β-cell function and proliferation. In human pancreatic islet, NKX6.1 expression is exclusive toβ-cells and is undetectable in other islet cells. Several reports showed that activation of NKX6.1 in PSC-derived pancreatic progenitors (MPCs), expressing PDX1 (PDX1⁺/NKX6.1⁺), warrants their future commitment to monohormonal β-cells. However, further differentiation of MPCs lacking NKX6.1 expression (PDX1⁺/NKX6.1^-) results in an undesirable generation of non-functional polyhormonal β-cells. The importance of NKX6.1 as a crucial regulator in MPC specification into functional β-cells directs attentions to further investigating its mechanism and enhancing NKX6.1 expression as a mean to increase β-cell function and mass. Here, we shed light on the role of NKX6.1 during pancreatic β-cell development and in directing the MPCs to functional monohormonal lineage. Furthermore, we address the transcriptional mechanisms and targets of NKX6.1 as well as its association with diabetes.

The aim of our study was to describe our experience using a Spectra Optia® automated apheresis system in children with sickle cell disease (SCD). We used automated red blood cell exchange (RCE) to treat acute and chronic complications in 75 children with SCD who had a median age of 10 years [7-13]. We analysed 649 exchange sessions. Peripheral venous access was limited in a number of the children, thus requiring a femoral central double‐lumen venous catheter (CVC). We recommend the use of heparin locking, with 500 units in each lumen of a CVC. This method was well tolerated, with few complications during the procedures. For preoperative prevention, all of the patients had achieved a post-RCE HbS level of <30% since this is a mandatory condition imposed by the anaesthesiologist. With a post-RCE Hb level of approximately 10-11 g/dL, a blood exchange volume of ≥32 mL/kg, and an interval between each RCE procedure of ≤30 days, it was able to maintain the residual HbS level below 30%. Despite a target pre‐exchange HbS level of 47%, we did not encounter a single stroke recurrence. Erythrocytapheresis is useful and safe for children with SCD.

Cellular substructure has been widely observed in the sample fabricated by laser powder bed fusion, while its growth direction and the crystallographic orientation have seldom been studied. This research tries to build a general model to construct the substructure from its two-dimensional morphology. All the three Bunge Euler angles to specify a unique growth direction are determined, and the crystallographic orientation corresponding to the growth direction is also obtained. Based on the crystallographic orientation, the substructure in the single track of austenitic stainless steel 316L is distinguished between the cell-like dendrite and the cell. It is found that, with the increase of scanning velocity, the substructure transits from cell-like dendrite to cell. When the power is 200 W, the critical growth rate of the transition in the single track can be around 0.31 ms^-1.

Fossil fuels and carbon origin resources are affecting our environment. Therefore, alternative energy sources have to be established to co-produce energy along with fossil fuels and carbon origin resources until it is the right time to replace them. Microbial Fuel Cell (MFC) is a promising technology in the field of energy production. Compared to the conventional power sources it is more efficient and not controlled by the Carnot cycle. Its high efficiencies, low noise, and less pollutant output could make it revolutionize in the power generation industry with a shift from centrally located generating stations and long-distance transmission lines to dispersed power generation at load sites. In this review, several characteristics of the MFC technology will be highlighted. First, a brief history of abiotic to biological fuel cells and subsequently, microbial fuel cells is presented. Second, the focus is then shifted to elements responsible for the making MFC working with efficiency. Setup of the MFC system for every element and their assembly is then introduced, followed by an explanation of the working machinery principle. Finally, microbial fuel cell designs and types of main configurations used are presented along with scalability of the technology for the proper application.

Cells take decisions on their responses depending on the stimuli received by the surrounding extracellular environment, that provides the essential cues at the micro and the nano-lengthscales required for adhesion, orientation, proliferation and differentiation. In this study, discontinuous microcones on silicon (Si) and continuous microgrooves on polyethylene terephthalate (PET) substrates were fabricated via ultrashort-pulsed laser irradiation at various fluences, resulting in microstructures with different roughness and geometrical characteristics. The topographical models attained were specifically developed to imitate the guidance and alignment of Schwann cells for oriented axonal regrowth, towards nerve regeneration. At the same time, positive replicas of the silicon microstructures formed were successfully reproduced, via soft lithography, on the biodegradable polymer poly(lactide-co-glycolide) (PLGA). The anisotropic continuous (PET) and discontinuous (PLGA replicas) microstructured polymeric substrates were assessed in terms of their influence on the Schwann cells responses. It is shown that the developed micropatterned substrates enable control over the cellular adhesion, proliferation and orientation and are thus useful to engineer cell alignment in vitro. This property could be potentially useful in the fields of neural tissue engineering and for dynamic microenvironment systems that simulate in vivo conditions.

Gene electrotransfer is one of the main non-viral methods for intracellular delivery of plasmid DNA, wherein pulsed electric fields are used to transiently permeabilize the cell membrane allowing enhanced transmembrane transport. By localizing the electric field over small portions of the cell membrane using nanostructured substrates, it is possible to increase considerably the gene electrotransfer efficiency while preserving cell viability. In this study, we design an electrotransfer approach based on commercially available cell culture inserts with polyethylene-terephthalate (PET) porous substrate. We first use multiscale numerical modelling to determine the pulse parameters, substrate pore size, and other factors that are expected to result in successful gene electrotransfer. Based on numerical results we design a simple device combining an insert with substrates containing pores with 0.4 um and 1.0 um diameter, a multiwell plate, and a pair of wire electrodes. We test the device in three mammalian cell lines and obtain transfection efficiencies similar to those achieved with bulk electroporation, but with low-voltage pulses that do not require the use of expensive electroporators. Our combined theoretical and experimental analysis calls for further systematic studies that will investigate the influence of substrate pore size and porosity on gene electrotransfer efficiency and cell viability.

Approximately half of head and neck squamous cell carcinoma (HNSCC) cases recur, and most of them recur within the first two years after treatment. Although it has been suggested that the interval to recurrence after radical treatment and prognosis in patients with HNSCC are associated, investigations are insufficient. In this study, patients diagnosed with HNSCC at Kyushu University Hospital were retrospectively analyzed (n = 500). A total of 234 patients experienced recurrence, with 110 and 124 patients experiencing early recurrence (ER) (recurrence within 2–6 months) and late recurrence (LR) (recurrence after 7 months), respectively. There were two independent risk factors for poor prognosis in the multivariate analyses: ER (hazard ratio [HR] = 3.200, 95% confidence interval [CI] = 1.570–6.521, p = 0.001) and no radiotherapy (HR = 0.374, 95% CI = 0.191–0.733, p = 0.004). In patients with recurrent HNSCC, a short interval to recurrence is a risk factor for poor prognosis and survival. This study demonstrated the prognostic value of ER in patients. During the selection of treatment for patients with recurrence, the recurrent area, initial treatment content, and strategy of changing salvage therapy depending on the recurrence status should be considered.

Host immunological pathways have been proposed including TH1, TH2, TH3, TH9, TH17, TH22, TH1-like, and THαβ immune reactions. Besides TH2 and TH9 immune responses which are against multicellular parasites, host immunological pathways against viruses, intracellular micro-organisms (bacteria, protozoa, and fungi), and extracellular micro-organisms can use programmed cell death pathways to trigger immune reactions or to execute effective strategies to eliminate these pathogens. These programmed cell deaths include apoptosis, autophagic death, pyroptosis, ferroptosis, necroptosis, and NETosis. Apoptosis is related to host anti-virus eradicable THαβ immunity. Autophagic death is related to host anti-virus tolerable TH3 immunity. Pyroptosis is related to host anti-intracellular micro-organism eradicable TH1 immunity. Ferroptosis is related to host anti-intracellular micro-organism tolerable TH1-like immunity. Necroptosis is related to host anti-extracellular micro-organism eradicable TH22 immunity. NETosis is related to host anti-extracellular micro-organism tolerable TH17 immunity.

(1) Background: This study aimed to investigate the effect of increased HER-2 expression on tumor-infiltrating lymphocytes (TILs) and determine its impact on the prognosis of colorectal cancer (CRC) patients; (2) Methods: HER-2, CD4, CD8, CD19, LY6G, CD56, CD68, CD11b, and EpCam expression in CRC tissues and adjacent paracancerous tissues were assessed using multiplex fluorescence immunohistochemical staining. The correlation between HER-2 expression and the number of TILs in CRC tissues was analyzed. Kaplan-Meier and Cox proportional hazards models were used to analyze survival outcomes; (3) Results: The expression of HER-2 in tumor tissues was higher than that in paracancerous tissues (1.31 ± 0.45 vs. 0.86 ± 0.20, P < 0.05). Additionally, there was an increase in the numbers of CD4+, CD8+, CD19+, and CD68+ cells in CRC tissues (14.11 ± 1.10 vs. 3.40 ± 0.18, P < 0.005; 0.16 ± 0.12 vs. 0.04 ± 0.04, P < 0.005; 0.71 ± 0.46 vs. 0.25 ± 0.13, P < 0.0005; 0.27 ± 0.24 vs. 0.03 ± 0.11, P < 0.05). The increase in HER-2 expression was positively correlated with an increase in CD4, CD8, and CD19 (p < 0.0001). In HER-2-positive CRC tissues, CD68 expression was increased (0.80 ± 0.55 vs. 0.25 ± 0.22, P < 0.05). In HER-2-upregulated CRC tissues, CD4, CD8, CD19, CD68, CD11b, Ly6G, and CD56 expressions were elevated (0.70 ± 0.37 vs. 0.32 ± 0.17, P = 0.03; 0.22 ± 0.13 vs. 0.09 ± 0.06, P = 0.03; 0.31 ± 0.19 vs. 0.12 ± 0.08, P = 0.02; 1.05 ± 0.62 vs. 0.43 ± 0.21, P < 0.01; 1.34 ± 0.81 vs. 0.53 ± 0.23, P < 0.01; 0.50 ± 0.31 vs. 0.19 ± 0.10, P < 0.01; 1.26 ± 0.74 vs. 0.52 ± 0.24, P < 0.01). Furthermore, increased HER-2 expression is an independent risk factor for recurrence-free survival (RFS) in patients (P < 0.01, HR = 3.421); (4) Conclusions: The increased expression of HER-2 and its relationship with immune cells will provide new insights for immunotherapy in CRC patients.

Food allergies are a growing public health concern worldwide, especially in children and young adults. Allergen-specific IgE plays a central role in the pathogenesis of food allergies, but their titers poorly correlate with allergy development. Host immune systems yield allergen-specific immunoglobulin (Ig)A, IgE and IgG subclasses with low or high affinities and differential Fc N-glycosylation patterns that can affect the allergic reaction to food in multiple ways. High affinity IgE is required to induce strong mast cell activation eventually leading to allergic anaphylaxis while low affinity IgE can even inhibit the development of clinically relevant allergic symptoms. IgA and IgG antibodies can inhibit IgE-mediated mast cell activation through various mechanisms, thereby protecting IgE-positive individuals from allergy development. The production of IgE and IgG with differential allergenic potential seems to be affected by the signaling strength of individual B cell receptors, and by cytokines from T cells. This review provides an overview of the diversity of the B cell response and the diverse roles of antibodies in food allergy.

This study aimed to optimize the bioelectricity production process using a vinasse solution through the application of Plackett-Burman and Box-Behnken designs. An electrochemical cell was constructed using Arduino to measure the potential difference between the anode and cathode immersed in the vinasse solution, a byproduct of wine production containing organic compounds and ions that undergo redox reactions. The Plackett-Burman design identified the most influential variables among eight previously selected, including vinasse concentration, agitation, and yeast, which positively affected millivolt production, while temperature showed a negative correlation. Based on these results, the Box-Behnken design was used for process optimization, varying parameters such as concentration, stirring, and sodium chloride. Response surface graphs demonstrated the relationship between these variables and millivolt production. The findings indicate that higher agitation levels, lower concentrations of vinasse, and the addition of sodium chloride can enhance bioelectricity generation. The study provides insights into the bioelectricity production process from vinasse, contributing to the understanding and potential for sustainable energy generation. The methodology involving Arduino-based measurement and the utilization of experimental designs offers a systematic approach to optimize bioelectricity production from vinasse.

Cellular response to mechanical stimuli is a crucial factor for maintaining cell homeostasis. The interaction between extracellular matrix and mechanical stress plays a significant role in organ-izing the cytoskeleton and aligning cells. Tools that apply mechanical forces to cells and tissues, as well as those capable of measuring the mechanical properties of biological cells, have greatly contributed to our understanding of fundamental mechanobiology. These tools have been exten-sively employed to unveil the substantial influence of mechanical cues on the development and progression of various diseases. In this report, we present an economical and high-performance uniaxial cell stretching device. This paper reports the detailed operation concept of the device, ex-perimental design, and characterization. The device was tested with MDA-MB-231 breast cancer cells. Experimental results agree well with previously documented morphological changes re-sulting from stretching forces on cancer cells. Remarkably, our new device demonstrates compa-rable cellular changes within a 30-minute compared to the previous 2-hour stretching duration. Moreover, the device design incorporates an open-source software interface, facilitating conven-ient parameter adjustments such as strain, stretching speed, frequency, and duration. Its versatil-ity enables seamless integration with various optical microscopes, thereby yielding novel insights into the realm of mechanobiology.

Brain capillary endothelial cell(s) (BECs) have numerous functions including their semipermeable interface-barrier (transfer and diffusion of solutes), trophic (metabolic homeostasis), tonic (vascular hemodynamics), and trafficking (vascular permeability, coagulation, and leukocyte extravasation) functions to provide brain homeostasis. BECs also serve as the brain’s sentinel cell of the innate immune system and are capable of antigen presentation. In metabolic syndrome (MetS) there are two regions resulting in proinflammatory signaling of BECs. Namely, visceral adipose tissue depots supplying excessive peripheral cytokines/chemokines (pCC) and gut microbiota dysbiotic regions supplying excessive soluble lipopolysaccharide (sLPS), small LPS-enriched extracellular vesicle exosomes (lpsEVexos), and pCC. This dual signaling of BECs at their receptor sites results in BEC activation and dysfunction (BECact/dys) and neuroinflammation. sLPS and lpsEVexos signal BECs toll-like receptor four, which then signals translocated nuclear factor kappa B (NFkB). Translocated NFkB promotes the synthesis and secretion of BEC proinflammatory cytokines and chemokines. Specifically, the chemokine CCL5 (RANTES) is capable of attracting microglia cells to BECs. BEC neuroinflammation activates perivascular space(s) (PVS) resident macrophages. Excessive phagocytosis by reactive resident PVS macrophages results in a stagnation-like obstruction, which along with increased capillary permeability due to BECact/dys could expand the fluid volume within the PVS to result in enlarged PVS (EPVS). Importantly, this remodeling may result in pre- and post-capillary EPVS that would contribute to their identification on T2-weighted MRI, which are considered to be biomarkers for cerebral small vessel disease.

P53 is known as the most critical tumor suppressor and is often referred to as the guardian of our genome. More than 40 years after its discovery, we are still struggling to understand all molecular details on how this transcription factor prevents oncogenesis or how to leverage current knowledge about its function to improve cancer treatment. Multiple cues, including DNA-damage or mitotic errors, can lead to the stabilization and nuclear translocation of p53, initiating the expression of multiple target genes. These transcriptional programs may well be cell type and stimulus-specific, as is their outcome that ultimately imposes a barrier to cellular transformation. Cell cycle arrest and cell death are two well-studied consequences of p53 activation, but, while being considered as critical, they do not fully explain the consequences of p53 loss-of-function phenotypes in cancer. Here, we discuss how mitotic errors alert the p53 network and give an overview on multiple ways how p53 can trigger cell death. We argue that a comparative analysis of different types of p53 responses, elicited by different triggers in a time-resolved manner in well-defined model systems is critical to understand cell type specific cell fate induced by p53 upon its activation, in order to resolve the remaining mystery of its tumor suppressive function.

Necroptosis is an inflammatory form of lytic programmed cell death that is thought to have evolved to defend against pathogens. Genetic deletion of the terminal effector protein – MLKL – shows no overt phenotype in the C57BL/6 mouse strain under conventional laboratory housing conditions. Small molecules that inhibit necroptosis by targeting the kinase activity of RIPK1, one of the main upstream conduits to MLKL activation, have shown promise in several murine models of non-infectious disease and in phase II human clinical trials. This has triggered multi-billion-dollar investments into the emerging class of necroptosis blocking drugs, and the potential utility of targeting the terminal effector is being closely scrutinised. Here we review murine models of disease, both genetic deletion and mutation, that investigate the role of MLKL. We summarize a series of examples from several broad disease categories including ischemia reperfusion injury, sterile inflammation, pathogen infection and haematological stress. Elucidating MLKL’s contribution to mouse models of disease is an important first step to identify human indications that stand to benefit most from MLKL-targeted drug therapies.

Magnetic Particle Imaging (MPI) is a new imaging modality that sensitively and specifically detects superparamagnetic iron oxide nanoparticles (SPIONs). Many labs have been developing cellular magnetic resonance imaging (MRI) tools using both SPIONs and fluorine-19 (19F)-based contrast agents for numerous important applications, including tracking of immune and stem cells used for cellular therapies. SPION-based MRI cell tracking has very high sensitivity, but low specificity. SPIONs produce negative contrast in MRI, or signal voids. SPIO is not directly detected by MRI, but indirectly through its relaxation effects on protons, therefore, it is not possible to reliably quantify the local tissue concentration of SPION particles and cell number cannot be determined. 19F based cell tracking uses perfluorocarbons (PFC) to label cells. The number of 19F atoms can be directly measured from 19F MR images and related to cell number. 19F MRI has high specificity, but low sensitivity. MPI cell tracking displays great potential for overcoming the challenges of MRI-based cell tracking allowing for both high cellular sensitivity and high specificity and quantification of SPIO labeled cell number. In this paper we describe nanoparticle and MPI system factors that influence MPI sensitivity and resolution, quantification methods and give our perspective on testing and applying MPI for cell tracking.

ACE2, the putative receptor for the novel coronavirus (2019-nCoV), played an important role in cell entry of 2019-nCoV. However, it is not yet clear what cell types within the human body express ACE2. Here, a systematic analysis was undertaken using published single cell datasets. In total, our study analyzed 229652 cells, from five different organs, derived from 88 donors. The top ACE2 expressing cells include proximal tubule cells in the kidney and enterocytes in the intestine. Other major ACE2 expressing cells in the kidney include podocytes, intercalated cells and endothelial cells. Our results offer a comprehensive atlas of ACE2 expression at the single cell level and unravel the enormous potential targets of 2019-nCoVinfection beyond the lung.

Hepatocellular carcinoma (HCC) is currently the third leading cause of malignancy-related mortalities worldwide. Natural killer (NK) cells are involved in the critical role of first line immunological defense against cancer development. Defects in NK cell functions are recognized as important mechanisms for immune evasion of tumor cells. NK cell function appears to be attenuated in HCC, and many previous reports suggested that NK cells play a critical role in controlling HCC, suggesting that boosting the activity of dysfunctional NK cells can enhance tumor cell killing. However, the detailed mechanisms of NK cell dysfunction in tumor microenvironment of HCC remain largely unknown. A better understanding of the mechanisms of NK cell dysfunction in HCC will help in the NK cell-mediated eradication of cancer cells and prolong patient survival. In this review, we describe the various mechanisms underlying NK cell dysfunction in HCC. Further, we summarize current advances in the approaches to enhance endogenous NK cell function and in adoptive NK cell therapies, to cure this difficult-to-treat cancer.

Propagation of human cytomegalovirus (CMV) in cultured cells results in genetic adaptations that confer improved growth in vitro and significant attenuation in vivo. Mutations in RL13 arise quickly during cell culture passage, while mutations in the UL128-131A locus emerge later during fibroblast passage and disrupt expression of a glycoprotein complex that is important for entry into epithelial and endothelial cells. As in vivo CMV replicates in the context of host antibodies, we reasoned that antibodies might mitigate the accumulation of adaptive mutations during cell culture passage. To test this, CMV in infant urine was used to infect replicate fibroblast cultures. One lineage was passaged in the absence of CMV-hyperimmuneglobulin (HIG) while the other was passaged with HIG in the culture medium. The former lost epithelial tropism and aquired mutations disrupting RL13 and UL131A expression, whereas the latter retained epithelial tropism and both gene loci remained intact after 22 passages. An epitheliotropic RL13+/ UL131A+ virus was isolated by limiting-dilution in the presence of HIG and expanded to produce a working stock sufficient to conduct cell tropism experiments. Thus, culture in the presence of antibodies may facilitate in vitro experiments using viruses that are genetically more authentic than has been previously possible.

Cellular response to mechanical stimuli is an integral part of cell homeostasis. The interaction of the extracellular matrix with the mechanical stress plays an important role in cytoskeleton organisation and cell alignment. Insights from the response can be utilised to develop cell culture methods that achieve predefined cell patterns, which are critical for tissue remodelling and cell therapy. We report the working principle, design, simulation and characterisation of a novel electromagnetic cell stretching platform based on the double-sided axial stretching approach. The device is capable of introducing a cyclic and static strain pattern on a cell culture. The platform was tested with fibroblasts. The experimental results are consistent with the previously reported cytoskeleton reorganisation and cell reorientation induced by strain. The orientation of the cells is highly influenced by external mechanical cues. Cells reorganise their cytoskeleton to avoid external strain and to maintain intact extracellular matrix arrangements.

(1) Background: The lateral arm flap has been the very useful choice in the reconstruction of small- to medium-sized defects like hand, extremity, oral head and neck area reconstructions. Its versatile characteristics and surgical feasibility allow this flap to be widely applied, but the reconstructive potential in facial subunit after tumor ablative procedures has never been reported. In this study, we aimed to utilize the advantages of the flap to treat facial temple subunit defect reconstruction. (2) Methods: Between 2020 and 2023, 12 patients underwent temple reconstruction with lateral arm free flaps after malignant tumor wide excision. There were 7 women and 5 men, and the mean patient age was 60.6 years old. Among the patients with cancer, 6 had squamous cell carcinoma, 5 had basal cell carcinoma and 1 had myxofibrosarcoma. All the flaps were elevated under general anesthesia. Aloprostadil(PGE1, Eglandin®) were administered postoperatively. (3) Results: All the flap types were fasciocutaneous type with varied sizes from 3 × 4 to 5 × 7 cm (Average size of flap 22.7cm2) were utilized. The average pedicle length was 6.1cm. The versatility of the lateral arm flap enabled successful coverage of all cases with no specific complications. Good functional outcome and range of motion in the recipient arm were obtained after surgery. (4) Conclusion: The authors successfully verified the advantages of lateral arm flaps in the treatment of medium sized facial subunt temple defect reconstruction.

The generation of high-quality wideband frequency sweeps presents a significant challenge, particularly in modern telecommunication, radar, and measurement systems where miniaturization is paramount. While phase-locked loops (PLLs) have become the dominant technique for signal generation, their application in broadband sweeps necessitates fractional-N operation. This, in turn, degrades phase noise and introduces unwanted spurs. This paper proposes a novel approach for broadband signal generation. By cascading two PLLs and utilizing a coaxial resonator, we achieve a high-performance oscillator that operates without the excessive fractional spurs, maintaining their level below -80 dBc across the entire frequency band. The prototype demonstrates non-degraded phase noise performance, reaching -102 dBc/Hz at 100 kHz offset and -121 dBc/Hz at 1 MHz offset for signal at 10 GHz. Despite significant frequency jumps, our design achieves lock times below 41 µs. These results, supported by theoretical analysis, validate the proposed method's effectiveness in generating low-noise broadband frequency sweeps, ideal for local oscillator applications.

This paper addresses the input coupling problem for the shape memory alloy (SMA) actuated parallel platform with completely unknown nonlinear dynamics. The problem means that in a parallel platform with multiple SMA actuators acting together, the displacement of one of the actuators will simultaneously affect the remaining actuators to change. Due to the coupling problem and nonlinear characteristics of the SMA actuators, it is not easy to control the platform to achieve bi-directional swing with completely unknown nonlinear dynamics. Therefore, a model-free adaptive sliding mode control method is proposed to improve the control accuracy of the complex motion of the platform, avoiding the complex modeling process of the SMA actuated parallel platform. Based on the model-free adaptive control (MFAC) theory, a multiple input and multiple output (MIMO) dynamic linearized mathematical model of the parallel platform is established using the online input and output data of the system. Then, a sliding mode controller is designed based on the dynamic model. A rigorous theoretical analysis proves that the proposed model-free adaptive sliding mode controller is able to stably control the SMA actuated parallel platform, and its tracking error is uniformly ultimately bounded (UUB). Finally, experiments are conducted on the established SMA actuated parallel platform. The results show that the proposed model-free controller is feasible and effective, and can control the system well to achieve the complex motion of bi-directional swing.

We presented unusual case of double left ventricular false aneurysm complicating late presentation AMI successfully treated with the combination of urgent surgical drainage of tamponade, staged PCI of non-culprit lesion, preventive implantation of ICD-DR, guideline directed heart failure medical therapy and delayed but effective reconstructive operation.

This is a retrospective chart review of outcomes of maxillofacial microvascular free flap reconstructions in pediatric and adolescent patients. A single head and neck surgical team performed all the included 136 procedures. Demographic and surgical patient data were recorded. Type of transfer performed in each recipient site and major complications were analyzed. Relevant influencing factors, such as age, gender and etiology of defect were determined using the ANOVA test and χ² test of independence. Results indicate a 90% success rate. No significant relation was found between the incidence of total flap loss and patient age, etiology or graft source. The maxillary reconstructions showed a higher incidence of total flap loss compared to mandibular ones (11 vs. 3 cases). Despite the high success rate, the findings underline the necessity for further research to validate these observations and enhance surgical methods for pediatric and adolescent patients.

Excessive body fat is a major contributor to obesity, which is related to high blood, total cholesterol and triglycerides. Lemons (Citrus limon) are renowned for their antioxidant and lipid-lowering properties. First, Sugar-free fermentation demonstrated better results lower sugar content and was identified as the preferred fermentation method. Next, the effect of two doses of sugar-free fermented lemon peel juice (SF-FLPJ) on obesity was investigated. Sprague Dawley (male rats) were randomly divided into 4 groups and fed a standard feed or high-fat diet (HFD) to induce fatness for eight weeks. The two groups of rats fed an HFD were administered SF-FLPJ at 0.45 or 0.9 g/kg body weight daily for eight weeks. The obese rats administered 0.9 g/kg (body weight/day) of SF-FLPJ exhibited significant reductions in body fat mass and percentage; they also had lower blood cholesterol and triglyceride levels than the other groups. Additionally, the rats displayed diminished liver fat accumulation. The results suggest that SF-FLPJ can be a supplement in managing body fat, contributing positively to addressing obesity within the context of health management, and reduce obesity-associated issues.

De-escalation is currently taking place both in surgical and systemic treatment of breast cancer. The introduction of trastuzumab, the first monoclonal antibody against the HER2 receptor over 20 years ago was a milestone in the treatment of HER2 positive breast cancer and marked the beginning of a new era in targeted tumor therapy. In the sense of de-escalation, omitting non-targeted cytotoxic chemotherapy altogether is often hailed as the ultimate goal of oncological research. Especially in case of small, node-negative, HER2 positive early breast cancer, it remains a challenge for clinicians to establish the safest and most efficient treatment plan while considering the significant potential for toxic side effects associated with chemotherapy and HER2 targeted therapy, and the generally excellent prognosis. In this context, several ongoing studies are currently assessing chemotherapy-free regimens as part of strategies aimed at de-escalating therapy in the field of HER2 positive early breast cancer. Despite promising early results from these studies, combination of anti-HER2 treatment with chemotherapy backbone remains standard of care.

Amid the deepening imbalance in the supply and demand of allogeneic organs, xenotransplanta-tion can be a practical alternative because it makes an unlimited supply of organs possible. How-ever, to perform xenotransplantation on patients, the source animals to be used must be free from infectious agents. This requires breeding of animals using assisted reproductive techniques, such as somatic cell nuclear transfer, embryo transfer, and cesarean-section, without colostrum de-rived in designated pathogen-free (DPF) facilities. Most infectious agents can be removed from animals produced by these methods, but several viruses known to pass through the placenta are not easy to remove, even with these methods. Therefore, in this review, we look at the characteris-tics of several viruses known to cross the placenta and determine how they can be detected. This review is intended to help maintain DPF facilities by preventing animals infected with the virus from entering DPF facilities and to help select pigs suitable for xenotransplantation.

The incidence of celiac disease and gluten intolerance has been significantly rising globally. Gluten-free product consumption registered a sudden rise also among tolerant people, due to psychosocial factors. Biscuits are popular, low-cost bakery foods, consumed by nearly everyone worldwide. The removal of gluten from the baked product causes some undesirable traits and different textures and tastes. The main goal consists of creating a food product with the same taste and texture as a product with gluten. Moreover, gluten-free bakery products are usually low-grade sources of protein and poor in dietary fiber. Quinoa is a source of TDF and valuable protein. In this study, quinoa flour was used as the main constituent in the formulation of gluten-free c to improve their nutritional properties. Six different recipes with different percentages of quinoa flour have been realized. The formulations were compared, by rheological analysis, of each other and with a wheat flour control shortbread. The recipes with rheological features more similar to control shortbread were subjected to a discrimination analysis and the preferred was characterized from a chemical-physical and sensorial point of view. The experimental shortbreads constituted a good compromise to exploit the good nutritional composition of quinoa maintaining an acceptable sensory profile.

The retrospective noninterventional study investigated the kinetic energy of video images of 18 fertilized eggs (7 were normal and 11 were abnormal) recorded by a time-lapse device leading up to the beginning of the first cleavage. The norm values of cytoplasmic particles were measured by the optical flow method. Three phases profile for normal cases were found regarding the kinetic energy that were 2.199×10⁻²⁴±2.076×10⁻²⁴, 2.369×10⁻²⁴±1.255×10⁻²⁴, and 1.078×10⁻²⁴±4.720×10⁻²⁵ (J) for the phases 1, 2, and 3, respectively. In phase 2, the energies were 2.369 × 10⁻²⁴ ± 1.255 × 10⁻²⁴ and 4.694 × 10⁻²⁴ ± 2.996 × 10⁻²⁴ (J) (mean ± SD, P = 0.0372), and the time required was 8.114 ± 2.937 and 6.018 ± 5.685 (H) (P = 0.0413) for the normal and abnormal cases, respectively. The kinetic energy change was considered a condition for applying the free energy principle that states that, for any self-organized system to be in equilibrium in its environment, it must minimize its informational free energy. The kinetic energy while interpreting it in terms of the free energy principle suggesting clinical usefulness would further our understanding of the phenomenon of fertilized egg development with respect to the birth of human life.

.Celiac disease (CeD) is a chronic, autoimmune disorder triggered by the ingestion of gluten, affecting around 1% of the global population. It is a multifactorial disease involving both genetics and environ-mental factors. Nowadays, the only available treatment for CeD is a life-long gluten-free diet (GFD), which can cause a significant burden for patients, since symptoms and mucosal injury can persist de-spite apparent compliance with a GFD. That could also lead to psychological consequences and affect the quality of life of these patients. Thankfully, recent advances in understanding the pathogenesis of CeD and the availability of various targets have made it feasible to explore pharmaceutical treatments specific to CeD. Recently, the FDA has highlighted the unmet needs of adult patients on GFD who expe-rience ongoing symptoms attributed to CeD and also show persistent duodenal villous atrophy. This re-view will outline the limitations of a GFD, describe the targets of potential novel treatment of CeD and provide an overview of the primary clinical trials involving oral and injectable agents for a non-dietary treatment of CeD.

Dacomitinib is an irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor indicated for the treatment of patients with advanced non-small cell lung cancer (NSCLC) and EGFR-activating mutations. Proton pump inhibitors decreased dacomitinib exposure. This anal-ysis summarizes the effect of H2RA on dacomitinib exposure. A within-patient comparison of steady-state trough concentrations (Ctrough,ss) of dacomitinib and its active metabolite and active moiety with and without concomitant use of H2RA was conducted using a linear mixed effects model with pooled data from 11 clinical studies in patients with NSCLC. An oral absorption PBPK model was constructed and verified using clinical PK data after a single dose of dacomitinib in healthy volunteers to estimate the effect of gastric pH altered by an H2RA on dacomitinib PK. The adjusted geometric mean of dacomitinib Ctrough,ss of dacomitinib parent, metabolite and active moiety following co-administration with H2RA was approximately 86%, 104% and 100% relative to that following dacomitinib 45 mg administration without H2RA (P>0.05). The PBPK modeling showed negligible change in dacomitinib Cmax and AUC over 0-24 hours after H2RA administra-tion, when compared with those administered dacomitinib alone. Co-administration of an H2RA with dacomitinib is not expected to have any clinically relevant effect on dacomitinib exposure.

Photosystem II (PSII) is a quinone-utilising photosynthetic system that converts light energy into chemical energy and catalyses the splitting of water. PsbA (D1) and PsbD (D2) are the core subunits of the reaction centre that provide most of the ligands to the redox-active cofactors and exhibit photooxidoreductase activities that convert quinone and water into quinol and oxygen. This analysis explored the putative uncoupled electron transfer pathways surrounding P680+ induced by far-red light (FRL) based on photosystem II (PSII) complexes containing substituted D1 subunits in Halomicronema hongdechloris. Chlorophyll f-synthase (ChlF) is a D1 protein paralog. Modelling PSII-ChlF complexes determined several key protein motifs of ChlF. The PSII complexes showed a dysfunctional Mn4CaO5 cluster if ChlF replaced the D1 protein. We propose the mechanism of chlorophyll f synthesis from chlorophyll a via free radical chemistry in an oxygenated environment created by over-excited pheophytin a and an inactive water splitting reaction due to an uncoupled Mn4CaO5 cluster in PSII-ChlF complexes. The role of ChlF in the formation of an inactive PSII reaction centre is under debate and the putative mechanisms of chlorophyll biosynthesis are discussed.

Oriented object detection is a challenging task in scene text detection and remote sensing image analysis, which has attracted extensive attention in recent years with the development of deep learning. Currently, mainstream oriented object detectors are based on preset anchor boxes. This method increases the computational load of the network and cause a large amount of anchor box redundancy. To solve this problem, we propose anchor-free oriented object detection based on the Gaussian centerness(AOGC), a single-stage anchor-free detection method. Our method uses contextual attention FPN(CAFPN) to obtain the contextual information of the target. Then we design a label assignment method for oriented objects. Finally, we develop a Gaussian kernel-based centerness branch, which can effectively determine the significance of different anchors. AOGC achieves mAP of 74.30% on the DOTA-1.0 datasets and 89.80% on the HRSC2016 datasets, respectively. AOGC exhibits superior performance to other methods in oriented anchor-free object detection methods.