Vitamin D is a nutrient with anti-inflammatory properties whose role is currently being evaluated in COVID-19. Although studies are conflicting, they seem to suggest a role for vitamin D in reducing disease susceptibility but not in improving clinical outcome. In order to understand why vitamin D does not seem to have much effect on decreasing disease severity, it is essential to appreciate pulmonary vitamin D metabolism. To reach the pulmonary compartment, vascular endothelial cells would need to take up vitamin D from the blood stream, but they lack vitamin D receptor (VDR) and the activating enzyme CYP27B1. Endothelialitis – an important disease manifestation of COVID-19 – is therefore not expected to be directly affected by vitamin D. Bronchial epithelial cells are usually among the first to be infected with SARS-CoV-2. They do express both VDR and CYP27B1, but circulating vitamin D may not reach bronchial epithelial cells without transportation from the blood stream through the blood vessel wall. Inhalation therapy with vitamin D has therefore been suggested as an alternative for oral administration to bypass endothelial cells and efficaciously target bronchial epithelium. In conclusion, based on the principles of pulmonary vitamin D metabolism, it is not expected that vitamin D administration has a significant effect on COVID-19 severity. Vitamin D is more likely to reduce SARS-CoV-2 susceptibility, but reaching the airways with oral supplementation will be difficult and vitamin D inhalation therapy should be considered.

The performance of a normal-strength SHCC under impact loading was studied using the results obtained from a split Hopkinson tension bar (SHTB). The focus of the investigation is to explain the mechanisms behind the peculiar rate-dependent behavior of SHCC under tensile loading. With the help of frames obtained by high-speed cameras and the subsequent Digital Image Correlation (DIC) analysis, the stress-strain relation of the SHCC obtained in SHTB was analyzed. The investigation of the composite’s behavior was supported by constituent-level experiments on the non-reinforced matrix of the SHCC and on the fiber-matrix bond. In the case of the constituent matrix, the well-known apparent increase in the tensile strength of the cement-based matrix and its influence on the behavior of SHCC was studied. For this purpose, experiments on the SHCC specimens with different geometries were performed in the SHTB. The results obtained from these experiments and those obtained by DIC show that commonly used analytical models, in which the specimen is assumed elastic, cannot capture the effects of structural inertia on the results. Thus, an alternative novel method based on the results of DIC has been used to explain and quantify the contribution of structural inertia. The rate-dependent behavior of the fiber-matrix bond was studied by performing high-speed single fiber pullout tests in a miniaturized split Hopkinson tension bar. This novel experimental technique enabled explanation of the rate-dependent bridging action of the fibers in SHCC. Based on the results, the enhanced behavior of SHCC under impact loading is explained.

The extracts from the aerial parts of Helianthus salicifolius A. Dietr and Helianthus tuberosus L. collected in June were obtained using carbon dioxide supercritical fluid extraction with water as co-solvent. The antimicrobial activity in vitro of these extracts were determined against the reference species of Gram-positive and Gram-negative bacteria as well as fungi, representing by the yeast species of Candida spp. The following parameters were estimated: minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) or minimum fungicidal concentration (MFC). Both extracts were found to possess antimicrobial activity with MIC = 0.62-5 mg mL-1 for bacteria and MIC = 5-10 mg mL-1 for yeasts, showing bactericidal (MBC/MIC = 2-4) or fungicidal effect (MFC/MIC = 1-2 ). The highest activity was observed against S. aureus ATCC 29213 (MIC = 0.62 mg mL-1 for H. salicifolius extract; MIC = 2.5 mg mL-1 for H. tuberosus extract). Bactericidal effect of both extracts against S. aureus ATCC 29213 was confirmed by time-kill assay. Higher antioxidant activity was found for H. tuberosus extract (EC50 = 0.332 mg mL-1) as compared to that of H. salicifolius (EC50 = 0.609 mg mL-1). The total polyphenol content (TPC) expressed as gallic acid equivalents (GAE) was 13.75 ± 0.50 mg GAE (g of H. salicifolius extract)-1 and 33.06 ± 0.80 mg GAE (g of H. tuberosus extract)-1. There was a correlation between the antioxidant potential of both extracts and TPC but not between antistaphylococcal activity and TPC. The obtained data suggest potential application of these extracts as the natural preparations with the biocidal activity, including those with antistaphylococcal activity. Besides, both extracts may be regarded as potential natural conservants in cosmetics as well as natural preservatives in food.

In this paper we will find that, according to holographic principle {\cite{Holografico}} and thus considering Universe as the ensemble of $\aleph$ information bits or minimum particles of mass $m_{g}$, the contribution to galactic rotation curves can be due the rest of the visible Universe through a non-local collective gravitational interaction of all particles within the Universe's horizon, as a consequence of which all particles are gravitationally entangled and form a unified statistical ensemble. Therefore, we can to describe this global effect in terms of standard local Newtonian gravity within galaxies for the explanation of flatness galactic rotation curves as a possible alternative to the dark matter or MOND hypothesis. We will find a solution for the baryonic Tully-Fischer relation: $M_{b} = A v_{f}^4 \iff A = \left[a_{0}G \right]^{-1}$ with $a_{0} = \frac{cH_{0}}{2\pi}$, where $H_{0}$ is the Hubble constant at present Time $t_{0}$ and $M_{b}$, $G$ and $c$ are the galaxy baryonic mass, gravitational constant and constant speed of light in vacuum respectively. Also we will find the mass discrepancy-acceleration relation, thus obtaining a possible solution for each of the three laws of rotationally supported galaxies proposed in ({\cite{McGaugh}},{\cite{McGaugh1}}).

Stable isotope-assisted approaches can improve untargeted LC-HRMS metabolomics studies. Here, we demonstrate at the example of chemically stressed wheat that metabolome-wide internal standardization by globally 13C-labeled metabolite extract (GLMe-IS) of experimental-condition-matched biological samples can help to improve coverage of treatment-relevant metabolites and aid in the post-acquisition assessment of putative matrix effects in samples obtained upon different treatments. For this, native extracts of toxin- and mock-treated (control) wheat ears were standardized by the addition of uniformly-13C-labeled wheat ear extracts that were cultivated under similar experimental conditions (toxin-treatment and control) and measured with LC-HRMS. The results show that 996 wheat-derived metabolites were detected with the non-condition-matched 13C-labeled metabolite extract, while another 68 were only covered by the experimental-condition-matched GLMe-IS. Additional testing is performed with the assumption that GLMe-IS enables compensation for matrix effects. Although on average no severe matrix differences between both experimental conditions were found, individual metabolites may be affected as is demonstrated by wrong decisions with respect to the classification of significantly altered metabolites. When GLMe-IS was applied to compensate for matrix effects, 272 metabolites showed significantly altered levels between treated and control samples, 42 of which would not have been classified as such without GLMe-IS.

Magneto-optic (MO) imaging and sensing are at present the most developed practical applications of thin-film MO garnet materials. However, future component and system-level sensors and imagers technology improvements are still necessary in order to improve sensitivity for a range of established and also the forward-looking applications. These improvements are expected to originate from new material system development. We propose a set of technological modifications for the RF-magnetron sputtering deposition and crystallization annealing of magneto-optic bismuth-substituted iron-garnet films and investigate the improved material properties. Results show that standard crystallization annealing for the as-deposited ultrathin (sputtered 10 nm thick, amorphous phase) films resulted in more than a factor of two loss in the magneto-optical activity of the films in visible spectral region, compared to the liquid-phase grown epitaxial films. Results also show that an additional 10 nm-thick metal-oxide (Bi2O3) protective layer above the amorphous film results in ~2.7 times increase in the magneto-optical quality of crystallized iron-garnet films. On the other hand, the effects of post-deposition oxygen (O2) plasma treatment on the magneto-optical (MO) properties of Bismuth substituted iron garnet thin films material is investigated. Results show that, in the visible part of the electromagnetic spectrum (at 532 nm), the O2 treated (up to 3 minutes) garnet films retain higher specific Faraday rotation and figure of merit than those of non-treated garnet films.

This research paper is mainly aimed to elaborate the initial risk management and measures which government of Pakistan took towards Novel Corona Virus (COVID-2019). This initial response and planning was devised after the early outbreak of COVID-2019 in Wuhan, China in early time of January 2020. Pakistan devised a comprehensive plan that not to evacuate their student from Wuhan, China. The government of Pakistan in compliance with the National Institute of Health (NIH) devised and documented comprehensive plans such as the flight operations postponed related to Umerah pilgrims, which were intended to go to sacred places of KSA (The Kingdom of Saudi Arabia). The process of visa, immigration policy totally changed and the government of Pakistan notified it officially that, no new visas of visit, student, and business would be issued in due course of uncertainty due to COVID-2019. The government of Pakistan also announced medical emergency and notified through the country’s provinces the process of testing and treatment of COVID-2019. The government of Pakistan also allocated funds for medical supplies and named out the particular country’s best laboratories. The government of Pakistan also locked down all the cities with the emergency announcement that people should stay inside the home in quarantine or self-isolation. NIH (The National Institute of Health) played a vital role in executing the planning to cope with COVID – 2019). The National Institute of Health responded as “The Centre for Disease Control”. In aid to the government, the national army of Pakistan responded in a proactive manner towards planed execution. The medical corps of Pakistan army dedicated themselves to treat the suspected patients of COVID – 2019. Due to plans, policies being documented, implemented in such a way productive way that from February 28, 2020 to till date there is not much critical situation and issues are not present. There are much productive results as there is not much boom in a rise of COVID-2019 patients. This lockdown under the authority of the provinces resulted in fruitful outcomes. Background: On January 02, 2020, authorities of the People Republic of China elaborated that they have encountered with a novel type of infectious viral disease 2019. Later on January 12, the authorities from China elaborated the related sequence of Corona Virus diseases 2019 names as COVID – 2019. When COVID-2019 being identified in Wuhan, Hubei China, as an early response the Government of Pakistan in support of the National Institute of Health (Field Epidemiology & Disease Surveillance Division) published a health advisory about novel coronavirus. Methods: According to Global Health Security Index, Pakistan is ranked as 105th country among 195 countries in GHS index. Overall Score of Pakistan is 35.5. The score of Early Detection and Reporting for Epidemics of Potential International Concern is 41.7. A Graphical depiction of the COVID-19 cases placed until April 10, 2020 as well as a graph trend line of recovered as well as death rate is also depicted. According to the graphical facts of Government of Pakistan and World meters, the recovery rate of COVID-19 is about 98 percent and 2.1 percent death rate is reported against the total cases. Trend analysis with line graph was drawn based on available data from official dashboard web portal of the government of Pakistan and worldometers.info. Data figures were incorporated from March to August 18, 2020 in MS Excel and then subsequently deployed to draw trend analysis from managing risk to recovery. Results: The line graph showed a slowdown in the COVID-19 cases and high rate of recoveries from COVID-19 in Pakistan. On March 11, 2020, there were 20 confirmed cases of coronavirus reported in Pakistan. No death was recorded in very first seven days, on March 18, 2020 only two deaths were reported. On August 18, 2020, there were 272128 recoveries, 6201 deaths, total confirmed cases 290445, and total test were 2340072 in Pakistan. As a results, we can report that due to early measures taken by government of Pakistan no mass scale destruction in terms of death and cases been recorded in Pakistan. Conclusions: To till date, the government of Pakistan tried its level best to minimize the coronavirus cases as much as they can. However, the ending of the potential attack of an outbreak would depend upon the well organized and coordinated approach at all levels such as true directed decisions, fully preparedness, as well implementation and evaluation of continuous decisions. As the recovery rate of the cases is 98 percent and merely death rate is 2.1 percent, concluded that in future it would be a good sign to stop the potential outbreak. Also, lock down as well as precautionary measurement taken by the provincial governments resulted a decline number of COVID-19 cases in the country. Another good sign is that merely 4 percent population of Pakistan is of more than 60 years of old it can be concluded that there are less chances of mass death due to outbreak of COVID-19.

A patient will visit physicians when he/she feels ill. This illness is not for COVID-19 but it is a general tendency of human being to visit doctor probably it can not be controlled by general drug. When a patient comes to a doctor, the doctor examines him/her after knowing his/her problem. The physician always asks him/her about some questions related to him/her daily life. For example, if a young male patient comes to a doctor with a symptom of fever and cough, the first question doctor asked him that he has a habit of smoking. Then doctor asks him whether this type of symptom appeared often to him previously or not. If the answers of both questions are yes, then the first one is habit and the second one is that he may suffering from some serious disease or a disease due to the weather. The aim of this paper is to consider habit of the patient as well as he/she has been affected by a critical disease. This information is used to build a model that will predict whether there is any possibility of his/her being affected by COVID-19. This research work contributes to tackle the pandemic situation occurred due to Corona Virus Infectious Disease, 2019 (Covid-19). Outbreak of this disease happens based on numerous factors such as past health records and habits of patients. Health records include diabetes tendency, cardiovascular disease existence, pregnancy, asthma, hypertension, pneumonia; chronic renal disease may contribute to this disease occurrence. Past lifestyles such as tobacco, alcohol consumption may be analyzed. A deep learning based framework is investigated to verify the relationship between past health records, habits of patients and covid-19 occurrence. A stacked Gated Recurrent Unit (GRU) based model is proposed in this paper that identifies whether a patient can be infected by this disease or not. The proposed predictive system is compared against existing benchmark Machine Learning classifiers such as Support Vector Machine (SVM) and Decision Tree (DT).

This review and meta-analysis (PROSPERO registration number: CRD42020138845) critically evaluates test-retest reliability, concurrent validity and criterion validity of different physical activity (PA) levels of three most-common used international PA questionnaires (PAQs) in national language versions of EU-28: IPAQ-SF, GPAQ, and EHIS-PAQ. In total, 4969 abstracts were read, 287 full-text articles were identified as relvant to the study objectives, and 19 studies were included in the final meta-analysis. The studies’ results and quality were evaluated using the Quality Assessment of Physical Activity Questionnaires (QAPAQ) checklist. Results indicate that only five EU-28 countries validated national language versions of selected PAQs. Meta analysis revealed that assessment of moderate-to-vigourus PA (MVPA) is the most relevant PA level outcome, since no publication bias in any of measurement properties was detected while test-retest reliability was the moderately-high (rw=0.74), and moderate for both criterion (rw=0.41) and concurrent validity (rw=0.72). Reporting of methods and results of the studies was poor with overall moderate risk of bias with total score of 0.43. In conclusion, where only self-reporting is feasible, assessment of MVPA with selected PAQs in EU-28 adult population is recommended for policymaking.

Since the beginning, humans advanced their civilization by making better tools to improve their lives. Tools and products were designed for better living considering manufacturing issues, cost and time as predominant criteria. It has become clear that not considering environment and society, both at local/global levels, has now become a major impediment affecting living conditions on a large portion of the Earth and in many societies. Design methodologies should lead to creative solutions with consideration to engineering and economics for practicality but also to environmental and social constraints for sustainability. We propose a comprehensive design methodology based on multidisciplinary design to include the knowledge of humanities, environmentalists, science and engineering, and allowing for experts’ inputs from these areas to provide a holistic approach to engineering design . For example, experts in humanities are expected to interact with stakeholders to evaluate their value systems to provide guidance for the design. The methodology that we synthesize is new and combines (i) Societal level impacts at all scales, (ii) Environmental impacts and (iii) Engineering design with economic impacts, including uncertainty considerations. The proposed design methodology is called Social-Environmental-Economical-Engineering Framework (SEEEF). It can utilize concepts and tools such as Circular Design, Doughnut Economics, design based on environmental life cycle analysis, among others. SEEEF is quantity based and provides steps for evaluating any project or product in an objective manner and will help train engineers in design for sustainability. It also provides non-engineers with a significant role in design to increase their understanding of the hard constraints of engineering. Ultimately, SEEEF allows society to take an informed decision considering short/long term and local/global impacts of the design and the pertinent uncertainties.

Background: Coronavirus disease (COVID-19) related pneumonia is leaded by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which infects host cells through receptors named Angiotensin-converting enzyme 2 (ACE2). Smoking is thought to be related to poor disease prognosis, as a large amount of evidence highlights the negative effects of smoking on lung health and its causal relationship with various respiratory diseases. Methods: We first evaluated the role of ACE2 expression level with tobacco effect. And correlation analyses were used to identify the related genes of ACE2 both in smoker trait and human normal multi-tissues. After intersections, hub genes were later used to further GSEA and co-regulated mechanisms were explored by GeneMANIA. We used UALCAN to perform survival curves of pan-cancers included 33 types of cancers. New clinical model of top co-occurrence cancer type was constructed and validated. Results: Effected by cigarette smoking, the expression level of ACE2 expressed statistically upwards in current smokers compared with never smokers, upwards in groups after acute smoke exposed compared with normal control. But no strong evidence detected in third-hand smoke, as poor amounts of samples, only 4. A little trend of expressing upwards became in groups after third-hand smoke compared with groups after clean air exposing. 4 genes included PIR, ADH7, AKR1C2 and AKR1C3 were identified as ACE2 related genes in smoker trait and human normal multi-tissues. Then, we made the survival curves of pan-cancers in 4 genes. Brain lower grade glioma was the co-occurrence type as both ACE2, PIR and AKR1C3 had the significantly prognostic situation. Later, we made the new clinical prediction model as the C-index was 0.827 and the Area Under Curves (AUCs) of 1-year survival, 2-year survival and 3-year survival were 0.921(95%CI, 0.882-0.961), 0.911(95%CI, 0.860-0.962) and 0.878(95%CI, 0.818-0.939). In inner validation, the AUCs of 1-year survival, 2-year survival and 3-year survival were 0.777(95%CI, 0.640-0.914), 0.916(95%CI, 0.842-0.990) and 0.888(95%CI, 0.768-1.000). In outer validation one, the AUCs of 1-year survival, 2-year survival and 3-year survival were 0.764(95%CI, 0.672-0.856), 0.848(95%CI, 0.783-0.913) and 0.748(95%CI, 0.656-0.841). And in outer validation two the AUCs of 1-year survival, 2-year survival and 3-year survival were 0.740(95%CI, 0.654-0.826), 0.766(95%CI, 0.688-0.843) and 0.794(95%CI, 0.721-0.866). Conclusions: In our study, we compared the ACE2 expression level between smokers and non-smokers crowds and identified associated hub genes. Then we explored the further role of hub genes in tumor fields to identify the correlation and influence between the avoidable host factors such as smoking on COVID-19 contamination and tumor. ACE2 and AKR1C3 are potential prognostic genes for brain lower grade glioma, and we created the web dynamic nomogram and encapsulation app through validations.

Patients with transfusion-dependent thalassemia (TDT) show disorders in calcium metabolism. The α-klotho protein is predominantly expressed in tissues that are involved in calcium homeostasis, and lowered levels are associated with bone disease. Aim of the study. To study the associations between low α-klotho status and calcium metabolism in relation to iron status in children with TDT. Methods. α-klotho, calcium, parathyroid hormone (PTH), calcyphosin, vitamin D3, phosphorous, fibroblast growth factor receptor 2 (FGFR2), as well as iron and erythron biomarkers were measured in 60 children with TDT and 30 healthy control children. Results. A meaningful part of TDT patients showed lowered α-klotho levels, and those children also showed low serum total and ionized calcium concentrations. TDT patients showed increased PTH, FGFR2, and calcyphosin and lowered vitamin D3 as compared with healthy children. The α-klotho levels were significantly correlated with total and ionized calcium (positively) and with iron overload biomarkers and the number of blood transfusions (inversely). Partial Least Squares path analysis showed that 40.1% of the variance in serum total calcium could be explained by the regression on α-klotho, vitamin D3 (both positively), and calcyphosin (inversely) and that the effects of the latter are mediated by iron overload and the number of blood transfusions. Conclusion. In TDT, iron overload and its consequences may induce lowered levels of α-klotho which in turn may lead to lower calcium thereby explaining at least in part the effects of TDT on bone metabolism including spontaneous pathological fractures, osteoporosis, osteopenia, and skeletal deformities.

Herein we report on the use of different metal precursors in the synthesis of MoSe2 nanomaterials in order to control their morphology. The use of Mo(CO)6 as the metal precursor resulted in the formation of wrinkled few-layer nanosheets, while the use of H2MoO4 as the metal precursor resulted in the formation of nanoflowers. To investigate the effect of the morphologies on their performance as catalysts in the hydrogen evolution reaction, electrochemical characterization was done using linear sweep voltammetry, cyclic voltammetry and impedance spectroscopy. The MoSe2 nanomaterials were found to have superior electrochemical performance towards the hydrogen evolution reaction with a lower Tafel slope, on-set potential and potential at 10 mA/cm2 compared to the wrinkled few-layer nanosheets. This was found to be due to the higher effective electrochemical surface area of the nanoflowers compared to the nanosheets which suggests a higher number of exposed edge sites in the nanoflowers.

The coronavirus disease (COVID-19), an emerging viral infection, is impacting the social, economic and political patterns of the world. To contain the spread of this pandemic, Nigeria like many countries globally, has imposed drastic preventive measures such as physical distancing and lockdown/curfew. This study assessed the knowledge, attitude and perception (KAP) about COVID-19 among members of staff of a university community in southwest, Nigeria. A cross-sectional survey using an anonymous, self-designed, online KAP questionnaire was conducted from April 18 to May 31, 2020. Purposive and chain referral sampling techniques were used to recruit respondents from the teaching and non-teaching categories of the university. The KAP questionnaire consisted of ten knowledge questions regarding the identification of clinical characteristics, transmission and prevention of COVID-19. The questions on attitude (15) and perception (10) assessed respondents on adherence to policies and their views on government efforts to contain the spread of the infection respectively. A total of 125 (teaching) and 102 (non-teaching) staff responded. The respondents had scientific (78.8 %) and non-scientific (28.2 %) work background. Approximately 59.1 % of the respondents were males. The mean knowledge and positive attitude levels were 70.8 % (SD ± 9.6 %) and 83.1 % (SD ± 13.07 %) respectively. Significant differences in the knowledge mean scores were observed for demographic categories such as educational qualification (p = 0.0006), staff work category (p = <0.0001), work background (p = <0.0001), and type of lockdown (p = 0.0271). Most of the respondents (85.3 %) opined that COVID-19 was a biological weapon and viewed the lockdown as necessary (81.5 %). However, they thought that the Nigerian government was not doing enough to mitigate COVID-19 spread. The perception of COVID-19 in the university community bear implications across public health initiatives, compliance with precautionary behaviour and bilateral relations with foreign nations.

Background: Treatment at stabilization center is an important intervention to avert the huge burden of mortality for children with complicated severe acute malnutrition (SAM). Recent reviews indicated a wide range in recovery rate (34-88%) due to several context-specific factors. This study aimed to estimate time to recovery and to determine predictors of time to recovery among children aged 6-59 month with severe acute malnutrition. Method: Retrospective cohort study was used among 375 children aged 6-59 months admitted in Jimma university medical center, from September 2015 to September 2017. Kaplan Meir estimate and survival curve was used to compare the time to recovery using log-rank test among different characteristics. Cox Proportional Hazard Model was used to identify significant predictors of time to recovery. Results: Median time of recovery for cohort of SAM children’s was 19 days (95%CI: 17.95-20.05). Independent predictors of time to recovery were: Play stimulation, vaccination status, Tuberculosis, malaria, use of amoxicillin, deworming and shock. Conclusion: The findings of this study showed that the average length of stay on treatment and median time for recovery are within the sphere standard. Psychosocial stimulation, appropriate provision of routine medication and management of medical co-morbidity are needed to promote fast recovery.

Social distancing, washing hands and good hygiene are essential and currently the most potent methods available to curb down the unprecedented speed by which the new coronavirus is spreading across the globe. Even under lockdown, which is necessary to significantly reduce the number of people that get infected by an ill person, are there additional measures that each of us can embrace to even further reduce the risk of infection and the severity of the COVID-19 disease? Given the lack of licensed drugs that target SARS-CoV-2 specifically, we have to look into additional non-specific defense mechanisms that animals and humans evolved to protect themselves from pathogen invasions. The goal of this article is to describe how various of our non-specific defense mechanisms work, which actually precede the inflammatory response, and to discuss whether we can exploit the unique features of the coronavirus envelope and the self-cleaning machinery of the human respiratory tract to strengthen our self-defense. The challenge is to actively interfere with supportive measures during the short time window between getting exposed and before an inflammatory response gets initiated.

Conventional radiation therapy uses white X-rays that consist of a mixture of X-ray waves with various energy levels. In contrast, a monochromatic X-ray (monoenergetic X-ray) has a single energy level. Irradiation of high Z elements with a synchrotron generated monochromatic X-ray with the energy at or higher than the K-edge energy of the element results in the production of the Auger electrons that cause DNA damage leading to cell killing. Delivery of high Z elements into cancer cells and tumor mass can be facilitated by the use of nanoparticles. Mesoporous silica nanoparticles (MSNs) have been shown to be effective in delivering high Z elements to cancer cells. A proof of principle experiment was reported that demonstrated the feasibility of this approach. This opens up a possibility to pursue the Auger cancer therapy by the combined use of MSNs loaded with high Z elements and monochromatic X-rays. Similar cancer therapies using other types of quantum beams such as neutron, proton and carbon ion beams can be envisioned.

The Novel Coronavirus (COVID-19) is a positive-sense single-stranded RNA ((+)ssRNA) virus. The COVID-19 Main Proteases play very important role in the propagation of the Novel Coronavirus (COVID-19). It has already killed more than 8000 people around the world and thousands of people are getting infected every day. Therefore, it is very important to identify a potential inhibitor against COVID-19 Main Proteases to inhibit the propagation of the Novel Coronavirus (COVID-19). We have applied a drug repurposing approach of computational methodology, depending on the synergy of molecular docking and virtual screening techniques, aimed to identify possible potent inhibitors against Novel Coronavirus (COVID-19) from FDA approved antiviral compounds and from the library of active phytochemicals. On the basis of recently resolved COVID-19 Main Protease crystal structure (PDB:6LU7), the library of 100 FDA approved antiviral compounds and 1000 active components of Indian Medicinal Plants extracted for screening against COVID-19 Main Protease. The compounds were further screened using Pyrex virtual screening tool and then best inhibitors, top 19 compounds optimally docked to the COVID-19 Main Protease structure to understand the participation of specific amino acids with inhibitors at active sites. Total 19 best compounds were identified after screening based on their highest binding affinity with respect to the other screened compounds. Out of 19, 6 best compounds were further screened based on their binding affinity and best ADME properties. Nelfinavir exhibited highest binding energy -8.4 kcal/mol and strong stability with the TRP207, ILE281, LEU282, PHE3, PHE291, GLN127, ARG4, GLY283, GLU288, LYS5, LYS137, TYR126, GLY138, TYR126, SER139 and VAL135 amino acid residues of COVID-19 Main Protease participating in the interaction at the binding pocket. In addition to Nelfinavir (-8.4), Rhein (-8.1), Withanolide D (-7.8), Withaferin A (-7.7), Enoxacin (-7.4), and Aloe-emodin (-7.4) also showed good binding affinity and best ADME properties. Our findings suggest that these compounds can be used as potential inhibitors against COVID-19 Main Protease, which could be helpful in inhibiting the propagation of the Novel Coronavirus (COVID-19). Moreover, further in vitro and in vivo validation of these findings would be very helpful to bring these inhibitors to next level study.

The recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a major outbreak of coronavirus disease 2019 (COVID-19) and instigated a widespread fear and has threatened global health security. Although phenomenal efforts are in progress to effectively combat this COVID-19 outbreak. Still, no licensed antiviral drugs or vaccines are available, and treatment is limited to supportive care and few repurposed drugs. In this urgency situation, computational drug discovery methods provide both an alternative and a supplement to tiresome high-throughput screening, particularly in the hit-to-lead-optimization stage. Identification of small molecules that specifically target viral replication apparatus has shown the most successful strategy in antiviral drug discovery. The present study deals with the identification of potential compounds that specifically interact with SARS-CoV-2 vital proteins, including main protease (Mpro), Nsp12 RNA-dependent-RNA-polymerase (RdRp) and Nsp13 helicase. A constructive and integrated virtual screening efforts together with molecular dynamics simulations identified potential binding modes and favourable molecular interaction profile of corresponding compounds. Moreover, structurally important binding site residues in conserved motifs located inside the active site are elucidated, which displayed relative importance in ligand binding based on residual energy decomposition analysis. Although the current study lacks experimental validation, the structural information obtained from this computational study paved the way to identify and design specific targeted inhibitors to combat COVID-19 outbreak.

Natural killer (NK) cell therapy is one of the most promising treatments for Glioblastoma Multiforme (GBM). However, this emerging technology is limited by the availability of sufficient numbers of fully functional cells. Here, we investigated the efficacy of NK cells that were expanded and treated by interleukin-2 (IL-2) and heat shock protein70 (HSP70), both in vitro and in vivo. Proliferation and cytotoxicity assays were used to assess the functionality of NK cells in vitro, after which treated and naïve NK cells were administrated intra-cranially and systemically to compare the potential antitumor activities in our in vivo rat GBM models. In vitro assays provided strong evidence of NK cell efficacy against C6 tumor cells. In vivo tracking of NK cells showed efficient homing around and within the tumor site. Furthermore, significant amelioration of the tumor in rats treated with HSP70/Il-2 treated NK cells as compared to those subjected to non-treated NK cells, as confirmed by MRI, proved the efficacy of adoptive NK cell therapy. Moreover, results obtained with systemic injection confirmed migration of activated NK cells over the blood brain barrier and subsequent targeting of GBM tumor cells. Our data suggest that administration of HSP70/Il-2 treated NK cells may be a promising therapeutic approach to be considered in the treatment of GBM.

In December 2019, a novel coronavirus (SARS-CoV-2) was identified in patients with pneumonia (called COVID-19) in Wuhan, Hubei Province, China. SARS-CoV-2 shares high sequence similarity and uses the same cell entry receptor, angiotensin-converting enzyme 2 (ACE2), as does severe acute respiratory syndrome coronavirus (SARS-CoV). Several studies have provided bioinformatic evidence of potential routes for SARS-CoV-2 infection in respiratory, cardiovascular, digestive and urinary systems. However, whether the reproductive system is a potential target of SARS-CoV-2 infection has not been determined. Here, we investigate the expression pattern of ACE2 in adult human testis at the level of single-cell transcriptomes. The results indicate that ACE2 is predominantly enriched in spermatogonia, Leydig and Sertoli cells. Gene ontology analyses indicate that GO categories associated with viral reproduction and transmission are highly enriched in ACE2-positive spermatogonia while male gamete generation related terms are down-regulated. Cell-cell junction and immunity related GO terms are increased in ACE2-positive Leydig and Sertoli cells, but mitochondria and reproduction related GO terms are decreased. These findings provide evidence that human testes are a potential target of SARS-CoV-2 infection which may have significant impact on our understanding of the pathophysiology of this rapidly spreading disease.

Curcumin is the main secondary metabolites of Curcuma longa and other Curcuma spp, and has been reported to have some potential in preventing and treating some physiological disorders. This study investigated the effect curcumin in inhibiting high-fat diet and streptozotocin (STZ)-induced hyperglycemia and hyperlipidemia in rats. Twenty-six male Sprague-Dawley (SD) rats (170-190 g) were randomly divided into a standard food pellet diet group (Control group), a high-fat diet and streptozotocin group (HF+STZ group), and a high-fat diet combined with curcumin and STZ group (HF+ Cur +STZ group). Compared with the HF+STZ group, the HF+Cur+STZ group exhibited significantly reduced fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (AST) and aspartate transaminase (ALT) levels, and liver coefficients; in the livers of these rats, the expression of malondialdehyde (MDA) and Bax was downregulated, whereas that of superoxide dismutase (SOD) and Bcl-2 was upregulated. Moreover, the liver histology of these rats was improved and resembled that of the control rats. These results suggest that curcumin prevents high-fat diet and STZ-induced hyperglycemia and hyperlipidemia, mainly via anti-oxidant and anti-apoptotic mechanisms in the liver.

High frequency knowledge of the spatio-temporal distribution of the Downwelling Surface Shortwave Flux (DSSF) and its diffuse fraction (fd) at the surface is nowadays essential for understanding climate processes at the surface-atmosphere interface, plant photosynthesis and carbon cycle, and for the solar energy sector. The EUMETSAT Satellite Application Facility for Land Surface Analysis operationally delivers estimation of the MDSSFTD (Downwelling Surface Short-wave radiation Fluxes – Total and Diffuse fraction) product with an operational status since the year 2019. The method for the retrieval was presented in the companion paper [40]. The part 2 now focuses on the evaluation of the MDSSFTD algorithm and presents the comparison of the corresponding outputs, i.e. total DSSF and diffuse fraction (fd) components, against in-situ measurements acquired at four BSRN stations over a seven-month period. The validation is performed on an instantaneous basis. We show that the satellite estimates of DSSF and fd meet the target requirements defined by the user community for all-sky (clear and cloudy) conditions. For DSSF, the requirements are 20Wm^-2 for DSSF<200Wm^-2, and 10% for DSSF>=200Wm^-2. The MBE and rMBE compared to the ground measurements are 3.618Wm^-2 and 0.252%, respectively. For fd, the requirements are 0.1 for fd<0.5, and 20% for fd>=0.5. The MBE and rMBE compared to the ground measurements are -0.044 and -17.699%, respectively. The study also provides a separate analysis of the product performances for clear sky and cloudy sky conditions. The importance of representing the cloud-aerosol radiative coupling in the MDSSFTD method is discussed. Finally, it is concluded that the quality of the Aerosol Optical Depth (AOD) forecasts currently available is enough accurate to obtain reliable diffuse solar flux estimates. This quality of AOD forecasts was still a limitation a few years ago.

Several studies have shown that changes in incoming solar radiation and variations of the diffuse fraction can significantly modify the vegetation carbon uptake. Hence, monitoring the incoming solar radiation at large scale and with high temporal frequency is crucial for this reason along with many others. The EUMETSAT Satellite Application Facility for Land Surface Analysis (LSA SAF) operationally disseminates in near real time estimates of the downwelling shortwave radiation at the surface since 2005. This product is derived from observations provided by the SEVIRI instrument onboard the Meteosat Second Generation series of geostationary satellites, which covers Europe, Africa, the Middle East, and part of South America. However, near real time generation of the diffuse fraction at the surface level has only recently been initiated. The main difficulty towards achieving this goal was the general lack of accurate information on the aerosol particles in the atmosphere. This limitation is nowadays less important thanks to the improvements in atmospheric numerical models. This study presents an upgrade of the LSA-SAF operational retrieval method, which provides the simultaneous estimation of the incoming solar radiation and its diffuse fraction from satellite every 15 minutes. The upgrade includes a comprehensive representation of the influence of aerosols based on physical approximations of the radiative transfer within an atmosphere-surface associated medium. This article explains the retrieval method, discusses its limitations and differences with the previous method, and details the characteristics of the output products. A companion article will focus on the evaluation of the products against independent measurements of solar radiation. Finally, the access to the source code is provided through an open access platform in order to share with the community the expertise on the satellite retrieval of this variable.

The molecular dynamics simulation has been used to investigate the structural and transport properties of (Ba_0.5-xSr_x)La_0.5InO_3-δ (x=0, 0.1, 0.2) oxygen-ion conductor. The previous studies reported that the ionic conductivity of Ba-doped LaInO3 decreases because Ba dopant forms narrow oxygen path in the lattice, which could hinder the diffusion of oxygen ion. In this study, we reveal the mechanism to improve the ionic conductivity by Ba and Sr co-doping on La site in LaInO3 perovskite oxide. The results show that the ionic conductivity of (Ba_0.5-xSr_x)La_0.5InO_3-δ increases with increasing numbers of Sr ions, which oxygen diffusion paths including Sr ion have larger critical radius than Ba ions. The RDF calculations showed the heights of peak in composition including Sr ions is lower and broaden, so oxygen ions moved easily into other oxygen sites.

Mast cells (MC) are resident tissue cells found primarily at the interphase between tissues and environment. These evolutionary old cells store large amounts of proteases within cytoplasmic granules, and one of the most abundant of these proteases is the tryptase. To look deeper into the question their in vivo targets, we have analyzed the activity of the human MC tryptase on 69 different human cytokines and chemokines, and the activity of the mouse tryptase (mMCP-6) on 56 mouse cytokines and chemokines. These enzymes were found to be remarkably restrictive in their cleavage of these potential targets. Only five were efficiently cleaved by the human tryptase: TSLP, IL-21, MCP3, MIP-3b and eotaxin. This strict specificity indicates a regulatory function of these proteases and not primarily as unspecific degrading enzymes. We recently showed that the human MC chymase also had a relatively strict specificity, indicating that both of these proteases have regulatory functions. One of the most interesting such regulatory functions may involve controlling excessive TH2 mediated inflammation by cleaving several of the most important TH2-promoting inflammatory cytokines, including IL-18, IL-33, TSLP, IL-15 and IL-21 indicating a potent negative feedback loop on TH2 immunity.

Beta-thalassemia major (β-TM) patients are treated with repeated blood transfusions, which may cause iron overload (IO), which in turn may induce immune aberrations. Patients with β-TM have an increased risk of major depressive disorder (MDD). The aims of the present study are to examine whether repeated blood transfusions, IO and immune-inflammatory responses are associated with MDD in children (6-12 years) with β-TM. The Children’s Depression Inventory (CDI), iron status (serum iron, ferritin, transferrin, TS%) and serum levels of CCL11, IL-1β, IL-10, and TNF-α were measured in β-TM with (n=54) and without (n=57) MDD and in healthy children (n=55). The results show that MDD in β-TM is associated with a greater number of blood transfusions, increased IO and IL-1β levels. Partial Least Squares path analysis shows that 68.8% of the variance in the CDI score is explained by the number of blood transfusions, IO, and increased levels of IL-1β and TNF-α. The latter two cytokines partly mediate the effects of IO on the CDI score, while the effects of blood transfusions on the CDI score are partly mediated by IO and the path from IO to immune activation. IO is also associated with increased IL-10 and lower CCL11 levels but these alterations are not significantly associated with MDD. In conclusion, blood transfusions may be causally related to MDD in β-TM children and their effects are in part mediated by increased IO and the consequent immune-inflammatory response. The results suggest that not only IO and its consequences including inflammation and ferroptosis, but also other factors related to the number of transfusions may cause MDD including psychosocial stressors. Current treatment modalities with folic acid and vitamin C are insufficient to attenuate IO and immune-inflammatory responses and to prevent MDD is children with β-TM undergoing blood transfusions.

Background and objective: Addressing the global morbidity associated with pulmonary disease is an important need for the respiratory community. However, there is also a growing momentum to show the efficacy of new tools of diagnosis. Despite this, there are few physiotherapeutic tools that help identify and categorize these conditions. The aim was to analyze the variables of physiotherapy index of the ventilatory workload (PIVW) in people with chronic obstructive pulmonary disease (COPD) during stability and exacerbation in an outpatient setting. Material and Methods: Analyzed retrospectively of 198 clinical records were reviewed. The PIVW was extracted in stability and exacerbation of these patients with COPD. After applying the exclusion and inclusion criteria; 54 patients were classified. Through the statistical analysis of chi-square, a significant association was reported for each of the variables and the total PIVW score. Results: when analyzing the baseline with the peak of PIVW, there was a significant increase in patients COPD exacerbation. Similarly, the variables that constitute the loads, translations and supports underwent a significant increase from baseline to exacerbation (p<0.0001), except for the additional oxygen contribution, where the frequency of patients was the same in basal and exacerbation as well. Conclusions: the PIVW, serves to determine ventilatory problemas in outpatients, characterizing the specific changes of loads, translators or assistance.

Silybum marianum (L.) Gaertn. (aka milk thistle) constitute the almost exclusive source of silymarin, a mixture of different flavonolignans, and is thus considered as a unique model for their extraction. The present research deals with ultrasound-assisted extraction (UAE) of S. marianum flavonolignans and their quantification using LC system. The optimal conditions for UAE were: aqueous EtOH 54.5% (v/v) as solvent, applying an ultrasound frequency of 36.6 kHz during an extraction time of 60 min at 45°C with a liquid to solid ratio of 25:1 ml/g DW. Following optimization, the extraction method was validated according to international standards of the association of analytical communities (AOAC) in order to ensure its precision and accuracy for the quantitation of the individual silymarin components. The efficiency of UAE was compared with maceration protocol of the same duration. The optimized and validated conditions allowed highest extraction yields of flavonolignans in comparison to maceration. The antioxidant capacity of the extracts was confirmed by the CUPRAC assays and inhibition of advanced glycation end products. The skin anti-aging action was also confirmed toward the strong in vitro inhibition capacity of the obtained extract against collagenase and elastase enzymes. The procedure presented here allows a green efficient extraction and quantification of the main flavonolignans from the fruits of S. marianum with attractive antioxidant and anti-aging activities for future cosmetic applications.

Using co-precipitation to synthesize (CeO2)0.95(Y2O3)0.05 (YDC) and solid reaction method to synthesize (CeO2)0.75(ZrO2)0.25 (ZDC), and the characterization for both crystal structure and micro-structure of the two materials was conducted with X-ray diffraction (XRD) and scanning electron microscope (SEM) methods. Prepare the YDC and ZDC based limited current O2 sensor by employing platinum pasting bonding method. Sensing characteristics of the sensor were obtained at different conditions and study on the impact of temperature, O2 concentration as well as water vapor pressure on the sensing characteristics had been conducted. XRD results show that the phase structure of both YDC and ZDC is cubic phase. SEM results show that both YDC and ZDC layers are dense layers, which are then qualified to be the composition materials of the sensor. This limited current O2 sensor shows good sensing performance and conforms to the Knudsen model. Log(IL•T) depends linearly on 1000/T with R2 of 0.9904, IL depends linearly on x(O2) with R2 of 0.9726 and sensing characteristics are not affected by p(H2O).

The quality of dietary patterns can be optimized using a mathematical technique known as linear programming (LP). LP methods have rarely been applied to individual meals. The present LP models optimized the breakfast meal for those participants in the nationally representative National Health and Nutrition Examination Survey 2011-2014 who ate breakfast (n=11,565). The Nutrient Rich Food Index (NRF9.3) was a measure of diet quality. Breakfasts in the bottom tertile of NRF9.3 scores (T1) were LP-modeled to meet nutrient requirements without deviating too much from current eating habits. Separate LP models were run for children and for adults. The LP-modeled breakfasts resembled the existing ones in the top tertile of NRF9.3 scores (T3), but were more nutrient-rich. Favoring fruit, cereals, and dairy, the LP-modeled breakfasts had less meat, added sugars and fats but more whole fruit and 100% juices, more whole grains, and more milk and yogurt. LP modeling methods can build on existing dietary patterns to construct food-based dietary guidelines and identify individual meals and/or snacks that need improvement.

As climate change should lead to an increase in the vulnerability and the sensitivity of forests to extreme climatic events, quantifying and predicting their response to more severe droughts remains a key task for foresters. Furthermore, recent works have suggested that tree diversity may affect forest ecosystem functioning, including their response to extreme events. In this study we aimed at testing whether the growth response of forest stands to stressful climatic events varied between mixed and monospecific stands, under various environmental conditions. We focused on beech-fir forests (Fagus sylvatica [L.] and Abies alba [L.]) and beech-oak forests (Fagus sylvatica [L.] and Quercus pubescent [L.]) in the French Alps. We used a dendrochronological dataset sampled in forest plots organized by triplets (one mixture and two monospecific stands) distributed in six sites along a latitudinal gradient. We tested (1) whether stand diversity (two-species stands vs monospecific stands) modulates the stands’ response to drought events in terms of productivity, (2) whether species identity may drive the diversity effect on resistance and recovery, and (3) whether this can be explained by interspecific interactions. We found that (1) interspecific differences in response to extreme drought events (possibly due to interspecific differences in hydraulic characteristics) can induce a mixture effect on stand growth, although it appeared (2) to be strongly depending on species identity (positive effect only found for beech-fir mixed stands), while (3) there were no significant non-additive effects of diversity on stand resistance and recovery, except for some specific cases. Overall, our study shows that promoting selected mixed stands management may buffer extrem drought effect on stand productivity.

Background: Diets based on meat products are not recommended in the case of ulcerative colitis (UC). However, some foods, as those containing high oleic acid and a low omega-6/omega-3 ratio show anti-inflammatory properties. The objective here is to test if some traditional cured meat products, as acorn-fed ham (high levels of oleic acid), may be useful for controlling inflammatory diseases as UC in animal models. Methods: 3 rat cohorts have been used: vegetable rat feed, control ham and acorn-fed ham (a traditional ham where high oleic acid concentration from acorns is storage in the muscle fat). UC was induced with DSS in drinking water ad libitum for one week. Short-chain fatty acids (SCFAs) and 16S rRNA from bacterial populations were analyzed in cecum samples. Colon samples were analyzed for histological parameters (inflammatory cell density, mucosa damages, myeloperoxidase). Results: In the acorn-fed ham cohort, a protective effect was observed with respect to UC disease activity index, inflammatory cells density, colon mucosa alterations, myeloperoxidase levels, blood total antioxidant capacity and lower levels of pro-inflammatory cytokines, in comparison with feed cohort. Both ham diets caused a reduction in Firmicutes and an increase in Actinobacteria, Bacteroidetes and Proteobacteria in comparison with rat feed diet. Also, acorn-fed ham diet induced changes in gut microbiota composition, with pronounced enrichments in anti-inflammatory bacterial genera such as Alistipes, Bacteroides, Blautia, Butyricimonas and Parabacteroides. Conclusions: In the acorn-fed ham cohort, as a result of the dietary intake of oleic acid and low intake of omega-6 fatty acids, a strong preventive effect against UC symptoms was observed, indicating a valuable effect of this traditional Mediterranean cured meat product.

The potential of Sorghum bicolor L. (Moench) (Epuripur 1995) to phytoremediate petroleum oil-adulterated soils from an automobile repair workshop and the effect of enhancement factors: NPK fertilizer, cow dung and sewage sludge in in situ phytoremediation of the soil by the plant were assessed in this study. 50kg of petroleum oil-contaminated soil was collected from the workshop and divided into five equal portions. Four portions were potted with four sorghum plants with three subjected to equal amounts of enhancements (5%w/w) under normal growth conditions for 72 days. Representative soil samples were collected from spots at depths of 0–10 cm and 10–20 cm from the potted soils and subjected to Soxhlet oil extraction after 72 days. Experimental results revealed that S. bicolor survived in the petroleum oil-contaminated soils. Amendment of the petroleum oil-vitiated soils with cow dung, sewage sludge and NPK fertilizer augmented the remediation capacity of Epuripur 1995 by 12.5%, 6.3% and 9.1%. Addition of cow dung to crude oil contaminated soils could make such soils fully reestablished for agricultural activities. Further research aimed at determination of the phytoremediation potential of cereals such as corn, barley, rye, millet should be done.

By means of density functional theory (DFT) calculations, we have investigated the effect of hydrostatic pressure on the structural, electronic and elastic properties of the barium-doped silicon clathrate Ba8Si46 in the type-VIII structure (α phase). Physical properties are calculated under different conditions of pressure (0 GPa to 45 GPa) using the GGA-PBE functional, those calculations have been performed using the Cambridge serial total energy package CASTEP code within the Materials Studio package. Electronic properties have shown that the type-VIII Ba8Si46 has metal-like properties with a fundamental bandgap of 1 eV. Under pressure the fundamental bandgap increases slightly and the positions of the valence band maximum VBM and the conduction band minimum CBM remain unchanged. We found that the compound is mechanically stable under the pressure range, but this needs to be confirmed experimentally through synthesis, a comparison with the type-I and the guest-free counterparts has exhibited promising features for the type-VIII Ba8Si46.

Taking four of the United Nations Development Goals as reference, this overview describes the need to see from a systemic perspective, the food certifications programs along the food chain in Mexico as today food certifications are voluntary. Using secondary data, the main objectives were: a) there is a fall short in food safety policies and those federal agencies responsible for food safety, to guarantee safe food along the whole domestic food chain, especially in that for low income players; b) the amount of the Mexican Federal Budget Expenses devoted to safety food issues is really low, considering the health, well- being, and food security consequences; and c) due the structural heterogeneity of the Mexican food market, there is a lack of coordination in food regulations along all agents of the food supply chain, bringing to alternate informal markets that put at risk peoples´ health, increasing poverty and inequalities. According to this exercise, only 0.7- 8.7% of producers, 12.5% of supermarkets as well as 42.8% of restaurants would have some type of certifications. Public policies must attend this issue in order to improve food safety and security for the whole population, reducing inequalities, poverty and ensuring them a healthy live.

Restricted feeding is well known to affect expression profiles of both clock and metabolic genes. However, it is unknown whether these changes in metabolic gene expression result from changes in the molecular clock or in feeding behavior. Here we eliminated the daily rhythm in feeding behavior by providing 6-meals evenly distributed over the light/dark-cycle. Animals on this 6-meals-a-day feeding schedule retained the normal day/night difference in physiological parameters including body temperature and locomotor activity. The daily rhythm in respiratory exchange ratio (RER), however, was significantly phase-shifted through increased utilization of carbohydrates during the light phase and increased lipid oxidation during the dark phase. This 6-meals-a-day feeding schedule did not have a major impact on the clock gene expression rhythms in the master clock but did have mild effects on peripheral clocks. By contrast, genes involved in glucose and lipid metabolism showed differential expression. Concluding, eliminating the daily rhythm in feeding behavior in rats does not affect the master clock and only mildly affects peripheral clocks, but disturbs metabolic rhythms in liver, skeletal muscle and brown adipose tissue in a tissue-dependent manner. Thereby a clear daily rhythm in feeding behavior strongly regulates timing of peripheral metabolism, separately from circadian clocks.

Background: Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality in both sexes globally. This is not unconnected with the heterogeneity and plasticity of CRC stem cells (CRC-SCs) which stealthily exploit niche-related and (epi)genetic factors to facilitate metastasis, chemoresistance, tumor recurrence, and disease progression. Despite accumulating evidence of the role of dysregulated microRNAs in malignancies, the therapeutic efficacy of pharmacological-targeting of CRC-SC-associated microRNAs is relatively under-explored. Experimental approach: In this present study, we employed relatively new bioinformatics approaches, analyses of microarray data, western blot, RT-PCR, and functional assays to show that hsa-miR-324-5p expression is significantly suppressed in CRC cells, and inversely correlates with the aberrant expression of SOD2. Results: This converse hsa-miR-324-5p/SOD2 relationship is associated with enhanced oncogenicity, which is effectively inhibited by 4-AAQB as evidenced by inhibited cell viability and proliferation, as well as, attenuated migration, invasion and clonogenicity in 4-AAQB-treated DLD1 and HCT116 cells. We also showed that 4-AAQB-induced re-expression of hsa-miR-324-5p, akin to short-interfering RNA reduced SOD2 expression, correlates with the concurrent down-regulation of SOD2, N-cadherin, vimentin, c-Myc, and BcL-xL2, with concomitant up-regulation of E-cadherin and BAX2 proteins. Enhanced expression of hsa-miR-324-5p in the CRC cells suppressed their tumorigenicity in vitro and in vivo. Additionally, 4-AAQB synergistically potentiates FOLFOX anticancer effect by eliciting the re-expression of SOD2-suppressed hsa-miR-324 and inhibiting SOD2-mediated tumorigenicity. Conclusion: Our findings highlight the pre-clinical anti-CSC efficacy of 4-AAQB, with or without FOLFOX in CRC, and suggest a potential novel therapeutic strategy for CRC patients.

Engineering properties of bedrock materials at Badlands National Park were used to develop models for Park managers to assess slope erosion and stability for fossil resource protection. Six fully instrumented sites were used to document slope conditions. Bedrock consisted of Oligocene White River Group rocks. Bulk erosion rates correlated to grain size with silty-sandy materials producing higher mass erosion rates as a function of the silt-to-clay ratio and plastic index. Data indicated that as grain size decreased, plastic index increased leading to a decrease in erodibility. These parameters were used to construct a grain-size proxy, ψ, that was substituted for grain size, D, in Bagnold’s entrainment equation and provided significant improvement in calculation of critical entrainment velocities for fine-grained materials. Hydraulic analyses of slope and pediment surface processes indicated surface roughness was a controlling factor and materials washed from rough steep slopes were effectively transported across smooth low-angle pediments with slope-to-pediment angle ratios of nearly 6:1. Slope stability modeling of ten slopes produced high factors of safety for all slopes, even under saturated conditions and was attributable to clay cohesion. All results were used to construct models that predicted years until net slope erosion equaled 2.5 cm (1 inch). Using these results, Park managers were advised to visit erosion-prone sites on a 1 to 6 year schedule, based on site geology and slope aspect, to adequately protect critical fossil resources from destruction.

In this paper we illustrate a new, simple and complementary ground-based methodology to retrieve the vertically resolved atmospheric precipitation intensity through a synergy between measurements from the National Aeronautics and Space Administration (NASA) Micropulse Lidar network (MPLNET), an analytical model solution and ground-based disdrometer measurements. The presented results are obtained at two mid-latitude MPLNET permanent observational sites, located respectively at NASA Goddard Space Flight Center, USA, and at the Universitat Politècnica de Catalunya, Barcelona, Spain. The methodology is suitable to be applied to existing and/or future lidar/ceilometer networks with the main objective of either providing near-real time (3h latency) rainfall intensity measurements and/or to validate satellite missions, especially for critical light precipitation (<3 mm hr⁻¹).

The calculation of the surface tension of ordinary organic and ionic liquids, based on a computer algorithm applying a refined group-additivity method, is presented. The refinement consists of a complete breakdown of the molecules into their constituting atoms, further distinguishing them by their immediate neighbour atoms and bond constitution. The evaluation of the atom-groups’ contributions was carried out by means of a fast Gauss-Seidel fitting method founded upon the experimental data of 1895 compounds from literature. The result has been tested for plausibility using a 10-fold cross-validation (cv) procedure. The direct calculation and the cv test proved the applicability of the present method by the close similarity and excellent goodness of fit R2 and Q2 of 0.9023 and 0.8821, respectively. The respective standard deviations are ±2.01 and ±2.16 dyn/cm. Some correlation peculiarities have been observed in a series of ordinary and ionic liquids with homologous alkyl chains which are illustrated and discussed in detail, exhibiting the limit of the present method.

Aedes aegypti mosquito is a vector that could transmit various pathogens, such as viruses, bacteria, and parasites. Several human diseases transmitted by Ae. aegypti mosquito are dengue fever (DHF), Chikungunya, Yellow Fever and Zika. The occurance of resistance to various insecticides, including pyrethroid, is a current problem faced by various countries. In this research, a WHO bioassay test on Palembang and Jakarta Ae. aegypti was conducted using 0.25% permethrin pyrethroid insecticide. VGSC gene fragments associated with pyrethroid resistance (L982, S989, I1011, L1014, V1016 and F1534) of resistant and sensitive strains were amplified and analyzed. The test showed the presence of resistance in Ae. aegypti isolates from Palembang and Jakarta. From the results of VGSC gene fragment analyses, it was known that there were mutations (S989P and/or V1016G) on isolates from Palembang and (S989P and/or V1016G) on resistant isolates from Jakarta.

This study uses data from the pilot project "Community Monitoring for Better Health and Education Services Delivery Project'' in Burkina Faso, to model the joint impact of generic essential drugs and nursing staff supplies constraints on access to primary health care in the country. The results show that statistical endogeneity of supply side constraints are present in the standard univariate probit specification of access to care. However, when accounted for, the resulting Trivariate Probit model shows that although shortages of generic essential drugs supply do not seem to constitute a significant barrier to access in Burkina Faso, shortages in nursing staff supply do. In fact, the likelihood of primary care access is reduced by 85.5% among those that reported having experienced a shortage in nursing staff, while paradoxically increasing by 60.3% among those that reported having experienced a shortage in generic essential drugs. A potential explanation for these findings is that overall the health care needs in the three surveyed regions in the country were more linked to primary health care services consumption from nurses, although further research would be important to clearly elucidate the position of health goods such as generic essential drugs.

High-performance poly(1,4-butylene terephthalate (PBT) nanocomposites have been developed via the consideration of phosphorus-containing agents and amino-carbon nanotube (A-CNT). One-pot functionalization method has been adopted to prepare functionalized CNTs via the reaction between A-CNT and different oxidation state phosphorus-containing agents, including chlorodiphenylphosphine (DPP-Cl), diphenylphosphinic chloride (DPP(O)-Cl), and diphenyl phosphoryl chloride (DPP(O3)-Cl). These functionalized CNTs, DPP(Ox)-A-CNTs (x = 0, 1, 3), were respectively mixed with PBT to obtain the CNTs-based polymer nanocomposites through a melt blending method. SEM observations demonstrated that DPP(Ox)-A-CNT nano-additives were homogeneously distributed within PBT matrix compared to A-CNT. The incorporation of DPP(Ox)-A-CNT improved the thermal stability of PBT. Moreover, PBT/DPP(O3)-A-CNT showed the highest crystallization temperature and tensile strength, due to the superior dispersion and interfacial interactions between DPP(O3)-A-CNT and PBT. PBT/DPP(O)-A-CNT exhibited the best flame retardancy resulting from the excellent carbonization effect. The radicals generated from decomposed polymer were effectively trapped by DPP(O)-A-CNT, leading to the reduction of heat release rate, smoke production rate, carbon dioxide and carbon monoxide release during cone calorimeter tests.

One source of kaolinite-rich wastes is from mine tailings and the generation of enormous volumes of mine tailings waste is standard practice in this industry. These volumes of waste are, at present, dumped, provoking significant environmental impact and transforming the environment. The impact of storing coal waste requires the study of eco-innovative solutions for the assessment of waste types. The present investigation has the objective of expanding the knowledge on the behavior of new siliceous-aluminum minerals with pozzolanic activity, of added value in the manufacture of similar cements. Four samples were characterized to determine their chemical, morphological and mineralogical composition. The samples were subjected to different thermal activation conditions for the transformation of an inert waste into a material with cementitious properties. XRD analysis have confirmed the total transformation of kaolinite into metakaolinite. The results have shown that after the activation process, the coal refuse presented good pozzolanic activity, meaning that it may be used as a pozzolanic addition in industrial cements, thereby removing high levels of contaminated waste from the environment. In subsequent investigations, research work will continue with the replication of cements with this pozzolanic addition for use in the manufacture of sleepers and slab track railway system.

Energy is a fundamental ingredient in economic development and energy consumption is an index of prosperity and the standard of living. The consumption of energy has increased significantly in the last number of decades, as the standard of living has improved. Renewable energy is a sustainable and clean source of energy derived from nature. Renewable energy technology is one of the solutions, which produces energy by transforming natural resources into useful energy forms. When you do something for the first time in the world, you never attain a perfect product or solution from the start. In Central Greece Lamia city, we are the first to design and implement an off-grid energy system using hydrogen energy storage technology and phase change materials for a house residence. The action plan for energy efficiency, a series of directives and incentive mechanisms, mandatory energy certification of buildings, indicate the urgent need to reduce energy consumption in buildings, which results in a more comfortable living, long service life of buildings, which in turn preserves the environment.

A marine fibrinolytic compound FGFC1 enhancing fibrinolysis was obtained involving in enzymatic kinetic parameters of reciprocal activation system with single chain urokinase type plasminogen activator and plasminogen. FGFC1, a kind of bisindole alkaloid from a metabolite of rare marine fungi Starchbotrys longispora FG216, modulated enzymatic kinetic parameters including fibrinolytic reaction rate and fibrin degradation characteristics. The enzymatic kinetics of fibrinolysis was described based on enzymatic reaction of chromogenic-substrate associated with p-nitroaniline (p-NA). While single chain urokinase-type plasminogen activator (pro-uPA) actived plasminogen, K_cat and k_cat/k_m increased significantly with increase of FGFC1 concentration. Moreover, K_cat and k_cat/k_m exhibited 26.5-fold and 22.8-fold enhanced activity at the concentration of 40 μg•mL⁻¹ of FGFC1, respectively. The results suggested that FGFC1 improved significantly the maximum catalytic efficiency and the total catalytic activity of fibrinolysis base on the reciprocal activation of pro-uPA and plasminogen. K_m increased with increasing FGFC1 concentration, which indicated that FGFC1 decreased slightly the affinity activity of pro-uPA and plasminogen versus enzyme substrate. The marine bisindole alkaloid FGFC1 enhanced fibrinolysis which was taken on enzymatic kinetic characteristics.

The intracellular calcium dynamics in vascular endothelial cells (VECs) in response to wall shear stress (WSS) and/or adenosine triphosphate (ATP) have been commonly regarded as an important factor in regulating VEC function and behavior including proliferation, migration and apoptosis. However, the effects of time-varying ATP signals have been usually neglected in the past investigations in the field of VEC mechanobiology. In order to investigate the combined effects of WSS and dynamic ATP signals on the intracellular calcium dynamic in VECs, a Y-shaped microfluidic device, which can provide the cultured cells on the bottom of its mixing micro-channel with stimuli of WSS signal alone and different combinations of WSS and ATP signals in one single micro-channel, is proposed. Both numerical simulation and experimental studies verify the feasibility of its application. Cellular experimental results also suggest that a combination of WSS and ATP signals rather than a WSS signal alone might play a more significant role in VEC Ca²⁺ signal transduction induced by blood flow.

Seroconversion surveys of anti-SARS-CoV-2 antibodies provide accurate estimates of the SARS-CoV-2 infection. This nationwide population-based cross-sectional serosurvey aimed to evaluate the prevalence of SARS-CoV-2 antibodies among residents in Gabon and compare the estimated cumulative number of COVID-19 cases with the officially registered number of laboratory-confirmed cases up to December 2021. Households in each province were randomly selected. Twenty-eight localities including 16 urban and 12 rural, were randomly selected to participate in the study. Whole blood samples were collected in dry tubes from all study participants around the country within 15 days. Serum samples were used to measure the total Immunoglobulin antibodies. Overall, data of 1672 households were analyzed. Out of the 3659 participants, 3175 were found positive for SARS-CoV-2 antibodies, resulting in a crude seroprevalence of 86.77%. Stratification of study participants by age group has shown highest seroprevalences in 20–29 and 40-49 age groups with 91.78% (95% CI:89.5–93.6) and 91.42% (95% CI:88.7–93.5), respectively. Nyanga province had the lowest prevalence (72,8%), and Estuaire and Ogoué-Lolo provinces had the highest prevalence (90 and 92%, respectively). Our results suggest a high transmission rate in the Gabonese population, 21 months after the first SARS-CoV-2 case in the country. This high seroprevalence estimate could indicate that the applied infection control measures may not have been adequately implemented or appropriately adhered to by the population.

Background/Objectives: Diagnosis of encephalitis is a challenging problem due to the heteroge-neity of clinical presentations and the myriad of aetiology. The objective was to determine the ae-tiology, clinical features, laboratory parameters, radiological findings and in-hospital outcome of acute encephalitis syndrome (AES) cases in Myanmar. Methods: A prospective analytic study was conducted at Neuromedical Ward of Yangon General Hospital during March to August 2023. 81 AES cases were enrolled and cerebrospinal fluids (CSF) samples were collected. Qiastat ME Panelwas used to detect viral, bacterial and fungal pathogens. Results: 17 out of 81 (21%) cases were non-encephalitis with alternative definite diagnosis. Among the remaining 64 enceph-alitis cases, the exact infectious and immune aetiologies were identified in 31/64 (48.4%); 26/31 cases (83.9%) were infectious causes and 5/31 patients (16.1%) were immune encephalitis. Among the infection causes, six Herpes Simplex Virus-1, one bacteriologically confirmed and seven probable Mycobacterium tuberculosis, three Haemophilus influenzae, two Streptococcus pneumoniae, one Streptococcus pyogenes, one Varicella-Zoster Virus (Ramsay Hunt Syndrome with menin-goencephalitis), two Cryptococcus neoformans infected patients and rare causes such as Listeria monocytogenes, Burkholdelria cepacia, Sphingomonas paucimobilis and Aspergillus were identified. One case was dual infection with Haemophilus influenzae and Cryptococcus neformans. Abnormal protein levels and CSF pleocytosis were significantly higher among bacterial causes (P

Anxiety-based cognitive distortions pertaining to somatic perception (ABCD-SP) - primarily catastrophizing, fear avoidance and kinesiophobia- have been repeatedly linked to worsening chronic, non-cancer pain (CNCP) outcomes of increased disability, amplified pain, ineffective opioid use, and opioid misuse. Several studies have suggested that treating ABCD-SP can improve pain outcomes, yet identification and targeting of ABCD-SP is not part of the standard medical pain assessment and treatment plan. Utilizing a narrative review of proposed mechanisms, published patient perspectives, and study correlates connecting these cognitive distortions with CNCP outcomes, a better practice approach to the delivery of standard medical CNCP care can be deduced and formulated into a Belief and Behavior Action Plan (BBAP) for medical clinicians treating CNCP to implement into initial and maintenance care planning. These recommendations require relatively few resources to implement and have the potential to disseminate more effective CNCP treatment on a large scale now, and into the new frontier of cognitive computing within medicine.

The emergence of few-shot learning as a potential approach to address the problem of data scarcity by learning underlying pattern from a few training sample had so far given a mix-result especially on the suitability of model-agnostic meta learning, transfer learning, and optimization strategy to rapidly learn valid information from few sample. In this research, we did an in-depth evaluation of meta- learning to determine their plausibility and suitability for previously unknown cyberattack detection by first retrieving the original research artifacts of current state of the art meta learning to repeat the experiment with original dataset before replicating the experiment with two different malware dataset which had not been previously done with meta-transfer learning. On each of the experiments, meta-transfer learning gave good results on digital character recognition dataset but abysmal result on Malimg and Malevis malware images datasets thereby indicating its unreliability for detecting cyberattacks and the need for an improvement to the state-of-the-art meta transfer learning towards a better attack detection. Transfer learning performance is independent on imbalance and hence does not influence its performance since both malware dataset used for this experiment result in high validation loss and balancing the dataset doesn't result in reduced validation loss,the successful learning transfer seen on digital character recognition dataset is not unconnected to the fact that several languages have similar characters and digits thereby enhancing the successful learning transfer unlike malware datasets, and more importantly the finding that current meta-learning transfer approach doesn't generalize well on malware dataset and hence not suitable for detecting previously unseen out-of-distribution attack.

Background: The chin tuck maneuver has been suggested to increase suprahyoid muscle activation, but a method to measure the strength of the chin tuck maneuver has not been established. We developed a method to measure the strength of the chin tuck maneuver (chin tuck strength) and examined the reliability and validity of chin tuck strength measurement in community-dwelling older adults. Subjects and Methods: The participants were 233 older adults aged ≥65 years without dysphagia or physical disability. Chin tuck strength was measured twice consecutively using the developed device, and reproducibility was analyzed using intraclass correlation coefficients (ICCs). In addition, maximum tongue pressure, oral diadochokinesis, grip strength, knee extension strength, and the timed up and go test (TUGT) were measured as indices of swallowing-related muscle function and appendicular muscle function. The associations of chin tuck strength with swallowing-related muscle function and appendicular muscle function were analyzed statistically. Results: The ICCs for chin tuck strength were 0.82 (95% confidence interval [CI]: 0.73-0.88) in males and 0.87 (95%CI: 0.70-0.93) in females. Chin tuck strength was significantly associated with maximum tongue pressure, grip strength, knee extension strength, and TUGT. Conclusions: This study suggests that chin tuck strength is a reliable and valid assessment of swallowing-related muscle strength.

A truss network was applied to analyze morphometric differentiation among three wild populations of Hoplias microlepis, captured in three different sites from two habitats of Guayas Hydrographic Basin: Daule-Peripa dam, Quevedo and Babahoyo rivers. This study can help to deepen to the knowledge of the species adaptation to different environments and highlights some factors which may be helpful for future management and conservation of the freshwater resources of Ecuador. A sample of 225 adult fish were collected, 49 morphometric characteristics and 6 meristic counts were analyzed, and a statistical model was built through multifactorial discriminant analysis. The standard length of Hoplias microlepis was 32.14 cm, total length 37.82 cm and sexual maturity index 4.39. The Hoplias microlepis with the greatest weight, length and sexual maturity index were in the dam where the food availability is better, and the fishing pressure is lower. Finally, the cluster analysis grouped the fish from the rivers in cluster 1 and those from the dam in cluster 2, being samples of dam clearly distinct from rivers, probably due to differences in the habitat condition. Fish body condition and morphological variation at different sites may be useful indicators for both, habitat disturbance and consequently its conservation, and the sustainability of fishery management plans.

Equine laminitis is a debilitating condition characterized by the breakdown of the dermal–epidermal junction, resulting in severe lameness and pain, often requiring euthanasia. This study aimed to establish an in vitro model of laminitis using a continuous keratinocyte cell line exposed to anoxia-reoxygenation and activated neutrophil supernatant. A significant decrease in keratinocytes metabolism was noted during the reoxygenation period, indicative of cellular stress. Adding muscle-derived mesenchymal stem/stroma cells during reoxygenation demonstrated a protective effect, restoring keratinocytes metabolic activity. Moreover, incubation of keratinocytes with activated neutrophil supernatant or myeloperoxidase alone induced increased keratinocyte myeloperoxidase activity, which was modulated by stem cells. These findings underscore the potential of muscle-derived mesenchymal stem/stroma cells in mitigating inflammation and restoring keratinocyte metabolism, offering insights for future cell therapy research in laminitis treatment.

The Asia-Pacific region contains almost half of the planet’s coastal carbon-sequestering (blue carbon) environments (mangroves, salt marshes, seagrasses). These habitats are highly valuable to sequester carbon and mitigate climate change, but are under threat throughout the region, due in significant part to an insufficient policy environment to protect, restore, or create new coastal wetlands/blue carbon environments. Using a systematic evidence synthesis we reviewed the existing literature on blue carbon policy, and found that gaps and challenges fall under three themes, “Land Tenure and Ownership”, “Funding and Protecting Blue Carbon Habitat”, and “Conflicting Priorities and Jurisdictions”, with two overarching issues, the inconsistent recognition of rights of indigenous peoples and local communities (IPLCs) and women, and sea-level rise. This study makes recommendations to ensure high-quality blue carbon projects through improving equitable outcomes, particularly for women and IPLCs, and to reduce barriers to implementing blue carbon projects. These recommendations include gender sensitive and participatory mapping along with a registry of ownership with extensive gender equitable IPLC consultation to resolve ownership uncertainties. Recommendations for community level and gender equitable benefits beyond individual land owners are important to address the inequity of land ownership. Where land ownership changes under sea-level rise and intentional barrier removal, carbon rights should be retained by the landowner; otherwise, there is little incentive to undertake blue carbon projects. Due to the limited income that results from some carbon credit payments, other crediting and non-market methods can be considered to supplement landowners’ incomes and encourage habitat protection. Conflicting priorities between authorities responsible for managing coastal wetlands can be resolved through systematic restructuring/streamlining and collaborative workshops. Some will require changes to policies and amending delegated legislation.

Reducing and time-shifting household energy demand is important for a sustainable transition of energy systems, and dynamic electricity pricing, like real-time pricing (RTP), is a popular instrument to incite households to change energy demand. However, the effect of such products relies on the assumption that dynamic price signals incorporate into everyday routines and rhythms. This paper investigates the flexibility of households’ everyday routines and rhythms. The study provides three insights based on 11 Danish household visits and interviews with electricity customers who are new to RTP. First, the interviews indicated confusion over terminology for dynamic pricing products and low interest in flexible energy demand. Second, everyday practices (already) appeared flexible but for other reasons than energy demand flexibility. Third, energy habits were important for providing meaning to everyday practices. In addition, the study shows that energy flexibility is not just about energy demand, but rather about all the other activities that form routines and rhythms in everyday life. We suggest 1) designing products that reflect ‘natural’ or ‘societal’ daily rhythms, 2) focusing on the engaged households, and 3) being aware that for some households, changes in pricing, including new payment schemes, might put extra pressure on already harried everyday routines.

Background. The role of exercise programs during Substance Use Disorder (SUD) treatment is considered particularly supportive in fostering positive psychological and behavioral changes. The aim of this feasibility study was to explore the acute effects of cycling exercise in an immersive virtual reality (IVR) environment on attentional control and self-efficacy expectations of indi-viduals undergoing SUD treatment. Methods. A total of 20 individuals (mean age of 37.75 years) enrolled in a SUD treatment program participated in the study. They were instructed to complete a single session of cycling with a self-selected duration within the IVR system. Results. Following the cycling session, pre-post measures indicated a statistically significant im-provement in self-efficacy expectations and attentional control measured with the Stroop test. The results revealed that participants expressed high levels of intention for future use, inter-est/enjoyment, and positive attitudes toward the IVR exercise system. Qualitative data indicated that participants found the IVR exercise system enjoyable, expressed a strong intention to use it, and did not encounter technical difficulties or negative emotions. Conclusions: In conclusion, it seems that engaging in a brief period of self-selected exercise within a virtual environment can result in temporary activation of cognitive changes, heightened self-efficacy expectations, and a motivating approach to increasing physical activity participation among individuals with SUD, thus suggesting the feasibility of this approach.

This study evaluates the R3THA™ technology-supported assessment protocol for home-based rehabilitation in children with cerebral palsy (CP). It focuses on the reliability and validity of R3THA™ in assessing hand and arm function, comparing kinematic assessments with standard clinical assessments. Conducted during a 4-week summer camp, the study involved children with CP aged 3-18, assessing their functional and impairment levels. The findings suggest that R3THA™ is more reliable for children aged 8 and older, indicating that age significantly influences the protocol's effectiveness. Results also showed that R3THA-AP's kinematic measurements of hand and wrist movements were positively correlated with the Box and Blocks Test Index (BBTI), reflecting hand function and dexterity. Additionally, R3THA-AP's accuracy metrics for hand and wrist activities aligned with the Melbourne Assessment 2's Range of Motion (MA2-ROM) scores, suggesting a meaningful relationship between R3THA-AP data and clinical assessments of motor skills. However, no significant correlations were observed between R3THA-AP and MA2's accuracy and dexterity measures, indicating areas for further research. These findings validate R3THA-AP's utility in assessing motor abilities in CP, supporting its integration into clinical practice.

Background/aim: Insulin- and non-insulin treated diabetes (ITDM and NITDM) may have different prognostic impact in patients with ST-elevation myocardial infarction (STEMI) and /or heart failure. The aims of this study were to analyze the impact of ITDM and NTIDM on the incidence of all-cause mortality and major adverse cardiovascular events (MACE- cardiovascular death, non-fatal infarction, non-fatal stroke and tagert vessel revascularization) in the eight-year follow-up of STEMI patients with a reduced ejection fraction (EF). Method: we analysed 2,230 STEMI patients with EF <50%. Patients presenting with cardiogenic shock were excluded. Results: The incidence of DM was 20.7%; among the patients with DM, 103 (22.3%) had ITDM, and 358 (77.7%) patients had NITDM. Eight year mortality and MACE were higher in patients with ITDM than in patients without DM (19.8% vs. 37.8%, and 15.2% vas 40.8%, respectively, p<0.001); there was no difference in mortality and MACE between patients without DM and patients with NITDM. IDM was an independent predictor for 8-year mortality (HR 1.72, 95%CI 1.12-2.62, p=0.013) and MACE (HR 1.49, 95%CI 1.01-2.19, p=0.041). Conclusion: ITDM independently increased long-term mortality and MACE in patients with EF<50% after STEMI. NITDM had no significant influence on long-term mortality and MACE in analyzed patients.

Introduction:The concept of same-day discharge has garnered increasing significance within orthopedic surgery, particularly in hip and knee procedures. Despite initial concerns surrounding the absence of prolonged hospital care, a burgeoning body of evidence highlights numerous advantages associated with same-day discharge, ranging from mitigating in-hospital infections to offering substantial financial and psychosocial benefits for both patients and healthcare providers. In this study, we aim to scrutinize the trends in same-day discharge specifically within the realm of total hip arthroplasties. Method:This retrospective analysis delves into the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database spanning from 2016 to 2021. Result:In this study, same-day hip patients skewed younger, comprising 48.3%females compared to 55.6% in hospitalized hip patients. Operatively, same-day hip surgeries boasted shorter durations, averaging 83.9 minutes, in contrast to the 92.3minutes for hospitalized hip procedures. Postoperatively, same-day hip patients exhibited significantly diminished rates of 30-day readmissions (1.7%vs. 3.5%), procedure-related readmissions (1.0%vs.2.1%), reoperations (1.1%vs.1.9%), and mortality (0.02% vs. 0.04%). In addition, we found that that unplanned readmissions in the same-day group are significantly predicted by being over 65 years old (OR: 2.0), having hypertension (OR: 1.6), chronic steroid usage (OR: 2.2), and severe COPD (OR: 2.0), while gender, emergent surgery indication, and smoking were not significant predictors. Moreover, the prevalence of the same-day discharge concept experienced a remarkable ascent from 2016 to 2021, with rates escalating from 1.5% to 25.6% of all total hip arthroplasties over a span of just six years. Conclusion:In conclusion, same-day discharge is a feasible and safe option for selected THA patients, improving healthcare efficiency and patient satisfaction.

Hydroponic farming systems play an increasingly important role in the sustainable production of nutrient-rich foods. The contamination of surfaces in hydroponic fresh produce production poses risks to the food safety of crops, potentially endangering public health and causing economic losses in the industry. While sanitizers are widely used in commercial hydroponic farms, their effectiveness against human pathogens on surfaces, and their impact on plant health and quality are not known. In this study, we evaluated the efficacy of chemical sanitizers in eliminating Salmonella Typhimurium from inanimate surfaces in commercial hydroponic Nutrient Film Technique (NFT) systems. Further, we assessed the impact of sanitizers on the yield, quality, and nutritional value of lettuce and basil. Sanitizers (Virkon, LanXess; Sanitate 12.0, Bi-oSafe Systems; Kleen Grow, Pace Chemical Ltd.; Green Shield, United Labs Inc.; Zerotol, BioSafe Systems; Bleach, Pure Bright), were tested against Salmonella Typhimurium inoculated on NFT surfaces (nutrient reservoirs, growing channels, top covers, drain lines). The effective treatments were then tested for their impact on lettuce and basil in a split-plot experiment conducted in commercial NFT units. Crop yield, color, and nutrient content were measured throughout the crop life cycle. While all quaternary ammonium compounds (QAC), SaniDate 12.0 (200ppm), Zorotol (5%), and Virkon (1%) eliminated Salmonella Typhimurium from commercial NFT surfaces, chlorine-based sanitizer treatments were statistically similar to water treatments on most surfaces. All chemical sanitizers impacted the yield, color, and nutritional value of lettuce and basil. SaniDate 12.0 (200ppm) was the least detrimental to crops and was identified as a potential candidate for further validation in commercial hydroponic settings. The findings of this study will be translated into recommendations for the industry and will contribute to the development of future food safety guidelines and policies.

This paper presents a methodology for the integration of Building Information Modeling (BIM) and Life Cycle Cost Analysis (LCCA) to assess the economic implications of designing aging-in-place (AIP) homes at the conceptual stage. With the global increase in the aging population, there is an increased demand for housing solutions tailored to the needs of elderly individuals. Focusing on the importance of the early phase of design, this study aims to improve the process of making efficient decisions by providing a comprehensive assessment of the life cycle costs associated with AIP homes. The study introduces a semi-automated model for the economic evaluation of AIP homes, enabling the estimation of costs throughout the houses’ entire life cycle, from design and construction to operation, maintenance, and eventual renovation or disposal. The said model facilitates the exploration of the long-term economic feasibility of design’s related decisions with an emphasis on the importance of considering the life cycle costs early during the design process to optimize the functionality and economic viability. By investing in accessible and universal design features upfront, the initial costs for modifications can lead to long-term savings by reducing the need for extensive retrofits. The model can easily do comparison between different design alternatives in terms of their lifecycle costs, allowing designers to assess the financial impact of using important features in their design such as wider doorways, accessible bathrooms, and elevators. Overall, this study provides valuable insights for designers and homeowners about the economic aspects of designing AIP homes as a support for efficient decision-making during the early stages of the design process.

The influence of the secondary process of evaporation of the reaction product on the kinetics of interaction of gases (O₂, Cl₂, NH₃, H₂O and N₂H₄ vapors) with the surface of some metals (Cr, Pb, Si, Ge) and compounds (BN, SiO₂, SiC) is discussed. Also is considered the case when the growth of the scale is preceded by the process of gas etching of the metal surface. A general equation is given that describes the scale growth-evaporation kinetic (sample mass change - time) curves during the interaction of gases with the surface of metals and compounds. Special cases of parabolic, cubic and fourth degree processes are discussed.

It is essential to have a thorough knowledge of the genetic variation among different strains of Xanthomonas citri pv. citri (Xcc), which is responsible for causing citrus bacterial canker. This understanding is important for studying the disease’s characteristics, population structure, and evolution, and ultimately for developing sustainable methods of control. A total of 48 strains, obtained from citrus production areas in Burkina Faso in 2012, 2020, and 2021, were subjected to polymerase chain reaction (PCR) tests using specific primers. The aim was to examine the distribution of type 3 effectors (T3E) and determine the geographical origins of the strains. The examination of the distribution of type 3 non-transcription activate like effectors (TALE) indicates a broader range in strains obtained in 2020 and 2021 compared to those obtained in 2012. However, all strains possess a shared set of three genes, specifically XopE2, XopN, and AvrBs2. Furthermore, all examined effectors were observed in the Bobo-Dioulasso region. Regarding the characterization of TALEs, two profiles containing two to three TALEs were discovered. Profile 1, consisting of two TALEs, was found in 37 Xcc strains, whereas Profile 2, comprising three TALEs, was detected in 11 strains. Out of the three TALEs (A, B, and C) that were identified, TALEs B and C were present in all strains. The correlation matrix indicated a positive association between the T3E content of strains and the duration of their isolation. Principal component analysis revealed a limited organization of the strains under investigation

An Indo-French campaign was conducted during May 2014 at Gadanki (13.5^oN, 79.2^oE), India, for investigating gravity wave (GW) coupling between the lower and middle atmospheres using a suite of experimental techniques. In this paper we are presenting the sources for those GWs which are observed at airglow layer (~87 km) using (OH) Airglow Imager during the campaign. For this purpose we have developed a background model atmosphere by combining the ERA-Interim, MSIS E 90 model and HWM 07 model data sets. Uniqueness of the present study lies in using near-real time background atmosphere data from simultaneous radiosonde and SVU Meteor Radar covering both source and propagation/ dissipation regions of GWs. We have observed 17 wave events and used GROGRAT model for reverse tracing to locate the source(s). When we searched for the sources near the terminal points or along the ray path, deep convection is found to occur but no strong wind shear. This indicates that the source for the observed GWs is deep convection. We have also simulated small scale waves that can reach mesosphere during different seasons (background conditions). GWs with periods less than 100 minutes and horizontal wavelengths less than 200 km are mostly reaching the mesospheric altitudes. Interestingly, it is found that only few GWs that are generated in the troposphere reach the mesospheric altitudes during the monsoon season, though strong sources like convection and wind shear persist throughout this season. Thus, background wind plays significant role in deciding the propagation of GWs in to upper atmosphere.

The ultimate goal of our review is to draw clinician’s attention, especially of those who are managing pediatric patients with permanent, long-standing, ventriculoperitoneal or, less commonly, ventriculo-atrial shunts. This specific subgroup of patients may eventually suffer from severe, intractable headaches which may negatively impair their quality of daily living. In the absence of any other clinical condition that could be attributed as the cause of the headache, shunt overdrainage should not be overlooked but, on the contrary, should be seriously taken into consideration in the therapeutic armamentarium of such cases, that are difficult to be handled.

Background: Since there is no cure for amyotrophic lateral sclerosis (ALS) currently, it is very important for searching diagnostic biomarkers and novel treatments to reduce the severity of this disease; one of these treatment approaches is stem cell transplantation. This study aims to evaluate the safety and efficacy of repeated transplantation of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) in patients with ALS by analyzing molecular data. Methods: In this single-centre, open-label, phase II clinical trial, retrospective study, fifteen confirmed ALS patients entered the study based on defined inclusion and exclusion criteria and underwent repeated stem cell transplantation (3 times BM-MSCs transplantation (1×10^6) , MSC/Kg BW per injection) concurrently intrathecally (IT) and intravenously (IV), with one-month interval). Clinical assessment of molecular investigation by evaluating specific microRNAs expression (Mir206, 133a-3p, 338-3p) in the patient's serum and Cerebra spinal fluid (CSF) samples were done three times during the 3-month follow-up. Statistical analysis includes paired T-test or Wilcoxon signed ranks. Results: No serious adverse effects were reported following stem cell transplantation. Besides, the mentioned microRNA expression slightly increased but still non-significant (P&gt;0.05). Conclusions: Although Our study demonstrated non-signifying results. However, the still increasing of these MircRNAs in serum and CSF overall, can indicate that repeated transplantation of BM-MSCs was a safe procedure in ALS patients, leading to delay in disease progression and improvement in clinical symptoms. Future studies are needed to confirm these results.

The new observations, including the fastest star, the circular velocity curve of the Milky Way and the fast galaxy bar, should imply that the mass of the center of the Milky Way is almost 10¹¹ times the mass of the Sun.

In this study, vermiculite was explored as a support material for nickel catalysts in two key processes in syngas production through dry reforming of methane with CO2 and steam reforming of ethanol. The vermiculite was subjected to acid or base treatment, then, Ni catalysts were prepared through incipient wetness impregnation and characterized using various techniques, including X-ray, FTIR, temperature programmed reduction (H2-TPR). TG-TD analyses were performed to assess the formation of carbon deposits on spent catalysts. The Ni based catalysts were used in the reaction tests without a reduction pre-treatment. Initially, raw vermiculite-supported nickel showed limited catalytic activity, however after acid (Ni/VTA) or base (Ni/VTB) treatment, vermiculite became an effective support for nickel in dry methane reforming. The resulting catalysts (Ni/VTB and Ni/VTA) displayed outstanding performance, with high methane conversion and hydrogen yield. Acidic treatment improved the reduction of nickel species and reduced carbon deposition, outperforming alkali treatment. The prepared catalysts were also explored in ethanol steam reforming. The performance was investigated as a function of the temperature, water/ethanol ratio, and space velocity, with acid-treated catalysts performing as the best. The study emphasized the importance of contact time with the catalyst and addressed challenges related to carbon formation and sintering for long-term stability. In conclusion, acidic treatment of the vermiculite support, before Ni deposition, significantly enhanced the catalytic activity and stability of nickel catalysts in both dry methane reforming and ethanol steam reforming processes.

Understanding clinical significance of variants of unknown significance (VUS) reported in next-generation sequencing (NGS) has become essential in cancer treatment. Our study examined six widely used in silico tools: PolyPhen-2, Align-GVGD, MutationTaster2, CADD, REVEL, and Chat-GPT. We utilized a dataset of gene variants known to potentially affect immune therapy. No single tool could comprehensively determine mutation variant pathogenicity. MutationTaster2021 showed the highest overall accuracy and MCC among the tools. Notably, REVEL and Chat-GPT exhibited 100% specificity, suggesting their proficiency in accurately identifying pathogenic variants and minimizing false positives. In contrast, CADD displayed optimal sensitivity, making it suitable for effectively ruling out benign variants.

In children, the global burden of vaccines-preventable diseases (VPDs) and deaths can be averted by adopting timely immunization practices. Administering immunization to a child within 28 or 30 days of the designated immunization date is referred to as timely immunization. Delaying or missing vaccinations puts children, especially those in urban slums, at a higher risk of getting sick or dying from different diseases. This study was designed to examine the immunization practices and to measure the determinants of immunization non-compliance in children living in urban slums of Karachi, Pakistan. A community-based retrospective cohort was carried out from October-2018- to August-2019 in six different urban slums of Karachi. Immunization status of children aged less than 2 years was assessed by reviewing their vaccination card. Children from each slum were approached via 30x7 multistage stratified cluster sampling technique. Data of each child was analysed descriptively and inferentially using a statistical software, i.e., Jamovi version 1.2.25. The practice of timely immunization was observed in approximately half of children, i.e., 49.8%(n=457). The immunization rate at birth (first-visit) was 100%, of which 95.7% were timely immunized. Following the second immunization visit, a sharp decline in the immunization rate, including timely immunization rate was observed. Lack of knowledge, childhood illnesses, lack of interest, and vaccines unavailability were the main reasons of immunization non-compliance. However, an increase in paternal education was significantly associated to decrease the odds of immunization non-compliance. A decrease in the practice of timely immunization is replaced by either invalid and/or delayed and/or missed immunization practices. Thus, timely immunization is crucial for preventing the infectious diseases and promoting the health of a child.

The epigenetic mechanism of DNA methylation is essential for regulating gene expression and adaptation in plants, especially when exposed to various environmental stressors such as drought, heat, and nutrient availability. The impact of these stressors can lead to alterations in DNA methylation patterns and gene expression, which this study aims to investigate. Specifically, we are interested in understanding how DNA methylation plays a role in controlling the expression of stress-response genes, as well as genes involved in plant growth and development. To accomplish this, we are analyzing the changes in DNA methylation patterns and gene expression in response to different stressors like drought and heat. Our research findings suggest that DNA methylation is a vital regulator of plant adaptation to environmental stress, and we hope to gain further insight into these mechanisms by identifying genes that exhibit differential expression in response to stress and analyzing their DNA methylation status. This study offers valuable insights into the development of crops that can thrive under changing climate conditions.

The development of saltiness enhancement peptides is important in reducing salt intake and promoting dietary health. Our study aimed to analyze and identify straw mushroom enzymatic peptides with salty taste enhancing effects. The taste-related peptides within the straw mush-room extract were isolated via ultrafiltration and identified using UPLC-Q-TOF-MS/MS. Sub-sequent, E-tongue and sensory analyses unveiled that the ultrafiltration fraction (500-2000 Da) of straw mushroom peptides exhibited a saltiness enhancement effect. The UPLC-Q-TOF-MS/MS analysis identified 220 peptides within the ultrafiltration fractions (500-2000 Da), which were then assessed for their interaction with the T1R1/T1R3 receptor. The investigation underscored the significant involvement of Asp223, Gln243, Leu232, Asp251, and Pro254 in the binding of peptides from triple enzymatically hydrolyzed straw mushrooms to T1R1/T1R3. Based on the binding energy and active site analysis, three peptides were selected for synthesis: DFNALPFK (-9.2 kcal/mol), YNEDNGIVK (-8.8 kcal/mol), and VPGGQEIKDR (-8.9 kcal/mol). Notably, 3.2 mmol of VPGGQEIKDR enhanced a 0.05% NaCl solution to the saltiness level of a 0.15% NaCl solution. Also, 0.8 mmol of YNEDNGIVK elevated a 0.05% NaCl solution to the saltiness of a 0.1% NaCl solution.

Whether and how P2X7 receptor knockout (KO) modulates central post-stroke pain (CPSP) induced by lesions of the ventrobasal complex (VBC) of the thalamus regarding behavioral, molecular, and electrical recording parameters remains unclear. Following the experimental protocols of a rat hemorrhage CPSP model, the VBC of the thalamus of wild-type and P2X7 receptor KO mice was injected with 10 mU/0.2 μl type IV collagenase to produce an animal model of stroke-like thalamic hemorrhage. Behavioral data showed that the CPSP group induced thermal and mechanical pain, while the P2X7 receptor KO group showed reduced thermal and mechanical pain behaviors. Molecular assessments revealed that the CPSP group had lower expression of NeuN and KCC2 and higher expression of GFAP, IBA1, and BDNF. The P2X7 KO group showed lower expression of GFAP, IBA1, and BDNF and higher expression of KCC2 than the CPSP group. The expression of NKCC1, GABAa receptor, and TrkB did not differ significantly between the control, CPSP, and P2X7 receptor KO groups. Muscimol application increased multiunit numbers and [Cl-] influx in the membrane in the CPSP group, while P2X7 receptor KO reduced multiunit activity and [Cl-] outflux. P2X4 receptor expression was significantly decreased in the 100 kb but not the 50 kb site in the P2X7 receptor KO group. Altogether, the P2X7 hypothesis of CPSP was proposed, wherein P2X7 receptor KO changed the CPSP pain behavior, numbers of astrocytes and microglia, CSD amplitude of the anterior cingulate cortex and the medial dorsal thalamus, BDNF and KCC2 expression, [Cl-], and P2X4 activation in 100 kb with P2X7 receptors. The present findings have implications for the clinical treatment of CPSP symptoms.

The aim of this study is to investigate transient dynamic flow characteristics of the fluid flow through 5-way electric coolant valve (PCCV : Penta-Control Coolant Valve). To achieve this goal, the present paper attempts the three-dimensional dynamic simulation of the fluid flow through the valve using a commercial CFD solver with moving mesh technique to consider flow inertia and dynamic flow in the opening and closing stages of the ball valve rotating motion. Firstly, dynamic flow characteristics and the thermal mixing inside the PCCV ball valve during the opening and closing stage was analyzed. It is found that the discrepancies between dynamic and steady state simulation is remarkable when fluxes with different levels of enthalpy and momentum flow into the PCCV leads to strong flow interference and flow inertia, while the discrepancies are relatively small at low rotation speed and weak flow interference. Then, the effect of dynamic flow characteristics of the valve on dynamic thermal mixing characteristics at two different ball valve rotational speeds and rotational directions were investigated. It was found that the dynamic flow and thermal mixing characteristics inside the PCCV are greatly affected by the rotation speed, rotation direction, and degree of flow interference between fluxes. It is helpful for the design of the better coolant control strategies and the improvement of the FCEV thermal management system.

Functional health literacy is the ability to read, write, and speak about health. Functional health literacy events can nudge the development of children’s health identity when using valid and reliable reading materials that portray the “what, where, when, why, and with whom” to eat nutritious foods and be physically active. Children who lack social role models for healthy eating and physical activity may also lack development in language and motor skills. Therefore, literacy-rich environments are needed when developing cognitive-motor language skills with children. Children with obesogenic body frames can gain from the production of childcentric health narratives that draw upon the Habits of Mind and Habits of Health© Model to produce Electronic Texts for Health Literacy©. When health professionals plan and implement functional health literacy events so children can read, write, and speak about their own health, new behavioral patterns and routines emerge into performances of understanding. Constructivist pedagogical approaches can help children to create health narratives using multimodal language while practicing health literacy skills as a foundational impetus to health behaviors. Children who struggle with obesity can also gain social agency when writing with peer partners who serve as supportive collaborators when developing interactive health literacy.

This study investigated the impact of seven-strain probiotic supplementation on the frequency of T helper 17 (Th17) cells, regulatory T (T-reg) cells, Treg/Th17 ratio, and their gene expression in individuals with severe traumatic brain injury (STBI). Probiotics can influence the gut microbiota, modulate the immune response, and prevent or alleviate certain immune diseases. However, it is necessary to clarify whether probiotics can effectively impact Th cells in STBI patient. Despite the great attention to improving the immune system in most diseases, there is currently no accurate mechanism for the use of probiotics in diseases with damage to the head injury, which can be a basis for the use of probiotics. The primary objective of this study is to address this research gap. The present study was a randomized, double-blind, placebo-controlled trial that enrolled 48 STBI patients. They were treated with probiotics or placebo: 4 capsule/day for 14 days. The pre- and post-study evaluation included examining the frequency of Treg, Th17 cells, as well as the expression of associated immunological parameters (Foxp3 and RORγt) and Treg/Th17 ratio in both groups. No significant differences were found between the two groups in terms of subject characteristics (P>0.05). GCS scores at 14 days were significantly higher in the probiotic compared to the placebo group. The probiotic group showed a significant decrease in Th17 cell and RORγt gene expression (P = 0.022 and P< 0.001, respectively), a notable increase in T-reg and FoxP3 gene expression (P= 0.025 and P< 0.001, respectively), and a higher Treg/Th17 ratio compared to the placebo group. Our study provides promising evidence of the beneficial effects of seven-strain probiotic supplementation on Th cells in individuals with STBI.

This review article focuses on the upstream pertinent pathophysiology leading to neurodegenerative disease. Specifically, the nexus appears to be blood brain barrier (BBB) leakiness resulting in a two-prong inflammatory disease spectrum damaging the microvasculature and corrupted protein synthesis and degradation with accumulating misfolded toxic proteins. The suboptimal results of removing misfolded proteins means a new approach to disease in the preclinical state is required aimed at other targets.Validated noninvasive imaging and serologic biomarkers of early preclinical disease implemented in the high-risk patient cohort along with periodic surveillance once effective treatments are developed will be required.This review discusses the physiology and pathophysiology of the BBB, new MRI imaging techniques identifying the leak and altered fluid dynamic effects in the preclinical state. The risk factors for disease development, preventative measures, and potential treatment targets are also discussed.

Platelet-activating factor (PAF) is a phospholipid-derived inflammatory mediator, triggering various inflammatory conditions, including eosinophil activation and recruitment. Despite the unclear mechanism underlying the formation and maintenance of nasal polyp in chronic rhinosinusitis with nasal polyps (CRSwNP), there is strongly indication of its association with type 2 inflammation. This study aimed to quantify PAF-associated gene expression, examining enzymes involved in PAF synthesis (lysophosphatidylcholine acyltransferase 1 (LPCAT1), LPCAT2, LPCAT3, and LPCAT4), and PAF degradation (PAF acetylhydrolases 1 B2 (PAFAH1B2), PAFAH1B3, and PAF acetylhydrolases 2 (PAFAH2)), and PAF receptor (PTAFR). Transcriptomic analysis encompassed CRSwNP, including eosinophilic CRS (ECRS) (n=9), nonECRS (n=8), and a subgroup of ECRS with aspirin exacerbated respiratory disease (Asp) (n=3) based on the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) criteria. Gene expression profiles from nasal polyps in CRSwNP patients and the uncinate process in normal subjects (controls) (n=6) were analyzed using bulk RNA barcoding and sequencing (BRB-seq). Hierarchal analysis, utilizing the average linkage method with iDEP1.1, clarified the relationship between Differentially Expressed Genes (DEG) expressions and cluster formation. Two clusters (cluster 1 (n=11) and cluster 2 (n=9)) of CRSwNP divided by hierarchal analysis showed distinct gene expression profiles in the specific pathway of “cytokine-cytokine receptor interaction” in KEGG pathway and upregulated type 2 inflammatory gene expression in cluster 2. In CRSwNP subclassification of ECRS, nonECRS, and Ctrl, PTAFR was only upregulated in ECRS and nonECRS. In cluster analysis, cluster 1 showed significant downregulation of LPCAT2 and upregulation of PTAFR expression, while cluster 2 showed significant upregulation of LPCAT1, PAFAH1B2, and PTAFR and downregulation of PAFAH2 expression. These findings suggest that cluster 2, characterized by severe type 2 inflammatory gene expression, manifest a prominent PAF-associated pathophysiology. Understanding this high PAF-associated pathophysiology in cluster 2 could provide valuable insights into the treatment and management of CRSwNP.

The studied Khanbogd pluton of peralkaline granite is located in southern Mongolia and occupies an area of ~1000 sq. km. Previously, two ring-shaped bodies were constructed in a flattened shape pluton. However, this shape was not used for the genesis of this pluton. A recent study of Landsat image showed a several elliptical intrusions in two bodies. Chemistry interpretation shows that each intrusion differs in ASI, CIPW norms, 87Sr/86Sri and δ18O isotopes. Elliptical intrusions, uplifted country rocks between them, and roof pendants suggest magma penetration along fractured country rocks. Furthermore, two adjacent intrusive bodies and undeformed host rocks at the front part of the pluton are consistent with underplating magmatic factors during duplex-type thrusting. This magma event is also supported by low of Sr, Ba, Eu and high of Th, U, Pb anomalies and a few amount of garnet crystals in the granites, implying vapor absent melt crystallization associated with underplating. Multiple melt sources, as well as from mantle and recycled sea floor rocks, are identified by ratio of 87Sr /86Sri and δ18O values. The low isotope values, the thrust nature and 295–286 Ma ages of the alkali granites, indicate an underplate magma evidenced during Permian rifting.

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

This study outlines a comprehensive examination of risks and hazards in three egg sorting and packing stations, covering the entire process from supplier selection and evaluation to egg delivery in chain stores. The analysis is conducted within the framework of Codex Alimentarius and GFSI-integrated food safety programs. Salmonella is the greatest significant threat. To enhance the Hazard Analysis of Critical Control Points (HACCP), preparatory programs were incorporated into the quality management system (QMS) by monitoring and assessing the biological, chemical, and physical threats according to Code Alimentarius and further integrated into GFSI food safety programs, including food authenticity and food defense. The procedure offered sophisticated preventive tools, hand-on at any time, for eliminating, reducing, or mitigating the risks encountered in egg packing and sorting facilities.

Background: Pediatric Rapid Response Teams (RRTs) are expected to significantly lower pediatric mortality in healthcare settings. This study evaluates RRTs' effectiveness in decreasing cardiac arrests and unexpected Pediatric Intensive Care Unit (PICU) admissions. Methods: A quasi-experimental study (2014-2017) at King Abdulaziz University Hospital, Jeddah, Saudi Arabia, involved 3,261 pediatric inpatients, split into pre-intervention (1,604) and post-intervention (1,657) groups. The intervention entailed pediatric specialists collaboratively managing acute decompensations following set protocols. Results: RRT was activated 471 times, primarily for respiratory distress (29.30%), sepsis (22.30%), clinical anxiety (13.80%), and hematological abnormalities (6.7%). Family concerns triggered 0.1% of activations. Post-RRT implementation, unplanned PICU admissions significantly reduced (RR = 0.552, 95% CI 0.485-0.628, P < 0.0001), and non-ICU cardiac arrests were eliminated (RR = 0). Patient care improvement was notable, with a -9.61 coefficient for PICU admissions (95% CI: -12.65 to -6.57, P < 0.001) and a -1.641 coefficient for non-ICU cardiac arrests (95% CI: -2.22 to -1.06, P < 0.001). Sensitivity analysis showed mixed results for PICU admissions, while zero-inflation Poisson analysis confirmed a reduction in non-ICU arrests. Conclusions: The deployment of pediatric RRTs is associated with fewer unexpected PICU admissions and non-ICU cardiopulmonary arrests, indicating improved PICU management. Further research using robust scientific methods is necessary to conclusively determine RRTs' clinical benefits.

Active vitamin D derivatives (VDDs) – 1α,25-dihydroxyvitamin D3/D2 and their synthetic analogs – are well-known inducers of cell maturation with the potential for differentiation therapy of acute myeloid leukemia (AML). However, their dose-limiting calcemic activity is a significant obstacle to using VDDs as an anticancer treatment. We have shown that different activators of the NF-E2-related factor-2/Antioxidant Response Element (Nrf2/ARE) signaling pathway, such as the phenolic antioxidant carnosic acid (CA) or the multiple sclerosis drug monomethyl fumarate (MMF), synergistically enhance the antileukemic effects of various VDDs applied at low concentrations in vitro and in vivo. This study aimed to investigate whether glutathione, the major cellular antioxidant and the product of the Nrf2/ARE pathway, can mediate the Nrf2-dependent differentiation-enhancing activity of CA and MMF in HL60 human AML cells. We report that glutathione depletion using L-buthionine sulfoximine attenuated the enhancing effects of both Nrf2 activators concomitant with downregulating vitamin D receptor (VDR) target genes and the activator protein-1 (AP-1) family protein c-Jun levels and phosphorylation. On the other hand, adding reduced glutathione ethyl ester to dominant negative Nrf2-expressing cells re-stored both the suppressed differentiation responses and the downregulated expression of VDR protein, VDR target genes, as well as c-Jun and P-c-Jun levels. Finally, using the transcription factor decoy strategy, we demonstrated that AP-1 is necessary for the enhancement by CA and MMF of 1α,25-dihydroxyvitamin D3-induced VDR and RXRα protein expression, transactivation of the vitamin D response element, and cell differentiation. Collectively, our findings suggest that glutathione mediates, at least in part, the potentiating effect of Nrf2 activators on VDDs-induced differentiation of AML cells, likely through the positive regulation of AP-1.

Cathepsin B (CatB) is thought to be essential for the induction of Porphyromonas gingivalis lipopolysaccharide (Pg LPS)-induced Alzheimer’s disease- like pathologies in mice, including interleukin-1β (IL-1β) production and cognitive decline. However, little is known about the role of CatB in Pg virulence factor-induced IL-1β production by microglia. We first subjected IL-1β-luciferase reporter BV-2 microglia to inhibitors of Toll-like receptors (TLRs), IκB kinase, and the NLRP3 inflammasome following stimulation with Pg LPS and outer membrane vesicles (OMVs). To clarify the involvement of CatB, we used several known CatB inhibitors, including CA-074Me, ZRLR, and human β-defensin 3 (hBD3). IL-1β production in BV-2 microglia induced by Pg LPS and OMVs was significantly inhibited by the TLR2 inhibitor C29 and the IκB kinase inhibitor wedelolactonne, but not by the NLRPs inhibitor MCC950. Both hBD3 and CA-074Me significantly inhibited Pg LPS-induced IL-1β production in BV-2 microglia. Although CA-074Me also suppressed OMV-induced IL-1β production, hBD3 did not inhibit it. Furthermore, both hBD3 and CA-074Me significantly blocked Pg LPS-induced nuclear NF-κB p65 translocation and IκBα degradation. In contrast, hBD3 and CA-074Me did not block OMV-induced nuclear NF-κB p65 translocation or IκBα degradation. Furthermore, neither ZRLR, a specific CatB inhibitor, nor shRNA-mediated knockdown of CatB expression had any effect on Pg virulence factor-induced IL-1β production. Interestingly, phagocytosis of OMVs by BV-2 microglia induced IL-1β production. Finally, the structural models generated by AlphaFold indicated that hBD3 can bind to the substrate-binding pocket of CatB, and possibly CatL as well. These results suggest that Pg LPS induces CatB/CatL-dependent synthesis and processing of pro-IL-1β without activation of the NLRP3 inflammasome. In contrast, OMVs promote the synthesis and processing of pro-IL-1β through CatB/CatL-independent phagocytic mechanisms. Thus, hBD3 can improve the IL-1β-associated vicious inflammatory cycle induced by microglia through inhibition of CatB/CatL.

Background: Anthropometric measurements play a crucial role in medico-legal practices. Actually, several scanning technologies are employed in post-mortem investigations for forensic anthropological measurements. This study aims to evaluate the precision, in-ter-rater reliability, and accuracy of a hand-held scanner in measuring various body parts. Methods: Three independent raters measured seven longitudinal distances using an iPad Pro equipped with a LiDAR sensor and specific software. These measurements were sta-tistically compared to manual measurements conducted by an operator using a laser level and a meterstick (considered the gold standard). Results: The Friedman’s test revealed minimal intra-rater variability in digital measurements. Inter-rater variability analysis yielded an ICC=1, signifying high agreement among the three independent raters. Addi-tionally, the accuracy of digital measurements displayed errors below 2%. Conclusions: Preliminary findings demonstrate that the pairing of LiDAR technology with the Polycam app showcases high precision, inter-rater agreement, and accuracy. Hand-held scanners show potential in forensic anthropology due to their simplicity, affordability, and porta-bility. However, further validation studies under real-world conditions are essential to es-tablish the reliability and effectiveness of handheld scanners in medico-legal settings.

In hepatocellular carcinoma (HCC), recurrence usually occurs after curative surgical resection. Currently, no approved adjuvant therapy has been shown to reduce recurrence rates. In this report, the in vivo mouse effect of sequential combination treatment with recombinant mouse interferon-alpha (rmIFN-α) and an anti-mouse-PD1 antibody on hepatitis B virus (HBV) clearance was evaluated. A phase I clinical trial was then conducted to assess the safety, tolerability, and inhibitory activity of sequential therapy with ropeginterferon alfa-2b and nivolumab in HCC recurrence in patients who have undergone curative surgery for HBV-related HCC. In animal modeling, HBV suppression was significantly greater with rmIFN-α and anti-PD1 sequential combination treatment than with their treatment alone. In the Phase I study, eleven patients completed the sequential therapy with ropeginterferon alfa-2b every two weeks at the dose of 450 µg for six doses, followed by three doses of nivolumab every two weeks up to 0.75 mg/kg. A notable decrease or clearance of HBV surface antigen was observed in two patients. Dose-limiting toxicity of grade 3 alanine transaminase and aspartate aminotransferase increases was observed in one patient. The maximum tolerated dose was determined. Currently no HCC recurrence has been observed. The treatment modality was well tolerated. The data support further clinical development of sequential combination therapy as a post-surgery prophylactic measure against the recurrence of HBV-related HCC.

While considering the sensitivity over the parameter optimization, it is essential to determine which parameters have the most significant implications on model performance. This study focuses on the baseflow recession constant as one of the independent basin parameters to forecast low flows, perform hydrograph analysis, and calibrate rainfall-runoff models for significant improvement. Prior studies examined that the optimization of data adjustment parameters can improve the hydrological model performance and determine the minimum acceptable data length for data scarce regions using the Xinanjaing model. However, it is essential to pay special attention to the sensitivity of the recession constant, which can also impact the model performance during the data scarcity. Therefore, this study extends the research to comprehend the recession constant sensitivity over data adjustment parameters in the shorter datasets leading to more reliable parameter estimation. In terms of that, this study explores how recession constant affects hydrological parameter estimation on annual scale while keeping data adjustment parameters constant in continuous hydrological modeling, employing the Xinanjiang (XAJ) model as a case study. This study considered two approaches of recession constant (cg); (i) assessing the relationship between cg and the data adjustment parameter (Cep), for the 28-year datasets, (ii) investigating the significant impacts of the sensitivity of cg over Cep in shorter datasets which can affect the estimation of the acceptable minimum data length in the data scarce basins. The study underscores the importance of the recession constant sensitivity for reliable continuous hydrological model predictions, especially in data-scared areas. The study’s outcomes enhance the understanding of the importance of parameter sensitivity and its relationship in conceptual hydrological modeling during the data limitations.

Infectious illnesses have always posed a threat to human health, with tuberculosis being a major concern. The use of various drugs in the fight against such TB has led to the emergence of drug-resistant tuberculosis, which has become increasingly difficult to manage. While there have been a few studies and proposed conceptual models on how to manage and prevent various drug-resistant TB mutations and lineages, a model aimed at limiting and controlling such mutations in rural areas burdened with tuberculosis is lacking. This study seeks to map a model that is to be used to bridge the gap by facilitating the exchange of knowledge among healthcare professionals in healthcare facilities, diagnostic laboratories, and research institutes, particularly for underprivileged communities in the Eastern Cape. The model information is based on three published manuscripts; therefore, this is a follow-up study. The model will also serve as a practical guide to monitor and evaluate epidemiological TB management plans.

Among all the active confinement techniques, the use of pre-tensioned stainless steel straps has recently gained much attention. The flexibility of the stainless steel straps allows us to bend and pass them through the thickness of the masonry, thus creating a three-dimensional strengthening system between the two opposite facings. The use of the same perforation for the passage of several straps closed in a loop generates a continuous strengthening system that prevents parts of the structure from falling and injuring the occupants during seismic events. However, the perforations can nullify the in-plane strengthening, as they act as cylindrical hinges and make the reinforcement system labile for certain strap arrangements. Diagonal compression tests on square masonry panels performed in the present study show that the straps improve neither strength nor ductility when running along the mortar head and bed joints, arranged in square meshes. Conversely, they improve both strength and ductility when the straps make angles of 45° with the mortar joints. Furthermore, the experimental results show that the straps exert an anisotropic effect that decreases the apparent in-plane Poisson ratio. They also provide new insights into the diagonal compression test and allow formulating a new proposal for the pseudo-ductility factor.

Dry eye syndrome (DES) has become increasingly prevalent due to the prolonged use of digital devices in modern society. Individual supplementation with lutein or docosahexaenoic acid (DHA) demonstrated potential benefits for eye health. This study aimed to investigate the effects of lutein plus DHA complex supplementation on DES, visual function, and memory in healthy individuals. Thirty-four participants, aged 40~60 years, received lutein/DHA complex supplements (containing 10 mg free-form lutein, 200 mg DHA, 30 mg red algae extract (astaxanthin), phosphatidylserine, and vitamin A) for 12 weeks. Ophthalmological examinations and memory tests were carried out, and a questionnaire was administered at weeks 0, 6, and 12 of the study. After 12 weeks of the intervention, the tear break-up time had significantly increased, and intraocular pressure (IOP) had significantly decreased. This suggests that lutein/DHA complex supplementation may reduce the IOP and offer potential benefits for DES, as indicated by improved tear stability.

The cancer burden is increasing worldwide with contrasting national patterns. Therefore, providing national estimations is necessary to understand and control this health issue. Herein, we comparatively describe incidence, mortality, and disability-adjusted lived years (DALYs) due to 29 groups of cancer in Mexico from 1990 to 2019 by sex and age. Using public data from the Global Burden of Disease Study 2019, we assessed the national burden of cancer using counts and crude and age-standardized rates per 100,000 people with 95% uncertainty intervals for 2019 and their trends using the annual percentage of change from 1990 to 2019. In 2019, cancer caused 222,060 incident cases, 105,591 deaths, and 2,86,054 DALYs in the general population. Nonmelanoma skin cancer, prostate cancer, and breast cancer had the highest incidence, and six groups of cancer (lung, colorectal, stomach, prostate, breast, and pancreatic) caused 53% of the deaths in 2019. From 1990 to 2019, incidence and mortality showed an increasing trend that varied between 10% and 436% among the groups of cancer, whereas the crude and age-standardized rates showed cancer-specific sex disparities. Our results demonstrate a substantial growth of the national burden of cancer with sex-specific patterns of change. These results may guide national efforts toward reducing health loss due to cancer.

Regular assessment of mood is used in Brazil for a wide variety of purposes, including screening athletes to provide an indicator of psychological wellbeing and risk of mental health issues. The present study tested the psychometric characteristics of the Brazil Mood Scale (BRAMS) using both “right now” and “past week” response time frames and investigated between-group differences in mood based on athlete sex, age, and social vulnerability. Participants were 898 athletes (511 male, 387 female, age range: 12–44 years) from eight sports. Structural equation modelling supported the BRAMS measurement model using both response time frames independently and in a multi-sample analysis. Subscale reliability was supported for both time frames. Fatigue, depression, and tension scores were higher using the past week time frame than the right now time frame. Males reported higher vigor scores than females, and younger participants (&lt;18 years) reported lower scores for anger and depression than older participants (18+ years). No significant between-group differences emerged for social vulnerability. Findings supported the psychometric integrity of the BRAMS and its use as a screening measure for psychological wellbeing among youth and elite athletes in Brazil.

The goal of the current study was to discover a novel potential probiotic strain of Lactobacillus spp. with anti-Escherichia coli activity from locally produced yogurt in Tongi, Gazipur, Bangladesh, compare its antagonistic activity with a commercial probiotic mixture of several strains, and approve a novel method for confirming the viability and relative abundance of the microbial community in a probiotic mixer. We carried out 16S sequencing, 16S metagenomics, Transmission Electron Microscopy (TEM) analysis, and other in vitro laboratory experiments to reach this objective. The strain TY-11 was identified as Lactobacillus delbrueckii subsp. indicus (16S sequence accession number OQ652026). It was gram-positive, anaerobic, lactose fermenting, and round-ended rod that typically measured 0.7 to 1.3 µm by 2.2 to 9 µm. In addition to having seven probiotic characteristics, it also showed an antagonistic impact on six different pathogens, but what's more noteworthy is that E. coli was the pathogen it inhibited most strongly (inhibition zone diameter was 18.88±0.18 mm). The most important and ground-breaking finding of this work was determining the probiotic features of a new probiotic strain, TY-11, whose antibacterial activity was virtually as effective as that of the probiotic combination with three different strains. Furthermore, the results of 16S high throughput sequencing and the conventional plate count method demonstrated a strong correlation (0.999) at the genus level, indicating that the use of both of these approaches in combination may be a practical way to assess the relative abundance of the microbial community and their viability in commercially available probiotic blends.

This article presents a proposed system that enables energy transfer from the dc grid to a single-phase onboard grid, operating at an hi frequency. In addition to the energy transfer function, it additionally enables compensation of reactive power in the ac grid when the converter operates at less than rated power. To operate in compensator mode, it is necessary to decouple the current from the grid into active and reactive components and control them independently. To achieve good dynamics, synchronizers that operate in the dq system are used. In the case of a single-phase grid, it requires such a synchronizer to generate virtual quadrature signals. The used systems based on second-order generalized integrator are good, but to improve dynamics in the work a quadrature generator based on trigonometric calculations was proposed. The developed system was implemented in a proportional resonant current control system. Tests performed in steady state and in dynamic states related to typical grid disturbances showed better dynamic properties than the standard integrator-based system.Keywords: power transfer; compensator; P+R controller

Bone morphogenetic protein (BMP) and platelet-derived growth factor (PDGF) are known to regulate and stimulate osteogenesis, both proteins playing an important role in bone homeostasis, constituting good candidates for osteoporosis´ treatment. Herein we aim to evaluate the effects of recombinant human BMP-7 (rhBMP7) and PDGF-BB (rhPDGF-BB) in oophorectomy-induced osteoporosis in rats. To this end, 40 Sprague-Dawley rats were submitted to oophorectomy surgery and treatments were started at the 100th day after the surgery, when all animals showed signs of osteoporosis. These peptide growth factors were applied intravenously once or twice a week and animals were followed for a total of five weeks. Two weeks after the end of the treatments, the animals were euthanized, the tissues were collected and Alkaline Phosphatase, X-ray, micro-CT and histology were assessed. The results indicate that the most promising treatments are: 20 µg/kg PDGF-BB + 30 µg/kg BMP-7 2x/week and 30 µg/kg BMP-7 2x/week, presenting an increase of 15% (p&lt;0.05) and 13% (p&lt;0.05) in bone volume fraction and 21% (p&lt;0.05) and 23% (p&lt;0.05) in trabecular number, respectively. In conclusion, rhPDGF-BB and rhBMP-7 are capable of inducing an increase in bone volume and density in this osteoporotic animal model, constituting interesting candidates for osteoporosis treatment.

This study explores the intricate relationship between the angle of vehicle-to-vehicle (V2V) conflicts and the severity of conflicts at signalized intersections during traffic signal failures, leveraging the advanced capabilities of LiDAR sensor technology. The research delves into the impact of conflict angles on collision outcomes and introduces LiDAR as a novel and precise tool for capturing spatial dynamics during unregulated traffic movements. Findings reveal that as the angle of V2V conflicts increases, indicating a wider approach between vehicles, the severity of conflicts tends to decrease. This reduction in severity is attributed to the detailed spatial data provided by LiDAR, enabling the identification of glancing impacts rather than direct head-on collisions. The mitigation of forces involved in collisions at increased angles contributes to a decreased likelihood of severe consequences, such as extensive vehicle damage and serious injuries to occupants.Conversely, as the angle of V2V conflicts decreases, signifying a narrower approach between vehicles, the potential for severe collisions tends to increase. LiDAR technology facilitates precise measurements of spatial coordinates and temporal dynamics, revealing that collisions occurring at smaller angles involve more direct and concentrated impact forces. This heightened risk of extensive damage to vehicles and increased injury severity is crucially captured by LiDAR, providing valuable insights into the relationship between conflict angles and collision outcomes during traffic signal failures. This study underscores the efficacy of LiDAR sensor technology in understanding the nuanced dynamics of V2V conflicts and highlights its role in developing targeted safety interventions. The integration of LiDAR data into traffic safety analyses offers a sophisticated approach to mitigating the impact of conflicts and enhancing overall safety at signalized intersections during signal failures. The research also highlighted that as the angle of V2P conflicts widens, PET experiences a proportional increase. A larger conflict angle signifies a more complex interaction between vehicles and pedestrians, leading to prolonged PET values. Conversely, a decrease in the angle of V2P conflicts is associated with a reduction in PET during traffic signal failures.The study commences with an examination of traffic characteristics at the E Cold Spring Ln – Hillen Rd intersection in Baltimore City, MD, utilizing a deployed LiDAR sensor. When the signal at this intersection experienced a temporary malfunction on a regular working day in September 2023, the LiDAR captured data related to vehicle and pedestrian volumes, as well as V2V and V2P conflicts. The primary objective of the research is to evaluate the repercussions of traffic signal failures on both traffic flow and safety, specifically V2V and V2P conflicts, occurring during periods of improper signal functionality. Additionally, this investigation delves into various factors that impact traffic signal performance, encompassing traffic demand, geometric layout, pedestrian interactions, and the incorporation of emerging technologies.

This article aims to assess the benefits of floor-slab insulation measures using extruded polystyrene (XPS) and polyisocyanurate (polyiso) insulation materials at various levels of insulation thicknesses for a detached residential building. The EnergyPlus simulation analysis was carried out within the seven energy zones (represented by eight locations) of South Africa in accordance with the South African national code for building energy efficiency (SANS10400-XA). The energy savings and payback periods due to use of the insulation over a lifecycle period of 50 years were assessed. Cape Town (zone 4) behaved differently from other locations and hardly benefitted from the application of floor-slab insulation measures. Generally, polyiso insulation performed better than XPS, for vertical gap insulation. For vertical gap insulation, lower insulation thicknesses required higher insulation depths to maximize energy savings. Similarly, lower insulation thicknesses required higher perimeter insulation widths to maximize energy savings, for the horizontal perimeter insulation method. The locations that benefitted most from vertical gap floor-slab insulation were Pretoria (zone2), Kimberley (zone6), Nelspruit (zone3), Fraserburg (zone7), Welkom (zone1), Mthatha (zone5), Ixopo (zone5H) and Cape Town (zone4) in that order. This order was almost similar with those for the horizontal perimeter floor-slab insulation and horizontal full floor-slab insulation methods.

In addition to nucleic acids, various viral proteins are involved in the assembly of virion. If it is possible to create a biologically active agent that leads to the degradation of one of the key proteins for virus assembly and/or destroys the viral factory, then this agent will effectively cope with virus replication. One of these key proteins for the SARS-CoV-2 virus is the nucleocapsid protein (N-protein). As such a bioactive agent, we offer a modular nanotransporter (MNT) developed by us, which, in addition to an antibody mimetic to the N-protein, contains an amino acid sequence for the attraction of the Keap1 E3 ubiquitin ligase. This should lead to the subsequent degradation of the N-protein. We have shown that functional properties of modules within the MNT permit its internalization into target cells, endosome escape into the cytosol, and binding to the N-protein. Using flow cytometry and Western blot, it was demonstrated that significant degradation of N-protein is observed when A549 and A431 cells transformed with N-protein are incubated with the developed MNTs. The proposed MNTs open up a new approach for the treatment of viral diseases.