Teachability has been extensively studied under the context of making industrial robots to be programmable and reprogrammable. However, it is only recently that the artificial intelligence (AI) research community is accelerating the research works with the objective of making humanoid robots and many other robots to be teachable under the context of using natural languages. We human beings spend many years to learn knowledge and skills despite our extraordinary mental capabilities of being teachable with the use of natural languages. Therefore, if we would like to develop human-like robots such as humanoid robots, it is inevitable for us to face the issue of making future humanoid robots to be teachable with the use of natural languages as well. In this paper, we present the key details of a top-down design for achieving a teachable mind which consists of two major processes: the first one is the process which enables humanoid robots to gain innate mental capabilities of transforming incoming signals into meaningful crisp data, and the second one is the process which enables humanoid robots to gain innate mental capabilities of undertaking incremental and deep learning with the main focus of associating conceptual labels in a natural language to meaningful crisp data. These two processes consist of the two necessary and sufficient conditions for future humanoid robots to be teachable with the use of natural languages. In addition, this paper outlines a very likely new finding underlying human brain’s neural systems as well as the obvious mathematics underlying artificial deep neural networks. These outlines provide us the strong reason to separate the study of mind from the study of brain. Hopefully, the content discussed in this paper will help the AI research community to venture into the right direction which is to make future humanoid robots, non-humanoid robots, and many other systems to achieve human-like self-intelligence at cognitive level with the use of natural languages.

The neural system has limited resources to interact with the environment, and this is where attention comes into play. Attention is a complex process that provides numerous benefits, but there has been a longstanding debate about the mechanisms involved in attentional orientation. Two widely proposed mechanisms are top-down and bottom-up, which relate to the organism's current behavioral goal and the salience of environmental stimuli, respectively. However, distinguishing between these mechanisms can be challenging in both behavioral and neural studies. This review introduces a new conceptualization in which both top-down and bottom-up mechanisms are viewed as aspects of the same process. This unified approach aims to prepare the organism to face stimuli and events based on its prior experiences, immediate (the current task that he/she is aware of), and innate (to be alive) demands.

No doubt pollution is a global problem which must be holistically tackled. In doing this, adequate knowledge of the sources of pollution is important, therefore the aim of this paper is to review source apportionment with reference to top-down and bottom-up methods. In this paper, dispersion modeling, emissions inventory, and sampling methods were discussed. Also, analytical methods involved in top-down source apportionment were mentioned. The two techniques are needed to evaluate pollutants and their sources. Based on these two approaches, pollution control strategy would be developed and decisions can be made in deciding the right approach to solve or reduce the pollution problems.

Methane is a greenhouse gas and identified as a key driver of near-term climate change. Bottom-up approaches estimate annual methane loss from US natural gas production and transport at 6 Tg, but recent studies suggest this may be an underestimate. To investigate this possibility, an equipment-based emissions inventory, using EPA emission factors, was developed to calculate methane emissions from oil and gas operations in the Delaware Basin, USA. Emission factors and activity data were then updated using contemporary and region-specific measurement data. The original inventory estimated emissions at 315 Gg CH4 y-1 (gas production-normalized rate of 0.6% loss), while the updated inventory estimated emissions of 1,500 Gg CH4 y-1 (2.8% loss). The largest changes resulted from large fugitive emissions from oil production (+430 Gg CH4 y-1), updating maintenance activity emissions (+214 Gg CH4 y-1), considering flaring inefficiency (+174 Gg CH4 y-1), and the inclusion of associated gas venting (+136 Gg CH4 y-1). This study suggests that a systematic underestimate probably exists in current bottom-up inventories and identifies sources currently missing or may be incorrect. We also strongly recommend that emission factors should be validated through direct comparison against measurement campaigns that include long-tail distributions typical of oil and gas activities.

Top-down models are defined by hardware architects to provide information on the utilization of the different hardware components. The target is to isolate the users from the complexity of the hardware architecture while giving them insight into how efficiently the code is using the resources. In this paper, we explore the applicability of 4 top-down models defined for different hardware architectures powering state-of-the-art HPC clusters (Intel Skylake, Fujitsu A64FX, IBM Power9, and Huawei Kunpeng 920) and propose a model for AMD Zen 2. We study a parallel CFD code used for scientific production to compare these 5 Top-Down models. We evaluate the level of insight achieved, the clarity of the information, the ease of use, and the conclusions that each one allows us to reach.

The visual span refers to the number of letters readers can identify in a single fixation without using linguistic skills. Proponents of the visual span hypothesis postulate an influence of early visual processing on reading speed. Given the slowness of reading Arabic texts, the present work aims to study the development of the visual span and its effects on reading speed in the Arabic-speaking context. Thirty-four subjects participated in the study. The trigram task and the rapid serial visual presentation (RSVP) paradigm were used to estimate visual span size and reading speed. In line with our initial assumptions, the results showed a significant effect of grade level on reading speed (F(2,31) = 30.93, p<0.001), visual span size (F(2,31) = 20.57, p<0.001). In good alignment with previous work, our results show that visual span size could explain around 40% of the reading speed variability. Interestingly, our analyses revealed a narrowing of visual span size in our Arabic sample. The results of study 2, suggest that the poor performance in the trigram task is due to poor visual attention capacities in our Arabic readers

Color can direct visual attention to specific locations through bottom-up and top-down mechanisms. Using Continuous Flash Suppression (CFS) as way to investigate the factors that gate access to consciousness, the current study investigated whether color also directly affected the timing of conscious perception. Low or high spatial frequency (SF) gratings with different orientations were shown as targets to the non-dominant eye of human participants. CFS patterns were presented at a rate of 10Hz to the dominant eye to delay conscious perception of the targets, and participants had the task to report the target’s orientation as soon as they could see it. With low-SF targets, two types of color-based effects became evident. First, when the targets and the CFS patterns had different colors, the targets entered consciousness faster than in trials where the targets and CFS patterns had the same color. Second, when participants searched for a specific target color, targets that matched these search settings entered consciousness faster compared to conditions where the target color was irrelevant and could vary from trial to trial. Thus, the current study demonstrates that color is a central feature of human perception and leads to faster conscious perception of visual stimuli through bottom-up and top-down attentional mechanisms.

In this review we extensively describe the main post-translational modifications that give rise to the multiple proteoforms characterized to date in the human salivary proteome and their potential role. Most of the data reported were obtained by our group in over twenty-five years of research carried out on human saliva mainly by applying a top-down strategy. At the beginning we describe the products generated by proteolytic cleavages, which can occur before and after secretion. In this section the most relevant families of salivary proteins are also described. Next, we report the current information concerning the human salivary phospho-proteome and the limited news available on sulfo-proteome. Three sections are dedicated to the description of the glycation and enzymatic glycosylation. Citrullination and N- and C- terminal PTMs and a miscellaneous of other modifications are described in the last two sections. Results highlighting the variation in the level of some proteoforms in local or systemic pathologies are also reviewed along the sections of manuscript to underline the impact and relevance of this information for the development of new diagnostic biomarkers useful in clinical practice.

Wetlands play a crucial role not only in providing ecological services but also in enriching the cultural and spiritual life of human society. Despite this, their cultural values have often been overlooked. The formal recognition of cultural values began with the Ramsar Convention in the 1970s, which acknowledged wetlands as resources of great economic, cultural, scientific, and recreational value. The wetlands of Majuli are of profound cultural and socio-cultural importance, particularly in terms of religious and spiritual significance, as well as recreational value. This study examines the cultural services provided by the wetland ecosystem of Majuli, focusing on its significance in the local human-environment nexus. Utilizing a qualitative approach with quantitative aspects, data was collected from primary sources through observation, interviews, and group discussions, along with secondary sources such as books, journals, and web portals.

Watching the international COVID-19 epidemics unfold during February and early March 2020, we began to highlight how outbreaks in care homes were inevitable, given the vulnerable patients in close proximity, and pressures on social care to help relieve pressure on the NHS. We suggested public health measures would significantly impact on care homes. Specifically we felt all homes would have multiple individuals isolated within days of introduction of guidance requiring isolation of new cough (or fever), and that a clear definition of an outbreak would be needed that differentiated COVID19 from influenza. We share the experiences of a GP practice looking after 900 nursing or dual registration care homes in the London Borough of Ealing in the early stages of the COVID19 Pandemic 2020. We believe that the altered presentation of cases of COVID19 in care homes contributed to the size of outbreaks, and that keeping COVID19 out of homes is the only way to manage this disease, with early isolation and complete segregation of positive and negative cases. We have seen over 300 suspected cases resulting in four fold (n=175) average monthly death rates, three fold usual issue of anticipatory medications, and approximately 32% mortality rate (up to 43% in over 90’s). Discharge pathways from hospital and admissions to care homes must be clear and robust. COVID19 naïve patients should not be admitted to units with outbreaks and COVID19 positive patients should not be admitted to anything other than a designated “hot” home until risk of contagion is passed. Some patients are testing positive at over 30 days since initial mild symptoms.

We addressed whether arbitrary top–down regulation based on self-referential thinking could be valid for sensorimotor synchronization. We hypothesized that the dorsal anterior cingulate cortex (dACC) could regulate sensorimotor synchronization in accordance with internal models generated by self-referential processing. To illustrate the validity of the hypothesis, we conducted a missing oddball task with musical students. Utilizing the event-related deep-brain activity (ER-DBA) method cooperatively with the event-related potential (ERP) method, we found that dACC activation promotes repetitive tapping supported by modal completion, whereas dACC deactivation promotes precise tapping under avoiding erroneous responses for the missing pulses. Endogenous ERP components including P150 as a marker of modal completion and N200 as a marker of response inhibition supported this claim. Furthermore, combining the ER-DBA and ERP results, it was suggested that the brain creates a coherent story to promote repetitive tapping by mediating sensory evidence via modal completion. The free energy measurements theoretically support these findings, thereby confirming the validity of our hypothesis.

When all countries are battling Covid-19 by adopting different policies, it could help address the issue of government response policy efficiency. This study examines the efficiency of government intervention policies in 19 countries, the efficiency of preventing the spread, and also the mortality caused by the virus. The policies are categorized based on the Oxford COVID-19 Government Response Tracker, which combines various indicators, including Containment and closure, Economic response, and Health systems. Given that the governments apply a top-down approach to design these policies, the current research evaluates the efficiency of policies based on the same approach. Here, two different models have been used to calculate the efficiency of policies. We designed a combined index in both models and applied Window DEA method to determine the output quantities in the efficiency ratio. The results of our study show that in both models, Japan, Finland and Thailand had the highest level of government response efficiency. The countries with the lowest government response efficiency were the United States, Spain, and Russia in the first model, and China, Italy, and Spain in the second.

This brief communication intends to develop critical thinking on the development at different levels that could be evaluated in the well-being of humans from the local development towards a global scale or planetary point of view. Therefore it was presented and discussed how Artificial Intelligence tools could provide important contributions and influence in the design of critical thinking to develop ideas and insights within Research as well as funding for technology transfer. In this context it should be highlighted that the generation of funding and economy for sustainability that it should be based on critical thinking and analysis of what is need it from the close surrounding towards longer distances as well as in the inversed direction. In this regard, the main axes that support it are based on the importance of entailment of individuals in their close surrounding as well as to longer physical distances and cultural differences. An in this context it should be highlighted the existence of large diversity and varied Multicultural differences. These factors could affect the developments of technology, education; level, and quality of life. Thus the Economical and development indexes could be largely varied and different between them. For this reason it should highlighted the local development within shortened times by interacting to receive or provide materials with aggregated value or non-tangible values. Therefore, it could be accelerated the process of improvement in a targeted field looking for average homogeneous development everywhere. And there, it is where the link-up and transfer strategies of technology and education by creation of varied strategies in communication media. As for example the communication plays an important role to transfer knowledge within the different social status and imagining the development of thinking that later it will be the basis for the next generation of technology. By this manner, it could be coupled different levels of educations degrees by a factor in common related with curiosity and open minds to learn, work, and live together in the context of developments of new smart manners of living where economy and new encrypted currency are involucred and provide by different manners sustainability. In these perspectives the development and education at the University and higher degrees taking into account the transmission of important factors such as; i) entailment , ii) development of knowledge, and iii) transference, is fundamental. Finally, it should be highlighted the particular need of good human relationships, emotional intelligence, and diplomacy to afford from the simplest challenges to the higher ones.

Alzheimer's disease (AD) is a neurodegenerative olfactory disorder affecting millions of people worldwide. Alterations in the hexosamine or glucose-related pathways have been described through AD progression. Specifically, an alteration in glucosamine 6 phosphate isomerase 2 (GNPDA2) protein levels has been observed in olfactory areas from AD subjects. However, the biological role of GNPDA2 in neurodegeneration remains unknown. Using mass-spectrometry, multiple GNPDA2 interactors were identified in human nasal epithelial cells (NECs) mainly involved in intraciliary transport. Moreover, GNPDA2 overexpression induced an increment in NEC proliferation rates, accompanied by transcriptomic alterations in Type II interferon signalling or cellular stress responses. In contrast, the presence of beta-amyloid or mutated Tau-P301L in GNPDA2-overexpressing NECs induced a slow-down in the proliferative capacity in parallel with a disruption in protein processing. The proteomic characterization of Tau-P301L transgenic zebrafish embryos demonstrated that GNPDA2 overexpression interfered with collagen biosynthesis and RNA/protein processing, without inducing additional changes in axonal outgrowth defects nor neuronal cell death. In humans, a significant increase in serum GNPDA2 levels was observed across multiple neurological proteinopathies (AD, Lewy body dementia, progressive supranuclear palsy, mixed-dementia, and amyotrophic lateral sclerosis) (n=187). These data shed new light on GNPDA2-dependent mechanisms associated to the neurodegenerative process beyond the hexosamine route.

The genus Strophantus belongs to the Apocynaceae family of flowering plants which grows primarily in tropical Africa. The plants are widely used in traditional herbal medicine. S. sarmentosus, in particular, is used for the treatment of, e.g., joint pain and rheumatoid arthritis, wound infections, head lice, diarrhoea, snake bite, and eye conditions. Despite the widespread use, dedicated research characterizing bioactive plant components is scarce. Investigations focussed mainly on the cardenolides, because of their cardioactivity and historical use as cardiotonic. There are also studies concerning the antibacterial, antioxidant and anti-inflammatory activity of plant extracts. This review summarizes the present knowledge about the biochemical and analytical reserach on Strophantus, in general, and S. sarmentosus, in particular, and describes the current state-of-the-field based on the available sientific literature.

Several studies have reported a relationship between autonomic dysfunction　 during tasks and Internet addiction. Changes within 24 h regarding heart rate variability (HRV) may be a more sensitive indicator than short term observations. We evaluated the influence of excessive Internet usage on HRV using a 24 h electrocardiogram (ECG) and examined acute changes during computer game tasks. A total 13 high school students and 22 young adults were recruited, and divided into excessive Internet user and non- excessive user groups based on Internet addiction test scores. The ECG was recorded continuously for 24 h by a wearable sensor and during two computer games (the Iowa gambling task and each participant’s preferred game) using a standard type ECG system. Multiple psychometric tests were also conducted. The excessive Internet user group exhibited clinically significant depressive symptoms, and higher self-reported scores for anxiety, impulsivity, autistic tendencies, and sleep problems than the non- excessive internet user group. There were weak differences within the 24 h high-frequency (HF) band power between two groups. During the Iowa gambling task, younger participants exhibited a reduced HF response, which may be related to weaker top- down self- regulatory mechanisms.

With a view to understand and resolve the complexity of the food matrix, ohmic technologies alone or in combination were extensively employed. In this sense, the newest developments and advances of proteomics, metabolomics, lipidomics whith their unique benefits could simplify and understand the link between physiological and pathological activities in biology, physiology, pathology, and food science and processing. This review aims to briefly introduce the basis of proteomics, metabolomics, lipidomics, then expansively review their impact on the assessment of meat quality and safety. Here, also, we discuss the application of proteomics, metabolomics, lipidomics for the authentication and adulteration of meat and meat derivatives from different sources, and provides some perspectives regarding the use of emerging techniques such as rapid mass spectrometry (MS) and non-invasive measurements for the analysis of meat quality and safety. This paper summarizes all significant investigation in these matters, and underlines the advances in analytical chemistry technologies and meat science areas. By emphasizing the requirement for additional examinations, this paper attempts a comprehensive knowledge of “foodomics” and their potential to improve their employment in meat science.

Background: People with Down syndrome (DS) have a trisomy of chromosome 21 and marked deficits in verbal memory but relatively preserved visuospatial perception. Verbal memories are related to semantic knowledge. Little is known about the organization of semantic knowledge in people with DS, which was the aim of this study. Aims: The extent of false memory in people with DS was examined. Possible differences in the number of false memories induced by nominal and verbal themes were examined. Methods and Procedures: In the study phase, ten word lists with semantically related associates were presented. In the recognition phase, participants made judgments on whether each word had been represented previously as semantically related lures, old words, and semantically unrelated new words. Outcomes and Results: Differences in the processing of nominal and verbal theme-related lures were observed among people with DS. When processing nominal theme-related lures, people with DS showed delayed false positives. When processing verbal theme-related lures, people with DS showed no differences compared to controls. Similar patterns have been observed in people with DS when processing nominal theme-related associates and verbal theme-related associates. People with DS have delayed recognition of associates. When processing unrelated words, they showed significantly higher false positives than controls for both nominal and verbal eliciting themes. Further analyses of the themes revealed differences in false positives across syntactic categories among groups. Conclusions and Implications: People with DS showed a delayed recognition of associates and deviance in recognizing unrelated words in the nominal and verbal theme categories. People with DS were delayed in terms of nouns, but deviated with verbs in associated and unrelated words. Additionally, people with DS showed distinct patterns in processing five nominal lures and three verbal lures, suggesting that they formed false memories differently based on distinct syntactic categories. Thus, it was concluded that people with DS develop a deviant semantic structure. Category-based interventions for people with DS should be implemented in order to improve their semantic knowledge through lexical connections.

This paper presents a novel approach to designing beam codebooks for downlink multiuser hybrid multiple input multiple output (MIMO) wireless communication systems, leveraging multi-agent reinforcement learning (MARL). The primary objective is to develop an environment-specific beam codebook composed of non-interfering beams, learned by cooperative agents within the MARL framework. Machine learning (ML) based beam codebook design for downlink communications have been based on channel state information (CSI) feedback or only reference signal received power (RSRP) consisting of an offline training and user clustering phase. In massive MIMO, the full CSI feedback data is of large size and is resource-intensive to process, making it challenging to implement efficiently. RSRP alone for a stand-alone base station is not a good marker of the position of a receiver. Hence, in this work, uplink CSI estimated at the base station along with feedback of RSRP and binary acknowledgment of the accuracy of received data is utilized to design the beamforming codebook at the base station. Simulations using sub-array antenna and ray-tracing channel demonstrate the proposed system’s ability to learn topography-aware beam codebook for arbitrary beams serving multiple user groups simultaneously. The proposed method extends beyond mono-lobe and fixed beam architectures by dynamically adapting arbitrary shaped beams to avoid inter-beam interference, enhancing overall system performance. This work leverages MARL’s potential in creating efficient beam codebooks for hybrid MIMO systems, paving the way for enhanced multiuser communication in future wireless networks.

Despite significant advancements in Artificial Intelligence (AI) and Large Language Models (LLMs), detecting and mitigating bias remains a critical challenge, particularly within social media platforms like X (formerly Twitter) and in addressing cyberbullying present on them. This research investigates the effectiveness of leading LLMs in generating synthetic biased and cyberbullying data and evaluates the proficiency of Transformer AI models in detecting bias and cyberbullying within both authentic and synthetic contexts. The study involves semantic analysis and feature engineering on a dataset of over 48,000 sentences related to cyberbullying collected from Twitter (before it became X). Leveraging state-of-the-art LLMs such as ChatGPT-4o, Pi AI, Claude 3 Opus, and Gemini-1.5, synthetic biased, cyberbullying, and neutral data were generated to deepen the understanding of bias in human-generated data. AI models including DeBERTa, Longformer, BigBird, HateBERT, MobileBERT, DistilBERT, BERT, RoBERTa, ELECTRA, and XLNet were initially trained to classify Twitter cyberbullying data and subsequently fine-tuned, optimized, and quantized for multilabel classification (detecting both biases and cyberbullying). The study's outcomes include a prototype of a hybrid application that combines a Bias Data Detector and a Bias Data Generator, validated through extensive testing.

The domestic ducks (Anas platyrhynchos domesticus) are resistant to most of the highly pathogenic avian influenza virus (HPAIV) infections. In this study, we characterized the lung proteome and phosphoproteome of ducks infected with HPAI H5N1 virus (A/duck/India/02CA10/2011/Agartala) at 12 hr, 48 hr and 5 days post infection condition. Total 2082 proteins were differentially expressed and 320 phosphorylation sites mapping to 199 phosphopeptides corresponding to 129 proteins were identified. Functional annotation of proteome data analysis reveals activation of RIG-I-like receptor and Jak-STAT signaling pathways, that lead to induction of interferon stimulated genes (ISGs) expression. The pathway analysis of phosphoproteome datasets also confirms the activation of RIG I, Jak-STAT signaling, NF-kappa B signaling and MAPK signaling pathways in the lung tissues. The induction of ISGs proteins (STAT1, STAT3, STAT5B, STAT6, IFIT5 and PKR) establishes protective antiviral immune response in duck lung tissue. Further, the protein-protein interaction network analysis identified proteins like AKT1, STAT3, JAK2, RAC1, STAT1, PTPN11, RPS27A, NFKB1 and MAPK1 as main hub proteins that might play important roles in disease progression in ducks. Together, functional annotation of proteome and phosphoproteome datasets reveals the molecular basis of the disease progression and disease resistance mechanism in ducks infected with HPAI H5N1 virus.

Many challenges in proteomics result from the high-throughput nature of the experiments. The paper first presents pre-analytical problems, which still occur, although the call for standardisation in omics has been ongoing for many years. This article also discusses aspects, which affect bioinformatic analysis, based on three sets of reference data measured with different orbitrap instruments. Despite continuous advances in mass spectrometer technology as well as analysis software, data set-wise quality control is still necessary and decoy-based estimation, although challenged by modern instruments, should be utilized. We draw attention to the fact that numerous young researchers perceive proteomics as a mature, readily applicable technology. However, it is important to emphasize that the maximum potential of the technology can only be realized by an educated handling of its limitations.

The present study aims at investigating the relationship between Initial Public Offerings (IPOs) variables mainly underpricing on one hand, and the brand value measures on the other. Our final data set is 104 international brand companies. We implement empirical approach using hierarchical OLS regression and descriptive statistics. We show that underpricing is positively related to brand value which emphasizes the marketing role of going public and underpricing in enhancing brand equity through the product market, which additionally confirms some information asymmetry models. We also find that on average brand companies had not been recognized as brands at the IPO time. Moreover, we show the positive role of private equity in enhancing brand value, additionally, the non-linear association between underpricing and brand value is not evident. Finally, we draw some policy implication and suggestions for future research.

Natural killer (NK) cells play a crucial role in innate immunity, particularly in combating infections and tumors. However, in hematological cancers, NK cells often exhibit impaired functions. Therefore, it is very important to activate its endosomal toll-like receptors (TLRs) as a potential strategy to restore its antitumor activity. We stimulate NK cells from the peripheral blood mononuclear cells from children with acute lymphoblastic leukemia and NK cells isolated, the NK cells were stimulated with specific TLR ligands (Poly I:C, Imiquimod, R848, and ODN2006) and evaluated changes in IFN-γ, CD107a, NKG2D, NKp44 expression, Granzyme B secretion, cytokine/chemokine release, and cytotoxic activity. Results revealed that Poly I:C and Imiquimod enhanced activation of both immunoregulatory and cytotoxic NK cells, increasing IFN-γ, CD107a, NKG2D, and NKp44 expression. R848 activated immunoregulatory NK cells, while ODN2006 boosted CD107a, NKp44, NKG2D, and IFN-γ secretion in cytotoxic NK cells. R848 also increased secretion of various cytokines/chemokines. Importantly, R848 and ODN 2006 significantly improved cytotoxicity against leukemic cells. Overall, TLR stimulation enhances NK cell activation, suggesting TLR8 (R848) and TLR9 (ODN 2006) ligands as promising candidates for antitumor immunotherapy.

Exosome-based therapy has emerged as a promising strategy for addressing diverse disorders, indicating the need for further exploration of the potential therapeutic effects of the exosome cargos. This study introduces "enhanced exosomes," a novel type of exosomes developed through a novel cell culture system. These specific exosomes may become potent therapeutic agents for treating ovarian disorders. In this study, we conducted a comparative analysis of the protein and miRNA cargo compositions of enhanced exosomes and naïve exosomes. Our findings revealed distinct cargo compositions in enhanced exosomes, featuring upregulated proteins such as EFEMP1, HTRA1, PAM, RSU1, and SDF4, suggesting their potential for treating ovarian disorders. MicroRNA profiling revealed that miR-1-3p, miR-103a-3p, miR-122-5p, miR-1271-5p, miR-133a-3p, miR-184, miR-203a-3p, and miR-206 are key players in regulating ovarian cancer and chemosensitivity by affecting cell cycle progression, cell proliferation, and cell development. We examined polycystic ovary syndrome and premature ovarian insufficiency and identified altered expression of various miRNAs, such as miR-106a-5p, miR-130b-5p, and miR-130b-3p, for diagnostic insights. This study highlights the potential of enhanced exosomes as new therapeutic agents for women's reproductive health, offering a detailed understanding of the impact of their cargo on ovarian disorders.

The main purpose of this work was to tests of form and size of fatigue wear of the top layer of oil gear pump wheel (3PW-BPF-24). The object of tests was operated during a determined number of hours at strictly controlled operational and environmental parameters. A microscope of focal differentiation by Alicona InfiniteFocus G4 (with Focus-Variation optical measuring technology) was used for an identification, measurement and description of noticed superficial defects, which resulted from the fatigue process of the top layer and an earlier thermochemical treatment. The work was finished with an analysis of obtained results (based on the analysis of 3D scans) and conclusions concerning about optimization of the thermal treatment. Taking into consideration the presented results (suggestions) in the technology of improving strength properties of gear wheels (of this type oil pumps) may render it possible to obtain an appropriate fatigue endurance of the top layer, i.e. a minimization of observed superficial defects.

This review presents an updated overview of research concerning Leishmania protein structures, primarily sourced from the Protein Data Bank (PDB), that play a role in the metabolic pathways of the Leishmania parasite. Furthermore, we assess the current progress in the identification and development of bioactive chemical agents aimed at addressing this substantially overlooked tropical disease. We have analyzed experimental data obtained from in vitro, in vivo and in silico sources. This data has been categorized into four main areas: a) vector taxonomy and geographic distribution; b) parasite taxonomy and geographic distribution; c) enzymatic functions of proteins engaged in parasite/host interactions throughout various developmental stages (such as oxidoreductases, transferases, hydrolases, lyases, isomerases, ligases, and cytokines); and d) established and experimental treatments employing bioactive chemical compounds. Our objective is to establish a foundational point of reference for research efforts concentrating on the elucidation of interaction mechanisms and the processes of ligand-protein activation/inactivation, specifically linked to Leishmania infections. Consequently, we emphasize enzymes recognized for their involvement in the biochemical pathways incited during Leishmania infection episodes. This review encapsulates the current understanding, offering insights to inform and direct future explorations aimed at targeting proteins and pathways to enhance the management of Leishmania-related diseases.

The traditional Chinese drug Bombyx Batryticatus mori.L (BBm) which is also named the white stiff silkworm has been widely used in Chinese clinics for thousands of years. It is famous for its antispasmodic and blood circulation promoting effects. Cardiomyocyte hypertrophy, interstitial cell hyperplasia and myocardial fibrosis are closely related to the N-glycosylation of key proteins. To examine the alterations of N-glycosylation that occur in diabetic myocardium during the early stage of the disease and clarify the therapeutic effect of 1-DNJ extracted from BBm, we used the db/db mouse model and an approach based on hydrophilic chromatography solid-phase extraction integrated with an LC-MS/MS identification strategy to perform a site-specific N-glycosylation analysis of left ventricular cardiomyocyte proteins. AGEs, hydroxyproline, CTGF and other serum biochemical indicators were measured with ELISA. In addition, the α1,6-fucosylation of N-glycans was profiled with LCA lectin blots and FITC-labelled lectin affinity histochemistry. The results indicated that 1-DNJ administration obviously downregulated myocardium protein N-glycosylation in db/db mice. The expression levels of serum indicators and fibrosis-related cytokines were reduced significantly by 1-DNJ in a dose-dependent manner. The glycan α1,6-fucosylation level of the db/db mouse myocardium was elevated, and the intervention effect of 1-DNJ administration on N-glycan α1,6-fucosylation was significant. To verify this result, the well-known TGF-β/smad2/3 pathway was selected, and core α1,6-fucosylated TGFR-βⅡ was analysed semi-quantitatively with western blotting. The result supported the conclusions obtained from LCA lectin affinity histochemistry and lectin blot analysis. The expression level of FUT8 mRNA was also detected, and the results showed that 1-DNJ administration did not cause obvious inhibitory effects on FUT8 expression. Therefore, the mechanism of 1-DNJ to relieve the DCM-associated fibrosis can be concluded as the inhibition of N-GlcNAc formation and the reduction of substrate concentration.

Down Syndrome (DS) is a chromosomal disorder due to the presence of an additional chromosome 21 that causes intellectual deficit and physical anomalies and predisposes patients to develop infections throughout their lives. Pneumonias are more serious in patients with DS, requiring hospitalization, and represent an important cause of mortality in this population. Cytomegalovirus (CMV) causes widespread and serious infections in immunocompromised individuals, affecting the respiratory tract and, causing interstitial pneumonia, is associated with a high mortality rate. However, CMV-induced pneumonia is not reported in DS patients. The prevalence and severity of CMV respiratory infections in subjects with DS is unknown. This case describes a 50-year-old female patient suffering from DS who developed extensive bilateral pneumonia with severe respiratory failure which required hospitalization in intensive care, intubation and mechanical ventilation after approximately 10 days of empiric antibiotic and anitimycotic therapy for fever, cough and dyspnea. The patient was diagnosed with CMV pneumonia and recovered after treatment with Ganciclovir. To the best of our knowledge, this is the first reported case of CMV pneumonia in a patient with DS. This case aims to highlight that CMV pneumonia in individuals with DS can be a life-threatening condition. It also clarifies the importance of early diagnosis of infections from opportunistic pathogens such as CMV to ensure timely and efficient treatment.

Proteomics in respiratory allergic diseases has such a battery of techniques and programs that one would almost think that there is nothing impossible to find, invent or mold. All these resources that we document here, are involved in solving problems in allergic diseases, both diagnostic, prognostic, treatment and immunotherapy development. The main perspectives, according to this version, are in three strands and / or lockout immunological system: 1) In blocking the diapedesis of cells involved, 2) modifications and blocking of paratopes and epitopes being understood by modifications to antibodies, antagonism or blocking them and 3) blocking FcεR1 receptors to prevent specific IgEs from sticking to mast cells and basophils. These tools and targets in the allergic landscape are, in our view, the prospects in the field.

Tandem mass tag (TMT)-based proteomics facilitate multiplexing in mass spectrometry (MS)-based quantification and identification of proteins and their post-translational modifications. The use of TMT isobaric tags can enable multiplexing of up to 18 samples using commercially available kits. A single TMT experiment can quantify proteome, serine, threonine phosphorylation, and tyrosine phosphorylation. Of note, tyrosine phosphorylation is of low abundance, and identification/quantification can be improved using two complementary strategies. First, by employing SH2 superbinder which increases the number of identified sites. The SH2 Superbinder is more cost-effective than the commonly used phosphotyrosine antibodies. Second, by employing phosphotyrosine booster strategy, a pervanadate-treated channel to boost the signal of low-abundant phosphotyrosine. Noteworthy, pervanadate boost increases the likelihood of low abundant peptide to be selected for MS2, and facilitating the detection of > 6000 proteins, 10,000 unique pS/T and 1000 unique pY sites.

This study aimed to elucidate the similarities and differences between amyloid-forming corpora amylacea (CA) in the prostate and lung, examine the nature of CAs in cystic tumors of the atrioventricular node (CTAVN), and clarify the distinctions between amyloid-forming CA and spheroid-type amyloid deposition. We conducted proteomics analyses using liquid chromatography–tandem mass spectrometry with laser microdissection and immunohistochemistry to validate the characteristics of CAs in the lung and prostate. Our findings revealed that CAs in these organs primarily consist of common proteins (β2-microglobulin and lysozyme) and locally produced proteins. Moreover, we observed a discrepancy between the histopathological and proteomic analysis results in CTAVN-associated CAs. In addition, while the histopathological appearance of amyloid-forming CAs and spheroid-type amyloid deposits were nearly identical, the latter deposition lacked β2-microglobulin and lysozyme, and exhibited evident destruction of surrounding tissue. A literature review further supported these findings. These results suggest that amyloid-forming CAs in the lung and prostate are formed through a shared mechanism, serving as waste containers (wasteosomes) and/or storage for excess proteins (functional amyloids). In contrast, we hypothesize that while amyloid-forming CA and spheroid-type amyloid deposits are formed, in part, through common mechanisms, the latter are pathological.

The Chinese drug Bombyx Batryticatus mori.L which also named as the white stiff silkworm is widely used in clinics, due to the significant antispasmodic and promotional blood circulation effects. In addition, its hypoglycemic effect is also recognized in recent years. From a pathological point of view, the enzymatic glycosylation and non-enzymatic glycation both have important roles in regulating properties of proteins and are associated with Diabetes. With the db/db mouse model, we examined the alterations of N-glycosylation of diabetic myocardium at primary stage and clarify the differences in glycosylation of myocardium before and after with 1-DNJ treatment. Hydrophilic chromatography solid phase extraction enrichment and LC-MS/MS identification was applied to profile the alternations in protein glycosylation. Meanwhile, N-glycan α1, 6-fucosylation alterations were profiled with LCA lectin blot and FITC-labelled lectin affinity histochemistry. Our results showed that AGES, hydroxyproline, CTGF and other serum indicators and fibrosis related cytokines expressional levels were reduced significantly by 1-DNJ in a dose-dependent manner. In order to verify this result, the well-known pathway of TGF-β/smad2/3 was picked out and α1, 6-core fucosylated TGFR-βⅡwas semi-quantified with western blot method. The result sustained the conclusion from LCA lectin affinity histochemistry and lectin blot analysis. The expressional level of α1, 6-fucosyltransferase mRNA was increased in the myocardium of db/db mice, however, the 1-DNJ administration did not show obvious inhibitory effect on FU8 expression. This unexpected result can be interpreted as 1-DNJ plays the roles by reducing the concentration of substrate rather than inhibiting α1，6-fucose glycosyltransferase expression. Meanwhile, 1-DNJ crude extract from BBm with some flavonoids accompany can also play the roles of anti-oxidant, and all the chemicals protect the diabetic myocardium from hyperglycemia damage commonly.

Myocardium transcriptomes of mouse left and right atria and ventricles were profiled separately to identify the differences that might be responsible for the distinct functional roles of the four heart chambers. In total, 16,886 distinct unigenes have been quantified in all 16 samples collected from four adult male mice from the same litter. 15.76% of the quantified genes on the left and 16.5% on the right exhibited differential expression between the corresponding atrium and ventricle of the same side, while 5.8% in atria and 1.2% in ventricles were differently expressed between the left and the right. Beyond the differentially expressed genes, the study revealed distinct expression control and coordination of ion channels and genes within the cardiac muscle contraction, oxidative phosphorylation, glycolysis/glucogenesis, calcium and adrenergic signaling pathways. Interestingly, while expression of Ank2 (encoding ankyrin-B) oscillates in phase with all its binding partners in the left ventricle, the percentage of synergistically expressed partners of Ank2 is 15% and 37% in the left and right atria and 74% in the right ventricle. The analysis revealed also the high interventricular synchrony of the expression of ion channels.

Seafood is considered one of the main food allergen sources by the European Food Safety Authority (EFSA). It comprises several distinct groups of edible aquatic animals including fish and shellfish such as crustacean and mollusks. Recently the EFSA recognized the high risk of food allergy over the world and established the necessity of developing new methodologies for its control. Consequently, accurate, sensitive and fast detection methods for seafood allergy control and detection in food products are highly recommendable. In this work, we present a comprehensive review of the applications of the proteomics methodologies for the detection and quantification of seafood allergens. For that, two consecutive proteomics strategies (Discovery and Targeted Proteomics) applied for the study and control of seafood allergy are reviewed in detail. In addition, future directions and new perspectives were also provided.

We study the propagation of a particular field that we call Gaussian-top-hat that presents self-focusing and maintains its shape for some propagation distances.

The aim of this paper is to analyse commenting activity and sentiment (polarity and subjectivity) in interactions in response to videos by Spain’s most-subscribed YouTubers. An exploratory study was conducted on the content of the comments, their relationship with other social media actions, subjectivity and polarity, as well as from the perspective of the participatory culture. The results show that commenting is a potential option for interaction that is underused by the communities of users. Replies to comments are found to be limited to the user-user level, while YouTubers themselves and the moderators that YouTube allows them to designate rarely comment or reply on social networks. However, creators do monitor comments and provide feedback to a limited selection thereof in subsequent videos. There thus appears to be a strategic, exploitative use of comments, marked by a delayed response aimed at attracting audiences to new content.

Epilepsy, a disorder of unprovoked recurring seizures, continues to be seen as a growing medical concern worldwide. It represents the most common, non-communicable brain disorder, affecting persons of all ages. Every year over five million persons are formally diagnosed with epilepsy when seeking medical care. Often diagnosed as a young child, most persons can live a seizure-free life once there is an early diagnosis, proper patient education, and keen clinical management. However, the reoccurrence of status epilepticus, a neurological emergency, can be linked to untreated underlying causes and lead to serious morbidity and even early mortality if not properly managed. The prognosis is heavily reliant on the discovery of the underlying cause. Epilepsy, in recent times, provides a terminology for ease of identification of the associated clinical symptomology. Epilepsy, an umbrella term, can manifest differently as either idiopathic, symptomatic, or cryptogenic. However, distinguishing epilepsy from other seizure mimics is critical to preventing complications. Epilepsy research, like many other neurological symptoms, is limited in low-resource areas. Therefore, through greater awareness of epilepsy and public education campaigns, better health outcomes can be achieved. There is huge utility in clear communication of medical information among healthcare providers as well as in optimizing treatment plans.

HLA class I alleles constitute established risk factors for non-infectious uveitis and preemptive genotyping of HLA class I alleles is standard practice in the diagnostic work-up. The HLA-A29 serotype is indispensable to Birdshot Uveitis (BU) and renders this enigmatic eye condition a unique model to better understand how the antigen processing and presentation machinery contributes to non-infectious uveitis or chronic inflammatory conditions in general. This review will discuss salient points regarding the protein structure of HLA-A29 using and how key amino acid positions impact the peptide binding preference and interaction with T cells. We discuss to what extent the risk genes ERAP1 and ERAP2 uniquely affect HLA-A29 and how the discovery of a HLA-A29-specific submotif may impact autoantigen discovery. We further provide a compelling argument to solve the long-standing question why BU only affects HLA-A29-positive individuals from Western-European ancestry by exploiting data from the 1000 Genomes Project. We combine novel insights from structural and immunopeptidomic studies and discuss the functional implications of genetic associations across the HLA class I antigen presentation pathway to refine the etiological basis of Birdshot Uveitis.

If one considers chemical-biology toolsets that have had the greatest impact on numerous fields of life sciences over the most recent years, proximity-labeling tools, such as APEX, and Bio-ID arguably lead the way. This article reflects upon the current state-of-the-art and discusses key limitations underlying these emerging approaches, in particular, the limited functional knowledge they provide in understanding local proteomes / interactomes. This limitation is directly linked to the use of non-biologically- or non-pharmaceutically-relevant reactive intermediates in the course of covalently labeling the local proteomes. As such, these methods cannot report on specific functions of localized protein players, nor can they scrutinize whether the specific functions of such proteins/interactomes can be directly manipulated by pharmacologically-relevant small-molecule ligands. The latest data hint that precision localized electrophile delivery concept ushers a means to address this limitation with high spatiotemporal resolution, and ultimately, in relevant live animals.

Predator-prey interactions present heightened opportunities for pathogen spillover, as predators are exposed to novel parasites through consumption of prey harboring potentially infectious agents. Epizootics with high morbidity and mortality have been recorded following prey-to-predator spillover events with significant conservation implications, particularly for sensitive species. However, relatively few virulent infections following prey consumption are reported, given the very large number of exposures that presumably occur. Further, many transmitted agents are infectious but clinically silent and thus go unrecognized. Mechanisms that determine outcome of predator exposure to prey-based pathogens therefore represent an important, understudied component of disease dynamics that should be considered in modeling approaches and empirical research to better understand disease risk and emergence, particularly in vulnerable or threatened species.

Citation frequencies represent the most significant contributions in any respective field. This bibliometric analysis aimed to identify and analyze the 100 most-cited publications in the field of antibiotics and to highlight the trends of research in this field. “All databases” of Clarivate Analytics' Web of Science was used to identify and analyze the 100 publications. The articles were then cross-matched with Scopus and Google Scholar. The frequency of citation ranged from 940 to 11051 for the Web of Science, 1053 to 10740 for Scopus, and 1162 to 20041 for Google Scholar. Five hundred thirteen authors made contributions to the ranked list, and Robert E.W. Hancock contributed in six articles, which made it to the ranked list. Sixty-six scientific contributions originated from the United States of America. In contrast, five publications were linked to the University of Manitoba, Canada, that was identified as the educational organization, which made the most contributions (n=5). According to the methodological design, 26 of the most cited works were review-type closely followed by 23 expert opinions/perspectives. Eight articles were published in Nature journal, making it the journal with the most scientific contribution in this field. Correlation analysis between the publication age and citation frequency was found statistically significant (P = .012).

. The Tau protein is associated with microtubule function in the neuron and is crucial for normal axonal transport. In several different neurodegenerative disorders, Tau misfolding leads to hyper-phosphorylation (p-Tau) and intracellular p-Tau aggregates known as neurofibrillary tangles (NFTs). This is particularly evident in individuals with Down syndrome (DS), who develop Alzheimer’s disease-like (AD) neuropathology early in life with almost complete penetrance, associated with the development of dementia symptoms in their 40s or 50s. Our previous findings have shown that certain forms of p-Tau are present already in childhood in individuals with DS in neuron-derived exosomes, suggesting an early phosphorylation profile in this population that could influence the development of AD pathology. Misfolded p-Tau isoforms are known to be seeding competent and may be responsible for spreading AD pathology in different regions of the brain. This review is focused on the accumulation of p-Tau in the brain of individuals with DS and potential consequences for brain function.

Background and Objectives: Down syndrome (DS) is the most common chromosomal disorder in the world. It is caused by the imbalance of the chromosomal constitution of 21, by free trisomy, translocation or mosaicism. Children and adolescents with Down syndrome have immune dysregulation and are more susceptible to infections. This study aims to evaluate hospitalizations of children and adolescents with DS in the pediatric ward of Botucatu Clinics Hospital (HCFMB), to classify the population of children included in the study regarding age, diagnosis, outpatient follow-up, length of stay and need for Intensive Care Unit (ICU). Thus, it will be possible to improve care for these children, aiming to reduce these hospitalizations. Materials and Methods: It was an observational, cross-sectional study, with retrospective data collection from the last 10 years of hospitalization, from January 2013 to December 2021, of children and adolescents with DS, in the pediatric ward, emergency room and ICU of HCFMB. Children hospitalized in this period in the pediatric ward and ICU, in the age range of 30 days to 15 years (age of acceptance for admission to this service) were included in this study. Those who at some point had the exclusion of the diagnosis of DS were excluded. The evaluation of comorbidities that culminated in the need for hospitalization in this population can be the focus of actions to improve diagnoses and conducts for this population, to prevent worsening and hospitalizations in future populations. Results: The statistical analysis of the data was performed. In this analysis, 80 children with DS were evaluated, with a total of 283 hospitalizations and it was noticed that 46 of them had more than one hospitalization in this period. The most prevalent age group was 1 to 3 years, and the main cause was due to problems in respiratory system (99 cases). Among respiratory causes, the main cause of hospitalization was due to pneumonia, in 50% of cases, followed by acute respiratory failure, in 14%. The average hospitalization time was 8 days and in 49 hospitalizations the children required the ICU. The main cause of hospitalization in the ICU was due to respiratory causes (36%), followed by cardiac malformations (14%). During the ICU hospitalizations, there were 13 deaths, and we observed a higher prevalence of heart conditions and, in some cases, positive urine cultures in these children. Conclusions: preventive actions, such as vaccinations and improved monitoring of these children, without outpatient follow-up or during hospitalization, should be carried out. Thus, it has been developed a proposal for a risk score for mortality in children and adolescents with DS admitted to the ICU, and those patients with five or more points should be monitored more closely. A meeting will be held with the genetics, cardiology, and pediatric ICU teams to discuss this score and propose a surveillance plan for these patients at the HCFMB and potentially for the pediatric community in the future.

People with Down syndrome have more visual problems than general population. They experience a premature aging, and it would be expected they will also have an acceleration in worsening visual function. A prospective observational study which includes visual acuity, refractive error, accommodation, binocular and colour vision was performed to young adults with (n=69) and without (n=65) Down syndrome and to a senior group (n=55) without Down syndrome. Results showed significant differences in visual acuity between groups (p&lt;0.001) and it can be improved with a new prescription in 40% of the participants with Down syndrome. Regarding to accommodative state, no significant differences were found between groups of young people. Concerning binocular vision, 64.7% of strabismus was observed in the group with Down syndrome (p&lt;0.001). Visual abnormalities are significant in young adults with Down syndrome and are different from those of older people without Down syndrome, some of which can be improved by providing the optimal prescription as well as regular eye examinations.

Milk is newborn’s food and an emulsion full of all necessary components for neonatal growth. Its consumption is worldwide and is the base for all dairy products. Because of the latter, many new technologies are growing, among them proteomics; in order to give new insights in milk’s compounds and to maximize the beneficial potential for consumers’ health. In this review, we aimed to gather data of proteomics studies for the majority of dairy animals and elucidate the role of milk bioactive compounds. Furthermore, special reference was made to milk fat globule membrane (MFGM) peptides and the result of thermal treatment in milk proteins. Finally, the proteomic approach regarding adulterations was included in the review.

It was previously reported that the peptide derived from LfcinB, R-1-R exhibited anti-Candida activity and this activity was enhanced in combination with an extract from the Bidens pilosa plant. However, the mechanism of action has not been studied. In the current study, a proteomic study was carried out, followed by a bioinformatic analysis and biological assays in both SC5314 strain and a fluconazole-resistant isolate of Candida albicans, after incubation with R-1-R. The proteomic data showed that after treatment with R-1-R in the two study strains, most of the differentially expressed proteins in comparison to controls were up-regulated. These proteins were mainly involved in membrane and cell wall biosynthesis, membrane transporters, oxidative stress, the mitochondrial respiratory chain, and response to DNA damage. Besides, the proteomic analysis of C. albicans parental strain SC5314 treated with R-1-R in combination with an ethanolic extract of B. pilosa was also undertaken. The proteins differentially expressed after this treatment were involved in similar functional processes as the proteins differentially expressed after treatment with R-1-R peptide alone, but at different levels and were mostly down-regulated. The biological assays allowed validation of the proteomic results, evidencing damage to the cell surface, generation of reactive oxygen species and decrease in mitochondrial membrane potential. The results provide information to begin to unlock the understanding of the complex antifungal mode of action of the R-1-R peptide, its combination with the extract, and possibly other derivatives of natural products.

Toxoplasma gondii, a protozoan parasite with the ability to infect various warm-blooded vertebrates, including humans, is the causative agent of toxoplasmosis. This infection poses significant risks, leading to severe complications in immunocompromised individuals and potentially affecting the fetus through congenital transmission. A comprehensive understanding of the intricate molecular interactions between T. gondii and its host is pivotal for the development of effective therapeutic strategies. This review emphasizes the crucial role of proteomics in T. gondii research, with a specific focus on host-parasite interactions, post-translational modifications (PTMs), PTM crosstalk, and ongoing efforts in drug discovery. Additionally, we provide an overview of recent advancements in proteomics techniques, encompassing interactome sample preparation methods such as BioID, APEX, and Y2H, as well as various proteomics approaches, including single-cell analysis, DIA, targeted, top-down, and plasma proteomics. Furthermore, we discuss the integration of proteomics with other omics technologies, highlighting its potential in unraveling the intricate mechanisms of T. gondii pathogenesis and identifying novel therapeutic targets.

The original purpose of this article was to modify the original SIR equations to allow for a direct source of infection (without which the original equations would have no solutions unless one starts with an already infected population) and also to see to what extent one could obtain multiple outbreaks of an infectious disease. In the course of developing the basic ideas several other factors arose to take prominent roles.Perhaps one of the more salient factors is the point that choosing an arbitrary time to change conditions from say a lock-down for the population to a less stringent social behavior, such as allowing partial or complete opening of businesses and schools, etc. should be based on knowledge of the disease and its evolution. Such decisions are usually made by politicians who have less than full information concerning the consequences of their actions. Several examples are given to illustrate these points.

The aim of this paper is to attempt to understand why the popular academic and policy field of promoting, studying and evangelising “entrepreneurship” should have been associated with great success but, in the past twenty years or more in many advanced economies, so much failure. From the US to lesser and developing countries, emerging economies and the European Union, entrepreneurship, especially in regard to start-ups and particularly high-tech start-ups have been in constant more or less recent decline. This is seldom registered in the mainstream literature where a positive and benign profile is generally presented. The paper examines this phenomenon, ties it partly with the “productivity paradox” and seeks tentative hypotheses in relation to the apparent illusions if not delusions regarding “entrepreneurship”.

Alzheimer’s disease (AD) is one of the most widespread neurodegenerative diseases affecting people averaging over 65 years. It manifests with severe cognitive damage, loss of memory, impairment in performing activities, ventricular expansion and final dementia. AD is associated with the deposit of amyloid β protein (Aβ) plaques, intracellular neurofibrillary tangles (NFTs), progressive inflammation and impairment of synaptic transmission and of mitochondrial function. Due to the poor diagnostic tools for the early stages of the disease, proteomics biomarkers have gained a paramount role because they can monitor the prodromal variations of the disease-linked molecular changes. Further, proteome biomarkers can help the follow up of AD progression over time and aid in setting personalized medical care, before the catastrophic consequences of dementia occurs. Research has focused on the identification of proteome biomarkers in cerebrospinal fluid (CSF) and plasma, which are discussed in the present review, but also in other matrices, as saliva and urine, revealing the high potentiality of proteomics approach and, at the same time, the difficulty to identify, for the different stages of the disease, sensitive and specific biomarkers clinically available.

Honey is a complex sweet food stuff with well-established antimicrobial and antioxidant properties. It has been used for millennia in a variety of applications, but those most noteworthy include treatment of surface wounds, burns and inflammation. A variety of substances in honey have been suggested as the key component to its antimicrobial potential; polyphenolic compounds, hydrogen peroxide, methylglyoxal and bee-defensin 1. These components vary greatly across honey samples due to botanical origin, geographical location and the individual bee. The use of medical grade honey, Medihoney and Revamil, in the treatment of surface wounds and burns has been seen to improve the healing process, reduce healing time, reduce scarring and prevent microbial contamination. Therefore, medical grade honeys should be used for these treatments and reduce the demand for antibiotic usage. In this review, we aim to outline the constituents of honey and how they affect the antibiotic potential of honeys in a clinical setting.

Aiming at the problems that the parameters of YOLOv5s model are too large and the computing resources of development board memory are limited, a new target detection method based on deep learning YOLOv5 algorithm model is proposed. First, the light-weight module Gz-ShffleNetv2 is used to construct cotton top bud feature extraction unit, which reduces the number of parameters and improves the running speed. It can be better applied in image classification, speed up detection and meet the requirements of mobile end of development board. Secondly, in order to solve the problem of decreasing detection accuracy caused by lightweight, BotNet and C3SE attention mechanism are added to focus on specific areas of cotton terminal bud. Combined with YYG loss function XIOU boundary frame regression loss, more feature information and rich feature MAP were obtained to further improve the accuracy of target detection. Through analysis of research and experimental results, the average accuracy map reached 91.3% under the Windos system NVIDIA Geforce RTX 2060 SUPER detection. While maintaining high precision identification, the number of parameters of YOLOv6 and YOLOv7-tiny network model is reduced by 83% and 53%, respectively, and the detection accuracy is increased by 1.2% and 7.7%, respectively. Compared with YOLOv5 reasoning image, the speed of image is increased by 0.035s, and the detection accuracy of MAP_0.5:0.95 is increased by 1%. At the same time, PyQt5 and YOLOv5 target detection algorithms are used to design a cotton top bud identification system, which makes cotton top bud detection more intuitive and convenient for subsequent hardware development and use.

Antimicrobial stewardship efforts are an emphasis among many institutions around the world to combat inappropriate antimicrobial utilization, rising healthcare costs and emerging antimicrobial resistance. Implementation of new innovative strategies may be challenging for many institutions with limited or constrained resources. Using proven effective methods as evidenced by other institutions in the peer-reviewed literature may offer an opportunity to evaluate institution-specific practices, which may be implemented locally. A structured examination and survey of the peer-reviewed, stewardship literature by an expert group of clinicians, scholars and educators determined the most influential publications from 2016. Herein, the top thirteen manuscripts are reviewed to aid clinicians identify potential stewardship opportunities and serve as an educational tool for trainees and others.

Pulmonary vein stenosis (PVS) causes a rare type of Pulmonary Hypertension (PH), by impacting the flow and pressure within the pulmonary vasculature resulting in endothelial dysfunction and metabolic changes. A prudent line of treatment in this type of PH would be targeted therapy in order to relieve the pressure and reverse the flow related changes. We used a swine model in order to mimic PH post PVS using pulmonary vein banding (PVB) of the lower lobes for 12 weeks to mimic the hemodynamic profile associated with PH and investigate the molecular alterations that provide an impetus for development of PH. Our current study aimed to employ unbiased proteomic and metabolomic analyses on both the upper and lower lobes of the swine lung to identify the regions with metabolic alterations. We detected changes in the upper lobes for the PVB animals mainly pertaining to fatty acid metabolism, ROS signaling and extracellular matrix remodeling, and small albeit significant changes in the lower lobes for purine metabolism.

The molecular basis of Down syndrome (DS) predisposition to leukemia is not fully understood but involves various factors such as chromosomal abnormalities, oncogenic mutations, epigenetic alterations, and changes in selection dynamics. Myeloid leukemia associated with DS (ML-DS) is preceded by a preleukemic phase called transient abnormal myelopoiesis driven by GATA1 gene mutations and progresses to ML-DS through additional mutations in cohesin genes, CTCF, RAS, or JAK/STAT pathway genes. DS-related ALL (ALL-DS) differs from non-DS ALL in terms of cytogenetic subgroups and genetic driver events and aberrant expression of CRLF2, JAK2 mutations, and RAS pathway activating mutations are frequent in ALL-DS. Recent advancements in single-cell multi-omics technologies have provided unprecedented insights into the cellular and molecular heterogeneity of DS-associated hematologic neoplasms. Single-cell RNA sequencing and digital spatial profiling enable the identification of rare cell subpopulations, characterization of clonal evolution dynamics, and exploration of the tumor microenvironment's role. These approaches may help identify new druggable targets and tailor therapeutic interventions based on distinct molecular profiles, ultimately improving patient outcomes with the potential to guide personalized medicine approaches and the development of targeted therapies.

Robotic-assisted hip and knee arthroplasty represents significant advancements in orthopedic surgery. Artificial intelligence (AI) - driven chatbots, such ChatGP, plays a significant role in healthcare education. This study aims to evaluate the quality of responses provided by ChatGPT to the top 20 questions concerning robotic-assisted hip and knee arthroplasty.We have asked ChatGPT to select the top 20 questions on Google concerning robotic hip and knee arthroplasty and to provide a detailed answer to each of them. The accuracy of the information provided were examined by three orthopedic surgeons with scientific and clinical experience in hip and knee replacement surgery. The accuracy was assessed through a 5-point Likert scale (from 1 – completely incorrect to 5 – correct); the completeness through a 4-point Likert scale (from 0 – comprehensiveness not assessable for completely incorrect answers to 3 – exhaustive information) on two different occasions to ensure the consistency of the assessment. Our analysis reveals that ChatGPT provides a relatively high degree of accuracy, moreover the explanations can be considered satisfy, especially for factual questions. The findings suggest that ChatGPT can serve as a valuable initial resource for general information on robotic hip and knee arthroplasty but the integration with human expertise remains essential.

Ischemic stroke is one of the leading causes of death and permanent disability in the world. Rapid diagnosis and intervention are crucial for reducing its consequences on individuals and societies. Identifying reliable biomarkers for early detection, prognostics and therapy is a criti-cal imperative for improving the stroke patient treatment. Metabolomics has been shown as a promising tool for biomarker discovery since many of the post-ischemic metabolites can found in the plasma or serum of the patient. In this research, we have performed comparative targeted metabolomic analysis of stroke thrombi, patient serums and healthy control serums in order to determine the alteration in the patients’ metabolome. The most statistically altered metabolites characterized in patient compared to control serums were glutamate and serotonin, followed by several lipid metabolites (phospholipids and triacylglycerols) and glucose. In stroke thrombi compared to patient’s serums, the most significantly altered metabolites were classified as li-pids, with choline-containing phospholipids and sphingomyelins having the highest discrimi-natory score. The results of this study could help in understanding the roles of different meta-bolic changes occurring during thrombosis and cerebral ischemia and possibly suggest new metabolic biomarkers of the ischemic stroke.

This work communicates cavity ring-down spectroscopy (CRDS) of methylidyne (CH) in a chemiluminescent plasma that is produced in a microwave cavity. Of interest are the rotational lines of the 0-0 vibrational transition for the A-X band and the 1-0 vibrational transition for the B-X band. The reported investigations originate from CH-radical research in 1996 that constituted the first case of applying CRDS to the CH radical. The report also includes recent analysis that shows excellent agreement of measured and computed data, and it communicates CH line strength data.

SARS-CoV-2, is the cause of the COVID-19 pandemic which has claimed more than six million lives worldwide, devastating the economy and overwhelming healthcare systems globally. The development of new drug molecules and vaccines has played a critical role in managing the pandemic; however, new variants of concern still pose a significant threat as the current vaccines cannot prevent all infections. This situation calls for the collaboration of biomedical scientists and healthcare workers across the world. Repurposing approved drugs is an effective way of fast-tracking new treatments for recently emerged diseases. To this end, we have assembled and curated a database consisting of 7817 compounds from the Compounds Australia Open Drug collection. We developed a set of eight filters based on indicators of efficacy and safety that were applied sequentially to down-select drugs that showed promise for drug repurposing efforts against SARS-CoV-2. Considerable effort was made to evaluate approximately 14000 assay data points for SARS-CoV-2 FDA/TGA-approved drugs and provide an average activity score for 3539 compounds. The filtering process identified 12 FDA approved molecules with established safety profiles that have a plausible mechanism for treating COVID-19 disease. The methodology developed in our study provides a template for prioritising repurposable drug candidates that are safe, efficacious, and cost-effective for the treatment of COVID-19, long COVID, or any other future disease. We present our database in an easy-to-use interactive interface (CoviRx, https://www.covirx.org/) that was also developed to enable scientific community to access to the data of over 7000 potential drugs and to implement alternative prioritisation and down-selection strategies.

Multisubunit RNA polymerases (RNAP) carry out transcription in all domains of life; during vi-rus infection, RNAPs are targeted by transcription factors encoded by either the cell or the virus, resulting in the global repression of transcription with distinct outcomes for different host-virus combinations. These repressors serve as versatile molecular probes to study RNAP mechanisms, as well as they aid the exploration of druggable sites for the development of new antibiotics. Here, we review the mechanisms and structural basis of RNAP inhibition by the viral repressor RIP and the crenarchaeal negative regulator TFS4, which follow distinct strategies. RIP operates by occluding the DNA-binding channel and mimicking the initiation factor TFB/TFIIB. RIP binds tightly to the clamp and locks it into one fixed position, thereby preventing conformational oscil-lations that are critical for RNAP function as it progresses through the transcription cycle. TFS4 engages with RNAP in a similar manner to transcript cleavage factors such as TFS/TFIIS through the NTP-entry channel; TFS4 interferes with the trigger loop and bridge helix within the active site by occlusion and allosteric mechanisms, respectively. The conformational changes of RNAP described above are universally conserved and are also seen in inactive dimers of eukaryotic RNAPI and several inhibited RNAP complexes of both bacterial and eukaryotic RNA polymer-ases, including inactive states that precede transcription termination. A comparison of target sites and inhibitory mechanisms reveals that proteinaceous repressors and RNAP-specific antibiotics use surprisingly common ways to inhibit RNAP function.

The COVID-19 outbreaks have caused universities all across the globe to close their campuses and forced them to initiate online teaching. This article reviews the pedagogical foundations for developing effective distance education practices, starting from the assumption that promoting autonomous thinking is an essential element to guarantee full citizenship in a democracy and for moral decision making in situations of rapid change, which has become a pressing need in the context of a pandemic. In addition, the main obstacles related to this new context are identified, and solutions are proposed according to the existing bibliography in learning sciences.

Fabrication of a true-3D inorganic ceramic with resolution down to nanoscale using sol-gel resist precursor is demonstrated. The method has an unrestricted free-form capability, control of the fill-factor, and high fabrication throughput. A systematic study of the proposed approach based on ultrafast laser 3D lithography of organic-inorganic hybrid sol-gel resin followed by a heat treatment enabled formation of inorganic amorphous and crystalline composites guided by the composition of the initial resin. The achieved resolution of 100 nm was obtained for 3D patterns of complex free-form architectures. Fabrication throughput of 50×10³ voxels/s is achieved; voxel - a single volume element was recorded by a single pulse exposure. After a subsequent thermal treatment, ceramic phase was formed depending on the temperature and duration of the heat treatment as validated by Raman micro-spectroscopy. The X-ray diffraction (XRD) revealed a gradual emergence of the crystalline phases at higher temperatures with a signature of cristobalite SiO₂, a high-temperature polymorph. Also, the tetragonal ZrO₂ phase known for its high fracture strength was observed. This 3D nano-sintering technique is scalable from nano- to millimeter dimensions and opens a conceptually novel route for optical 3D nano-printing of various crystalline inorganic materials defined by an initial composition for diverse applications for microdevices in harsh physical and chemical environments and high temperatures.

In this experimental report the biocompatibility of elastomeric scaffold structures made via stereolithography employing table-top 3D printer (Ember, Autodesk) and commercial resin FormLabs Flexible (FormLabs) was studied. The samples were manufactured using standard printing and development protocol, which is known to inherit cytotoxicity due to remaining non-polymerized remaining monomers, despite the polymerized material being fully biocompatible. Additional steps were taken to remedy this problem: the fabricated structures were soaked in isopropanol and methanol for different conditions (temperature, duration) in order to leach out the non-polymerized monomers. Also printed structures were UV exposed to assure maximum polymerization degree of the material. Post-processed structures were seeded with myogenic stem cells and the number of live cells was evaluated as an indicator for the material biocompatibility. The straightforward post-processing protocol enhances the biocompatibility by 7 times after 7 days soaking in isopropanol and methanol and is comparable to control (glass and polystyrene) samples. This proposes the approach as a novel and simple method to be widely applicable for dramatic cytotoxicity reduction of optically 3D printed micro-/nano-scaffolds for biomedical applications.

Water quality assessments are crucial for human health and environmental safeguards. The utilization of a subset of artificial intelligence such as Machine Learning (ML) presents significant impacts to enhance the prediction and classification of water quality. In this research, a set of diverse ML algorithms was evaluated to handle a comprehensive dataset of water quality measurements over an extended period. The aim was to develop a robust approach for accurately forecasting water quality. This approach employed machine learning classifiers such as Logistic Regression (LR), Support Vector Machine (SVM), Stochastic Gradient Descent (SGD), K-Nearest Neighbors (KNN), Gaussian Process Classification (GPC), Gaussian Naive Bayes (GNB), Random Forest (RF), Decision Tree (DT), XGBoost, and Multilayer Perceptron (MLP). The water quality parameters assessed for pH, hardness, solids, chloramines, sulfate, conductivity, organic carbon, trihalomethanes and turbidity. The XGBoost model exhibited the highest accuracy of 89.47% among the classifiers and Stacked Ensemble Classifiers (SEC) improved the prediction further to 92.98%. The findings suggest that XGBoost and the SEC hold promise as reliable approaches for water quality assessments in contrast of artificial intelligence.

This bibliometric review is aimed to analyze the top 100 most-cited publications in dentistry and to compare its outcomes with similar analysis done by Feijoo et al., [1]. A literature search was performed using the Elsevier's Scopus without any restriction of language, publication year or study design. Of 336381 articles, the top 100 were included based on their citation count which ranged from 638 to 4728 citations (Feijoo et al., 326 to 2050). Most productive decade was the 2000s with 40 articles on the list (Feijoo et al., 1980s: 26). Marx RE (7%) was the major contributor in this study (Feijoo et al., Socransky SS: 9%) and a whopping 48% articles generated from the USA. 26% of top 100 articles focused periodontology (Feijoo et al., periodontology: 43%), while 17% of the total were published in the Journal of Dental Research (Feijoo et al., Journal of Clinical Periodontology: 20%). Most of the publications were narrative reviews/expert opinion (36%), (Feijoo et al., case series: 22%) and were within the evidence level V (64%) (Feijoo et al., 54%). The citation count that a paper secures is not necessarily a reflection of research's quality, however, the current analysis provides latest citation trends in dentistry.

The range of rating instruments in depression measurement and the depth of their analytical relevance constitutes a major development in this psychiatric and psychotherapeutic field of mental health. Though the competition is acute amongst these various instruments, the results for the public have been outstandingly positive. A depression rating scale is essentially a psychiatric measuring instrument utilized in the identification and ranking of depression severity within the patient. The scale provides the practitioner, psychiatrist or psychotherapist, with sufficient information to assess the severity of the depression plotted on the scale. Not used as a “diagnostic tool” itself, nevertheless, the depression rating scale does function as an effective device for designating and assigning a behavioral score which may, then, be used in establishing the severity of depression of value in the designation of a diagnosis and treatment formula. In this paper, we will take a close look at the leading depression rating scales and briefly summarize their scope of assessment value in rating depression.

Previously, we reported that metronidazole MICs are not dependent on the expression levels of nim genes in B. fragilis strains; and we also compared the proteomes of metronidazole-resistant laboratory B. fragilis strains to those of their susceptible parent strains. Here, we used RT-qPCR to correlate the expression levels of 18 candidate genes in a panel of selected, clinical nim gene-positive and -negative B. fragilis strains to their metronidazole MICs. Metronidazole MICs were correlated to the expression of certain tested genes. Specifically, lactate dehydrogenase expression correlated positively, whereas cytochrome fumarate reductase/succinate dehydrogenase, malate dehydrogenase, phosphoglycerate kinase redox and gat (GCN5-like acetyltransferase), and relA (stringent response) regulatory gene expressions correlated negatively with metronidazole MICs. This result provides evidence for the involvement of carbohydrate catabolic enzymes in metronidazole resistance in B. fragilis. This result was supported by direct substrate utilization tests. However, the exact roles of these genes/proteins should be determined in deletion–complementation tests. Moreover, the exact redox cofactor(s) participating in metronidazole activation need to be identified.

Rheumatoid arthritis (RA) is an autoimmune disease in which joints are gradually de-stroyed, and early diagnosis and treatment before joint deformation or destruction is im-portant. The detection of novel RA biomarkers in saliva may facilitate the early detection of RA before the onset of disease. In this study, we conducted a comprehensive proteomic analysis of salivary proteins from RA model mice. Proteins were identified by Western blotting and enzyme-linked immunosorbent assay in serum, saliva, and ankle joints from DBA/1JJmsSlc mice, a model of rheumatoid arthritis. Ankle joints and submandibular glands were hematoxylin and eosin stained and immunostained, and the results were compared with those of control mice. Citrullinated α1 antitrypsin (A1AT, 46 kDa) was commonly detected in saliva, serum, and ankle joints of severe RA model mice, and was confirmed by proteome analysis. Western blotting detected a band corresponding to 46 kDa in serum, saliva and ankle joints, and immunostaining of ankle joints with A1AT an-tibody showed a strong positive signal in the synovium. In DBA/1JJmsSlc mice, not only cyclic citrullinated peptide antibodies but also A1AT may be involved in protein citrulli-nation and contribute to the development and severity of RA.

Leaf variegation pale yellowing is observed in the Calcineurin B-Like-Interacting Protein Kinase14 (CIPK14) overexpression line (oeCIPK14) and double knockout WHIRLY1/WHIRLY3 (why1/3) lines of Arabidopsis, the distribution of WHIRLY1 (WHY1) protein between plastids and the nucleus are affected by the phosphorylation of WHY1 by CIPK14. To elucidate the coregulation of CIPK14 and WHIRLY1/WHIRLY3 mediated leaf pale yellowing, a differential proteomic analysis is conducted between the oeCIPK14 variegated (oeCIPK14-var) line, why1/3 variegated (why1/3-var) line and wild type (WT). More than 800 protein spots are distinguished on each gel, 67 differential abundance proteins (DAPs) are identified by matrix-assisted laser desorption ionization-time of flight/time of flight mass spectrometry (MALDI-TOF/TOF-MS), of which, 34 DAPs are in the oeCIPK14-var, 33 DAPs are in the why1/3-var compared to WT. Five overlapping proteins differentially change both in the oeCIPK14-var and in the why1/3-var. They are ATP-dependent Clp protease proteolytic subunit-related protein 3 (ClpR3), Ribulose bisphosphate carboxylase large chain (RBL), Beta-amylase 3 (BAM3), Ribosome-recycling factor (RRF), Ribulose bisphosphate carboxylase small chain (RBS). Bioinformatics analysis show that most of DAPs are involved in photosynthesis, defense and antioxidation pathway, protein metabolism, amino acid metabolism, energy metabolism, malate biosynthesis, lipid metabolism and transcription. Thus, the photosystem parameters are measured that the content of chlorophyll, the photochemical efficiency of PSⅡ (Fv/Fm), and electron transport rates (ETR) decrease in the why1/3-var and oeCIPK14-var, but the non-photochemical quenching (NPQ) increases. Both mutants show high sensitivity to strong light. Based on the annotation of DAPs from both why1/3-var and oeCIPK14-var lines, we conclude that CIPK14 phosphorylation mediated WHY1 deficiency in plastids is related to impairment of protein metabolism leading to chloroplast dysfunction.

People with Down syndrome present cognitive difficulties that affect their reading skills. In this study we present results about the use of gestural interaction with Kinect sensor to improve the reading skills of students with Down syndrome. Following a case of study method for small samples with disabilities, measuring different variables related to reading skills in an experimental group and in a control group. We found improvements in the visual association, visual comprehension, sequential memory, and visual integration after this stimulation in the experimental group compared to the control group. Also, we found that the number of error and delay time of interaction decrease between sessions in the experimental group.

The search for improved therapeutic approaches to breast cancer are still on going. Breast tumor kinase (BRK, also known as PTK6) is one of the targets, it is highly expressed in breast carcinomas while displaying low or no expression in the normal mammary gland, which hints at the oncogenic role of this enzyme in breast cancer. In these twenty years, an increasing number of studies have focused on understanding the cellular roles of BRK in breast cancers. This review outlines the advances made towards understanding the cellular and physiological role of BRK, the molecular and chemical inhibitors and its therapeutic significance in breast cancer.

The process of building microgrids on top of existing passive distribution networks warrants a multi-criteria analysis. Besides the calculation of investment outlays needed for the modernization of distribution networks, such an analysis covers an assessment of the technological and economic effects of building microgrids. The resulting effects depend on the topology and configuration of distribution networks, specific microgrid features, the choice of current type for the entire microgrid or its individual parts, the ways of connecting distributed energy resources (DER), the availability and condition of information and communications technology (ICT) infrastructure, and other factors. Complete input data allow one to design an optimal microgrid configuration, but the main technological and economic effects are determined by the algorithms of operation and the parameters setting of the automatic control system (ACS) and the protection system. Known approaches to designing microgrids focus on addressing basic tasks while minimizing investment required for their implementation. The above is fully justified when constructing new microgrids, but building microgrids on top of existing distribution networks, given the uniqueness of their topology and configuration, does not allow the use of standardized solutions. The development of approaches to the design of microgrids under such constraints, with minimized investment for the modernization of existing distribution networks, is an urgent task. The use of different types of current for microgrid segments determines the choice of particular ACS and protection system, which depends on the availability of information and communications technology infrastructure. This article contributes a review of approaches to designing AC and AC-DC microgrids to maximize their technological and economic effects. We review techniques for analyzing existing distribution networks aimed at choosing the type of current for the entire microgrid or its individual parts, the optimal connection points of microgrids to distribution networks, the mix and capacity of DERs, with such choices informed by the condition of switching devices and information and communications technology infrastructure. The article presents the results of the analysis of approaches to choosing the optimal configuration of microgrids, microgrid ACS and protection system, with an evaluation of the technological and economic effects subject to minimization of investment for the modernization of existing distribution networks.

This article has been developed to assess the economic feasibility of a roof-top photovoltaic installation of industrial self-consumption. Numerical models that enable an interested person to obtain the main expected parameters will be generated. To do this, a calculation methodology will be generated through which the reader, knowing the location of the facility and dimensions of the roof, will be able to calculate the maximum installable power, the main parameters related to production, the cost of the installation, and the LCOE of the plant. The use of actual costs will be facilitated in case they are known, but it will remain possible to apply the costs of the major equipment (modules, inverter, and structure) considered throughout the article. This developed calculation methodology will also allow a quick comparison of the forecasts of production, CAPEX, and LCOE of plants designed with different inclinations and different types of modules. Consequently, it will be especially useful for decision-making before developing the plant's basic engineering. Moreover, the calculations used for modeling the LCOE will be analyzed in depth. This analysis will allow evaluating how the different technical variables affect the profitability of a photovoltaic installation, such as the selected tilt, the location, the module's technology, or the available area.

Glioblastoma (GBM), the most common and aggressive primary brain tumor in adults, remains one of the least treatable cancers. Current standard of care—combining surgical resection, radiation, and alkylating chemotherapy—results in a median survival of only 15 months. Despite decades of investment and research into the development of new therapies, most candidate anti-glioma compounds fail to translate into effective treatments in clinical trials. One key issue underlying this failure of therapies that work in pre-clinical models to generate meaningful improvement in human patients is the profound mismatch between drug discovery systems—cell cultures and mouse models—and the actual tumors they are supposed to imitate. Indeed, current strategies that evaluate the effects of novel treatments on GBM cells in vitro fail to account for a wide range of factors known to influence tumor growth. These include secreted factors, the brain’s unique extracellular matrix, circulatory structures, the presence of non-tumor brain cells, and nutrient sources available for tumor metabolism. While mouse models provide a more realistic testing ground for potential therapies, they still fail to account for the full complexity of tumor-microenvironment interactions, as well as the role of the immune system. Based on the limitations of current models, researchers have begun to develop and implement novel culture systems that better recapitulate the complex reality of brain tumors growing in situ. A rise in the use of patient derived cells, creative combinations of added growth factors and supplements, may provide a more effective proving ground for the development of novel therapies. This review will summarize and analyze these exciting developments in 3D culturing systems. Special attention will be paid to how they enhance the design and identification of compounds that increase the efficacy of radiotherapy, a bedrock of GBM treatment.

Research on microglia in Down syndrome (DS) has shown that microglial activation, increased inflammatory gene expression, and oxidative stress occur at different ages in DS brains. However, most studies resulted in simplistic definitions of microglia as quiescent or active, ignoring potential intermediate states. However, a recent work on microglial cells in young DS brains indicated that those evolve through different intermediate activation phenotypes before reaching a full activated state. Here we used single nucleus RNA sequencing, to examine how trisomy affects microglial states in the Ts65Dn mouse model of DS. Despite no substantial changes in the proportion of glial populations, differential expression analysis revealed cell type-specific gene expression changes, most notably in astroglia, microglia, and oligodendroglia. Focusing on microglia, we identified differential expression of genes associated with different microglial states, including disease-associated microglia (DAMs), activated response microglia (ARMs), and human Alzheimer’s disease microglia (HAMs), in trisomic microglia. Furthermore, pseudotime analysis reveals a unique reactivity profile in Ts65Dn microglia, with fewer in a homeostatic state and more in an intermediate aberrantly reactive state than in euploid microglia. This comprehensive understanding of microglial transcriptional dynamics sheds light on potential pathogenetic mechanisms but also possible avenues for therapy for neurodevelopmental disorders.

Abstract: Down Syndrome (DS) is a common genetic disorder characterized by an extra copy of chromosome 21, leading to dysregulation of various metabolic pathways. Oxidative stress in DS is associated with neurodevelopmental defects, neuronal dysfunction, and the onset of dementia re-sembling Alzheimer's disease. Additionally, chronic oxidative stress contributes to cardiovascular diseases and certain cancers prevalent in DS individuals. This study investigates the impact of ageing on oxidative stress and liver fibrosis using a DS murine model (Ts2Cje mice). The liver in DS mice shows increased oxidative stress and impaired antioxidant defenses, as evidenced by reduced glutathione levels and increased lipid peroxidation. Furthermore, DS liver exhibits an altered in-flammatory response as measured by the expression of cytokines and heat shock proteins. DS liver also displays dysregulated lipid metabolism, indicated by altered expression of peroxisome prolif-erator-activated receptors and fatty acid transport proteins. Consistently, these changes might contribute to non-alcoholic fatty liver disease development, a condition characterized by liver fat accumulation. Finally, histological analysis of DS liver reveals increased fibrosis and steatosis, in-dicative of potential progression to liver cirrhosis. This finding highlights the increased risk of liver pathologies in DS individuals, particularly when combined with the higher prevalence of obesity and metabolic dysfunctions in DS patients. These results shed light on the liver's role in DS-associated pathologies and suggest potential therapeutic strategies targeting oxidative stress and lipid metabolism to prevent or mitigate liver-related complications in DS individuals.

Mesenchymal stem cells (MSCs) are an attractive therapeutic tool for tissue engineering and regenerative medicine owing to their regenerative and trophic properties. The best-known and most widely used are bone marrow MSCs which are currently being harvested and developed from a wide range of adult and perinatal tissues. MSCs from different sources are believed to have different secretion potentials and production which may influence their therapeutic effects. To confirm it, we performed a quantitative proteomic analysis based on the TMT technique of MSCs from three different sources: Wharton’s jelly (WJ), dental pulp (DP) and bone marrow (BM). Our analysis focused on MSC biological properties of interest for tissue engineering. We identified a total of 611 differentially expressed human proteins. WJ-MSCs showed the greatest variation compared with the other sources. WJ produced more extracellular matrix (ECM) proteins and ECM-affiliated proteins and appeared more able to modulate the inflammatory and immune response. BM-MSCs displayed enhanced differentiation and paracrine communication capabilities. DP-MSC appeared to promote exosome production. The results obtained confirm the existence of differences between WJ, DP and BM-MSC and the need to select the MSC origin according to the therapeutic objective sought.

Collisional mountain belts commonly develop intramontane basins from mechanical and isostatic subsidence during orogenic development. These frequently display a relict top surface, evidencing a change interval from basin infilling to erosion often via capture or overspill. Such surfaces provide markers that inform on orogenic growth patterns via climate and base level interplay. Here, we describe the top surface from the Sorbas Basin, a key intramontane basin within the Betic Cordillera (SE Spain). The surface is fragmentary comprising high elevation hilltops and discontinuous ridges developed onto the variably deformed final basin infill outcrop (Gochar Formation). We reconstruct surface configuration using DEM interpolation and apply ¹⁰Be/²⁶Al cosmonuclides to assess surface formation timing. The surface is a degraded Early Pleistocene erosional pediment developed via autogenic switching of alluvial fan streams under stable dryland climate and base level conditions. Base level lowering since the Middle Pleistocene focused headwards incision up interfan drainages, culminating in fan head capture and fan morphological preservation within the abandoned surface. Post abandonment erosion has lowered the basin surface by 31 m (average) and removed ~5.95 km³ of fill. Regional basin comparisons reveal a phase of Early Pleistocene surface formation, marking landscape stability following the most recent Pliocene-Early Pleistocene mountain building. Post-surface erosion rate quantification is low and in accordance with ¹⁰Be denudation rates typical of the low uplift Betic Cordillera.

In the extra-thick coal seams and multi-layered hard roofs, the longwall hydraulic support yielding, coal face spalling, strong deformations of goaf-side entry, and severe ground pressure dynamic events typically occur at the longwall top coal caving longwall faces. Based on the Key strata theory an overburden caving model is proposed here to predict the multilayered hard strata behaviour. The proposed model together with the measured stress changes in coal seam and underground observations in Tongxin coal mine provides a new idea to analyse stress changes in coal and help to minimise rock bursts in the multi-layered hard rock ground. Using the proposed primary Key and the sub-Key strata units the model predicts the formation and instability of the overlying strata that leads to abrupt dynamic changes to the surrounding rock stress. The data obtained from the vertical stress monitoring in the 38 m wide coal pillar located adjacent to the longwall face indicates that the Key strata layers have a significant influence on ground behaviour. Sudden dynamically driven unloading of strata was caused by the first caving of the sub-Key strata while reloading of the vertical stress occurred when the goaf overhang of the sub-Key strata failed. Based on this findings several measures were recommended to minimise the undesirable dynamic occurrences including pre-split of the hard Key strata by blasting and using the energy consumption yielding reinforcement to support the damage prone gate road areas. Use of the numerical modelling simulations was suggested to improve the key theory accuracy.

Methionine oxidation to the sulfoxide form (MSox) is a poorly understood post-translational modification of proteins associated with nonspecific chemical oxidation from reactive oxygen species (ROS) whose chemistries are linked to various disease pathologies including neurodegeneration. Emerging evidence shows MSox site occupancy is in some cases under enzymatic regulatory control mediating cellular signaling including phosphorylation and/or calcium signaling, raising questions as to the speciation and functional nature of MSox across the proteome. The 5XFAD lineage of the C57BL/6 mouse has well-defined Alzheimer’s and aging states. Using this model, we analyzed age, sex and disease dependent MSox speciation in mouse hippocampus. In addition, we explore chemical stability and statistical variance of oxidized peptide signals to understand needed power for MSox based proteome studies. Our results identify mitochondrial and glycolytic pathway targets with increases in MSox with age as well as neuroinflammatory targets accumulating MSox with AD in proteome studies of mouse hippocampus. Further, the paper establishes a foundation for reproducible and rigorous experimental MSox-omics appropriate for biological discovery novel target identification, and biomarker analysis in ROS and other oxidation linked diseases.

Profiling technologies, such as proteomics, allow the simultaneous measurement and comparison of thousands of plant components without prior knowledge of their identity. The combination of these non-targeted methods facilitates a more comprehensive approach than targeted methods and thus provides additional opportunities to identify genotypic changes resulting from genetic modification, including new allergens or toxins. The purpose of this study was to investigate unintended changes in GM Bt maize grown in South Africa. In the present study, we used bi-dimensional gel electrophoresis based on fluorescence staining, coupled with mass spectrometry in order to compare the proteome of the field-grown transgenic hybrid (MON810) and its near-isogenic counterpart. Proteomic data showed that energy metabolism and redox homeostasis were unequally modulated in GM Bt and non-GM maize variety samples. In addition, a potential allergenic protein – pathogenesis related protein -1 has been identified in our sample set. These finding highlight the suitability of unbiased profiling approaches to complement current GMO risk assessment practices worldwide.

Optical communications are described and analyzed by shaped beams; we challenge the ‎effects of parameters that impact the profile of a Flat Top Gaussian (FTG) beam. When ‎the laser beam propagates throughout the atmosphere, it can be influenced by different ‎optical phenomena including scattering, absorption, and turbulence due to changes in the ‎scintillation index and the forms of intensity that are displayed in the source and receiver ‎planes. In this project, the FTG laser beam that propagates through a weak turbulent ‎region is numerically investigated using open-source software. This simulation will be ‎performed according to a mathematical model based on the split-step beam propagation ‎method. Intensity distributions at the source plane and the received average intensity in ‎atmospheric turbulence are calculated, and additional contour is in the transducer plane. ‎The scintillation index, structure constant, source size, and other parameters, are applied ‎in the Rytov method to quantify the weak turbulent model. Moreover, these parameters ‎are analyzed in near-field propagation. Also, the effects of the beam’s scintillation and ‎beam wander are determined. All results simulated are discussed and compared with the ‎TEM00 Gaussian beam. Finally, these results are compared to measurements in the ‎experimental part of the work.

This paper aims to explore the effect of humble leadership on project success by integrating the mediating role of employee creativity. Top management support moderates the direct relationship (humble leadership and project management effectiveness) and indirect relationships through employee creativity. Time-lagged data were obtained from 332 persons working in the matrix organization across the information technology. The results showed that humble leadership enhance project management effectiveness by mediating and moderating processes. This study provides a solution to an underlying research question that has gone unanswered in prior studies. What are the strategies proposed for humble leadership in fostering the effectiveness of the project?

To ensure the security of spatial-temporal Top-k query in two-tiered wireless sensor networks, many schemes have been proposed in the literature in the past decade. However, most of them only consider the scenario where sensor nodes are static, and cannot achieve the security goal for spatial-temporal Top-k query in mobile sensor networks, because the mobility of the sensor nodes will affect the spatial-temporal relationships of the sensory data items generated by the sensor nodes. Although we have proposed some schemes for two-tiered mobile wireless sensor networks (TMWSNs) in our previous work, there is still large room to improve their performances. In this paper, we proposed a novel scheme named STQ-TMWSN for secure fine-grained spatial-temporal Top-k query in TMWSNs based on the virtual-grid construction and the size-order encryption binding. Theoretic analysis shows that STQ-TMWSN can achieve low computation complexity and high security performance. Simulation results indicate that STQ-TMWSN brings much lower communication cost than the state-of-the-art schemes on securing Top-k query in TMWSNs.

Many ailments can be diagnosed while they are asymptomatic, meaning that the patient has no signs or symptoms of a progressing disease. If caught in their initial stage of formation, these maladies can be effectively treated, leading to successful outcomes; curative therapies can halt illnesses from advancing, thus improving the quality of life, and long-term survival of the patient. Still cutting-edge upgrades in precision technologies are necessary for early, reliable, affordable, and rapid disease detection, but also are vital for the well-being of people and the future of global public health. The emerging role and utility of non-invasive and repeatable diagnostic test approaches for detection of health conditions has been liquid biopsies based on genomic biomarkers. As such, biological fluids permit any measurable molecular indicator or signature (e.g., proteins), to provide valuable information on individual’s wellness and/or disease. Among the bodily secretions used for non-invasive diagnostics is sputum, a complex viscous gel-like biopolymeric network, that has gained growing recognition as a rich source of biomarkers of airway infections, pulmonary diseases, and serves as a determinant to reveal other illnesses. As per the World Health Organization, the burden of respiratory conditions is exacerbated by factors, ranging from considerable subjection to air pollution and occupational contaminants, to tobacco smoking and second-hand smoke, in addition to poor socio-economic status. Due to the likely increase of these determinants, respiratory tract ailments are on the rise, affecting the health of many individuals, in addition to putting stress on healthcare facilities and services worldwide. We therefore highlight the need to use expectorated or induced sputum specimens as a routine sample source for testing valuable protein biomarkers to diagnose these chronic maladies, to predict inflammation and disease progression, as well as monitor the effectiveness of treatments. Further, we discuss the urgency for fast and reliable point-of-care methods to detect and quantify crucial protein biomarkers in sputum specimens, and limitations faced when dealing with their complex matrices.

Protein translational modifications (PTMs) generate an enormous, but as yet undetermined, expansion of the expressed proteoforms. In this Viewpoint, we firstly differentiate the concepts of proteoform and peptidoform by reviewing and discussing previous literature. We show that the current PTM biological investigation and annotation largely follow a PTM site-specific rather than proteoform-specific approach. We further illustrate a potentially useful matching strategy in which a particular “modified peptidoform” is matched to the corresponding “unmodified peptidoform” as a reference for the quantitative analysis between samples and conditions. We suggest this strategy could provide directly relevant information for learning the PTM site-specific biological functions. Accordingly, we advocate for the wider use of the nomenclature “peptidoform” in the future bottom-up proteomic studies.

Salinity stress emerges as an important menace to global food security, particularly affecting susceptible crops such as common bean plants (Phaseolus vulgaris L.). The disruption of ion balances caused by salt stress withing plants cells reduces water and nutrient absorption, and hampers growth and productivity. Sacchorhiza polyschides, a brown macroalga rich in essential elements, and macrominerals, has drawn attention as a natural biostimulant, being a potential remedy to bolster crop resilience against salt stress. This study delves into the effect of water extracts of Sacchorhiza polyschides (SPE) across varying concentrations (1%, 2%, and 5%) in common bean plants under salt stress (68.4 mM NaCl) conditions. Two different methods of application were used: by spraying the aerial part of the plant or by irrigation together with the watering solution. The effects of both systems of application were studied on the aerial parts of the plants. SPE exhibited significant enhancements in morphological parameters, chlorophyll content, carbon-nitrogen activities, and antioxidant enzymatic system activities, alongside increasing osmolyte accumulation, compared to salt-stressed plants without biostimulation. Moreover, SPE reduced reactive oxygen species (ROS) levels caused by salt stress, mitigating lipid peroxidation. The concentrations of 2% and 5% SPE applied by spraying showed the most significant results in most of the parameters analyzed. By shedding light on the underlying science behind this biostimulant effect, this research underscores the potential of SPE to enhance crop resilience and augment food production in salt-challenged environments.

This study examines the unique circumstances surrounding state-owned equity participation in non-state-controlled enterprises in China. Specifically, this study examines the impact of state-owned equity participation on the environmental, social, and governance (ESG) performance of non-state-controlled enterprises. Focusing on A-share listed firms on the Shanghai and Shenzhen Stock Exchanges and using data from 2013 to 2021, empirical testing shows that state-owned equity participation can significantly improve the ESG performance of non-state-controlled enterprises, with this conclusion remaining reliable after a series of robustness tests. Top management incentives is a mediating mechanism for state-owned equity participation in enhancing ESG performance. This study also finds that when state-owned equity participates in large enterprises or companies with a high degree of digital transformation, the effect on ESG performance is greater than that of small to medium-sized enterprises (SMEs) or enterprises with a low level of digital transformation. The findings of this study add to the current body of the existing field of research on the factors influencing corporate ESG performance and the impact of state-owned equity on corporate non-financial performance.

Evidence-based canine decontamination protocols are underrepresented in the veterinary literature. Aerosolized microbiological and chemical contaminants can pose a risk in deployment environments highlighting the need for improved canine field decontamination strategies. Prior work has established the efficacy of traditional, water-intensive methods on contaminant removal from the coat of the working canine; however, it is not known if similar reductions can be achieved with simple field expedient methods when resources are limited. The objective of this study was to measure the reduction of aerosolized contamination via a practical “wipe-down” procedure performed on working canine coats contaminated with a fluorescent, non-toxic, water-based aerosol. Disposable, lint-free towels were saturated with one of three treatments: water, 2% chlorhexidine gluconate scrub (CHX), or 7.5% povidone-iodine scrub (PVD). Both CHX and PVD were diluted at a 1:4 ratio. Treatments were randomly assigned to one of three quadrants established across the shoulders and back of commonly utilized working dog breeds (Labrador retrievers, n = 16; German shepherds, n = 16). The fourth quadrant remained unwiped, serving as a control. Reduction in fluorescent marker contamination was measured and compared across all quadrants. PVD demonstrated greater marker reduction compared to CHX or water in both breeds (P < 0.0001). Reduction was similar between CHX or water in Labradors (P = 0.86) and shepherds (P = 0.06). Effective wipe-down strategies using common veterinary cleansers should be further investigated and incorporated into decontamination practices to safeguard working canine health and prevent cross-contamination of human personnel working with these animals.

Protein hydrolysates show great promise as bioactive food and feed ingredient and for valorization of side-streams from e.g. the fish processing industry. This study characterizes bulk emulsifying, foaming, and in vitro antioxidative properties of hydrolysates derived from cod frame by application of Alcalase and Neutrase, individually and sequentially as well as the influence of heat-treatment prior to hydrolysis. We present a novel approach that utilizes proteomics data for calculation of weighted mean peptide properties (length, molecular weight, and charge) and peptide-level abundance estimation. Using subsequent bioinformatic prediction of biofunctional properties to describe observed bulk properties, we are able to provide an in-depth hydrolysate characterization not previously seen. All hydrolysates displayed comparable or higher emulsifying activity and stability than sodium caseinate. Heat-treatment significantly increased stability but showed a negative effect on the activity and degree of hydrolysis. Combining peptide abundance with predicted emulsifying activity, we were able to identify several peptides that are likely linked to the observed differences in bulk emulsifying properties. In general, decreased hydrolysis resulted in significantly higher chelating activity, while the opposite was observed for radical scavenging activity. The study highlights the prospects of applying proteomics and bioinformatics for hydrolysate characterization and in food protein science.

We aimed to evaluate the protective effects of acetyl-xylogalactan on the activity of RAW264.7 macrophages against heat stress. To this end, we assessed cell survival, phagocytic activity, in-tracellular Ca2+ level, mitochondria potential exchange, apoptotic assay findings, galactosidase activity and the RNA-seq by NGS and real-time polymerase chain reaction (PCR) expression. In our evaluation of macrophage morphology at 37°C and 41°C, the macrophages showed an oval shape at 41°C , unlike the spindle shape at 37°C. Therefore, 41°C was chosen as the heat stress condition. Subsequently, we designed an experiment to evaluate changes in the RAW264.7 macrophages after acetyl-xylogalactan treatment under heat stress. The survival of RAW264.7 macrophages treated with acetyl-xylogalactan was higher than that of controls that were not treated with acetyl-xylogalactan. Moreover, on the basis of the results of the annexin-V detection assay, the apoptotic activity of macrophages appeared to have reduced after treatment with ac-etyl-xylogalactan. Moreover, treatment with acetyl-xylogalactan resulted in a stronger recovery trend in the intracellular Ca2+ and mitochondrial membrane potential after heat stress. RNA sequencing and real-time polymerase chain reaction (PCR) illustrated that Sarcodia suieae acetyl-xylogalactan could upregulate the expression of the anti-apoptosis Cflar gene and down-regulate the expression of the apoptosis factors Ddit3, and Hyou1 to protect macrophages under heat stress.

Photosynthetic function, photoprotection, and the response of related proteomics of mulberry (Morus alba L.) seedling leaves under NaCl and NaHCO3 stress with the same Na+ concentration (100 mmol•L-1) were studied by using photosynthetic gas exchange and chlorophyll fluorescence techniques combined with TMT proteomics. The results showed that NaCl stress had no significant effect on photosystem II (PSII) activity in mulberry seedling leaves, and the expressions of the related proteins, OEE3-1 and PPD4, of the PSII oxygen-evolving complex (OEC) and the antenna proteins, CP24 10A, CP26, and CP29, of LHCII in the leaves also increased to varying degrees. The photosystem I (PSI) activity in the leaves of mulberry seedling also increased, and the expressions of some proteins, PsaF, PsaG, PsaH, PsaL, PsaN, and Ycf4, in PSI increased significantly under NaCl stress. Under NaHCO3 stress, the activity of PSII and PSI and the expression of their protein complexes and the electron transfer-related proteins significantly decreased. NaCl stress had little effect on RuBP regeneration during dark reaction in the leaves and the expressions of glucose synthesis related proteins and net photosynthetic rate (Pn) did not decrease significantly. The leaves could adapt to NaCl stress by reducing stomatal conductance (Gs) to increase water use efficiency (WUE). Under NaHCO3 stress, the expression of dark reaction-related proteins was mostly down-regulated, and Gs was significantly reduced, which indicated that non-stomatal factors were important reasons for the significant inhibition of carbon assimilation. In the photoprotective mechanism under NaCl stress, the expression of cyclic electron flow (CEF) related proteins, ndhH, ndhI, ndhK, and ndhM, involved in NAD(P)H dehydrogenase (NDH) and the key enzyme of the xanthophyll cycle, violaxanthin de-epoxidase (VDE) were up-regulated. In addition, the ratio of xanthophyll cycle components (A+Z)/(V+A+Z) was increased. The expressions of proteins FTR and Fd-NiR, which are related to Fd-dependent ROS metabolism and nitrogen metabolism, were also significant up-regulated under NaCl stress, which can effectively reduce the electronic pressure on Fd. Under NaHCO3 stress, the expressions of CEF-related proteins, VDE, ZE, FTR, Fd-NiR, Fd-GOGAT, SGAT, and GGAT, were significant down-regulated, and the photoprotective mechanism, like the xanthophyll cycle, CEF, and photorespiration, might be damaged, resulting in the inhibition of PSII activity and carbon assimilation in leaves of mulberry seedling under NaHCO3 stress.

Analysis of liquid biopsy samples can reveal a wealth of molecular as well as cellular entities circulating in various body fluids. These entities include circulating tumor cells, circulating cell-free and tumor DNA, RNA, and proteins. Detection and characterization of this genetic and proteomic material can provide crucial information on tumor characteristics, including its heterogeneity, biology, tumor progression, staging, associated gene mutations and the course of therapy. The increased use of liquid biopsy in clinical oncology offers in non-invasive manner easier tumor sampling and continuous monitoring of the disease evolution through repetitive sampling from cancer patients. The continuous monitoring offered by this method is highly relevant to the assessment of a given therapeutic regime and early detection of markers associated with possible drug resistance, which may develop in the course of the therapy. The use of proteomic approaches, including mass spectrometry-based proteomics for the analysis of biofluids extends for over three decades, yet only in the last few years such methods have found their way to clinical oncology. The non-invasive nature of liquid biopsy and the simple procedures for sample collection made this approach far more attractive than the traditional and well-established tissue biopsy. Such preference becomes more practical in the analysis of solid tumors, particularly in pediatric population. In this review we discuss some works on the emerging role of liquid biopsy analyses in clinical oncology, and how such use allows a better understanding of diagnosis, prognosis, disease evolution and response to therapy of various forms of cancer. We also discuss the role of MS-based methods in the characterization of post-translational modifications of proteins circulating in liquid biopsies.

Primulina serrulata is a valuable ornamental herb with rosette leaves and vibrant flowers. Some leaves exhibit a bright and distinct white color along the upper veins, enhancing their ornamental value, while others are less white or entirely green. This variation is observed among adult leaves in natural habitats and among young leaves from seedlings grown in the laboratory. TMT-labeled proteomic technology was employed to study the protein-level biogenesis of white-veined (WV) leaves of P. serrulata. The chlorophyll (Chl) content was significantly lower in the WV group than in the control group. A total of 6,261 proteins were identified, revealing 69 differentially expressed proteins (DEPs), with 44 down-regulated and 25 up-regulated in WV plants. Some DEPs associated with chloroplasts and Chl biosynthesis were down-regulated, leading to the absence of green coloration. Concurrently, gene ontology enrichment analysis further underscored an insufficiency of magnesium , the key element in Chl biosynthesis. Many DEPs associated with abiotic or biotic stresses were down-regulated, suggesting an overall weakening of stress resistance with certain compensatory mechanisms in place. Similarly, many DEPs related to biomacromolecule modification were down-regulated, possibly influenced by the decrease in proteins involved in photosynthesis and stress resistance. Some DEPs containing iron were up-regulated, indicating that iron was mainly used to synthesize heme and ferritin instead of Chl. Additionally, several DEPs related to sulfur or sulfate were up-regulated, implying strengthened respiration. Expansin-A4 and pectinesterase displayed up-regulation, coinciding with the emergence of a rough and bright surface in the white area, indicative of the elongation and gelation processes in cell walls. These findings provide new insights that could be utilized by future studies to explore the mechanism of color formation in WV leaves.

Dawn of the omics revolution in biological sciences meant that we seek to understand more and in greater detail the molecular constituents of cells and biological systems. While we have gained significant insights from conventional omics tools, we now seek to understand the spatial dimensions of the data where subcellular localisation may impact on cellular physiology and phenotype. This review paper seeks to address current questions in the new field of image-based spatial proteomics as well as outline future challenges of the field. At first glance, spatial proteomics offers enormous potential to expand our understanding of different cell types in different disease and cell states. But limitations in types of fluorophores and issues with spectral overlap significantly hampers the practical implementation of the technique. On the other hand, while we have super-resolution microscopy techniques such as STED, PALM and STORM able to achieve 10 to 20 nm spatial resolution in single molecule localisation, problems with slow image acquisition limits high temporal resolution tracking of multiple protein targets in live cell imaging. Hence, the field of spatial proteomics is a mix of promises and challenges where we could image, in multi-colour, upwards of 10 well-chosen proteins that could inform on the molecular mechanisms of selected biological processes, but, at present, the method could not tackle larger scale questions. In essence, current implementation of image-based spatial proteomics is useful, but it is unable to fulfil the mission of large-scale projects such as the Human Protein Atlas or Human Cell Atlas. Future challenges in the field includes the development of more fluorophores (especially photoswitchable and photoactivable ones) for single molecule localisation microscopy, as well as seeking to improve temporal resolutions to the sub-millisecond range.

Amebiasis is an intestinal disease transmitted by the protist parasite, Entamoeba histolytica. Lactobacillus acidophilus is a common inhabitant of healthy human gut and a probiotic that has antimicrobial properties against a number of pathogenic bacteria, fungi, and parasites. The aim of this study was to investigate the amebicide activity of L. acidophilus and its mechanisms. For this purpose E.histolytica and L.acidophilus were co-incubated and the parasite’s viability was determined by eosin dye exclusion. The level of ozidized proteins (OXs) in the parasite was determined by resin-assisted capture RAC (OX-RAC). Incubation with L.acidophilus for two hours reduced the viability of E.histolytica trophozoites by 50%. As a result of the interaction with catalase, an enzyme that degrades hydrogen peroxide (H₂O₂) to water and oxygen, this amebicide activity is lost, indicating that it is mediated by H₂O₂ produced by L.acidophilus. Redox proteomics shows that L. acidophilus triggers the oxidation of many essential amebic enzymes like pyruvate:ferredoxin oxidoreductase, the lectin Gal/GalNAc and cysteine proteases (CPs). Further, trophozoites of E.histolytica incubated with L.acidophilus show reduced binding to mammalian cells. These results support L.acidophilus as a prophylactic candidate against amebiasis.

Murine herpesvirus-68 (MHV-68) productively infects the mouse lungs, exhibiting a complex pathology characteristic of both acute viral infections and chronic respiratory diseases. We sought to discover proteins differentially expressed in bronchoalveolar lavage (BAL) from mice infected with MHV-68. Mice were infected intranasally with MHV-68. After 9 days, as the lytic phase of infection resolved, differential BAL proteins were identified by 2D electrophoresis and mass spectrometry. Of 23 unique proteins, acute phase proteins, vitamin A transport, and oxidative stress response factors Pdx6 and EC-SOD (Sod3) were enriched. Correspondingly, iNOS2 was induced in lung tissue by 7 days post infection. Oxidative stress was partly a direct result of MHV-68 infection, as reactive oxygen species (ROS) were induced in cultured murine NIH3T3 fibroblasts and human lung A549 cells infected with MHV-68. Finally, mice were infected with a recombinant MHV-68 co-expressing inflammatory cytokine murine interleukin 6 (IL6) showed exacerbated oxidative stress and soluble type I collagen characteristic of tissue recovery. Thus, oxidative stress appears to be a salient feature of MHV-68 pathogenesis, in part caused by lytic replication of virus and IL6. Proteins and small molecules in lung oxidative stress networks therefore may provide new therapeutic targets to ameliorate respiratory virus infections.

Autophagy is a highly conserved catabolic process in eukaryotic cells. Reactive nitrogen species play roles as inductors and signaling molecules of autophagy. A key mechanism of NO-mediated signaling is S-nitrosylation, a posttranslational modification (PTM) of proteins at cysteine resi-dues. In the present work we analyzed the patterns of protein S-nitrosylation during the induc-tion of autophagy in Triticum aestivum roots. The accumulation of S-nitrosylated proteins in the cells during autophagy induced by KNO2 and antimycin A was visualized using monoclonal an-tibodies by Western blot analysis, and proteins were identified using a standard bottom-up pro-teomics approach. Protein S-nitrosylation is a labile and reversible PTM, and therefore SNO group can be lost during experimental procedures. Subsequent bioinformatic analysis using predictive algorithms and protein-ligand docking showed that identified proteins possess hypothetical S-nitrosylation sites. Analyzing protein-protein interaction networks enabled us to discover the targets that can directly interact with autophagic proteins, and those that can interact with them indirectly via key multifunctional regulatory proteins. In this study, we show that S-nitrosylation is a key mechanism of NO-mediated regulation of autophagy in wheat roots. A combination of in silico predictive algorithms with a mass spectrometry analysis provides a targeted approach for the identification of S-nitrosylated proteins.

Disorder of S-adenosylhomocysteine hydrolase (AHCY) activity leads to the potentially lethal rare disease AHCY deficiency, first described in 2004 by Baric and co-workers [1]. In order to shed new light on molecular aspects of the disease, in particular changes at transcriptome level, we enabled knock-down of AHCY expression in model systems such as the colon cancer cell line SW480 to simulate the environment occurring in AHCY deficiency patients. Further, we per-formed deep sequencing of mRNA, followed by differential expression and molecular pathway analysis. Fifteen differentially expressed networks were identified, and interestingly, we found a predicted effect of AHCY down-regulation on the expression of the Lymphoidphoid enhanc-er-binding factor 1 (LEF1) gene, indicating changes in the TCF4/LEF1 complex. LEF1, a member of the T-cell Factor (TCF)/LEF1 family of high-mobility group transcription factors, is a down-stream mediator of the Wnt/β-catenin signaling pathway [2]. LEF1 is essential in stem cell maintenance, and especially in its role in epithelial-mesenchymal transition (EMT). Western blot analysis of LEF1 protein expression confirmed our transcriptomic data predictions and revealed significantly increased LEF1 protein in AHCY- deficient cells, providing a novel link between AHCY and cancer cell phenotype.