Probiotic microorganisms are used in a variety of food supplements and medical formulations to promote human health. In periodontal therapy, probiotics are mainly used in the form of gels, tablets or rinses that often tend to leak from the periodontal pocket, resulting in a strongly reduced therapeutic effect. In this pilot in vitro study, we present biodegradable alginate-based particles as an alternative, highly efficient system for a periodontal delivery of probiotic bacteria to the inflammation site. For this purpose, Lactococcus (L.) lactis was encapsulated using a standardized pump-controlled extrusion-dripping method. Time-dependent bacterial release in artificial saliva was investigated over 9 days. The effect of freeze drying was explored to ensure long-term storage of L. lactis-loaded particles. Additionally, the particles were bound to dentin surface using approved bioadhesives and subjected to shear stress in a hydrodynamic flow chamber that mimics the oral cavity in vitro. Thus, round particles within the range of 0.80–1.75 mm in radius could be produced, whereby the diameter of the dripping tip had the most significant impact on the size. Although both small and large particles demonstrated a similar release trend of L. lactis, the release rate was significantly higher in the former. Following lyophilization, particles could restore their original shape within 4 h in artificial saliva; thereby, the bacterial viability was not affected. The attachment strength to dentin intensified by an adhesive could resist forces between 10 and 25 N/m². Full degradation of the particles was observed after 20 days in artificial saliva. Therefore, alginate particles display a valuable probiotic carrier for periodontal applications that have several crucial advantages over existing preparations: a highly stable form, prolonged continuous release of therapeutic bacteria, precise manufacturing according to required dimensions at the application site, strong attachment to the tooth with low risk of dislocation, high biocompatibility and biodegradability. Full article

This review article aims to provide an up-to-date overview of the main determinants of consumers’ acceptance of novel foods (new foods and ingredients) in the EU with emphasis on product’s intrinsic properties (sensory characteristics) and individual factors (socio-demographics, perceptive, psychological) by adopting a systematic approach following the PRISMA methodology. Case studies on terrestrial (i.e., insects, cultured meat and other animal origin products, plant-based food including mushrooms, plant-based analogues, pulses, and cereals) and aquatic systems (i.e., algae and jellyfish) are included focusing on age-related and cross-national differences in consumer acceptance of novel foods and ingredients. General trends have emerged that are common to all the novel foods analysed, regardless of their aquatic or terrestrial origin. Aspects such as food neophobia, unfamiliarity, and poor knowledge of the product are important barriers to the consumption of novel foods, while healthiness and environmental sustainability perception are drivers of acceptance. Sensory properties are challenging for more familiar ingredients such as plant-based food (e.g., novel food made by pulses, mushrooms, cereals and pseudocereals). Results are discussed in terms of feasibility of introducing these products in the EU food systems highlighting strategies that can encourage the use of new ingredients or novel foods. Full article

There is no practical and at the same time objective colour system available for describing cultivated roses (Rosa L. cultivars). For this reason, a new colour classification system was developed which is colorimetrically balanced and appropriate for algorithmic colour identification; however, it is also suitable for field-work. The system is based on the following colorimetric criteria: (A) Each colour category is characterised by a measured petal colour in the CIE L*a*b* standard as the centroid of the category. (B) The CIEDE2000 colour differences between the adjacent centroid colours are limited (5 < ΔE₀₀ < 7). (C) The maximal colour difference between the measured colours in a category is also limited (to 12.12 ΔE₀₀). (D) A measured petal colour can only be classified into an existing category if the colour difference from the centroid colour of the given category is less than 5.81 ΔE₀₀, otherwise a new category is required. (E) A category is only considered non-redundant if it has at least one measured petal colour that cannot be classified elsewhere. (F) The classification of the petal colours is based on the least colour difference from the centroid colours. As a result, 133 colour categories were required for describing all the 8139 petal colours of the rose cultivars of the Budatétény Rose Garden (Hungary). Each colour category has the following parameters: standardised colour name, the colorimetric parameters of the centroid, grouping, RHS colour chart coding, and reference cultivars, which are described in the article. Full article

Environmental degradation leads to an unsustainable food system. In addition to this issue, the consumption of foods that improve people’s health and well-being is recommended. One of the alternatives is undoubtedly the use of by-products of winemaking, namely in the form of grape pomace flour (GPF). To verify the benefits of using the Touriga Nacional and Arinto (Vitis vinifera L.) flour varieties, analytical determinations were made to identify and quantify different components. In terms of nutritional characterization, the Touriga Nacional GPF showed results that indicate better nutritional quality than the Arinto GPF. The Touriga Nacional and Arinto samples had protein contents of 10.13% and 8.38%, polyunsaturated fatty acids of 6.66% and 5.18%, soluble dietary fiber of 14.3% and 1.7%, and insoluble dietary fiber of 55.1% and 46.4%, respectively. The anthocyanins, proanthocyanidins, and flavonols presented in samples were detected by HPLC-DAD/ESI-MS. Atomic absorption spectrometry revealed elevated concentrations of certain elements in Touriga Nacional compared to Arinto, with the former showing higher levels of aluminum (130 mg/kg) and iron (146 mg/kg) against the latter’s Al (120 mg/kg) and Fe (112 mg/kg) content. GPF could become a valuable ingredient due to its nutritional quality and high content of various polyphenols. Full article

The Preboreal (11.75–10.70 ka BP) is still the least paleogeographically studied time interval in the central part of the East European Plain. High-resolution multi-proxy studies of lacustrine sediments at the Seltso site located in the Desna River floodplain (Dnieper River basin) were conducted. Radiocarbon dating, loss-on-ignition determination, sedimentological and palynological studies and identification of Non-Pollen Palynomorphs in lacustrine sediments allow us to reconstruct changes in vegetation caused by rapid warming at the Younger Dryas–Holocene boundary, short-term climatic fluctuations within the Preboreal and subsequent resumption of warming. Initial Preboreal warming reached its maximum at about 11.5 ka BP when a relatively dry continental climate existed. Between 11.4 and 11.2 ka BP, a short-term cooling corresponding to the Preboreal Oscillation in Greenland occurred, as indicated by a significant reduction of woody vegetation and expansion of open plant communities. In the Late Preboreal, approximately 11.2–10.7 ka BP, warming resumed, which was accompanied by a decrease in the climate continentality. Comparison with high-resolution lithological and palynological data from eight reliably dated sections of the central East European Plain indicates that in northwestern and central Europe, the impact of the Preboreal Oscillation cooling on the vegetation and the lake ecosystems’ development was probably somewhat stronger. Full article

Background: Traditional gel-based (wet) electrodes for biopotential recordings have several shortcomings that limit their practicality for real-world measurements. Dry electrodes may improve usability, but they often suffer from reduced signal quality. We sought to evaluate the biopotential recording properties of a novel mixed ionic–electronic conductive (MIEC) material for improved performance. Methods: We fabricated four MIEC electrode form factors and compared their signal recording properties to two control electrodes, which are electrodes commonly used for biopotential recordings (Ag-AgCl and stainless steel). We used an agar synthetic skin to characterize the impedance of each electrode form factor. An electrical phantom setup allowed us to compare the recording quality of simulated biopotentials with ground-truth sources. Results: All MIEC electrode form factors yielded impedances in a similar range to the control electrodes (all <80 kΩ at 100 Hz). Three of the four MIEC samples produced similar signal-to-noise ratios and interfacial charge transfers as the control electrodes. Conclusions: The MIEC electrodes demonstrated similar and, in some cases, better signal recording characteristics than current state-of-the-art electrodes. MIEC electrodes can also be fabricated into a myriad of form factors, underscoring the great potential this novel material has across a wide range of biopotential recording applications. Full article

The rise of e-commerce has significantly impacted consumer shopping habits, resulting in profit loss for traditional supply chains. In response to intense competition, numerous companies have transitioned their business models to embrace dual-channel configurations, seeking to captivate customers and increase their market share. Nonetheless, research on decentralized dual-channel supply chain configurations is scarce and predominantly concentrates on single-period pricing. This paper addresses this gap by employing Stackelberg’s game theory to investigate the multi-periodic pricing and remanufacturing decisions within a decentralized dual-channel supply chain with reverse logistics, specialized in the manufacturing and sales of pharmaceutical products. Moreover, this work considers that the online channel pays a sales commission to the pharmacy in return for the provided after-sales services, aiming to incorporate the aspect of sharing revenues. A mathematical formulation is proposed in a multi-periodic environment allowing us to simultaneously maximize the total profits of the manufacturer, the pharmacy and the online channel, by optimizing the pricing and remanufacturing strategies. Numerical analyses examine the customer purchasing preference’s effect on the demand and pricing decisions of each channel, the impact of the collection cost on the optimal remanufacturing strategy, and assess the break-even point of the total profits generated in both channels according to the sales commission. This study’s novelty lies in employing Stackelberg’s game theory to develop a mathematical formulation for the multi-periodic pricing and remanufacturing problem within a decentralized dual-channel supply chain, incorporating a sales commission between both distributors. Full article

Spina bifida includes a spectrum of different neural tube defects. Myelomeningocele is the most serious type and is associated with a risk of paralysis and sensory dysfunction below the affected level, bladder/bowel dysfunction, brain dysmorphology, and impaired health-related quality of life (HRQoL). The aim of this study was to describe the establishment of linguistic, content and face validity of the Swedish version of a Quality-of-Life Assessment for children (QUALAS-C, n = 10 items), teenagers (QUALAS-T, n = 10 items) and adults with spina bifida (QUALAS-A, n = 15 items) based on the original US English versions. The process included close collaboration with the original instrument developer and complied with international standards on patient-reported outcome measurements. The procedure includes forward translation, expert and patient/parent review and reconciliation, back translation, back translation review and cognitive debriefing interviews with 16 people with spina bifida aged 8 to 33, providing them with the possibility of evaluating the clarity, adequacy, and comprehensiveness of QUALAS-C, QUALAS-T and QUALAS-A, respectively. The interviews lasted a median of 15 min (range 8–16) for QUALAS-C, 10 min (range 9–15) for QUALAS-T and 24 min (range 9–38) for QUALAS-A. Four main issues/topics needed attention and discussion after both the forward and back translation. Following the back translation review, all issues were resolved. The patient feedback revealed recognition of the HRQoL issues included in QUALAS, and also difficulties in understanding some questions. After the patients’ evaluation, four items were reworded for clarity. No study participant reported a wish to add to or remove questions from QUALAS. Hence, the Swedish versions of QUALAS became conceptually equivalent to the original US English versions and achieved linguistic, content and face validity. While empowering the voices of people with spina bifida, these results also enable their HRQoL to be properly assessed in research and clinical care in Sweden and in international studies. Full article

B-cell lymphomas (BCL) is the most frequent hematological cancer in dogs. Treatment typically consists of chemotherapy, with CHOP-based protocols. However, outcome remains generally poor, urging the exploration of new therapeutic strategies with a targeted approach. Myc transcription factor plays a crucial role in regulating cellular processes, and its dysregulation is implicated in numerous human and canine malignancies, including canine BCL (cBCL). This study aims to evaluate the efficacy of indirectly inhibiting Myc in cBCL using BI2536 and MZ1 compounds in two in vitro models (CLBL-1 and KLR-1201). Both BI2536 and MZ1, alone and combined, affected cell viability in a significant concentration- and time-dependent manner. Western Blot revealed an upregulation of PLK1 expression in both cell lines upon treatment with BI2536, in association with a reduction in c-Myc protein levels. Conversely, MZ1 led to a decrease in its primary target, BRD4, along with a reduction in c-Myc. Furthermore, BI2536, both alone and in combination with MZ1, induced larger transcriptomic changes in cells compared to MZ1 alone, primarily affecting MYC target genes and genes involved in cell cycle regulation. These data underscore the potential role of Myc as therapeutic target in cBCL, providing a novel approach to indirectly modulate this molecule. Full article

(1) Objectives: A divergence in self- and preceptor-evaluations of clinical skills has been noted during Advanced Pharmacy Practice Experiences (APPEs). The goal of this study was to determine the domains of overestimation of clinical skills by students during their APPE rotations. (2) Methods: Preceptor-assigned grades for APPE rotations from 2017–2022 were analyzed to identify instances of letter grade B or lower. The self- and preceptor-evaluations of APPE rotation were compared to determine the domains of divergence in evaluation between students and preceptors. (3) Results: Between 2017 and 2022, 305 student APPE rotations were graded as B or lower (~14%) by the preceptors. A statistically significant difference was noted between self- and preceptor-assigned letter grades across all practice settings including ambulatory patient care, community pharmacy, general medicine patient care, hospital/health system pharmacy, and special population patient care APPE rotations. In addition, examining the self- and preceptor evaluation rubric for these rotations revealed a statistically significant overestimation of clinical skills by students in all 9 domains of APPE evaluation. Finally, the divergence in the rating of clinical skills between student- and preceptor evaluation was found to be highest in the domains of planning and follow-up of patient care, disease knowledge, and communication with patients. (4) Conclusions: Students who fail to exhibit exemplary practice readiness during APPEs tend to overestimate their clinical skills in all domains of APPE evaluation. The results from our study support the need for additional avenues to assist in the identification of deficits in student learning before APPEs to increase their self-awareness (metacognition). Full article

Background/Objective: To ensure that implants are able to support prosthetic rehabilitation, a stable and functional union between the bone and the implant surface is crucial to its stability and success. To increase bone volume and density and excel bone-implant contact, a novel drilling method, called osseodensification (OD), was performed. To assess the effectiveness of the osseodensification drilling protocol versus the conventional surgical technique on implant stability. Methods: Bone Level Tapered Straumann implants were placed side-by-side with both OD and subtractive conventional drilling (SD) in 90 patients from CESPU—Famalicão clinical unit. IT was measured using a manual torque wrench, and the Implant stability quotient (ISQ) value was registered using the Osstell^® IDX. Results: According to the multifactorial ANOVA, there were statistically significant differences in the mean IT values due to the arch only (F(1.270) = 4.702, p-value = 0.031 < 0.05). Regarding the length of the implant, there were statistically significant differences in the mean IT in the OD group (p = 0.041), with significantly lower mean IT values for the Regular implants compared to the Long. With respect to the arch, the analyses of the overall ISQ values showed an upward trend in both groups in the maxilla and mandible. High levels of IT also showed high ISQ values, which represent good indicators of primary stability. Conclusions: OD does not have a negative influence on osseointegration compared to conventional subtractive osteotomy. Full article

Glioblastoma multiforme (GBM) is a very aggressive and lethal primary brain cancer in adults. The multifaceted nature of GBM pathogenesis, rising from complex interactions between cells and the tumor microenvironment (TME), has posed great treatment challenges. Despite significant scientific efforts, the prognosis for GBM remains very poor, even after intensive treatment with surgery, radiation, and chemotherapy. Efficient GBM management still requires the invention of innovative treatment strategies. There is a strong necessity to complete cancer in vitro studies and in vivo studies to properly evaluate the mechanisms of tumor progression within the complex TME. In recent years, the animal models used to study GBM tumors have evolved, achieving highly invasive GBM models able to provide key information on the molecular mechanisms of GBM onset. At present, the most commonly used animal models in GBM research are represented by mammalian models, such as mouse and canine ones. However, the latter present several limitations, such as high cost and time-consuming management, making them inappropriate for large-scale anticancer drug evaluation. In recent years, the zebrafish (Danio rerio) model has emerged as a valuable tool for studying GBM. It has shown great promise in preclinical studies due to numerous advantages, such as its small size, its ability to generate a large cohort of genetically identical offspring, and its rapid development, permitting more time- and cost-effective management and high-throughput drug screening when compared to mammalian models. Moreover, due to its transparent nature in early developmental stages and genetic and anatomical similarities with humans, it allows for translatable brain cancer research and related genetic screening and drug discovery. For this reason, the aim of the present review is to highlight the potential of relevant transgenic and xenograft zebrafish models and to compare them to the traditionally used animal models in GBM research. Full article

Urban green infrastructure plays a crucial role in sustainable city development by offering a multitude of benefits, including improved environmental quality, increased social well-being, and enhanced economic prosperity. Evaluation and monitoring of regulatory implementation stand as essential components in the advancement of urban green infrastructure (GI) as they indicate the efficacy of regulatory acts and enable the assessment of their implementation success and adaptability to identified needs. This study identifies barriers and drivers based on the views of 352 professionals surveyed between 2018 and 2023 in Serbia. The primary data collection method employed questionnaire surveys. This study identified a range of barriers within existing legal frameworks, foremost of which include the lack of coordination and coherence between relevant ministries and governmental agencies, insufficient financial and human resources, the lack of transparency in the regulation development process, the need for strengthening technical capacities, and the absence of an adequate urban GI strategy. This research serves as a foundation for conceptualising GI regulatory elements that enhance urban GI development. Addressing these barriers necessitates efforts to improve coordination and collaboration among stakeholders, increase public participation, and enhance transparency in the regulatory process. Full article

Malaria is a parasitic infection that may result in an acute, life-threatening illness. It is a major public health problem in the tropical world. The disease is caused by the parasites of the genus Plasmodium and is transmitted by female Anopheles mosquitoes. Saudi Arabia is in the elimination phase of malaria control. Several parts of Saudi Arabia report cases of imported malaria among travelers and visitors. The city of Makkah in Saudi Arabia has a population of about 2.3 million. Moreover, over 6 million religious visitors from different parts of the world visit Makkah annually. During the COVID-19 outbreak, travel restrictions were enforced in Makkah to contain the spread of COVID-19. We compare the total reported cases of malaria in Makkah before, during, and after COVID-19 travel restrictions in this retrospective cross-sectional study. Data on demographics, clinical data, and laboratory parameters were collected from the medical records of the Ministry of Health, Saudi Arabia. The annual malaria incidence rates in Makkah were 29.13/million people (2018), 37.82/million people (2019), 15.65/million people (2020), 12.61/million people (2021), and 48.69/million people (2022). Most of the malaria cases in Makkah were caused by Plasmodium falciparum, followed by P. vivax. Sudan, Nigeria, Yamen, Pakistan, and India are the top five countries contributing to malaria cases in Makkah. Weekly malaria case analyses revealed that COVID-19-related travel restrictions resulted in zero malaria cases in Makkah, indicating the magnitude of the travel-related malaria burden in the city. Full article

The Hip Dysfunction and Osteoarthritis Outcome Score for Joint Replacement (HOOS-JR) was developed as a short-form survey to measure progress after total hip arthroplasty (THA). However, the longitudinal validity of the scale structure pertaining to the modified five-item HOOS-JR has not been assessed. Therefore, the purpose of this study was to evaluate the structural validity, longitudinal invariance properties, and latent growth curve (LGC) modeling of the modified five-item HOOS-JR in a large multi-site sample of patients who underwent a THA. A longitudinal study was conducted using data from the Surgical Outcome System (SOS) database. Confirmatory factor analyses (CFAs) were conducted to assess the structural validity and longitudinal invariance across five time points. Additionally, LGC modeling was performed to assess the heterogeneity of the recovery patterns for different subgroups of patients. The resulting CFAs met most of the goodness-of-fit indices (CFI = 0.964–0.982; IFI = 0.965–0.986; SRMR = 0.021–0.035). Longitudinal analysis did not meet full invariance, exceeding the scalar invariance model (CFI_DIFF = 0.012; χ²_DIFF test = 702.67). Partial invariance requirements were met upon release of the intercept constraint associated with item five (CFI_DIFF test = 0.010; χ²_DIFF = 1073.83). The equal means model did not pass the recommended goodness-of-fit indices (CFI_DIFF = 0.133; χ²_DIFF = 3962.49). Scores significantly changed over time, with the highest scores identified preoperatively and the lowest scores identified at 2- and 3-years postoperatively. Upon conclusion, partial scalar invariance was identified within our model. We identified that patients self-report most improvements in their scores within 6 months postoperatively. Females reported more hip disability at preoperative time points and had faster improvement as measured by the scores of the modified five-item HOOS-JR. Full article

In this paper, we consider a downlink non-orthogonal multiple access (NOMA) system over Nakagami-m channels. The single-antenna base station serves two single-antenna NOMA users based on statistical channel state information (CSI). We derive the closed-form expression of the exact outage probability under a given decoding order, and we also deduce the asymptotic outage probability and diversity order in a high-SNR regime. Then, we analyze all the possible power allocation ranges and theoretically prove the optimal power allocation range under the corresponding decoding order. The demarcation points of the optimal power allocation ranges are affected by target data rates and total power, without an effect from the CSI. In particular, the values of the demarcation points are proportional to the total power. Furthermore, we formulate a joint decoding order and power allocation optimization problem to maximize the sum throughput, which is solved by efficiently searching in our obtained optimal power allocation ranges. Finally, Monte Carlo simulations are conducted to confirm the accuracy of our derived exact outage probability. Numerical results show the accuracy of our deduced demarcation points of the optimal power allocation ranges. And the optimal decoding order is not constant at different total transmit power levels. Full article

The rapid and accurate estimation of forest carbon stock is important for analyzing the carbon cycle. In order to obtain forest carbon stock efficiently, this paper utilizes airborne LiDAR data to research the applicability of different feature screening methods in combination with machine learning in the carbon stock estimation model. First, Spearman’s Correlation Coefficient (SCC) and Extreme Gradient Boosting tree (XGBoost) were used to screen out the variables that were extracted via Airborne LiDAR with a higher correlation with carbon stock. Then, Bagging, K-nearest neighbor (KNN), and Random Forest (RF) were used to construct the carbon stock estimation model. The results show that the height statistical variable is more strongly correlated with carbon stocks than the density statistical variables are. RF is more suitable for the construction of the carbon stock estimation model compared to the instance-based KNN algorithm. Furthermore, the combination of the XGBoost algorithm and the RF algorithm performs best, with an R² of 0.85 and an MSE of 10.74 on the training set and an R² of 0.53 and an MSE of 21.81 on the testing set. This study demonstrates the effectiveness of statistical feature screening methods and Random Forest for carbon stock estimation model construction. The XGBoost algorithm has a wider applicability for feature screening. Full article

Posiphen is a small molecule that exhibits neuroprotective properties by targeting multiple neurotoxic proteins involved in axonal transport, synaptic transmission, neuroinflammation, and cell death. Its broad-spectrum effects make it a promising candidate for treating neurodegenerative conditions, including Alzheimer’s and Parkinson’s diseases. Despite extensive investigation with animal models and human subjects, a comprehensive comparative analysis of Posiphen’s pharmacokinetics across studies remains elusive. Here, we address this gap by examining the metabolic profiles of Posiphen and its breakdown into two primary metabolites—N1 and N8—across species by measuring their concentrations in plasma, brain, and CSF using the LC-MS/MS method. While all three compounds effectively inhibit neurotoxic proteins, the N1 metabolite is associated with adverse effects. Our findings reveal the species-specific behavior of Posiphen, with both Posiphen and N8 being predominant in various species, while N1 remains a minor constituent, supporting the drug’s safety. Moreover, in plasma, Posiphen consistently showed fast clearance of all metabolites within 8 h in animal models and in human subjects, whereas in CSF or brain, the compound has an extended half-life of over 12 h. Combining all our human data and analyzing them by population pharmacokinetics showed that there are no differences between healthy volunteers, Alzheimer’s, and Parkinson’s patients. It also showed that Posiphen is absorbed and metabolized in a similar fashion across all animal species and human groups tested. These observations have critical implications for understanding the drug’s safety, therapeutic effect, and clinical translation. Full article

Laser activation can lead to the formation of a layer of aluminum on the surface of aluminum nitride ceramics, thereby preparing metal circuits. Under various gas environments, there are differences in the aluminum layers precipitated by laser-activated aluminum nitride ceramics. The existing literature uses the width of the metal layer to characterize this difference, and these data are very imprecise. Usually, laser energy density is used to describe this processing difference. However, the existing concept of laser energy density is an average value and is not suitable for the threshold of laser activation, because the intensity gradient of the focused Gaussian beam is large, and different intensity distributions represent different energy levels. This article applied a precise concept of laser energy density that sees it as being proportional to light intensity and can be used to evaluate the difference in laser energy density required for the decomposition of aluminum nitride ceramics under various gas bath conditions precisely. Due to the strong energy of a focused Gaussian beam, it is not possible to directly obtain the intensity distribution. Here, the intensity distribution of the collimated beam was used to indirectly obtain the intensity distribution of the focused Gaussian beam, and the threshold values for laser activation under different gas baths were calculated. It was found that the minimum energy density in air increased by 12.5%, and the minimum energy density in nitrogen increased by 3%, using the minimum energy density required for laser activation in argon as the reference. Full article

SARS-CoV-2 primarily infects the lungs via the ACE2 receptor but also other organs including the kidneys, the gastrointestinal tract, the heart, and the skin. SARS-CoV-2 also infects the brain, but the hematogenous route of viral entry to the brain is still not fully characterized. Understanding how SARS-CoV-2 traverses the blood-brain barrier (BBB) as well as how it affects the molecular functions of the BBB are unclear. In this study, we investigated the roles of the receptors ACE2 and DPP4 in the SARS-CoV-2 infection of the discrete cellular components of a transwell BBB model comprising HUVECs, astrocytes, and pericytes. Our results demonstrate that direct infection on the BBB model does not modulate paracellular permeability. Also, our results show that SARS-CoV-2 utilizes clathrin and caveolin-mediated endocytosis to traverse the BBB, resulting in the direct infection of the brain side of the BBB model with a minimal endothelial infection. In conclusion, the BBB is susceptible to SARS-CoV-2 infection in multiple ways, including the direct infection of endothelium, astrocytes, and pericytes involving ACE2 and/or DPP4 and the blood-to-brain transcytosis, which is an event that does not require the presence of host receptors. Full article

The glyoxalase system, comprising GLO1 and GLO2 enzymes, is integral in detoxifying methylglyoxal (MGO) generated during glycolysis, with dysregulation implicated in various cancer types. The MEK/ERK/SMAD1 signaling pathway, crucial in cellular processes, influences tumorigenesis, metastasis, and angiogenesis. Altered GLO1 expression in cancer showcases its complex role in cellular adaptation and cancer aggressiveness. GLO2 exhibits context-dependent functions, contributing to both proapoptotic and antiapoptotic effects in different cancer scenarios. Research highlights the interconnected nature of these systems, particularly in ovarian cancer and breast cancer. The glyoxalase system’s involvement in drug resistance and its impact on the MEK/ERK/SMAD1 signaling cascade underscore their clinical significance. Furthermore, this review delves into the urgent need for effective biomarkers, exemplified in ovarian cancer, where the RAGE-ligand pathway emerges as a potential diagnostic tool. While therapeutic strategies targeting these pathways hold promise, this review emphasizes the challenges posed by context-dependent effects and intricate crosstalk within the cellular milieu. Insights into the molecular intricacies of these pathways offer a foundation for developing innovative therapeutic approaches, providing hope for enhanced cancer diagnostics and tailored treatment strategies. Full article

Essential trace elements are micronutrients whose deficiency has been associated with altered fertility and/or adverse pregnancy outcomes, while surplus may be toxic. The concentrations of eight essential trace elements were measured using inductively coupled mass spectrometry (ICP-MS) and assessed with respect to clinical in vitro fertilization (IVF) outcomes in a population of 51 women undergoing IVF with intracytoplasmic sperm injection (ICSI), pre-implantation genetic screening for aneuploidy (PGT-A), and single frozen euploid embryo transfer (SET/FET). Specifically, copper (Cu), zinc (Zn), molybdenum, selenium, lithium, iron, chromium, and manganese were quantified in follicular fluid and whole blood collected the day of vaginal oocyte retrieval (VOR) and in urine collected the day of VOR and embryo transfer. We found that the whole blood Cu/Zn ratio was significantly associated with superior responses to ovarian stimulation. Conversely, the whole blood zinc and selenium concentrations were significantly associated with poor ovarian response outcomes. Higher levels of whole blood zinc and selenium, urinary selenium, lithium, and iron had significant negative associations with embryologic outcomes following IVF. Regarding clinical IVF outcomes, higher urinary molybdenum concentrations the day of VOR were associated with significantly lower odds of implantation and live birth, while higher urinary Cu/Mo ratios on the day of VOR were associated with significantly higher odds of implantation, clinical pregnancy, and live birth. Our results suggest that essential trace element levels may directly influence the IVF outcomes of Spanish patients, with selenium and molybdenum exerting negative effects and copper-related ratios exerting positive effects. Additional studies are warranted to confirm these relationships in other human populations. Full article