Apis mellifera, especially weak ones, are highly vulnerable to Carpoglyphus lactis mites, which can rapidly infest and consume stored pollen, leading to weakened colonies and potentially colony collapse. This study aimed to ascertain and investigate the prevalence of this mite in honeybee colonies across 9 provinces in the Republic of Korea (ROK). A total of 615 honeybee colonies were collected, from 66 apiaries during the spring and 58 apiaries during the summer of 2023. A 1,242 bp segment of the the Cytochrome c oxidase subunit 1 (COI) gene was amplified using the polymerase chain reaction method. The detection levels of C. lactis in the honeybees were compared between winter and summer. Based on the COI sequence analysis, the nucleotide sequence similarity of C. lactis mites isolated in the ROK with those from China (NC048990.1) was found to be 99.5%, and with those from the United Kingdom (KY922482.1) was 99.3%. This study is the first report of C. lactis in Korean apiaries. The findings in this study demonstrate a significantly higher detection rate in winter, which is 4.1 times greater than that in summer (p < 0.001). Furthermore, the results underscore the usefulness of molecular diagnostic techniques for detecting C. lactis mites.

COX II containing a dual core CuA active site is one of the three core subunits of mitochondrial Cco, which plays a significant role in the physiological process. In this report, the full-length cDNA of COXⅡ gene was cloned from Sitophilus zeamais, which had an ORF of 684 bp encoding 227 amino acids residues. The predicted COXⅡ protein had a molecular mass of 26.2 kDa with pI value of 6.37, and multiple sequence alignment and phylogenetic analysis indicated that Sitophilus zeamais COXⅡ had high sequence identity 78.51% with the COXⅡ of other insect species, especially similarity to sitophilus oryzae. This gene was subcloned into the prokaryotic expression vector pET-32a, and induced by IPTG in E.coli Transetta (DE3) expression system. Finally the COXⅡ with 6-His tag was purified using affinity chromatography with Ni²⁺-NTA agarose. WB showed the recombinant COXⅡ was about 44 kD, and the concentration of fusion protein was 50μg/mL. UV-spectrophotometer and infrared spectrometer analysis showed that recombinant COXⅡ could catalyze the oxidation of substrate Cytc, and influenced by AITC. It was found that AITC could form a hydrophobic region with COXⅡ protein via molecular docking, besides, a sulfur atom of AITC structure could form a length of 2.9 Å hydrogen bond with Leu-31. These results will provide valuable information for elucidating the role of COXⅡ in Sitophilus zeamais responses to AITC, meanwhile, it will helpful to carry out a point mutation in AITC binding sites for the future research.

The properties of the annual, semiannual and triennial oscillations (AO, SAO and TO) in the middle atmosphere have been investigated using the TIMED/SABER temperature data. The Lomb-Scargle and wavelet spectra were used to determine the dominant oscillations in the background temperature field. The AO is prominent at the mid-latitudes. The AO amplitudes present an asymmetry between the two Hemispheres, being larger in the mesosphere than in the stratosphere. The SAO dominates the tropical regions, with three amplitude maxima at altitudes of 45, 75, and 85 km. The SAOs in the upper mesosphere (75 km) are out of phase with those in the mesopause (85 km) in the tropical regions, which can generate an enhancement of 11 K at each equinox, contributing to the lower mesospheric inversion layer. The TO is significant in the tropical region, with amplitude being maximum at 35, 45 and 85 km. Result shows that there may be potential interaction by the TO with SAO at 85km at the equator. The relation between ENSO and TO has also been discussed. The ENSO signal may modulate the amplitude of the TO, mainly in the lower stratosphere. The real origin of the TO may lie in the wave-mean-flow interaction.

Laboratory diagnosis of leishmaniasis remains a major challenge, demonstrating variable efficacy in detecting infected mammalian hosts. Thus, there is a great need for the accuracy of the identification of appropriate antigens to also improve diagnostic tests. This review brings to the fore the sensitivity of the balance in canine and human leishmaniasis, which greatly influences the progression of the disease and especially the diagnostic methods. The problem of diagnosis arises in asymptomatic leishmaniasis, since in these conditions the methods considered as reference in the diagnosis of leishmaniasis no longer show certainty, being influenced for the most part by the immune response of the host, which is different according to the presence of other associated diseases or even according to the breed, when we talk about dogs. Consequently, the diagnosis and surveillance of leishmaniasis cases remains an open topic, with the need for new methods adapted to the immunological status of the host.

Alpha-fetoprotein (AFP) is a major embryo- and tumor-associated protein capable of binding and transporting variety of hydrophobic ligands including estrogens. AFP has been shown to inhibit estrogen receptor (ER)-positive tumor growth and this can be attributed to its estrogen-binding ability. Despite AFP has long been investigated, its three-dimensional (3D) structure has not been experimentally resolved and molecular mechanisms underlying AFP-ligand interaction remain obscure. In our study we constructed homology-based 3D model of human AFP (HAFP) with the purpose to perform docking of ERα ligands, three agonists (17β-estradiol, estrone and diethylstilbestrol) and three antagonists (tamoxifen, afimoxifene and endoxifen) into the obtained structure. Based on ligand docked scoring function, we identified three putative estrogen- and antiestrogen-binding sites with different ligand binding affinities. Two high-affinity sites were located in (i) a tunnel formed within HAFP subdomains IB and IIA and (ii) opposite side of the molecule in a groove originating from cavity formed between domains I and III, while (iii) the third low-affinity site was found at the bottom of the cavity. 100 ns MD simulation allowed studying their geometries and showed that HAFP-estrogen interactions occur due to van der Waals forces, while both hydrophobic and electrostatic interactions were almost equally involved in HAFP-antiestrogen binding. MM/GBSA rescoring method estimated binding free energies (ΔG_bind) and showed that antiestrogens have higher affinities to HAFP as compared to estrogens. We performed in silico point substitutions of amino acid residues to confirm their roles in HAFP-ligand interactions and showed that Thr132, Leu138, His170, Phe172, Ser217, Gln221, His266, His316, Lys453, and Asp478 residues along two disulfide bonds, Cys224-Cys270 and Cys269-Cys277 have key roles in both HAFP-estrogen and HAFP-antiestrogen binding. Data obtained in our study contribute to understanding mechanisms underlying protein-ligand interactions and anti-cancer therapy strategies based on ER-binding ligands.

The paper describes the new method for image compression based on coordinated group signal transformation. The algorithm is a type of difference coding. Coordinated processing significantly simplifies the difference signal conversion scheme using a single group codec for all signals. The described method considers color channels as correlated signals of a multi-channel communication system. The specifics of the processed data required modification of the coordinated group processing algorithm. First, we changed how to calculate the difference signals to prevent data loss. Secondly, the group codec was supplemented with a neural network to improve the quality of reconstructed images. We considered the following types of neural networks: fully connected, recurrent, convolution, and convolution in the Fourier space. Based on the simulation results, it is best to use fully connected neural networks if the goal is to minimize processing delay time. These networks have a response time of 13 ms. On the other hand, if the priority is to improve quality in cases where delays are not critical, then convolution neural networks in the Fourier space should be used. These networks have a response time of 140 ms and are of significant interest.

As the world population grows, fulfilling the need for biomaterials in the healthcare system becomes increasingly important. Biomaterials, which include metals, polymers, ceramics, and composites, play an important role in the creation of medical devices that improve people's lives. The European Society for Biomaterials described biomaterials as non-biological materials used in medical devices to interact with biological systems. This definition has developed to encompass materials that treat, assess, or replace tissues or bodily functions. Biocompatibility, as defined by the FDA, is a key feature of biomaterials, as is the requirement to fulfil design requirements such as mechanical performance, geometry, and electrical control. Over the last decade, advances in regenerative medicine and tissue engineering have boosted biomaterials' usage in medical applications dramatically. Despite its promise, scientists, engineers, and physicians continue to face significant challenges due to the complexity of biomaterials. Biomaterials have various benefits, including biodegradability, non-toxicity, and biocompatibility, making them extremely useful for replacing, sustaining, or improving biological activities in damaged tissues. They are used in a wide range of applications, including tissue engineering implants, human tissue healing and regeneration, medication delivery systems, and biosensors. This study gives insights into the fundamental characteristics, case studies, and ethical issues associated with the usage and use of biomaterials, further examining their potential and significance in healthcare and medicine.

The studied solar pot is a recent invention, which gained a utility model protection in 2021 from the Hungarian Intellectual Property Office under patent number 5489. The device is made for environmentally friendly cooking or heating (by utilizing solar energy) of foods and liquids. Its structure is similar to a double pipe heat exchanger, it has an outer mantle and an inner cooking tank. The goals of the paper are proposing a new physically-based mathematical model describing the solar pot and carrying out computer experiments with it, assembling an experimental system of the pot connected with a solar collector and performing measurements on it. Based on the results, the solar pot can successfully be used for cooking or sterilizing foods or liquids during the studied time period, in Hungary.

This qualitative research investigates the pivotal role of Human Resource Management (HRM) in enhancing supply chain effectiveness. Through semi-structured interviews with 25 professionals across various industries, the study explores how HRM practices influence key aspects of supply chain management (SCM), including talent management, training and development, leadership, organizational culture, and technology integration. Findings highlight the strategic alignment between HRM and SCM as crucial for optimizing supply chain performance and responsiveness. Effective talent management strategies, such as recruitment, development, and succession planning, emerged as critical factors in ensuring operational stability and innovation within supply chains. Training programs were identified as instrumental in equipping employees with the necessary skills to navigate technological advancements and market complexities, fostering collaboration and enhancing decision-making capabilities. Leadership development initiatives were also found to be pivotal in promoting organizational effectiveness and fostering a culture of continuous improvement. The study further underscores the role of HRM in cultivating a collaborative and inclusive organizational culture that enhances communication, trust, and teamwork among supply chain stakeholders. Additionally, the integration of digital technologies and sustainability considerations emerged as transformative trends shaping modern supply chains, with HRM practices playing a crucial role in facilitating technological adoption and promoting environmentally responsible practices. Addressing challenges such as resource constraints, regulatory compliance, economic uncertainties, and global supply chain complexities remains crucial for organizations aiming to optimize HRM practices and achieve sustainable supply chain performance. Overall, this research contributes to a deeper understanding of how HRM can drive innovation, collaboration, and resilience within supply chains, positioning organizations for long-term success and growth.

The management of an organization's human resources is the first stage in the governance process for any operation. This present study examine the strategies employed in Saudi Arabia for establishing effective governance through the implementation of human resource management practices and the key sustainable strategies criteria for effective human resource management practices. This step is considered crucial in governance as it involves the selection of highly qualified individuals who are expected to contribute to the achievement of optimal governance outcomes and the overall well-being of the population within a nation as well as the key criteria involves. Qualitative research methodology as well as Decision making trial and evaluation laboratory (DEMATEL) were utilized with a sample of 31 participants from 8 government ministries and 14 companies in Saudi Arabia. The study's findings from qualitative interview exert four key criteria influencing sustainable effective human resources management practices. Cultural reflection" is the most important long-term goals of Saudi Arabia's HRM initiatives found from DEMATEL evaluation impacting three criteria with7.9181, 8.2294, 8.1961 above the threshold value of 7.783599781. This means that HR professionals should take the time to study and evaluate the cultural dynamics at work, in order to promote cultural introspection and understanding of cultural differences.

Survivin was initially identified as a member of the inhibitor apoptosis (IAP) protein family and has been shown to play a critical role in regulation of both apoptosis and mitosis. Survivin has emerged as an attractive target for cancer therapy because its overexpression has been found in most human cancers and is frequently associated with chemotherapy resistance, recurrence, and poor survival rate in cancer patients. In this review, we discuss our current understanding of how survivin mediates various aspects of malignant transformation and drug resistance, as well as efforts that have been made to develop therapeutics targeting survivin for the treatment of cancer.

Erastin (ER) induces cell death by utilizing the process of ferroptosis via generation of reactive oxygen species (ROS). Ferroptosis is characterized by accumulation of ROS within the cell, leading to an iron-dependent oxidative damage-mediated cell death. Here, we have examined ferroptosis-dependent mechanism(s) of cytotoxicity of ER in K-RAS mutant human ovarian tumor OVCAR-8 and NCI/ADR-RES cell lines. We used these cell lines to decipher the mechanisms of ER as NCI/ADR-RES cells express higher activities of SOD, glutathione peroxidase and transferases than OVCAR-8 cells. We found that ER was equally cytotoxic to both cells; ER formed more ROS in OVCAR-8 cells than in NIH/ADR-RES cells. Ferrostatin-1, an inhibitor of ferroptosis, inhibited ER-induced cell death in both cell lines. In contrast, RSL3 (RAS-selective lethal 3), an inducer of ferroptosis, significantly enhanced cell death in both cell lines. ER induced significant lipid peroxidation only in OVCAR-8 cells. We found that RSL3 was more cytotoxic to NCI/ADR-RES cells and significantly enhanced ER-induced lipid peroxidation in both cells, indicating GPX4 was involved in the process of ER-mediated ferroptosis. ER treatment also differentially modulated several ferroptosis related genes (e.g., HMOX1/OH1, and CHAC1) in these cells, indicating ER-induced cell death may be mediated differently in OVCAR-8 and NCI/ADR-RES ovarian cells. Our studies suggest that combinations of ER and RSL3 may contribute significantly to the treatment of ovarian cancers, including those that are resistant to other therapeutic agents due to the presence of P-gp or tumors with Ras mutation in the clinic. ER induced ferroptosis may also be an important treatment modality for resistant tumors expressing MDR1 in the clinic.

The ingestion of contaminated aquatic products presents a potential risk for human exposure to bisphenols (BPs) residues. Nevertheless, there is little empirical research on this topic. To fill the current data gap, this study used stochastic sampling to gather 245 representative samples of aquatic products from local markets in Shenzhen. The samples comprised eight species and fell into three aquatic product categories: fish, crustaceans, and bivalves. A total of eight BPs were detected from aquatic products, namely, bisphenol A (BPA), bisphenol AF (BPAF), bisphenol AP (BPAP), bisphenol B (BPB), bisphenol S (BPS), bisphenol P (BPP), bisphenol Z (BPZ), and bisphenol F (BPF). All BPs were detected in aquatic products, except for BPAF, indicating pervasive contamination by BPs in aquatic products. BPS demonstrated the highest detection rate both before and after enzymatic hydrolysis, whereas BPAP exhibited the lowest detection rate before enzymatic hydrolysis, and BPB displayed the lowest detection rate after enzymatic hydrolysis. The concentration difference before and after enzymatic hydrolysis proved to be statistically significant. Moreover, 49%-96% of BPs in aquatic products were found in the combined state, underscoring the essentiality of conducting detections on aquatic product samples following enzymatic hydrolysis. While the health risks associated with ingesting BPs residues through aquatic product consumption were found to be minimal for residents at risk of exposure, the results suggest the necessity for more stringent regulations governing the consumption of aquatic products.

Model animals are employed in experiments as substitutes for human tissues and fluids, particularly when accessing particular human samples (such as cerebrospinal fluid, brain, ocular tissues, etc.) poses significant challenges or is ethically constrained. Nonhuman primates are frequently regarded as superior animal models for investigating human ophthalmological diseases. However, despite this recognition, the metabolomic composition of ocular tissues in non-human primates remains predominantly unexplored. In this work, we present a dataset on metabolite concentrations in serum and ocular tissues, including aqueous humor (AH), vitreous humor (VH), and lens, in two Macaque species: crab-eating macaque (Macaca fascicularis) and rhesus macaque (Macaca mulatta). A total of 99 compounds were quantified in 45 samples, shedding light on the previously unknown metabolomic profiles of primate eye tissues.

Mammalian cells have evolved to function under Earth’s gravity, but how they respond to microgravity remains largely unknown. Neural stem cells (NSCs) are essential for the maintenance of central nervous system (CNS) functions during development and the regeneration of all CNS cell populations. Here, we examined the behavior of space (SPC)-flown NSCs as they readapted to Earth’s gravity. We found that most of these cells survived the space flight and self-renewed. Yet, some showed autophagy-like behaviors (ALB). To ascertain if the secretome from SPC-flown NSCs contained molecules inducing this behavior, we incubated naïve, non-starved NSCs in a medium containing SPC-NSCs secretome. We found a four-fold increase in the ALB rate. Proteomic analysis of the secretome revealed that the protein of highest content produced by SPC-NSCs was secreted protein acidic and rich in cysteine (SPARC), which triggers endoplasmic reticulum (ER) stress leading to lethal ALB. These results offer novel knowledge on the response of neural cells, particularly NSCs, subjected to space microgravity. Moreover, some secreted proteins have been identified as microgravity sensing, paving a new venue for future research aiming at targeting SPARC metabolism. Although we did not establish a direct relationship between ALB and SPARC as a potential marker, these results represent the first step in the identification of gravity sensing molecules as targets to be modulated and to design effective countermeasures to mitigate intracranial hypertension in astronauts using structure-based-protein design.

The Vitamin D Receptor (VDR) mediates the actions of vitamin D, which has important roles in bone homeostasis, growth/differentiation of cells, immune functions and reduction of inflammation. Emerging evidences suggest that epigenetic modifications of the VDR gene, particularly DNA methylation, may contribute to the onset and progression of many human disorders. This review aims to summarize the available information on the role of VDR methylation signatures in different pathological contexts, including autoimmune diseases, infectious diseases, cancer and others. The reversible nature of DNA methylation could enable the development of therapeutic strategies, offering new avenues for the management of these worldwide diseases.

In the wake of the rapid deployment of Small Modular Reactors (SMRs), this study aims to enhance the efficiency, reliability, and safety of SMR operations through a deeper understanding of human factors in their interaction within digital control room systems. Recognizing the pivotal role of human understanding in this new era of nuclear power, we employed electroencephalogram (EEG)-based monitoring to provide an unparalleled real-time view into operators' cognitive states. By interfacing detailed human models, informed by EEG metrics, with specific operational tasks, we recreate potential operational scenarios using an SMR simulator and capture intricate human responses therein. Our results elucidated the intricate relationship between EEG-derived data and human performance shaping factors, indicating a marked correlation between certain EEG patterns and operational efficiencies. Conclusively, these findings underscore the potential of EEG monitoring not only as a diagnostic tool but as an instrumental aid in the design and operation of future SMR digital control rooms. The insights derived offer a roadmap for the development of practical strategies, ensuring more effective and safer SMR operations.

It is generally accepted that the human abdominal wall is comprised of skin, subcutaneous tissues, muscles and their aponeuroses, and the parietal peritoneum. Understanding these layers and their mechanical properties provides valuable information to those designing procedural skills trainers, supporting surgical procedures (hernia repair), and engineering-based work (in silico simulation). However, there is little literature available on the mechanical properties of the abdominal wall in layers or as a composite. This work characterizes the tensile properties of the human abdominal wall by layer and as a partial composite. Tissues were collected from fresh-never-frozen and fresh-frozen cadavers and tested in uniaxial tension at a rate of 5 mm/min until failure. Stress-strain curves were created for each sample, and the values for elastic moduli, ultimate tensile strength, and strain at failure were obtained. The experimental outcomes from this study demonstrated variation of tensile properties within and between tissues. The data also suggest that the tensile properties of composite abdominal walls are not additive. Ultimately, this body of work contributes to a deeper comprehension of these mechanical properties and will serve to enhance patient care, refine surgical interventions, and assist with more sophisticated engineering solutions.

When attempting to quantify future harms caused by carbon emissions and to set appropriate energy policies, it has been argued that the most important metric is the number of human deaths caused by climate change. Several studies have attempted to overcome the uncertainties associated with such forecasting. In this article, approaches to estimating future human deaths tolls from climate change are compared and synthesized, and implications for energy policy are considered. Several studies are consistent with the “1000-ton rule,” according to which a future person is killed every time 1000 tons of fossil carbon are burned (order-of-magnitude estimate). If warming reaches or exceeds 2°C this century, mainly richer humans will be responsible for killing roughly 1 billion mainly poorer humans through anthropogenic global warming. Such mass manslaughter is clearly unacceptable. On this basis, relatively aggressive energy policies are summarized that would enable immediate and substantive decreases to carbon emissions. The limitations to such calculations are outlined and future work is recommended to accelerate the decarbonization of the global economy while minimizing the number of sacrificed human lives.

This work aims to describe the dielectric behaviours of four main tissues in the human forearm using mathematical modelling, including fat, muscle, blood, and bone. Determining the electrical response of multiple tissues can help develop physiological monitoring of an organ or a body’s section by filtering out the impedance contributions from the surrounding tissues to blood flow-induced impedance variations. Multi-frequency bioimpedance analysis (MF-BIA) was initially performed using the finite element method (FEM) with a 3D forearm model followed by a pilot study to characterise the response of actual forearm tissues from 1 kHz to 349 kHz. Both the simulation and experimental results were fitted to a single-dispersion Cole model (SDCM) and a multi-dispersion Cole model (MDCM) to determine the Cole parameters for each tissue. The correlation analysis and Bland-Altman plot indicated a good fit between raw and fitted impedance values using both SDCM and MDCM. Overall, MDCM exhibited better performance in fitting and estimation of the Cole parameters with correlation coefficient (R2) of 0.99 and 0.97, root mean squared error (RMSE) of 0.09 Ω and 0.14 Ω, and mean difference (mean±standard deviation) of 0.00±0.09 Ω and -0.03±0.14 Ω for the real part and imaginary part of impedance, respectively.

The oncogenic potential of human papillomavirus (HPV) may be used to determine the tissue tropism of each HPV type. Cervical cancer develops in the squamo-columar junction of the cervices, and most such lesions are induced by high-risk (HR) HPV types. This suggests that HR types preferentially infect the cervix, whereas the preferential infection site for low-risk (LR) types is not well defined. Determination of HPV tropism when using cytology samples can be uncertain since it is difficult to avoid contamination of cell samples between the cervix and the vagina. Herein, cell samples were carefully collected by independently scraping the cervix and vagina, after which the HPV types were determined. HPV tissue tropism was determined by considering what HPV types were positive at only one of the sites (the cervix or the vagina) as the viruses that preferentially infected that site. This method revealed that all LR types were only identified in vaginal samples, whereas 87% of HR types were identified in cervical sites. Thus, LR types may preferentially infect the vagina, whereas HR types infect the cervix. These findings suggest that preferential tissue tropism of certain HPV types is a probable factor for malignant progression.

Buckwheat is returning to the countries of Central Europe. There are several reasons for this: firstly, because of its interesting chemical composition, which is reflected in its nutritional value and potential health benefits. And secondly because buckwheat, and especially buckwheat flour, are suitable raw materials for the production of gluten-free foods. Buckwheat flours are classified similarly to wheat flours, but the different anatomy of wheat grains and buckwheat seeds makes this classification partly misleading. While wheat flours are largely produced by one standard process, the production process for buckwheat flours is more varied. For wheat and wheat flours, the basic quality parameters and their required ranges for different types of primary and secondary processing are clearly defined. This is not the case for buckwheat and buckwheat flours, and the definition of the parameters and their ranges that characterize its technological quality remain unclear. The standardization of quality parameters and production processes is likely to be necessary for the potential expansion of the use of buckwheat for food production and in particular for bakery products.

Introduction The increase in survival of extremely preterm infants has led to increased rates of bronchopulmonary dysplasia (BPD). Therefore, a potential role of human milk feeding in protecting against this condition has been suggested. Material and methods Retrospective descriptive study based on data about morbidity in the population of infants born from 22+0 to 26+6 weeks of gestation, included in the Spanish network SEN1500 during the period 2004-2019 and who were alive at discharge. The primary outcome was moderate-severe BPD. In addition, associated conditions were studied, including breastfeeding at discharge. The temporal trends of BPD and breastfeeding rates at discharge were also studied. Results In the study population of 4341 infants who survived to discharge, the rate of moderate-severe BPD was 43,7% and increased over the period to a rate >50% in the last three years. The factors significantly associated with a higher risk of moderate-severe BPD were male sex, high-frequency oscillatory ventilation, inhaled nitric oxide, patent ductus arteriosus, and late-onset sepsis. Exclusive human milk feeding at discharge and any amount of human milk at discharge were associated with a lower incidence of moderate-severe BPD (OR 0.752, 95% CI 0.629-0.901, and OR 0.714, 95% CI 0.602-0.847, respectively). The rates of human milk at discharge in infants with moderate-severe BPD increased over the period. In the last years, more than one-third of extremely preterm infants were discharged on exclusive human milk feeds, and about two-thirds of them on any amount of human milk feeding. Conclusions
The results of the present study strongly support the role of any amount of human milk in preventing BDP in extremely preterm infants.

Since 2000, caffeine is used as citrate salt of caffeine for treatment of apnea of prematurity. However, it remained elusive if caffeine citrate has a direct function in the respiratory epithelium, potentially as modulator for ciliary beat frequency (CBF) regulation in human respiratory cells (hRECs). Here, we studied the mechanism of action of caffeine citrate on the respiratory epithelium on hRECs derived from healthy donors and individuals with cystic fibrosis (CF) cultured under air-liquid-interface (ALI) conditions. CBF analyses of hRECs were performed by high-speed video microscopy. In the presence of caffeine, hRECs show a significant increase in CBF over ciliary base frequency (CBFb), demonstrating a direct influence of caffeine on ciliary function. We also demonstrate a specific action of caffeine at ryanodine receptor (RYR) channels, mediating calcium efflux from intracellular stores to increase CBF. We describe a novel pharmacological effect of caffeine citrate - direct increase of CBF of primary hRECs cultured at ALI. Caffeine citrate has certain advantages over other methylxanthines: it was shown to have stable plasma concentration, longer half-life, and is better tolerated than e.g. theophylline. We conclude that caffeine citrate therapy might be suitable strategy to treat respiratory diseases with compromised mucociliary clearance.

Cancer diseases lead to the second-highest death rate all over the world. The dynamics of invasion of cancer cells into the human body tissues and metastasis are the main causes of death in patients with cancer. This study deals with theoretical investigation of the dynamics of invasion of cancer cells for tumour growths in human body tissues using discretized Cahn-Hilliard, concentration and reaction-diffusion equations which were solved by Finite Difference Method with the aid of MATLAB computer software. A Crank-Nicolson numerical scheme was developed for the discretized model equations. The numerical result obtained was used to describe the dynamics of cancer invasion of tissues with respect to cancer cells density on tumour growth, turbulence and mobility and equilibrium between charge and discharge of cancer cells. The results of the study provide new insights into combating cancer disease by providing mitigating and intervention measures to this major health problem.

Backgrounds: The field of Artificial Intelligence (AI) has seen a major shift in recent years due to the development of new Machine Learning (ML) models such as Generative Pre-trained Transformer (GPT) and AI which are progressively becoming part our everyday lives. GPT has achieved previously unheard-of levels of accuracy in most computerized language processing tasks and their chat-based variations. Aim: The aim of this study was to investigate the problem-solving abilities of ChatGPT using two sets of verbal insight problems, with a known performance level established by a sample of human participants. Material and Methods: A total of 30 problems labelled as “practice problems” and “transfer problems”, as listed by Ansburg and Dominowski (2000), were administered to ChatGPT. The answers provided by ChatGPT received a score of "0" for each problem answered incorrectly and a score of "1" for each correct response, as per the correct solution specified in Ansburg and Dominowski's (2000) study. The highest score that could be attributed to both the practice and transfer problems was 15 out of 15. In order to compare ChatGPT performance to the performance to that of human subjects, the solution rate for each problem (based on a sample of 20 subjects) was used, as indicated by Ansburg and Dominowski (2000). Results: The study highlighted that ChatGPT can be trained in out-of-the-box thinking and demonstrated potential in solving verbal insight problems. The global performance of ChatGPT equalled the most probable outcome for the human sample in both practice problems and transfer problems as well as upon their combination. Additionally, ChatGPT answer combinations were among the 5% of most probable outcomes for the human sample both when considering practice problems and pooled problem sets. These findings demonstrate that ChatGPT performance on both set of problems was in line with the mean rate of success of human subjects, indicating that it performed reasonably well. Conclusions: The use of transformer architecture and self-attention in ChatGPT may have helped to prioritize inputs while predicting, contributing to its potential in verbal insight problem-solving. ChatGPT has shown potential in solving insight problems, thus highlighting the importance of incorporating AI in psychological research. However, it is acknowledged that open challenges still exist. Indeed, further research is needed to fully understand the capabilities and limitations of AI in insight problem-solving.

Expression analysis of small noncoding RNA (sRNA), including microRNA, piwi-interacting RNA, small rRNA-derived RNA, and tRNA-derived small RNA, is a novel and quickly developing field. Despite a range of proposed approaches, selecting and adapting a particular pipeline for transcriptomic analysis of sRNA remains a challenge. This paper focuses on the identification of the optimal pipeline configurations for each step of human sRNA analysis, including reads trimming, filtering, mapping, transcript abundance quantification and differential expression analysis. Based on our study, we suggest the following parameters for analysis of human sRNA in relation to categorical analyses with two groups of biosamples: (1) trimming with the lower length bound = 15 and the upper length bound = \(Read\ length - 40\% Adapter\ length\); (2) mapping on a reference genome with bowtie aligner with one mismatch allowed (-v 1 parameter); (3) filtering by mean threshold > 5; and (4) analyzing differential expression with DESeq2 with adjusted p-value < 0.05 or limma with p-value < 0.05 if there is very little signal and few transcripts.

Anatomical airways parameters as length, diameter and angles have a strong effect on the flow dynamics. Aiming to explore the effect of variations of the bifurcation angle (BA) and carina rounding radius (CRR) of lower human airways on the respiratory processes, numerical simulations of airflow during inhalation and exhalation were performed using a synthetic bifurcation models. Geometries for the airways models were parameterized based on a set of different BA's and several CRR's. A range of Reynolds numbers (\Reyn) relevant to the human breathing process were selected to analyzed the airflow behaviour. The numerical results show a significant influence of BA and the CRR on the development of the airflow within the airways, and therefore affecting some relevant features of the flow, namely the deformation of velocity profiles, alterations of pressure drop, the flow patterns, and finally enhance or attenuation of wall shear stresses (WSS) appearing during the regular respiratory process. Numerical results show that increases in the bifurcation angle value are accompanied by pressure increases of about 20\%, especially in the regions close to the bifurcation. Similarly, increases in the BA value lead to a reduction in peak shear stresses of up to 70\%. For the ranges of angles and radii explored, an increase in pressure of about 20\% and a reduction in wall shear stress of more than 400\% were obtained by increasing the carina rounding radius. Analysis of the coherent structures and secondary flow patterns also revealed a direct relationship between the location of the vortical structures, the local maxima of the velocity profiles and the local vorticity minima. This relationship was observed for all branches analysed, for both the inhalation and exhalation processes of the respiratory cycle.

Artificial intelligence’s rapid advancement has enabled various applications, including intelligent video surveillance systems, assisted living, and human-computer interaction. These applications often require one core task: video-based human action recognition. Research in human video-based human action recognition is vast and ongoing, making it difficult to assess the full scope of available methods and current trends. This survey provides an in-depth exploration of the vision-based human action recognition field, comprehensively offering the available techniques and their evolution, highlighting the cutting-edge ideas driving its development. We also analyze the most used keywords in research papers over the past years to identify trends and predict possible future directions. Hence, this concise survey helps researchers understand the breadth of existing approaches, evaluate current research trends, and stay up-to-date on potential developments.

Background: Strongyloidiasis, a neglected disease caused by intestinal nematodes of the genus Strongyloides, is endemic to tropical and subtropical areas such as Vietnam. The morphological diagnosis of larvae by Hara Mori culture technique and microscopicare are considered the standard diagnostic procedures in the endemic areas of Strongyloides spp. However, they could only identify the genus, not the species of Strongyloides. DNA-molecular techniques which are highly sensitive and more cost-effective have been increasingly utilized in detection of Strongyloides species. This study aims to determine prevalence and the species of Strongyloides among resident population in Duc Hoa district, Long An province, Southern Vietnam. Methods: A cross-sectional study was conducted using 1,190 stool samples collected in Duc Hoa district, Long An province, Vietnam, from July, 2017 to November 2018. The stool specimens were transported to the Laboratory of Medical Parasitology, Pham Ngoc Thach University of Medicine within two hours of collection at an appropriate temperature of 25 oC. All samples were stored at 2 - 8°C and processed within 48 hours for microscopic examination. Molecular detection was carried out at Laboratory of Molecular Biology, Pham Ngoc Thach University of Medicine, Hochiminh city, VietNam. Results: Of the 1,190 samples tested, Strongyloides spp. larvae were detected in 79 specimens (6.6%) by two classical parasitological methods, namely direct microscopy and the modified Harada-Mori filter paper culture. DNA was extracted from 70 of the 79 samples of Strongyloides spp. larvae, which was subsequently characterized by real-time PCR amplification of the 18S and 28S regions of the rDNA gene. The results showed that 97.1% of the DNA samples were S. stercoralis, 2.9% were co-infections with S. ratti and S. stercoralis, and 2.9% belonged to S. ratti. For all 14 isolates, nucleotide sequencing was compared with other human pathogenic species of Strongyloides whose sequences are available in GenBank. The identity of 12/14 sequences were confirmed as S. stercoralis with a high level of similarity (91.3% - 100%) and over 98% for S. ratti. Between the two co-infection samples, the higher similarity belonged to S. stercoralis. Conclusion: A molecular amplification of small subunit ribosome RNA followed by sequence analysis has been proved to be a suitable method for discrimination of Strongyloides spp. retrieved from stool samples.

Smart devices such as smartphones, smartwatches, etc. are promising platforms that are being used for automatic recognition of human activities. However, it is difficult to accurately monitor complex human activities due to inter-class pattern similarity, which occurs when different human activities exhibit similar signal patterns or characteristics. Current smartphone-based recognition systems depend on the traditional sensors such as accelerometer and gyroscope, which are inbuilt in these devices. Therefore, apart from using information from the traditional sensors, these systems lack contextual information to support automatic activity recognition. In this article, we explore environment contexts such as illumination(light conditions) and noise level to support sensory data obtained from the traditional sensors using a hybrid of Convolutional Neural Networks and Long Short Time Memory(CNN_LSTM) learning models. The models performed sensor fusion by augmenting the low-level sensor signals with rich contextual data to improve recognition and generalisation ability of the proposed solution. Two sets of experiments were performed to validate the proposed solution. The first set of experiments used inertial sensing data whilst the second set of extensive experiments combined inertial signals with contextual information from environment sensing data. Obtained results demonstrate that contextual information such as environment noise level and illumination using hybrid deep learning models achieved better recognition accuracy than the traditional activity recognition models without contextual information.

Platelets have long been associated with sustaining the balance between hemostasis and thrombosis. Platelets, however, are also involved in a wide range of biological activities, including inflammation, immunology, wound healing, cancer biology, and angiogenesis. Platelets' diverse roles are mediated by the expression of various adhesive and immune receptors and the secretion of a diverse array of bioactive proteins, ions stored in granules, and several lipid mediators. Platelets also release pro-inflammatory and anti-inflammatory, and angiogenic factors and shed microparticles into the bloodstream. The challenge for therapeutic intervention in non-hemostatic disease is identifying the factors that primarily inhibit specific targets implicated in platelets' complicated contribution to inflammation or tumor growth while leaving their hemostatic function intact. In addition, blood platelets are involved in infection and innate and adaptive immunity by mediating complicated vascular homeostasis via specialized receptors and granule release, RNA transfer, and mitochondrial secretion. Anti-platelet drugs/bioactive compounds are developed based on their platelet anti-aggregatory properties; however, very little information is available on their effects on non-hemostatic function. Therefore, a better understanding of the impact of the anti-platelet bioactive on the platelets' diverse roles and mechanisms may help develop new strategies and prevent CVD and other diseases. In this review, a comprehensive overview of platelet multifunctional roles in CVD and other diseases and dietary factors' modulatory effects are described.

Leader-follower autonomy (LFA) systems have so far only focused on vehicles following other vehicles. Though there have been several decades of research into this topic, there has not yet been any work on human-vehicle leader-follower systems. We present a system in which an autonomous vehicle — our ACTor 1 platform — can follow a human leader who controls the vehicle through gestures. We successfully developed a modular pipeline that uses artificial intelligence/deep learning to recognize hand-and-body gestures from a user in view of the vehicle’s camera and translate those gestures into physical action by the vehicle. We demonstrate our work using our ACTor 1 platform, a modified Polaris Gem 2 electric vehicle. This work has numerous applications, such as material transport in industrial contexts.

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

The liver is a key node of whole-body nutrient and fuel metabolism and is also the principal site for detoxification of xenobiotic compounds. As such, hepatic metabolite concentrations and/or turnover rates inform the status of both hepatic and systemic metabolic diseases as well as the disposition of medications. As a tool to better understand liver metabolism in these settings, in vivo magnetic resonance spectroscopy (MRS) offers a non-invasive means of monitoring hepatic metabolic activity in real time both by direct observation of concentrations and dynamics of specific metabolites as well as by observation of their enrichment by stable isotope tracers. This review summarizes the applications and advances in human liver metabolic studies by in vivo MRS over the past 35 years and discusses future directions and opportunities that will be opened by the development of ultra-high field MR systems and by hyperpolarized stable isotope tracers.

We systematically reviewed studies using wastewater for AMR surveillance in human populations, to determine: (i) the strength of the evidence for a wastewater-human AMR association, and (ii) methodological approaches which optimised identifying such an association, and which could be recommended as standard. We used Lin’s concordance correlation coefficient (CCC) to quantify agreement between AMR prevalence in wastewater and human compartments, and logistic regression to identify study features (e.g. sampling methods) associated with high-agreement (defined as wastewater-human AMR prevalences within ±10%). Of 8,867 records and 232 full-text methods reviewed, 29 studies were included. AMR prevalence data was extractable from 20 studies conducting phenotypic-only (n=11), genotypic-only (n=1) or combined (n=8) AMR detection. Overall wastewater-human AMR concordance was reasonably high for both phenotypic (CCC=0.81 [95% CI 0.74-0.87]) and genotypic comparisons (CCC=0.88 (95% CI 0.85-0.91)) despite diverse species-phenotypes/genotypes and study design. Logistic regression was limited by inconsistent reporting of study features, and limited sample size; no significant relationships between study features and high wastewater-human AMR agreement were identified. Based on descriptive synthesis, composite/flow-proportional sampling of wastewater influent, longitudinal sampling >12 months, and time/location-matched comparisons generally had higher-agreement. Further research and clear and consistent reporting of study methods is required to confirm optimal practice.

Because of their low cost and easy production silica nanoparticles (NPs) are amply used in multiple manufactures as anti-caking, densifying and hydrophobic agents. However, this has increased the exposure levels of the general population and has raised concerns about possible toxicity of this nanomaterial. NPs are known to affect the function of the airway epithelium, but the biochemical pathways targeted by these particles remain largely unknown. Here we investigated the effects of NPs on the responses of cultured human bronchial epithelial (16HBE) cells to the damage-associated molecular pattern ATP, using fluorometric measurements of intracellular Ca2+ concentration. Upon stimulation with extracellular ATP these cells displayed a concentration-dependent increase in intracellular Ca2+, which was mediated by release from intracellular stores. Silica NPs inhibited the Ca2+ responses to ATP within minutes of application and at low micromolar concentrations, which are significantly faster and more potent than those previously reported for the induction of cellular toxicity and pro-inflammatory responses. NPs-induced inhibition appeared to be independent from the increase in intracellular Ca2+ they produce, and via a non-competitive mechanism. These findings suggest that NPs reduce the ability of airway epithelial cells to mount ATP-dependent protective responses such as the increase in mucociliary clearance and cough.

In this article, we report how we constructed a dataset that contains the responses to a survey designed for investigating the relationship that humans have with their smart devices. The dataset has been collected in May-July 2020 and is a sample of over 500 respondents of various different ethnicities and backgrounds. These data have been used for modelling the ways people relate to their devices using the notion of agency. However, the data can be used for complementing any study that intends to investigate a tool-mediated communication from the perspective of the users and via a variety of attitudes and expectations the users invest in their devices and in themselves as users. This article presents the survey items as well as some preliminary data insights. The data have been collected in English and answers have been anonymized in order to ensure GDPR compliance. They are stored in a .csv file containing the respondents’ answers to the questions.

Transposable elements (TEs), also known as mobile elements (MEs), are interspersed repeats that constitute a major fraction of the genomes of higher organisms. As one of their important functional impacts on gene function and genome evolution, TEs participate in regulating the expression of genes nearby and even far away at transcriptional and post-transcriptional levels. There are two known principal ways by which TEs regulate expression of genes. First, TEs provide cis-regulatory sequences in the genome with their intrinsic regulatory properties for their own expression making them potential factors for regulating the expression of the host genes. TE-derived cis-regulatory sites are found in promoter and enhancer elements, providing binding sites for a wide range of trans-acting factors. Second, TEs encode for regulatory RNAs with their sequences showed to be present in a substantial fraction of miRNAs and long non-coding RNAs (lncRNAs), indicating the TE origin of these RNAs. Furthermore, TEs sequences were found to be critical for regulatory functions of these RNAs including binding to the target mRNA. TEs thus provide crucial regulatory roles by being part of cis-regulatory and regulatory RNA sequences. Moreover, both TE-derived cis-regulatory sequences and TE-derived regulatory RNAs, have been implicated to provide evolutionary novelty to gene regulation. These TE-derived regulatory mechanisms also tend to function in tissue-specific fashion. In this review, we aim to comprehensively cover the studies regarding these two aspects of TE-mediated gene regulation, mainly focusing on the mechanisms, contribution of different types of TEs, differential roles among tissue types, and lineage specificity, based on data mostly in humans.

NASA mission systems proposals are often compared using an equivalent system mass (ESM) framework wherein all elements of technology to deliver an effect- its components, operations and logistics of delivery- are converted to effective masses since this has a known cost scale in space operations. To date, ESM methods and the tools for system comparison have not considered complexities wherein systems that serve a mission span multiple transit and operations stages, such as would be required to support a crewed mission to Mars, and thus do not account for the different mass equivalency factors operational during each period and the inter-dependencies of the costs across the mission. Further, ESM does not account well for the differential reliabilities of the underlying technologies. Less reliability should incur an equivalent mass cost for technologies that might otherwise provide a mass advantage. We introduce an extensions to ESM to address these limitations and show that it provides a direct method for analyzing, optimizing and comparing different mission systems. We demonstrate our extended ESM (xESM) calculation with crop production technologies -- an aspect of the developing offworld biomanufacturing suite -- since it represents a case with strong coupling among stages of the mission and a relatively high-risk profile.

Symmetry in biological and physical systems is a product of self-organization driven by evolutionary processes, or mechanical systems under constraints. Symmetry-based feature extraction or representation by neural networks may unravel the most informative contents in large image databases. Despite significant achievements of artificial intelligence in recognition and classification of regular patterns, the problem of uncertainty remains a major challenge in ambiguous data. In this study, we present an artificial neural network that detects symmetry uncertainty states in human observers. To this end, we exploit a neural network metric in the output of a biologically inspired Self-Organizing Map, the Quantization Error (SOM-QE). Shape pairs with perfect geometric mirror symmetry but a non-homogenous appearance, caused by local variations in hue, saturation, or lightness within and/or across the shapes in a given pair produce, as shown here, longer choice RT for ‘yes’ responses relative to symmetry. These data are consistently mirrored by the variations in the SOM-QE from unsupervised neural network analysis of the same stimulus images. The neural network metric is thus capable of detecting and scaling human symmetry uncertainty in response to patterns. Such capacity is tightly linked to the metric’s proven selectivity to local contrast and color variations in large and highly complex image data.

Objectives: Our objective was to assess employer preparedness to protect their employees’ health and safety and promote their well-being in the face of potential disasters in a sample of Northeast United States employers. We developed survey instrument and index based on our model of Total Worker Health® (TWH) Employer Preparedness.Methods: We conducted a 40-question on-line survey with the membership of the Northeast Human Resources Association (US). Human resource managers reported their perceptions of their employers’ preparedness in seven domains: planning, human resources policies, hazard reduction, training, staffing, communications, and resources for resilience. Respondents were categorized by size, sector and reach and their responses scored.Results: Seventy-six individuals representing a diverse group of employers responded to the survey. Mean preparedness was “moderate,” with almost an equal number reporting a high level of preparedness as no preparedness. Employers were most prepared for severe weather events and least prepared for acts of violence. There were no significant differences by sector, size, or reach, although the healthcare sector was more prepared than others.Conclusions: There is a range of TWH® Employer Preparedness among Northeast US employers. The survey and model are important tools that can aid employers in the face of growing threats to “business as usual.”

Gastrointestinal tumors including pancreatic and colorectal cancers represent one of the greatest public health issues worldwide, leading to million global deaths. Recent research demonstrated that the human heavy chain ferritin (HFt) can encapsulate different type of drugs in its cavity and can bind to its receptor, CD71, in several solid and hematological tumors, thus highlighting the potential use of ferritin for tumor-targeting therapies. Here, we describe the development and characterization of a novel nanomedicine based on the HFt that is named The-0504. In particular, this novel system is a nano-assembly comprising an engineered version of HFt that entraps about 80 molecules of a potent, wide-spectrum, non-camptothecin topoisomerase I inhibitor (Genz-644282). The-0504 can be produced by a standardized pre-industrial process as a pure and homogeneously formulated product with favourable lyophilization properties. The preliminary anticancer activity was evaluated in cultured cancer cells and in a mouse model of pancreatic cancer. Overall results reported here make The-0504 a candidate for further preclinical development against CD-71 expressing deadly tumors

Nowadays, with smartphones people can easily take photos, post photos to any social networks and use the photos for some purposes. This leads to a social problem that unintended appearance in photos may threaten the privacy of photographed person. Some solutions to protect facial privacy in photos have already been proposed. However, most of them rely on different techniques to de-identify photos which can be done only by photographers, giving no choice to photographed person. To deal with that, we propose an approach that allows photographed person to proactively detect whether someone is intentionally/unintentionally trying to take pictures of him/her. Thereby, he/she can have appropriate reaction to protect the privacy. In this approach, we assume that the photographed person uses a wearable camera to record the surrounding environment in real-time. The skeleton information of likely photographers who are captured in the monitoring video is then extracted to be put into the calculation of dynamic programming score which is eventually compared with a threshold for recognition of photo-taking behavior. Experimental results demonstrate that by using the proposed approach, the photo-taking behavior is precisely recognized with high accuracy of 92.5%.

While visual assessment is the standard technique for burn evaluation, computer-aided diagnosis is increasingly sought due to high number of incidences globally. Patients are increasingly facing challenges which are not limited to shortage of experienced clinicians, lack of accessibility to healthcare facilities, and high diagnostic cost. Certain number of studies were proposed in discriminating burn and healthy skin using machine learning leaving a huge and important gap unaddressed; whether burns and related skin injuries can be effectively discriminated using machine learning techniques. Therefore, we specifically use pre-trained deep learning models due to deficient dataset to train a new model from scratch. Experiments were extensively conducted using three state-of-the-art pre-trained deep learning models that includes ResNet50, ResNet101 and ResNet152 for image patterns extraction via two transfer learning strategies: fine-tuning approach where dense and classification layers were modified and trained with features extracted by base layers, and in the second approach support vector machine (SVM) was used to replace top-layers of the pre-trained models, trained using off-the-shelf features from the base layers. Our proposed approach records near perfect classification accuracy of approximately 99.9%.

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

Cardiac hypertrophy is an important and independent risk factor for the development of heart failure. To better understand the mechanisms and regulatory pathways involved in cardiac hypertrophy, there is a need for improved in vitro models. In this study, we investigated how hypertrophic stimulation affected human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs). The cells were stimulated with endothelin-1 (ET-1) for 8, 24, 48, 72, or 96h. Parameters including cell size, ANP-, proBNP-, and lactate concentration were analyzed. Moreover, transcriptional profiling using RNA-sequencing was performed to identify differentially expressed genes following ET-1 stimulation. The results show that the CMs increase in size by approximately 13% when exposed to ET-1 in parallel to increases in ANP and proBNP protein and mRNA levels. Furthermore, the lactate concentration in the media was significantly increased indicating that the CMs consume more glucose, a hallmark of cardiac hypertrophy. Using RNA-seq, a hypertrophic gene expression pattern was also observed in the stimulated CMs. Taken together, these results show that hiPSC-derived CMs stimulated with ET-1 display a hypertrophic response. The results from this study also provide new molecular insights about the underlying mechanisms of cardiac hypertrophy and may help accelerate the development of new drugs against this condition.

This article argues for five correctives to the current ethical debate about speciesism, and proposes normative, conceptual, methodological and experimental avenues to move this debate forward. Firstly, it clarifies the Principle of Equal Consideration of Interests and points out limitations of its scope. Secondly, it disambiguates between ‘favouritist’ and ‘species-relative’ views about moral treatment. Thirdly, it argues that not all moral intuitions about speciesism should be given equal weight. Fourthly, it emphasizes the importance of empirical research to corroborate statements about ‘folk speciesism’. Fifthly, it disambiguates between the moral significance of species and the moral status of their individual members. For each of these issues, it is shown that they have either been overlooked, or been given inapt treatment, in recent contributions to the debate. Building on the correctives, new directions are proposed for ethical inquiry into the moral relevance of species and species membership.

As a universal pathogen leading to neonatal defects and transplant failure, Human cytomegalovirus (HCMV) has strict species specificity that the inability to using this virus in animals has hampered its pathogenesis study. However, the mechanism of cross-species barrier remains elusive that no non-human cell model has been established to fill this knowledge gap. We observed that primary dermis fibroblasts (TSDF) isolated from the Chinese tree shrew (Tupaia belangeri chinensis), a small laboratory animal with close affinity to primates, were permissive to HCMV replication. In TSDF infected with GFP-expressing HCMV, the green fluorescence and cytopathic effect were observed and the expression of 3 kinetic genes and replication of viral genome were detected. The cell-free viruses produced in TSDF reached 103 pfu/mL at 96 hpi, which were 10-fold lower than in primary human foreskin fibroblasts. Our results demonstrated that TSDF supported low level of lytic replication of HCMV. The TSDF model provides a useful platform for the mechanism study of species barrier of HCMV.

Wearable sensors for human physiological monitoring have attracted tremendous interest from researchers in recent years. However, most of the research was only done in simple trials without any significant analytical algorithms. This study provides a way of recognizing human motion by combining textile stretch sensors based on single-walled carbon nanotubes (SWCNTs) and spandex fabric (PET/SP) and machine learning algorithms in a realistic applications. In the study, the performance of the system will be evaluated by identification rate and accuracy of the motion standardized. This research aims to provide a realistic motion sensing wearable products without unnecessary heavy and uncomfortable electronic devices.

To cope with a projected global population increase from 7.2 bn to 9.6 bn by 2050, many more cities must be built. Although there are great benefits to modern urban living, there also great costs, such as the seemingly unstoppable rise in Type 2 diabetes, obesity, coronary issues and various cancers. The new towns should be designed to contain or constrain the epidemic of those ‘Western Lifestyle Diseases’ that currently plagues today’s cities. But how might this be achieved? It is suggested here that a greater understanding of human evolution combined with the potency of the ‘Palaeolithic genome’ holds the key to our future urban wellbeing. Consequently, a new paradigm is suggested that underpins positive forward thinking on townplanning and city lifestyles to create healthier urban environments. This builds directly on the ‘Evolutionary Determinants of Health’ programme initiated at University College London (UCL). A four-stage model is proposed that integrates and develops both evolutionary-concordant personal and institutional health behaviours with appropriately reconfigured town-planning and building regulations. When integrated, these strands could deliver a healthier urban culture within greened, active townscapes by proactively constraining or eliminating some of the key underlying causes of the so-called ‘Western Lifestyle Diseases’.

This paper is focused on typical rural settlements in the Stara Planina Mountain area in Serbia. They are distinguished by their authenticity, identity and character, and they have still not been destroyed by inappropriate development as is the case in some other mountain areas in Serbia, where the effects of urbanization, globalization and homogenization are obvious. Consequently, there is a need to prevent these effects in mountain areas where there is a threat of disbalance between development and the inherited natural and cultural values. The paper starts from several important concepts that relate contemporary approaches to cultural heritage preservation, place morphology and planning future development. The concept definitions from recent documents from related fields are used. These concepts are then applied to the area of Stara Planina Mountain and its rural settlements. The necessity for an integrative approach to planning this area with significant natural and anthropogenic potential is pointed out, including its integration into international programs of sustainable development.

Abstract: Transcription factors are crucial pre-transcriptional regulatory mechanisms that can modulate the expression of downstream genes by binding to their promoter regions. DOF (DNA binding with One Finger) proteins are a unique class of transcription factors with extensive roles in plant growth and development. Our previous research indicated a decrease in iron content in chlorotic bamboo leaves. However, to our knowledge, genes related to iron metabolism pathways in bamboo species have not yet been studied. Therefore, in the current study, we identified iron metabolism-related (IMR) genes in bamboo and determined the transcription factors that significantly influence them. Among these, DOFs were found to have widespread effects and potentially significant impacts on their expression. We identified specific DOF members in Dendrocalamus latiflorus with binding abilities through homology with Arabidopsis DOF proteins, and established connections between some of these members and IMR genes using RNA-seq data. Additionally, molecular docking confirmed the binding interactions between these DlDOFs and the DOF binding sites in the promoter regions of IMR genes. The co-expression relationship between the two gene sets was further validated using q-PCR experiments. This study paves the way for research into iron metabolism pathways in bamboo and lays the foundation for understanding the role of DOF transcription factors in D. latiflorus.

Protein glycation impacts enzymatic activity, disrupts metabolic processes, and is associated with chronic degenerative diseases. The human glycolytic enzyme triosephosphate isomerase (HsTIM, TPI1, or HsTPI) is associated with various disorders, such as enzymopathies originating from mutations. It also possesses moonlighting functions and is now recognized as a cancer marker. Previous reports of HsTPI mutants have demonstrated a significant increase of methyl-glyoxal (MGO) due to trioses accumulation. We compared how catalytic activity exerts differen-tial kinetic and structural stability effects due to mutations by tracking fluorescent argpyrimi-dine adduct (ARGp) through interaction with Arginine-MGO. Circular dichroism and fluores-cence spectroscopy were explored in HsTPI-WT and mutants HsTPI-C217K “Like-WT”, HsTPI-N16D accumulated in cancer, and HsTPI-E104D human deficiency mutant, by cysteines accessibility and time loss of activity and unfolding propensity in mutant enzymes with aggre-gates refractory to proteolysis in the C217K. Our study sheds new light on the increased suscep-tibility of mutants to generate MGO adducts due to TPI isomerization of MGO precursor sub-strates. Nevertheless, mutations enhance a negative feedback cycle, in which accumulated MGO access promotes accelerated loss of activity that leads to unfolding and aggregation. The cumu-lative and accelerated increase in MGO adducts, which probably are responsible for the patho-logical state in this TPI variant, are partially reversed by adding MGO-scavenger molecules.

The orbitofrontal cortex (OFC) area plays a critical role in human brain functions. However, susceptibility differences between paranasal sinuses and nasal cavity tissues often cause local field variations in the OFC during MRI, resulting in image distortions and signal loss. In this paper, we introduce a subject-friendly neck passive shim solution aimed at enhancing field homogeneity in the brain, specifically in the OFC region. Utilizing 3D gradient-echo pulse sequences, main magnetic field (B0) maps of four subjects’ brains were acquired at 4T MRI. Subsequently, these maps were decomposed into spherical harmonic coefficients and averaged. Optimal positions for placing shim elements on a semi-cylindrical surface, positioned slightly above the neck and below the chin, were computed. The findings indicate a substantial enhancement in B0 homogeneity, particularly within the OFC region, through the integration of this semi-cylindrical passive shim system in conjunction with first and second-order active shimming.

Hyperplastic dental follicles (HDFs) represent odontogenic hamartomatous lesions originating from pericoronal tissues and are often associated with impacted or embedded teeth. These lesions may occasionally feature unique calcifying bodies, known as calcifying whorled nodules (CWN), characterized by stromal cells arranged in a whorled or spiral fashion. CWNs are typically observed in multiple calcifying hyperplastic dental follicles or regional odontodysplasia. In our study, we examined 40 cases of HDFs, including nine instances with characteristics of CWNs, which were infrequently accompanied by odontodysplasia. Histological examination was conducted on all 40 cases, with immunohistochemical analysis performed on 21 of them. Among the cases with CWN, nine affected a single embedded tooth, with one exception. CWNs exhibited diverse calcifications featuring sparse or entirely deposited psammoma bodies, and some displayed dentinoid formation. Immunohistochemically, stromal cells of HDFs were frequently positive for CD56 and nestin. In contrast, CWNs were negative for CD56 but positive for nestin and HES1, with a few DSP-positive calcified bodies. Our results revealed that hamartomatous calcifying HFDs can impact multiple and single-embedded teeth. CWNs composed of nestin and HES1-positive ectomesenchymal cells demonstrated the potential to differentiate into odontoblasts and contribute to dentin matrix formation under the influence of HES1. This study is the first report documenting odontoblastic differentiation in HDFs.

We report a simple and high-performance flexible strain sensor based on liquid metal nanoparticles (LMNPs) on polyimide substrate by laser induced deposition. The LMNPs were prepared by ultrasonic method, and then the femtosecond laser direct writing technology was used to induce the assembly and deposition of the LMNPs to form liquid metal microwires. Laser local sintering enhances the connection between particles, and a wearable strain sensor was fabricated with the high sensitivity as high as 76.18, the good linearity (a correlation coefficient of 0.999) in a wide sensing rage, the fast response/recovery time of 159 ms/120 ms. Attributed to these extraordinary strain sensing performances, the sensor can sense various dynamic strains in real time, monitor both subtle physiological activities and large human motions. It can be adhered to human skin, and well reflect the change of facial expression and realize real-time monitoring of facial expression. And the vocal cord vibration can be detected for speech recognition while the sensor attached to the outside of the throat.

The incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is rising in the West, but little is known in Asia. This study elucidated changes in the incidence and HPV-positive portion of OPSCC in Hong Kong. Data from population-based cancer registry were used to analyze the incidence of OPSCC in associate with other head and neck cancers. Archived tumour tissues were tested for HPV. From 1986 to 2020, there was a marked decrease in the incidence of nasopharyngeal and laryngeal cancers, but a persistent increase in OPSCC from 36 cases in 1986 to 116 cases in 2020. The average positive rate for high-risk HPV was 36.1% (112/310) among OPSCC diagnosed in 2010-2020. The HPV positive rate in recent years was significantly higher than earlier cases (tonsil SCC: 64.7% (55/85) in 2016-2020 vs. 40.4% (19/47) in 2010-2015, P = 0.007). Patients with HPV-positive tonsil cancers were significantly younger than those negative (mean [SD]: 58.9 [9.9] vs. 64.3 [13.3] years, P = 0.006), but no significant difference between genders. A persistent increase in the incidence of oropharyngeal cancer over the last few decades was observed in Hong Kong, which can be explained by the remarkable increase in HPV-positive tonsil cancers.

Proximal tubular epithelial cells (PTEC) are constantly exposed to potentially toxic metabolites and xenobiotics. The regenerative potential of the kidney enables the replacement of damaged cells either via the differentiation of stem cells or the regain of proliferative properties of the PTEC. Nevertheless, it is known that renal function declines, suggesting that the deteriorated cells are not replaced by fully functional cells. To understand the possible causes of this loss of kidney cell function, it would be beneficial to understand the role of toxins during the regeneration process. Therefore, we investigated the sensitivity and function of human induced pluripotent stem cells (hiPSC), hiPSC differentiating, and hiPSC differentiated into proximal tubular epithelial-like cells (PTELC) to known nephrotoxins. hiPSC were differentiated into PTELC, exhibiting a similar morphology to PTEC, expressing prototypical PTEC markers and performing albumin endocytosis. When treated with two nephrotoxins, hiPSC and differentiating hiPSC were more sensitive to cisplatin than differentiated PTELC, whereas all stages were equally sensitive to cyclosporin A. Both toxins also had an inhibitory effect on albumin uptake. Our results suggest a high sensitivity of differentiating cells towards toxins, which could have an unfavorable effect on regenerative processes. To study this, our model of hiPSC differentiating into PTELC appears suitable.

We previously developed a highly sensitive and specific anti-PDPN mAb, LpMab-23 (mouse IgG1, kappa). In this study, we produced a humanized IgG1 version (humLpMab-23) and its defucosylated form (humLpMab-23-f) of an anti‑PDPN mAb to potentiate the ADCC activity. The humLpMab-23 could recognize PDPN‑overexpressed Chinese hamster ovary (CHO)-K1 (CHO/PDPN) and PDPN-positive PC-10 and LN319 cells by flow cytometry. Furthermore, we found that humLpMab-23-f exerted ADCC and complement-dependent cytotoxicity against CHO/PDPN, PC-10 and LN319 cells in vitro and exhibited potent antitumor activities in the xenograft models. These results indicated that humLpMab-23-f could be useful for an antibody treatment regimen for PDPN-positive human cancers.

While it is well known that 98-99% of the human genome do not encode proteins, but are nevertheless transcriptionally active and give rise to a broad spectrum of noncoding RNAs (ncRNAs) with complex regulatory and structural functions, specific functions have so far been assigned to only a tiny fraction of all known transcripts. On the other hand, the striking observation of an overwhelmingly growing fraction of ncRNAs, in contrast to an only modest increase in the number of protein-coding genes, during evolution from simple organisms to humans, strongly suggests critical but so far essentially unexplored roles of the noncoding genome for human health and disease pathogenesis. Research into the vast realm of the noncoding genome during the past decades thus lead to a profoundly enhanced appreciation of the multi-level complexity of the human genome. Here, we address a few of the many huge remaining knowledge gaps and consider some newly emerging questions and concepts of research. We attempt to provide an up-to-date assessment of recent insights obtained by molecular and cell biological methods, and by the application of systems biology approaches. Specifically, we discuss current data regarding two questions: (1) By which mechanisms could evolutionary recent ncRNAs with critical regulatory functions in a broad spectrum of cell types (neural, immune, cardiovascular) constitute novel thera-peutic targets in human diseases ? (2) Since noncoding genome evolution is causally linked to brain evolution, and given the pro-found interactions between brain and immune system, could human-specific brain-expressed ncRNAs play a direct or indirect (immune-mediated) role in human diseases? Synergistic with the remarkable recent progress regarding delivery, efficacy, and safety of nu-cleic acid-based therapies, the ongoing large-scale exploration of the noncoding genome for human-specific therapeutic targets is encouraging to proceed with the development and clinical evaluation of novel therapeutic pathways suggested by these research fields.

New in vitro approaches for the assessment of their toxicity are crucial for creating better risk assessments given the growing use of nanoparticles (NPs) in the production of consumer goods. Humans will be exposed to nanoparticles through the inhalation route from contaminated aerosol. A promising method for evaluating the genotoxicity of NPs in vitro uses human airway epithelial cells. This study aimed to determine whether there were differences in morphology change of human bronchial/tracheal epithelial (HBTEC) cells responded to NPs in 2D and 3D spheroid models and to evaluate genotoxicity in 2D and 3D cultures after 24 hr exposure to TiO2-, Ag- and ZnO-NPs using the comet assay. Our 2D and 3D HBTEC cultures with TiO2-NPs did not show any statistically significant genotoxicity compared to controls for concentration points tested in vitro. HBTEC cells grown as 2D indicated that exposure to ZnO-NPs at low concentrations (10-50 ug/mL) for 24 hr did not cause any genotoxic effect but, at high concentrations, genotoxicity was observed. In contrast, treatment of 2D HBTEC with AgO-NPs led to an elevated in percentage of tail DNA damage from 50 ug/mL to 100 ug/mL, which was concentra-tion-dependent. Using 3D spheroid assays revealed a lower %tail length in ZnO- and AgO-NPs, thus exhibiting in vitro genotoxicity of NPs in this cell model. Spheroids (3D) rather than mono-layer cultures (2D) are believed to more precisely represent in vivo-like cell behavior when evaluating genotoxicity. Together, our findings demonstrate the genotoxic effects of NPs and point to the critical role that cell culture models play in the evaluation of toxicological risk.

We have previously developed several successful decellularization strategies yielding porcine cardiac extracellular matrices (pcECMs), which exhibit tissue-specific bioactivity and bioinductive capacity when cultured with various pluri- and multipotent stem cells. Here, we studied the tissue-specific effects of the pcECM on seeded human mesenchymal stem cells (hMSCs) phenotype using reverse transcribed quantitative polymerase chain reaction (RT-qPCR) arrays for cardio-vascular related genes. We further corroborated interesting findings at the protein level (flow cytometry and immunological stains) as well as bioinformatically using several mRNA sequencing and protein databases of normal and pathologic adult tissue expression, as well as during human embryonic organogenesis. We discovered that upon seeding of human mesenchymal stem cells (hMSCs) on the pcECM they displayed partial MET toward endothelial phenotypes (CD31+) and morphologies, which were preceded by an early spike (~day 3 onward after seeding) in HAND2 expression at both the mRNA and protein levels compared to plate controls. CRISPR-Cas9 knockout (KO) of HAND2 and its associated antisense long non-coding RNA (HAND2-AS1) regulatory region resulted in proliferation arrest, hypertrophy, and senescent-like morphology. Bioinformatic analyses revealed that HAND2 and HAND2-AS1 are highly correlated in expression, are expressed in many different tissue types albeit at distinct yet tightly regulated expression levels. Deviation (down or up regulation) from these basal tissue expression levels are associated with a long list of pathologies. We thus suggest that HAND2 expression levels may finetune cell plasticity possibly affecting senescence and mesenchymal-to-epithelial transition states, through yet unknown mechanisms. Targeting this pathway may represent a promising new therapeutic approach for a wide range of diseases, including cancer, degenerative disorders, and aging. Nevertheless, further investigations are required to better understand the molecular players involved, potential inducers and inhibitors of this pathway, and eventually potential therapeutic applications.

The human ABCG2 multidrug transporter plays a crucial role in the absorption and excretion of xeno- and endobiotics, contributes to cancer drug resistance and the development of gout. In this work we have analyzed the effects of selected variants, residing in a structurally unresolved cytoplasmic region (a.a. 354-367) of ABCG2, on the function and trafficking of this protein. A cluster of four lysines (K357-360) and the phosphorylation of a threonine (T362) residue in this region have been previously suggested to significantly affect the cellular fate of ABCG2. Here we report that the naturally occurring K360del variant in human cells increased ABCG2 plasma membrane expression and accelerated cellular trafficking. The variable alanine replacements of the neighboring lysines had no significant effect on transport function, and the apical localization of ABCG2 in polarized cells has not been altered by any of these mutations. Moreover, in contrast to previous reports, we found that the phosphorylation incompetent T362A, or the phosphorylation mimicking T362E variants in this loop, had no measurable effects on the function or expression of ABCG2. Molecular dynamics simulations indicated an increased mobility of the mutant variants with no major effects on the core structure of the protein. These results may help to decipher the potential role of this unstructured region within this transporter.

The novel severe acute respiratory coronavirus-2 (SARS-Cov-2) constitutes the causative agent of coronavirus disease-2019 (COVID-19). Several mechanisms have been proposed regarding the development of cardiovascular complications during and after acute COVID-19 infection. COVID-19, caused by SARS-CoV-2, has emerged as one of the deadliest pandemics in modern history. Several clinical and pathophysiologic mechanisms have been proposed for development of cardiovascular complications during and after acute COVID-19 infection. The myocardial injury in patients with COVID-19 has been attributed to coronary spasm, microthrombi formation, plaque rupture, hypoxic injury or cytokine storm disposing the same pathophysiology with the three clinical variants of Kounis syndrome. One of the main proposed mechanisms for development of cardiovascular complications is the angiotensin converting enzyme 2 (ACE2) and its interactions with the renin-aldosterone system (RAAS) and the kinin-kallikrein system (KKS). The ACE2 receptors are expressed throughout the human body located mainly in heart, blood vessels endothelium, lungs, intestines, testes and neurons. The SARS-CoV-2 directly invades the endothelial cells that contain ACE2 receptors and constitutes the main pathway through which the virus enters the endothelial cells. This leads to downregulation of the ACE2 receptors and causes angiotensin II accumulation leading to prothrombotic effects such as hemostatic imbalance via activation of the coagulation cascade, impaired fibrinolysis, thrombin generation, vasoconstriction, endothelial and platelet activation, and pro-inflammatory cytokine release. Indeed, angiotensin I exerts no direct biological function except that its high levels can stimulate catecholamine production. It is metabolized to its biologically active byproduct angiotensin II, a potent vasoconstrictor, by angiotensin converting enzyme (ACE) through cleavage of the two terminal amino acids. SARS-CoV-2 infection prevents the counterbalancing action of the KKS system that normally causes vasodilation and regulates tissue repair, inflammation, cell proliferation, and platelet aggregation. All this cascade leads to the following cardiovascular events: cardiac arrhythmias, cardiac arrest, cardiomyopathy, cytokine storm, heart failure, ischemic myocardial injuries and microvascular disease, Kounis syndrome, long COVID, myocardial fibrosis, myocarditis, new onset hypertension, pericarditis, postural orthostatic tachycardia syndrome (POTS), pulmonary hypertension, stroke, Takotsubo Syndrome, venous thromboembolism and thrombocytopenia. In this narrative review we describe and elucidate when and how the COVID-19 affects the human cardiovascular system, in various areas on the human body that are vulnerable in every category of patients including children and athletes.

Background: Recently the role of nutraceutical compounds in the prevention of human diseases is rapidly increasing. Here, we aim to evaluate the beneficial effect of dietary supplementation with seven active principles, lycopene, sulphoraphane, silymarin, glutathione, escin, tryptophan, green tea catechins, on human health. Methods: An extensive search of PubMed and Medline database was performed with the following keywords: “silymarin”, “sulforaphane”, “lycopene”, “green tea catechins”, “tryptophan”, “glutathione” and “escin” accompanied by the keywords “supplement”, “supplementation”, “nutraceutics”. All pre-clinical and clinical trials have been considered for this review. Results: One-hundred and eighteen full-text articles were eligible for inclusion in this review. The papers examined presented considerable variability due to the wide heterogeneity of dosages administered, population involved and outcomes pursued. Conclusion: Nutritional supplementation with lycopene, sulphoraphane, silymarin, glutathione, escin, tryptophan and green tea catechins appears to exert a wide range of benefits on human health, ranging from mood and cognition to cardiovascular health, fertility, metabolism, antioxidant and anti-inflammatory capabilities, potential anti-cancer effects. Further studies are required to better define the potential synergic effect, optimal dosage, mechanism of action and tolerability profile of these substances.

The COVID-19 pandemic caused by the SARS-CoV-2 virus has led to significant global health implications. Although the respiratory manifestations of COVID-19 are widely recognized, emerging evidence suggests that the disease may also significantly affect the gut microbiota, the intricate community of bacteria that lives within the gastrointestinal system. This extensive article intends to investigate the impact of COVID-19 on the gut microbiota, examining the underlying mechanisms, clinical implications, and potential therapeutic interventions. Understanding the complex interactions between COVID-19 and the gut microbiota will help us to gain valuable insights into the broader consequences of this viral infection on human health.

Transcranial photobiomodulation (tPBM) has been suggested as a non-invasive neuromodulation tool. Repetitive administration of light-emitting diode (LED)-based tPBM for several weeks significantly improved human cognition. To understand the electrophysiological effects of LED-tPBM on the human brain, we investigated alterations by repeated tPBM in vigilance performance and brain networks using electroencephalography (EEG) in healthy participants. Active and sham LED-based tPBM were administered to the right forehead of young participants twice a week for four weeks. The participants performed a psychomotor vigilance task (PVT) during each tPBM/sham experiment. A 64-electrode EEG system recorded electrophysiological signals from each participant during the first and last visits in the 4-week study. Topographical maps of EEG power enhanced by tPBM were statistically compared for the repeated tPBM effect. A new data-processing framework combining the group singular value decompensation (gSVD) with eLORETA was implemented to identify EEG brain networks. The reaction time of PVT in the tPBM-treated group was significantly improved over four weeks compared to that in the sham group. We observed acute increases in EEG delta and alpha powers during 10-min LED-tPBM while the participants performed the PVT task. We also found that theta, beta, and gamma EEG powers significantly increased globally after four weeks of LED-tPBM. Combining gSVD with eLORETA enabled us to identify EEG brain networks and the corresponding network power changes by repeated 4-week tPBM. This study clearly demonstrated that 4-week prefrontal LED-tPBM can neuromodulate several key EEG networks, implying a possible causal effect between modulated brain networks and improved psychomotor vigilance outcomes.

In modern security situations, tracking multiple human objects in real-time within challenging urban environments is a critical capability for enhancing situational awareness, minimizing response time, and increasing overall operational effectiveness. Tracking multiple entities enables informed decision-making, risk mitigation, and the safeguarding of civil-military operations to ensure safety and mission success. This paper presents a multi-modal electro-optical/infrared (EO/IR) and radio frequency (RF) fused sensing (MEIRFS) platform for real-time human object detection, recognition, classification, and tracking in challenging environments. By utilizing different sensors in a complementary manner, the robustness of the sensing system is enhanced, enabling reliable detection and recognition results across various situations. Specifically designed Radar tag and thermal tag can be used to discriminate friendly and non-friendly objects. The system incorporates deep learning-based image fusion and human object recognition and tracking (HORT) algorithms to ensure accurate situation assessment. After integrating into an all-terrain robot, multiple ground tests were conducted to verify the consistent HORT in various environments. The MEIRFS sensor system has been designed to meet the Size, Weight, Power, and Cost (SWaP-C) requirements for installation on autonomous ground and aerial vehicles.

There was no significant difference in bacterial adhesion between the 3 bone graft types tested, regardless of the bacterial strain used (p &gt; 0.22). After 72 hours of culture, there was no significant difference between the Fresh and Frozen bone groups, while the number of CFU in the Decellularised group was significantly lower (p &lt; 0.01), averaging -0.72 +/- 0.08 lg, -0.20 +/- 0.01 lg and -0.78 +/- 0.48 lg with S. epidermidis, S. aureus and E. coli respectively. Absolute values differences are low, and considering fresh bone (equivalent to autograft) as the gold standard due to its low infection rates in clinical studies, we can conclude that adhesion and biolfilm development characteristics are similar between Fresh, Frozen and Decellularised bone grafts..

Evapotranspiration (ET) is an essential part of energy flow between the surface of the earth and the atmosphere, simultaneously involving the water, carbon, and energy cycles. It is mainly determined by climate change, land use, and land cover changes. Climate change is expected to intensify the hydrological cycle and alter ET. Land use affects ET within regional ecosystems mainly through vegetation changes and agricultural activities such as farmland reclamation, crop cultivation, and agricultural management. However, there is still a need for quantitative characterization of the impacts of climate change and human activities on ET and regional water resource efficiency in arid and semiarid regions. Based on Landsat-8 remote sensing imagery and land use data, the planting structure in the Liangzhou District of the middle reaches of the Shiyang River Basin was identified using a multiband and multitemporal approach in this study. Subsequently, the ET of major cash crops was inverted using the three-temperature model. This research quantitatively describes the responses of wheat and corn to the climate and human activities over a two-year period. Furthermore, the impact of planting structure and climatic factors on ET was elucidated. The results indicate that a combination of multitemporal green and shortwave infrared 1 bands is the optimal spectral combination to extract the planting structure. Compared to 2019, the wheat area decreased by 23.27% in 2020, while the corn area increased by 5.96%. Both crops exhibited significant spatial heterogeneity in ET during the growing season. The typical daily range of ET for wheat was 0.4–7.2 mm/day, and for corn, it was 1.5–4.0 mm/day. Among the climatic factors, temperature showed the highest correlation with ET (R = 0.80, p ≤ 0.05). Our research findings provide valuable insights for the fine identification of planting structures and a better understanding of the response of ET to climatic factors and human activities.

In this work, we developed a highly sensitive multiplexed immunosensor for direct simultaneous detection of both N-terminal Natriuretic Peptide (NT-proBNP) and Cortisol in human artificial saliva (AS). The developed biosensor platform based on silicon nitride was composed from four gold working microelectrodes (WEs) and an integrated counter and reference electrode. Gold WEs were biofunctionalized through carboxyl diazonium (4-APA) to immobilize both anti- NT-proBNP and anti-Cortisol antibodies for simultaneous detection. The electroaddressing of the 4-APA onto the gold WE surfaces was realized by cyclic voltammetry (CV), while the interaction between antibodies and antigens in PBS was monitored by electrochemical impedance spectroscopy (EIS). The antigen detection in human AS was realized by EIS combined with the standard addition method. The immunesensor was highly sensitive and selective toward the corresponding biomarkers in both PBS and artificial human saliva as well as in the presence of other potential interfering biomarkers such as tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10). The limit of detection (LOD) was at 0.2pg/mL for NT-proBNP within the range 0.03 to 0.9pg/mL, while the LOD for Cortisol was 0.06 ng/mL within the range 0.02 to 0.6 ng/mL for Cortisol in artificial saliva. The developed immunosensor is very promising for significant detection time reducing as it allows the simultaneous detection of various biomarkers.

Background: Sleeping Sickness, Human African Trypanosomiasis (HAT) is a vector- borne disease caused by Trypanosoma brucei (T.b). Sleeping sickness in Ethiopia was reported in 1967 for the first time. Recently in Southern parts of Ethiopia, in August 2022, five (5) cases of sleeping sickness (T. b. rhodesiense) were confirmed. Following this outbreak, the current investigation was aimed to identify the entomological and epidemiological drivers for the reemergence of HAT outbreak and recommend appropriate interventions. Methods: A cross sectional study design with descriptive data analysis was used. Tsetse fly collection and blood samples from cattle animals were taken. NGU and bio-conical traps were used to determine the distribution (density and abundance) of the vector. About 10μl of blood was collected from the marginal ear vein of 301 cattle animals using the heparinized microhematocrit capillary. The parasite detection was carried out through vector dissection under binocular stereo-microscope (magnification of 60X) and microscopic examination from serum of Animals using the Buffy coat method. Results: A total of 329 tsetse flies were captured and identified to Glosina (G.) pallidipes 259 (60.4%) and Glossina fuscipes 70 (16.3%). 188 (51.1%) of tsetse flies were collected from Dembagofa with 94 apparent density. Among all captured Tsetse flies, 39 (11.8%) of Tsetse were fed with high female apparent density in each ecological variation: wood land (51), Bush land (20) and grassland (11). Overall, the apparent density of tsetse fly was high in Wood land (93): G. pallidipes (76.5) and Bush land (36.5). Among all examined cattles for the presence of parasite, 9 cattles were detected positive with an overall prevalence of 3%. T. congolense 6 (2%) and T. vivax 1 (0.3%) with 2 (0.7%) suspected brucei. The parasite prevalence Trypanosoma was 4 (4.6%) in poor body condition (Bcs) cattle. The animals in the age range 5 - 9 years were infected high with 7 (5.3%) prevalence. Conclusion: The current study revealed that there are high-risk factors that predispose the community to Human African Trypanosomiasis (HAT) due to the presence of two different species of Tsetse flies and many animal reservoirs. The transmissions of Human African trypanosomiasis (HAT) are related to environmental, Vector, and human factors. Further geographically expanded investigation should be conducted throughout the country.

Yellow fever is an emerging and re-emerging viral disease transmitted through the bites of infective Aedes mosquitoes. Several outbreaks of yellow fever have been documented in southern Ethiopia.Understanding the transmission cycle is pivotal to manage arboviral disease outbreaks. Therefore, the present study aimed to evaluate which species of Aedes mosquitoes contribute to the YF virus transmission and the outbreaks that have occurred, and their behaviors (biting and resting) in the region. Two districts were selected based on previous Yellow Fever (YF) outbreak history. A longitudinal entomological sampling was carried out to collect adult Aedes mosquitoes using human landing catches, mechanical mouth aspirators and pyrethrum spreadsheet collection. Adult mosquito collections were conducted twice a month for six months from February 2019 to July 2020. Identification of mosquito species at the genus level was done using morphological keys and speciation using molecular techniques on 406 Aedes due to limited laboratory resources (primers and probe, reagents shortage) and budget limits. Aedes mosquitoes were pooled and tested for YFV, dengue virus (DENV, serotype 1-4) and chikungunya virus (CHKV) by qPCR. A total of 1689 mosquitoes 93.7% (1582/1689) of Aedes and 6.3% (107/1689) of Culex were collected. Of the total collected mosquitoes, 58.7% (991/1689) were from Ofa study sites whereas the left 41.3% (698/1689) were from Boko Dawula. 93.5% (1579/1689) of Aedes complex were collected during wet season. Most of the mosquitoes were collected during the wet season 97.9% (1653/1689). Of the 1582 Aedes simpsoni complex, 57.7% (913/1582) were from Ofa district and the remaining 42.3% (669/1582) were from Boko Dawula district. Of the 406 Aedes mosquitoes molecularly characterized to the species level, the Aedes simpsoni complex accounted for 99.5% (404/406), while Aedes aegypti found in the Ofa district accounted for only 0.5% (2/ 406). From the 934 Aedes simpsoni tested for viruses and none were positive. The human biting activities of Aedes (Ae.) simpsoni peaked at 8:00 – 9:00 hour and 16:00 – 17:00 hour, mostly outdoors, both within the villages and forests. The leaves of Ensete (E.) ventricosum appear to be ideal resting places for Aedes (Ae.) simpsoni complex. Although the tested Ae. simpsoni complex was negative for arboviruses; morning and afternoon activities of the species coincide with human outdoor activities and may therefore pose the risk of viral infection. The lower dominance of Aedes aegypti indicated that the major responsible vector for the occurrences of previous and current arboviral diseases was due to other mentioned Aedes species. It is of great importance to improve surveillance activities of arboviruses in reservoir hosts and vectors to establish control measures. Furthermore, the origin of bloodmeal and the mosquito’s role in the transmission of arboviral diseases need further study to improve the understanding of this species.

Background: Visceral leishmaniasis (VL) is s critical public health problem in over ninety countries. The control measures adopted in Brazil have been insufficient when it comes to preventing the spread of this neglected disease. In this context, a precise diagnosis of VL in dogs and humans could help to reduce the number of cases of this disease. Distinct studies for the diagnosis of VL have used single recombinant proteins in serological assays; however, results have been variable, mainly in the sensitivity of the antigens. The development of multiepitope-based proteins could be relevant in solving such a problem. Methods: A chimeric protein (rMELEISH) was constructed based on amino acid sequences from kinesin 39 (k39), alpha-tubulin, and heat shock proteins HSP70 and HSP 83.1, and tested in ELISA for the detection of L. infantum infection in humans and dogs. Results: rMELEISH was able to discriminate between VL cases and cross-reactive diseases and healthy samples, with sensitivity and specificity values of 100% as compared to the use of a soluble Leishmania antigenic extract (SLA). Conclusions: Preliminary data suggest that the rMELEISH protein presents a potential to be tested in future studies against a larger serological panel for the diagnosis of canine and human VL.

The enzyme N-acetylgalactosamine-4-sulfatase (Arylsulfatase B; ARSB) was originally identified as a lysosomal enzyme which was deficient in Mucopolysaccharidosis VI (MPS VI; Maroteaux-Lamy Syndrome). Newly directed attention to the impact of ARSB in human pathobiology indicates a broader, more pervasive effect, encompassing roles as a tumor suppressor, transcriptional mediator, redox switch, and regulator of intracellular and extracellular-cell signaling. By controlling the degradation of chondroitin 4-sulfate and dermatan sulfate by removal or failure to remove the 4-sulfate residue at the non-reducing end of the sulfated glycosaminoglycan chain, ARSB modifies the binding or release of critical molecules into the cell milieu. These molecules, such as galectin-3 and SHP-2, in turn, influence crucial cellular processes and events which determine cell fate. Identification of ARSB at the cell membrane and in the nucleus expands perception of the potential impact of decline in ARSB activity. Regulation of availability of sulfate from chondroitin 4-sulfate and dermatan sulfate may also affect sulfate assimilation and production of vital molecules, including glutathione and cysteine. Increased attention to ARSB in mammalian cells may help to integrate and deepen our understanding of diverse biological phenomenon and to approach human diseases with new insights.

One in four adults in the US suffer from cartilage degeneration of the Intervertebral Disc (DDD) or load bearing joints (DJD). Combined DDD and DJD leads to billions of dollars in surgical health care costs annually. Since cartilage is avascular, it has a limited regenerative capacity. Conventional non-surgical treatment modalities provide brief symptomatic relief, have sided effects, and do not address the actual structural tissue defect in the cartilage itself. As such, new alternatives are needed. Perinatal tissue allografts have emerged as a novel frontier for bio-mechanical cartilage engineering research. Birth product-specific therapeutic roles and clinical outcomes are actively being investigated. The tissues of interest include umbilical cord-derived Wharton’s Jelly (WJ). This study assessed WJ tissue samples via ZEISS Supra 55VP Field-Emission Scanning Electron Microscope (SEM) at 100 and 300nm resolution scales. The captured images of pre and post-processed structural tissue matrices in WJ allografts were analyzed against themselves and peer-reviewed SEM images of articular cartilage, intervertebral disc cartilage, and muscle fascia. SEM images of post-processed WJ structural tissue matrices were analogous to structural tissue matrices in human articular cartilage, intervertebral disc cartilage, and muscle fascia. Relevant characteristics of pre- and post-processed structural tissue matrices in WJ allografts were comparable. This is the first study, that we are aware of, to utilize SEM to compare the pre-and post-processing relevant structural characteristics of WJ allografts and additionally demonstrate that structural collagen matrices in post-processed WJ allografts are analogous in structure to the cartilage in articular joints, intervertebral discs, and muscle fascia.

All living cells maintain a charge distribution across their cell membrane (membrane potential) by carefully controlled ion fluxes. These bioelectric signals regulate cell behavior (such as migration, proliferation, differentiation) as well as higher-level tissue and organ patterning. Thus, voltage gradients represent an important parameter for diagnostics as well as a promising target for therapeutic interventions in birth defects, injury, and cancer. However, despite much progress in cell and molecular biology, little is known about bioelectric states in human stem cells. Here, we present simple methods to simultaneously track ion dynamics, membrane voltage, cell morphology, and cell activity (pH and ROS), using fluorescent reporter dyes in living human neurons derived from induced neural stem cells (hiNSC). We developed and tested functional protocols for manipulating ion fluxes, membrane potential, and cell activity, and tracking neural responses to wounding and re-innervation in vitro. Finally, using morphology sensor, we tested and quantified the ability of physiological actuators (neurotransmitters and pH) to manipulate nerve wound re-innervation. These methods are not specific to a particular cell type and should be broadly applicable to the study of bioelectrical controls across a wide range of combinations of models and endpoints.

Human Parechoviruses, officially known as Parechovirus A (PeV-A), is associated with mild gastrointestinal and respiratory illness in young children, however, they may also give rise to Central Nervous System (CNS) infections and neonatal sepsis. While studies have delved into the detection of PeV-A in different populations, the detection of PeV-A in Hispanic populations in Latin American countries is not well-known. The aim of this study was to determine the presence of PeV-A in respiratory, gastrointestinal, and neurological clinical samples of pediatric patients in Panama. Two hundred samples of pediatric patients with a negative diagnosis for the main respiratory viruses, rotavirus and neurological viruses such as herpesvirus, enterovirus and cytomegalovirus, collected between 2014 and 2015, were analyzed by real-time RT-PCR. Eight positive PeV-A infections were detected, 2 in respiratory samples, 5 in stool samples and one detected in cerebrospinal fluid. This is the fisrt report of PeV-A in Panamá.

Of the documented tick-borne diseases infecting humans in Mexico, Rocky Mountain spotted fever (RMSF), caused by the gram-negative bacterium Rickettsia rickettsia, is responsible for most fatalities. Given recent evidence of brown dog tick, Rhipicephalus sanguineus sensu lato, as an emerging vector of human RMSF, we aimed to evaluate dogs and their ticks for rickettsiae infections as an initial step in assessing the establishment of this pathosystem in a poorly studied region of northeastern Mexico while evaluating the use of dogs as sentinels for transmission/human disease risk. We sampled owned dogs living in six disadvantaged neighborhoods of Reynosa, Northern Mexico to collect whole blood and ticks. Of 168 dogs assessed, tick infestation prevalence was 53%, comprised of exclusively R. sanguineus s. l. (n=2,170 ticks). Using PCR and sequencing, we identified an overall rickettsiae infection prevalence of 4.1% (n=12/292) in ticks, in which eight dogs harbored at least one infected tick. Rickettsiae infections included R. amblyommatis and R. parkeri, both of which are emerging human pathogens, as well as candidatus R. andeanae. This is the first documentation of pathogenic Rickettsia in R. sanguineus s.l. collected on dogs from northeastern Mexico. Domestic dog infestation with Rickettsia-infected ticks indicates ongoing transmission, thus humans are at risk for exposure and underscores the importance of public and veterinary health surveillance for these pathogens.

The innovation driven Industry 5.0, in agreement with Industry 4.0, leads to consider human in a prominence position as the center of manufacturing field. This pushes towards the hybridization of manufacturing plants promoting a fully collaboration between human and robot. Furthermore, the new paradigm of "human centred design" and "anthropocentric design" allows enabling a synergistic combination of human and robot skills. However, properly collaborative workplaces are currently very few. Industry is still not confident, and systems integrators hesitate to venture into Human-Robot Collaboration (HRC). Despite the effort in collaborative robotics, a general solution to overcome the current limitations in designing of collaborative workplaces still misses. In the current work, a Knowledge-Based Approach (KBA) is adopted to face collaborative workplace designing problem. The framework resulting from the KBA allows developing a modelling paradigm that enable to define a streamlined approach for the layout designing of a collaborative workplace. Finally, a what-if analysis and a ANOVA analysis are performed to generate and evaluate a set of scenarios related to a collaborative workplace for quality inspection of welded parts. Facing the high complexity and multidisciplinary of HRC can be conveyed to develop a general design approach aimed at overcoming the difficulties that limit the spread of HRC in the manufacturing field.

Tuberculosis (TB) remains a major public health threat globally, especially in sub-Saharan Africa. Both human and Mycobacterium tuberculosis (MTBC) genetic variation affect TB outcomes, but few studies have examined if and how the two genomes interact to affect disease. We hypothesize that long-term coexistence between human genomes and MTBC lineages modulate disease to affect its severity. We examined this hypothesis in our TB household contact study in Kampala, Uganda, in which we identified 3 MTBC lineages of which one, L4.6-Uganda, is clearly derived and hence recent. We quantified TB severity using the Bandim TBscore and examined the interaction between MTBC lineage and human single nucleotide polymorphisms (SNPs) genome-wide, in two independent cohorts of TB cases (N=149 and N=127). We found a significant interaction between a SNP in PPIAP2 and the Uganda lineage (combined p=4x10-8). PPIAP2 is a pseudogene that is highly expressed in immune cells. Pathway and eQTL analyses indicated potential roles between coevolving SNPs and cellular replication and metabolism as well as platelet aggregation and coagulation. This finding provides further evidence that host-pathogen interactions affect clinical presentation differently than host and pathogen genetic variation independently, and that human-MTBC coevolution is likely to explain patterns of disease severity.

Human cytomegalovirus (HCMV) tegument protein pp150 is essential for the completion of final steps in virion maturation. Earlier studies indicated that three pp150nt (N terminal one-third of pp150) conformers cluster on each triplex (Tri1, Tri2A and Tri2B) and extend towards small capsid proteins atop nearby major capsid proteins forming a net-like layer of tegument densities that enmesh and stabilize HCMV capsids. Based on this atomic detail, we designed several peptides targeting pp150nt. Our data show significant reduction in virus growth upon treatment with one of these peptides (pep-CR2) with an IC50 of 1.33 μM. Based on 3D modeling, pep-CR2 specifically interferes with the pp150-capsid binding interface. Cells pre-treated with pep-CR2 and infected with HCMV sequester pp150 in the nucleus indicating a mechanistic disruption of pp150 loading onto capsids and subsequent nuclear egress. To enhance the in-vivo inhibitory potential and bioavailability of pep-CR2, we conjugated it with a carrier molecule (elastin like polypeptide (ELP)). The ELP-pep-CR2 conjugate was expressed in E.coli and purified. Upon treatment with ELP-pep-CR2, HCMV showed significant titer reductions with no significant impact on cell viability. These results indicate that CR2 of pp150 is amenable to targeting by a peptide inhibitor and can be developed into an effective antiviral.

The human adenovirus phylogenetic tree is split across seven species (A-G). Species D adenoviruses offer potential advantages for gene therapy applications, with low rates of preexisting immunity detected across screened populations. However, many aspects of the basic virology of species D, such as their cellular tropism, receptor usage and in vivo biodistribution profile, remain unknown. Here, we have characterized human adenovirus type 49 (HAdV-D49), a relatively understudied species D member. We report that HAdV-D49 does not appear to use a single pathway to gain cell entry but appears able to interact with various surface molecules for entry. As such, HAdV-D49 can transduce a broad range of cell types in vitro, with variable engagement of blood coagulation FX. Interestingly, when comparing in vivo biodistribution to adenovirus type 5, HAdV-D49 vectors show reduced liver targeting whilst maintaining transduction of lung and spleen. Overall, this presents HAdV-D49 as a robust viral vector platform for ex vivo manipulation of human cells and for in vivo applications where the therapeutic goal is to target the lung or gain access to immune cells in the spleen whilst avoiding liver interactions, such as intravascular vaccine applications.

We developed two human induced pluripotent stem cell (hiPSC)/human embryonic stem cell-specific glycan-recognizing mouse antibodies, R-10G and R-17F, using the Tic (JCRB1331) hiPSC line as an antigen. R-10G recognizes a low-sulfate keratan sulfate, and R-17F recognizes lacto-N-fucopentaose-1. To evaluate the general characteristics of stem cell glycans, we used the hiPSC line 201B7 (HPS0063), a prototype iPSC line. Using an R-10G affinity column, an R-10G-binding protein was isolated. The protein yielded a single but very broad band from 480 to 1,236 kDa by blue native gel electrophoresis. After trypsin digestion, the protein was identified as podocalyxin by liquid chromatography/mass spectrometry. According to Western blotting, the protein reacted with R-10G and R-17F. The R-10G positive band was resistant to digestion with glycan-degrading enzymes, including peptide N-glycanase, but the intensity of the band was decreased significantly by digestion with keratanase, keratanase II, and endo-β-galactosidase, suggesting the R-10G epitope to be a keratan sulfate. These results suggest that keratan sulfate-type epitopes are shared by hiPSCs. However, the keratan sulfate from 201B7 cells contained a polylactosamine disaccharide unit (Galβ1-4GlcNAc) at a significant frequency, whereas that from Tic cells consisted mostly of keratan sulfate disaccharide units (Galβ1-4GlcNAc(6S)). In addition, the abundance of the R-10G epitope was significantly lower in 201B7 cells than in Tic cells.

Dipeptidyl peptidase (DPP) 9, DPP8, DPP4 and fibroblast activation protein (FAP) are the four enzymatically active members of the S9b protease family. Associations of DPP9 with human liver cancer, exonic single nucleotide polymorphisms (SNPs) in DPP9 and loss of function (LoF) variants have not been explored. Human genomic databases including The Cancer Genome Atlas (TCGA) were interrogated to identify DPP9 LoF variants and associated cancers. Survival and gene signature analyses were performed on hepatocellular carcinoma (HCC) data. We found that DPP9 and DPP8 are intolerant to LoF variants. DPP9 LoF variants were most often associated with uterine carcinoma. Two DPP9 intronic SNPs that have been associated with lung fibrosis and COVID-19 were not associated with liver fibrosis or cancer. All four DPP4-like genes were overexpressed in liver tumours and their joint high expression was associated with poor survival in HCC. Increased DPP9 expression was associated with obesity in HCC patients.. High expression of genes that positively correlated with overexpression of DPP4, DPP8, and DPP9 were associated with very poor survival in HCC. Enriched pathways analysis of these positively correlated genes featured Toll-like receptor and SUMOylation pathways. This comprehensive data mining suggests that DPP9 is essential for human survival and the DPP4 protease family is important in cancer pathogenesis.

We recently found that in human osteoblasts Homer1 complexes to CaSR and mediates AKT initiation via mTORC2 leading to beneficial effects in osteoblasts including -catenin stabilization and mTORC1 activation (doi: 10.1074/jbc.RA118.006587). Herein we further investigated the relationship between Homer1 and CaSR and demonstrate a link between the protein levels of CaSR and Homer1 in human osteoblasts in primary culture. Thus, when siRNA was used to suppress the CaSR, we observed upregulated Homer1 levels and when siRNA was used to suppress Homer1 we observed downregulated CaSR protein levels using immunofluorescence staining of cultured osteoblasts as well as western blot analyses of cell protein extracts. This finding was confirmed in vivo as the bone cells from osteoblast specific CaSR(-/-) mice showed increased Homer1 expression compared to wild-type. Furthermore, when the commonly used osteosarcoma cell lines MG63 and SAOS-2 were compared to primary osteoblasts, higher levels of Homer1 protein were associated with increased protein levels of the CaSR as well as mTOR and Rictor. CaSR and Homer1 protein were both expressed in osteocytes embedded in the long bones of wild-type mice, and immunofluorescent studies of these cells revealed that Homer1 protein sub-cellular localization was markedly altered in the osteocytes of CaSR(-/-) mice compared to wt. The study identifies additional roles for Homer1 in the control of the protein level and subcellular localization of CaSR in cells of the osteoblast lineage, in addition to its established role of mTORC2 activation downstream of the receptor.

Prebiotic oligosaccharides are widely used as human and animal feed additives for their beneficial effects on the gut microbiota. However, there are limited data to assess the direct effect of such functional foods on the transcriptome of intestinal epithelial cells. The purpose of this study is to describe the differential transcriptomes and cellular pathways of colonic cells directly exposed to galacto-oligosaccharides (GOS) and fructo-oligosaccharides (FOS). We have examined the differential gene expression of polarized Caco-2 cells treated with GOS or FOS and their respective mock-treated cells using mRNA sequencing (RNA-seq). A total of 89 significant differentially expressed genes were identified between GOS and mock-treated groups. For FOS treatment, a reduced number of 12 significant genes were observed to be differentially expressed relative to the control group. KEGG and Gene Ontology functional analysis revealed that genes up-regulated in the presence of GOS were involved in digestion and absorption processes, fatty acids and steroids metabolism, potential antimicrobial proteins, energy-dependent and -independent transmembrane trafficking of solutes and amino acids. Using our data, we have established complementary non-prebiotic modes of action for these frequently used dietary fibers.

The outbreak of recently identified 2019 novel coronavirus (2019-nCOV) infection has become a world-wide health threat. Currently, more information is needed for further understanding the transmission, clinical characteristics, and infection control procedures of 2019-nCOV. Recently, the role of the eye in transmitting 2019-nCOV has been intensively discussed. Previous investigations about other high infectious human COVs, that is, severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), may provide helpful information. In this review, we describe the genomics and morphology of human CoVs, the epidemiology, systemic and ophthalmic manifestations, mechanisms of human CoVs infection, and infection control procedures. The role of the eye in the transmission of SARS-CoV and 2019-nCOV is discussed. Although the conjunctiva is directly exposed to extraocular pathogens, and the mucosa of ocular surface and upper respiratory tract is connected by nasolacrimal duct and share same entry receptors for some respiratory viruses. The eye is rarely involved in human CoVs infection, conjunctivitis is quite rare in patients with SARS-CoV and 2019-nCoV infection, and COV RNA positive rate by RT-PCR test in tears and conjunctival secretions from patients with SARS-CoV and 2019-nCoV infection is also very low, which imply that the eye is neither a preferred organ of human COVs infection, nor is a preferred gateway of entry for human COVs to infect respiratory tract. However, pathogens exposed to the ocular surface might be transported to nasal and nasopharyngeal mucosa by constant tear rinsing through lacrimal duct, and then cause respiratory tract infection. Considering close doctor-patient contact is quite common in ophthalmic practice which are apt to transmit human COVs by droplets and fomites, hand hygiene and personal protection are still highly recommended for health care workers to avoid hospital-related viral transmission during ophthalmic practice.

There is a strong anticipated future for human pluripotent stem cell-derived hepatocytes (hiPS-HEP), but so far their use has been limited due to insufficient functionality. We investigated the potential of hiPS-HEP as an in vitro model for metabolic diseases by combining transcriptomics with multiple functional assays. The transcriptomics analysis revealed that 86% of the genes were expressed at similar levels in hiPS-HEP as in human primary hepatocytes (hphep). Adult characteristics of the hiPS-HEP were confirmed by the presence of important hepatocyte features, e.g. Albumin secretion and expression of major drug metabolizing genes. Normal energy metabolism is crucial for modeling metabolic diseases, and both transcriptomics data and functional assays showed that hiPS-HEP were similar to hphep regarding uptake of glucose, LDL and fatty acids. Importantly, the inflammatory state of the hiPS-HEP was low under standard conditions, but in response to lipid accumulation and ER stress the inflammation marker TNFα was upregulated. Furthermore, hiPS-HEP could be co-cultured with primary hepatic stellate cells both in 2D and in 3D spheroids, paving the way for using these co-cultures for modeling NASH. Taken together, hiPS-HEP have the potential to serve as an in vitro model for metabolic diseases. Furthermore, differently expressed genes identified in this study can serve as targets for future improvements of the hiPS-HEP.

Multiple unique environmental factors such as space radiation and microgravity (µG) pose a serious threat to human gene stability during space travel. Recently, we reported that simultaneous exposure of human fibroblasts to simulated µG and radiation results in more chromosomal aberrations than in cells exposed to radiation alone. However, the mechanisms behind this remain unknown. The purpose of this study was thus to obtain comprehensive data on gene expression using a 3D clinostat synchronized to a carbon (C)-ion or X-ray irradiation system. Human fibroblasts (1BR-hTERT) were maintained under standing or rotating conditions for 3 or 24 h after synchronized C-ion or X-ray irradiation at 1 Gy as part of a total culture time of 2 days. Among 57,773 genes analyzed with RNA sequencing, we focused particularly on the expression of 82 cell cycle-related genes after exposure to the radiation and simulated µG. The expression of cell cycle-suppressing genes (ABL1 and CDKN1A) decreased and that of cell cycle-promoting genes (MKI67, KPNA2, CCNB1, STMN1, and MCM4) increased after C-ion irradiation under µG. The cell cycle may pass through the G1/S and G2 checkpoints with DNA damage due to the combined effects of C-ions and µG, suggesting that increased genomic instability might occur in space.

Exoskeleton robots are a rising technology in industrial contexts to assist humans in onerous applications. Mechanical and control design solutions are intensively investigated to achieve a high performance human-robot collaboration (e.g., transparency, ergonomics, safety, etc.). However, the most of the investigated solutions involve high-cost hardware, complex design solutions and standard actuation. In the presented work, an industrial exoskeleton for lifting and transportation of heavy parts is proposed. A low-cost mechanical design solution is proposed, exploiting compliant actuation at the shoulder joint to increase safety and transparency in human-robot cooperation. A hierarchic model-based controller is then proposed (including the modeling of the compliant actuator) to actively assist the human while executing the task. An inner optimal controller is proposed for trajectory tracking, while an outer fuzzy logic controller is proposed to online deform the task trajectory on the basis of the human’s intention of motion. A gain scheduler is also designed to calculate the optimal control gains on the basis of the performed trajectory. Simulations have been performed in order to validate the performance of the proposed device, showing promising results. The prototype is under realization.

The aim of this study is to emphasize on the clinical uses of amniotic membrane (AM) in multiple ocular disorders. AM possesses many properties including promotion of epithelialization, anti-fibrotic, anti-apoptotic, anti-angiogenic properties. Epithelial wound healing on the eye surface is promoted due to several epidermal and keratocyte growth factors as well as by its anti-inflammatory and anti-scarring effects due to interleukin-10, interleukin-1 receptor antagonists and inhibition of transforming growth factor- beta (TGF-β) signal transduction by AM in the corneal and conjunctival fibroblasts respectively. It plays a crucial role by functioning as a substitute of basement membrane (BM) and as a temporary graft material. It is not only being used as an eye graft but also its extract can be used as an eye drop for corneal and external eye diseases. So its proper preparation, preservation and clinical application can bring a revolutionary change in the treatment of different ocular disorders.

The improved understanding of the underlying mechanisms of oxidative damage and/or chronic diseases is of high priority in dietary research. Although the chemical extraction of biofunctional molecules from different fruits and cereals have been studied extensively, the impact of food processing and digestion on bioactivity has not been studied systematically. The aim of this study was to investigate the biofunctional potential of blackcurrant powder incorporated into wholemeal wheat and barley cookies in after simulated in vitro digestion. The incorporation of blackcurrant significantly (p<0.05) increased the total phenolic content (about 60 %), significantly improved oxygen radical absorbance capacity (about 25 %) of the cookie digesta. Additionally cellular antioxidant and anti-proliferative activity (lowest EC₅₀ value 1.02 mg/mL) on human liver cancer cell model, HepG2 was significantly enhanced. Bioactive metabolites of blackcurrant incorporated cookies were significantly supressed the inflammatory cytokine genes IL-1β (about 3-fold), IL-6 (about 0.5-fold) and NF-kB (about 2-fold) regulation and upregulated satiety gene NUCB-2/Nesfatin-1 (about 5-fold) compare with wholemeal wheat and barley control cookies. The exerted synergistic effects of this study suggest that there may be a new and effective option to prevent and control chronic diseases in human.

Barchan dune fields are a dominant landscape feature in SE Qatar and a key element of the peninsula’s geodiversity. The migration of barchan dunes is mainly controlled by dune size, wind pattern, vegetation cover and human impact. We investigate the variability of dune migration in Qatar over a time period of 50 years using high-resolution satellite and aerial imagery and explore its relation to the regional Shamal wind system, teleconnection patterns, and limitations in sand supply associated with the transgression of the Arabian Gulf. We detect strong size-dependent differences in migration rates of individual dunes as well as significant decadal variability on a dune-field scale, which was found to be correlating with the intensity of the North Atlantic Oscillation (NAO) and the Indian Summer Monsoon (ISM). High uncertainties associated with the extrapolation of migration rates back into the Holocene, however, do not permit to further specify the timing of the loss of sand supply and the onset of the mid-Holocene relative sea-level (RSL) highstand. For the youngest phase considered in this study (2006–2015), human impact is anticipated to have accelerated dune migration under a weakening Shamal regime through sand mining and excessive vehicle frequentation upwind of the core study area.

Epstein–Barr virus (EBV) has been recently shown to be co-present with high-risk human papillomaviruses (HPVs) in human cervical cancer; thus, these oncoviruses play an important role in the initiation and/or progression of this cancer. Accordingly, our group has recently viewed the presence and genotyping distribution of high-risk HPVs in cervical cancer in Syrian women; our data pointed out that HPVs are present in 95.45% of our samples. Herein, we aim to explore the co-prevalence of EBV and high-risk HPVs in 44 cervical cancer tissues from Syrian women using polymerase chain reaction (PCR), immunohistochemistry (IHC) and tissue microarray (TMA) analyses. We found that EBV and high-risk HPVs are co-present in 15/44 (34%) of the samples. Additionally, we report that the co-expression of LMP1 and E6 genes of EBV and high-risk HPVs, respectively, is associated with poorly differentiated squamous cell carcinomas phenotype; this is accompanied by a strong and diffused Id-1 overexpression, which is an important regulator of cell invasion and metastasis. These data imply that EBV and HPVs are co-present in cervical cancer in the Middle East area including Syria and their co-presence is associated with a more aggressive cancer phenotype. Future investigations are needed to elucidate the exact role of EBV and HPVs cooperation in cervical carcinogenesis.

Human footprint is having a unique set of ridges unmatched by any other human being, and therefore it can be used in different identity documents for example birth certificate, Indian biometric identification system AADHAR card, driving license, PAN card, and passport. There are many instances of the crime scene where an accused must walk around and left the footwear impressions as well as barefoot prints and therefore it is very crucial to recovering the footprints to identify the criminals. Footprint-based biometric is a considerably newer technique for personal identification. Fingerprints, retina, iris and face recognition are the methods most useful for attendance record of the person. This time world is facing the problem of global terrorism. It is challenging to identify the terrorist because they are living as regular as the citizens do. Their soft target includes the industries of special interests such as defense, silicon and nanotechnology chip manufacturing units, pharmacy sectors. They pretend themselves as religious persons, so temples and other holy places, even in markets is in their targets. These are the places where one can obtain their footprints easily. The gait itself is sufficient to predict the behaviour of the suspects. The present research is driven to identify the usefulness of footprint and gait as an alternative to personal identification.

In this study, the impact of energy, agriculture, macroeconomic and human-induced indicators on environmental pollution from 1971 to 2011 is investigated using the statistically inspired modification of partial least squares (SIMPLS) regression model. There was evidence of a linear relationship between energy, agriculture, macroeconomic and human-induced indicators and carbon dioxide emissions. Evidence from the SIMPLS regression shows that a 1% increase in crop production index will reduce carbon dioxide emissions by 0.71%. Economic growth increased by 1% will reduce carbon dioxide emissions by 0.46%, thus supports the environmental Kuznets curve hypothesis that an increase in a country’s economic growth leads to a reduction in environmental pollution. An increase in electricity production from hydroelectric sources by 1% will reduce carbon dioxide emissions by 0.30%, thus increasing renewable energy sources in Ghana’s energy portfolio will help mitigate carbon dioxide emissions. Increasing Enteric Emissions by 1% will increase carbon dioxide emissions by 4.22% and a 1% increase in the Nitrogen content of Manure Management will increase carbon dioxide emissions by 6.69%. The SIMPLS regression forecasting exhibited a 5% MAPE from the prediction of carbon dioxide emissions.

The wetlands in northeastern Bangladesh are home to some of the most prolific and valuable ecosystems on the planet, offering a wide range of benefits to both the local and wider communities. A limited number of research on this topic have been carried out in various wetlands in coastal hilsa, but none have been located in the northeastern region of Bangladesh. Thus, the goal of this study was to better understand the most commercially relevant species (anadromous hilsa) in northeastern Bangladesh as well as to assess the wetland ecosystem services more thoroughly with the contribution of their fish genetic resources. In addition to laboratory studies, fieldwork was done in the fishing settlements along the Surma River, Hakaluki Haor, and Tanguar Haor. The study classified 77 fish species into 21 subcategories of ecosystem services, of which 56% were not threatened, 17% were vulnerable, and 10% were highly endangered. The species Hilsa was found to be the most economically significant, accounting for 1% of the GDP overall. The study determined if the hilsa stock of the examined wetlands maintains a single or several subpopulations in comparison to other parts of the country when they migrate from saline water to northeastern Bangladesh (freshwater). But when compared to other groups, the FST score was between 0.000 to 0.017, indicating that the populations are identical and that there is genetic material sharing between them. Additionally, these statistics imply that the Sylhet haor and adjacent river systems contain a single stock of Hilsa fish. Nevertheless, a number of stresses and risks, including overexploitation, illicit and destructive fishing, siltation, and natural disasters like flash floods, have been linked to changes in the supply of hilsa and other ecosystem services. This study also emphasizes the necessity of policy attention and research to address the concerns.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) continues to be a global threat due to its ability to evolve and generate new subvariants, leading to new waves of infection. Additionally, other coronaviruses like Middle East respiratory syndrome coronavirus (MERS-CoV, formerly known as hCoV-EMC) which first emerged in 2012, persists and continues to present a threat of severe illness to humans. The continued identification of novel coronaviruses, coupled with the potential for genetic recombination between different strains, raises the possibility of new coronavirus clades of global concern emerging. As a result, there is a pressing need for pan-CoV therapeutic drugs and vaccines. After extensive optimization of an HCV protease inhibitor screening hit, a novel 3CLPro inhibitor (MK-7845) was discovered and subsequently profiled. MK-7845 exhibited nanomolar in vitro potency with broad spectrum activity against a panel of clinical SARS-CoV-2 subvariants and MERS-CoV. Furthermore, when administered orally, MK-7845 demonstrated a notable reduction of viral burdens by &gt;6 log orders in the lungs of transgenic mice infected with SARS-CoV-2 (K18-hACE2 mice) and MERS-CoV (K18-hDDP4 mice).