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Simple Summary: The paper describes the statistical analysis of the response of gastric cancer cells and normal cells to broadband terahertz radiation up to 4 THz, both with and without the use of nanostructured contrast agents. A statistical analysis was conducted towards multiple pairwise comparisons in order to identify the narrow THz frequency ranges where the contrast is enhanced and allows a clear identification of tumor cells in the presence of contrast agents. The paper describes the statistical analysis of the response of gastric cancer cells and normal cells to broadband terahertz radiation up to 4 THz, both with and without the use of nanostructured contrast agents. The THz spectroscopy analysis was comparatively performed under the ATR procedure and transmission measurement procedure. The statistical analysis was conducted towards multiple pairwise comparisons, including a support medium (without cells) versus a support medium with nanoparticles, normal cells versus normal cells with nanoparticles, and, respectively, tumor cells versus tumor cells with nanoparticles. When generally comparing the ATR procedure and transmission measurement procedure for a broader frequency domain, the differentiation between normal and tumor cells in the presence of contrast agents is superior when using the ATR procedure. THz contrast enhancement by using contrast agents derived from MRI-related contrast agents leads to only limited benefits and only for narrow THz frequency ranges, a disadvantage for THz medical imaging. [ABSTRACT FROM AUTHOR]

The blood-brain barrier (BBB) protects the brain by actively allowing the entry of ions and nutrients while limiting the passage of from toxins and pathogens. A healthy BBB has low permeability and high selectivity to maintain normal brain functions. Increased BBB permeability can result from neurological diseases and traumatic injuries. Modern engineering technologies such as microfluidics and fabrication techniques have advanced the development of BBB models to simulate the basic functions of BBB. However, the intrinsic BBB properties are difficult to replicate. Existing in vitro BBB models demonstrate inconsistent BBB permeability and selectivity due to variations in microfluidic design, cell types and arrangement, expression of tight junction (TJ) proteins, and use of shear stress. Specifically, microfluidic designs have flow channels of different sizes, complexity, topology, and modular structure. Different cell types are selected to mimic various physiological conditions. These factors make it challenging to compare results obtained using different experimental setups. This paper highlights key factors that play important roles in influencing microfluidic models and discusses how these factors contribute to permeability and selectivity of the BBB models. [ABSTRACT FROM AUTHOR]

This paper explores a formal model of autopoiesis as presented by Maturana, Uribe and Varela, and analyzes this model and its implications through the lens of the notions of eigenforms (fixed points) and the intricacies of Goedelian coding. The paper discusses the connection between autopoiesis and eigenforms and a variety of different perspectives and examples. The paper puts forward original philosophical reflections and generalizations about its various conclusions concerning specific examples, with the aim of contributing to a unified way of understanding (formal models of) living systems within the context of natural sciences, and to see the role of such systems and the formation of information from the point of view of analogs of biological construction. To this end, we pay attention to models for fixed points, self-reference and self-replication in formal systems and in the description of biological systems. [ABSTRACT FROM AUTHOR]

This review is intended to contribute to the evidence of the effects of static magnetic field on cells and tissue, as well as to present research results that will elucidate the complex matters involved in the formation and remodeling of cells. The cell characteristics studied in the papers that are reviewed include cell viability and proliferation, aggregation and their differentiation, structure and membrane potential. A moderate static magnetic field in the most commonly used range of 2-80 mT has potential application in the formation and remodeling of plant and human cells. However, in the case of cancer cells, the range of fields commonly used was 0.2-9 T. Magnetism promotes changes in plant cell growth, which prompts the cell to proliferate, thereby ensuring an increased rate of biomass production. Some researches presented the enhancement of the differentiation of plant cells and skeletal muscle tissue by over 30% at 80 mT static magnetic field. Changes in the cell cycle and growth reflect directly on the cell number and viability and provide useful information to detect modifications in the cell machinery. Static magnetic field, depending on its intensity, enhances cell proliferation and thus may improve, among other processes, tissue regeneration, wound healing and the inhibition of cancer cell proliferation. Researchers showed, among other things, that cells under the influence of static magnetic field changed their shape, had a larger chloroplast, stiffer cell wall, density of the cytoskeleton and cytoplasm contained several mitochondria. Numerous studies also discussed the behavior of the cell membrane of plant and animal organisms, including humans, under the influence of an static magnetic field. The effects of static magnetic field on the cell membrane of plant and human cells were similar. The research results indicate that static magnetic fields can significantly change membrane depolarization and its potential that regulates ion movement and thus can have a significant impact on the properties and biological functionality of the cell. Studies have shown that continuous application of static magnetic field caused deformation and damage of cell membrane. Based on the theoretical analyses presented also in this review, it can be concluded that static magnetic field affects cells and tissue, giving them changes in properties and behaviors and modulates, e.g. in the activity of ion channels. Thus it may produce effects leading to changes in the functioning of the cell. It is possible to formulate directions for further research aimed at using static magnetic fields for the non-invasive remodeling and formation of plant and human cells. [ABSTRACT FROM AUTHOR]

In the current paper we provide a proof of NP-completeness for the Cell Formation Problem (CFP) with the fractional grouping efficacy objective function. First the CFP with a linear objective function is considered. Following the ideas of Pinheiro et al. (2016) we show that it is equivalent to the Bicluster Graph Editing Problem (BGEP), which is known to be NP-complete due to the reduction from the 3-Exact 3-Cover Problem – 3E3CP (Amit, 2004). Then we suggest a polynomial reduction of the CFP with the linear objective to the CFP with the grouping efficacy objective. It proves the NP-completeness of this fractional CFP formulation. Along with the NP-status our paper presents important connections of the CFP with the BGEP and 3E3CP. Such connections could be used for "transferring" of known theoretical properties, efficient algorithms, polynomial cases, and other features of well-studied graph editing and exact covering problems to the CFP. [ABSTRACT FROM AUTHOR]

Many people find the manipulation of the human germline—editing the DNA of sperm or egg cells such that these genetic changes are passed to the resulting offspring—to be morally impermissible. In this paper, I argue for the claim that editing the human germline is morally permissible. My argument starts with the claim that outcome uncertainty regarding the effects of germline editing shows that the duty to not harm cannot ground the prohibition of germline editing. Instead, if germline editing is wrong, it is wrong because it violates a duty to protect. However, we also have an epistemic duty to gather evidence regarding the effects of editing the human germline which overrides any moral duty to protect future generations. Thus, we have a duty to gather evidence regarding the effects of editing the human germline, which is to say that we have a duty to edit the human germline. [ABSTRACT FROM AUTHOR]

Bouteloua gracilis (blue grama grass) is one of the most drought and grazing tolerant plants in the short-grass ecosystem. To obtain information on their photosystem activities, we measured the fast (< 1 s) chlorophyll a fluorescence transient (the OJIP curve) from their leaves, and isolated cells grown photoautotrophically in suspension in a culture medium, or with added sucrose. One of our goals was to study the effect of different sucrose concentrations (0, 0.15, 0.3, and 3%) on PSII activity in isolated cells. Our results on cells suspended in culture medium, using the JIP-test, showed a decrease in PSII activity at increasing sucrose concentrations, while the photoautotrophic cells showed an optimal PSII activity, close to that of the leaves. Further, our data on cells grown in 0, 0.15, and 0.3% sucrose, but with added CO2, and measured while the cells were deposited on filter paper, indicate that supplementary CO2 can increase the PSII activity in the presence of sucrose, although further research is necessary to understand these results. [ABSTRACT FROM AUTHOR]

Simple Summary: Oral lichen planus (OLP) is a chronic inflammatory disease of autoimmune nature and unknown etiology which affects approximately 1% of the world's population. The most important feature of OLP is its behavior as an oral potentially malignant disorder (OPMD). The current study is the first systematic review and meta-analysis designed to evaluate the degree of existing scientific evidence on the cancer hallmarks proposed in 2011 by Hanahan and Weinberg, defined as the characteristics that cells must fulfill in order to be considered neoplastic cells in all types of tumors that affect humans. This systematic review and meta-analysis includes 110 studies which recruited 7064 cases of OLP, in which the expression of 104 molecular biomarkers were analyzed through an immunohistochemical technique. The earliest oncogenic molecular mechanisms that could justify the malignant transformation of this disease are analyzed in depth and critically discussed on the basis of evidence. We aimed to qualitatively and quantitatively analyze, through a systematic review and meta-analysis, the current evidence on the differential expression of the hallmarks of cancer in oral lichen planus (OLP) samples, in order to know the earliest molecular mechanisms that could be involved in the malignant transformation of this oral potentially malignant disorder. We searched MEDLINE/PubMed, Embase, Web of Science, and Scopus for studies published before November 2023. We evaluated the methodological quality of studies and carried out meta-analyses to fulfill our objectives. Inclusion criteria were met by 110 primary-level studies, with 7065 OLP samples, in which the expression of 104 biomarkers were analyzed through immunohistochemistry. Most OLP samples showed sustained cell proliferation signaling (65.48%, 95%CI = 51.87–78.02), anti-apoptotic pathways (55.93%, 95%CI = 35.99–75.0), genome instability (48.44%, 95%CI = 13.54–84.19), and tumor-promoting inflammation events (83.10%, 95%CI = 73.93–90.74). Concurrently, OLP samples also harbored tumor growth suppressor mechanisms (64.00%, 95%CI = 53.27–74.12). In conclusion, current evidence indicates that molecular mechanisms promoting hyperproliferative signaling, an antiapoptotic state with genomic instability, and an escape of epithelial cells from immune destruction, are developed in LP-affected oral mucosa. It is plausible that these events are due to the actions exerted by the chronic inflammatory infiltrate. Malignant transformation appears to be prevented by tumor suppressor genes, which showed consistent upregulation in OLP samples. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is the predominant cause of dementia on a global scale, significantly impacting the health of the elderly population. The pathogenesis of AD is closely linked to neuroinflammation. The present study employs a bibliometric analysis to examine research pertaining to neuroinflammation and AD within the last decade, with the objective of providing a comprehensive overview of the current research profile, hotspots and trends. Methods: This research conducted a comprehensive review of publications within the Science Citation Index Expanded of the Web of Science Core Collection Database spanning the years 2014 to 2024. Bibliometric analyses were performed using VOSviewer (version 1.6.19) and CiteSpace (version 6.3.R1) software to visualize data on countries, institutions, authors, journals, keywords, and references. Results: A total of 3,833 publications on neuroinflammation and AD were included from January 2014 to January 2024. Publications were mainly from the United States and China. Zetterberg, Henrik emerged as the author with the highest publication output, while Edison, Paul was identified as the most cited author. The most productive journal was Journal of Alzheimers Disease, and the most co-cited was Journal of Neuroinflammation. Research hotspot focused on microglia, mouse models, oxidative stress, and amyloid-beta through keyword analysis. Additionally, keywords such as blood-brain barrier and tau protein exhibited prolonged citation bursts from 2022 to 2024. Conclusion: This study provides a comprehensive review of the last 10 years of research on neuroinflammation and AD, including the number and impact of research findings, research hotspots, and future trends. The quantity of publications in this field is increasing, mainly in the United States and China, and there is a need to further strengthen close cooperation with different countries and institutions worldwide. Presently, research hotspots are primarily concentrated on microglia, with a focus on inhibiting their pro-inflammatory responses and promoting their anti-inflammatory functions as a potential direction for future investigations. [ABSTRACT FROM AUTHOR]

Introduction: Cultivated meat has received growing attention since claims were made that cultivated meat can be produced more ethically and sustainably than the current meat production. However, there are still major challenges in the development of cell lines, scaffolding, growth media, and bioprocess, which need to be overcome to reach industrial production levels. Numerous technological innovations have been proposed to overcome these challenges but they have rarely been evaluated with regard to their social sustainability. Consequently, it remains unclear if and how cultivated meat would contribute towards creating inclusive food systems. Methods: To bring more clarity, the study identifies different technological solutions that are used or developed for production of cultivated meat and identifies the positive and negative claims about the expected contributions of these technological solutions to social inclusion in food systems, using evidence from the literature review and 11 expert interviews. An innovation radar for cultivated meat is proposed to visualise the variety of technological innovations and the claims about their expected contributions to social sustainability. Results: The technologies in the areas cell line development, scaffolding, growth media, and bioprocess are expected to have an impact on inclusion in consumption of cultivated meat. Some cell innovations are expected to raise cognitive barriers due to complex technologies that might be difficult for the consumer to understand. Cultural barriers are expected to be raised by cell innovation entailing genetic engineering and medium innovation using FBS or animal components, which is considered to harm animals. Further, regulatory barriers are expected in the EU if genetic modification is used in the production process, which concerns the areas cells, media, and scaffolding. The innovations for scaffolds are expected to mainly lower cost and cultural barriers since most technologies are already used in the food industry. Bioprocess innovations promise to lower cost barriers, however it must be considered, that most of the collected data for innovations in the bioprocess domain are based on assumptions. Discussion: The study concludes that at this point in time, the most socially sustainable approach to cultivated meat production is not obvious. Under the current technological state of the art, it is not thinkable that production and consumption of cultivated meat could be socially inclusive. As it remains poorly understood if technologies for cultivated meat production could raise or lower barriers to inclusive consumption and production, further research is needed. [ABSTRACT FROM AUTHOR]

Background: No other effects of atropine other than as an antagonist of muscarinic acetylcholine receptor (mAChR) have been found. Methods: In this study, human kidney epithelial cells were treated with different physiological regulators. Results: Subsequently, it was found that atropine could significantly induce autophagy as demonstrated by the appearance of autophagosome-like double- or single-membrane vesicles in the cytoplasm of host cells and the number of GFP-LC3 dots. In addition, increased conversion of the autophagy marker protein LC3-I and LC3-II and increased p62/SQSTM1 indicated incomplete autophagy. In addition, atropine induced autophagosome levels in a dose-dependent manner within a certain concentration range in human kidney epithelial cells. In atropine-treated mouse skeletal muscle cells containing nicotinic acetylcholine receptors and rat cardiac muscle cells containing mAchR, atropine induced autophagy in mouse skeletal muscle cells but not in rat cardiac muscle cells. Furthermore, atropine did not induce autophagy in tissue cells containing mAchR in vivo but did in tissue cells not containing mAchR. Conclusion: This study expands the application and understanding of atropine's action mechanism in the field of medicine. [ABSTRACT FROM AUTHOR]

Reversible protonic ceramic electrochemical cells (R-PCECs) demonstrate great feasibility for efficient energy storage and conversion. One critical challenge for the development of R-PCECs is the design of novel air electrodes with the characteristics of high catalytic activity and acceptable durability. Here, we report a donor doping of Hf into the B-site of a cobalt-based double perovskite with a nominal formula of PrBa0.8Ca0.2Co1.9Hf0.1O5+δ (PBCCHf0.1), which is naturally reconfigured to a double perovskite PrBa0.8-xCa0.2Co1.9Hf0.1-xO5+δ (PBCCHf0.1-x) backbone and nano-sized BaHfO3 (BHO) on the surface of PBCCHf0.1-x. The air electrode demonstrates enhanced catalytic activity and durability (a stable polarization resistance of 0.269 Ω cm² for ~100 h at 600 °C), due likely to the fast surface exchange process and bulk diffusion process. When employed as an air electrode of R-PCECs, a cell with PBCCHf0.1 air electrode demonstrates encouraging performances in modes of the fuel cell (FC) and electrolysis (EL) at 600 °C: a peak power density of 0.998 W cm-2 and a current density of -1.613 A cm-2 at 1.3 V (with acceptable Faradaic efficiencies). More importantly, the single-cell with PBCCHf0.1 air electrode demonstrates good cycling stability, switching back and forth from FC mode to EL mode ±0.5 A cm-2 for 200 h and 50 cycles. [ABSTRACT FROM AUTHOR]

Simple Summary: Spatial characteristics, including cell morphology and spatial distribution patterns, hold potential prognostic value in melanoma. This study builds on existing research by exploring these spatial factors through a computational pipeline, including both univariate and multivariate Cox proportional hazards models, supplemented by rigorous cross-validation techniques. Our findings reveal that spatial and morphological features can potentially enhance the prognostication of melanoma, supporting their integration into standard prognostic models. We also discuss potential limitations and outline directions for future research. In this study, the prognostic value of cellular morphology and spatial configurations in melanoma has been examined, aiming to complement traditional prognostic indicators like mitotic activity and tumor thickness. Through a computational pipeline using machine learning and deep learning methods, we quantified nuclei sizes within different spatial regions and analyzed their prognostic significance using univariate and multivariate Cox models. Nuclei sizes in the invasive band demonstrated a significant hazard ratio (HR) of 1.1 (95% CI: 1.03, 1.18). Similarly, the nuclei sizes of tumor cells and Ki67 S100 co-positive cells in the invasive band achieved HRs of 1.07 (95% CI: 1.02, 1.13) and 1.09 (95% CI: 1.04, 1.16), respectively. Our findings reveal that nuclei sizes, particularly in the invasive band, are potentially prognostic factors. Correlation analyses further demonstrated a meaningful relationship between cellular morphology and tumor progression, notably showing that nuclei size within the invasive band correlates substantially with tumor thickness. These results suggest the potential of integrating spatial and morphological analyses into melanoma prognostication. [ABSTRACT FROM AUTHOR]

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In this paper were analyzed the scientific bibliographic sources regarding the physiological and biochemical role of zinc on the tissues and organs of the organism of breeding roosters. In addition, in laboratory conditions, our researchers studied hematological, biochemical indices as well as glycine, glutamate and cysteine content in blood serum, seminal plasma and reproductive cells of breeding roosters. It is established that this element has a beneficial action on the organism of breeding roosters, maintaining and stabilizing the indices listed above at the level of physiological norms, compared to the roosters from the control group, and at the same time participating in the antioxidant protection of cells and maintaining cell homeostasis by balancing transmembrane metabolism. [ABSTRACT FROM AUTHOR]

Introduction: Alzheimer’s disease (AD) and Type 2 diabetes (T2D) are both ageassociated diseases. Identification of shared genes could help develop early diagnosis and preventive strategies. Although genetic background plays a crucial role in these diseases, we noticed an underrepresentation tendency of North African populations in omics studies. Materials and methods: First, we conducted a comprehensive review of genes and pathways shared between T2D and AD through PubMed. Then, the function of the identified genes and variants was investigated using annotation tools including PolyPhen2, RegulomeDB, and miRdSNP. Pathways enrichment analyses were performed with g:Profiler and EnrichmentMap. Next, we analyzed variant distributions in 16 worldwide populations using PLINK2, R, and STRUCTURE software. Finally, we performed an inter-ethnic comparison based on the minor allele frequency of T2D-AD common variants. Results: A total of 59 eligible papers were included in our study. We found 231 variants and 363 genes shared between T2D and AD. Variant annotation revealed six single nucleotide polymorphisms (SNP) with a high pathogenic score, three SNPs with regulatory effects on the brain, and six SNPs with potential effects on miRNA-binding sites. The miRNAs affected were implicated in T2D, insulin signaling pathways, and AD. Moreover, replicated genes were significantly enriched in pathways related to plasma protein binding, positive regulation of amyloid fibril deposition, microglia activation, and cholesterol metabolism. Multidimensional screening performed based on the 363 shared genes showed that main North African populations are clustered together and are divergent from other worldwide populations. Interestingly, our results showed that 49 SNP associated with T2D and AD were present in North African populations. Among them, 11 variants located in DNM3, CFH, PPARG, ROHA, AGER, CLU, BDNF1, CST9, and PLCG1 genes display significant differences in risk allele frequencies between North African and other populations. Conclusion: Our study highlighted the complexity and the unique molecular architecture of North African populations regarding T2D-AD shared genes. In conclusion, we emphasize the importance of T2D-AD shared genes and ethnicity-specific investigation studies for a better understanding of the link behind these diseases and to develop accurate diagnoses using personalized genetic biomarkers. [ABSTRACT FROM AUTHOR]

This paper details the content and structure of the folk concept of life, and discusses its relevance for scientific research on life. In four empirical studies, we investigate which features of life are considered salient, universal, central, and necessary. Functionings, such as nutrition and reproduction, but not material composition, turn out to be salient features commonly associated with living beings (Study 1). By contrast, being made of cells is considered a universal feature of living species (Study 2), a central aspect of life (Study 3), and our best candidate for being necessary for life (Study 4). These results are best explained by the hypothesis that people take life to be a natural kind subject to scientific scrutiny. [ABSTRACT FROM AUTHOR]

Molecular dynamics simulations require barostats to be performed at a constant pressure. The usual recipe is to employ the Berendsen barostat first, which displays a first-order volume relaxation efficient in equilibration but results in incorrect volume fluctuations, followed by a second-order or a Monte Carlo barostat for production runs. In this paper, we introduce stochastic cell rescaling, a first-order barostat that samples the correct volume fluctuations by including a suitable noise term. The algorithm is shown to report volume fluctuations compatible with the isobaric ensemble and its anisotropic variant is tested on a membrane simulation. Stochastic cell rescaling can be straightforwardly implemented in the existing codes and can be used effectively in both equilibration and production phases. [ABSTRACT FROM AUTHOR]

Cell penetration is a typical micromanipulation technique widely utilized in many cell biological applications. The significant cell deformation generated during penetration can mechanically damage the cell and even cause the death of the cell. Measuring the intracellular displacement resulting from cell deformation can provide a quantitative evaluation of the mechanical harm done to cells during penetration. The existing labeled intracellular displacement measurement approaches have limitations in spatial resolution and must introduce markers, which cause further harm to the cell. Moreover, label-free methods, such as traditional optical flow methods, are not suitable for measuring the inconsistent intracellular displacement distribution due to cell penetration. This paper presents a label-free noncontact method for measuring the intracellular displacements during penetration. First, based on a finite element simulation, the uneven distribution of intracellular displacements due to penetration was modeled by a quadratic model. Then, by combining the obtained displacement model with the Farnebäck dense optical flow method, a model-based optical flow method was developed to measure intracellular displacements. Finally, the method was used to ascertain the intracellular displacement in porcine oocyte penetration experiments. The forward-backward error of the proposed detection method is less than 0.5 pixels, lower by 49.3% and 26.1%, respectively, compared with two typical Farnebäck optical flow methods. This method could be used to analyze cell damage during penetration. With an appropriate extension, the method may be suitable for measuring the intracellular displacement due to cell manipulations other than penetration. [ABSTRACT FROM AUTHOR]

Since the establishment of regulations for exposure to extremely low-frequency (0–300) Hz electromagnetic fields, scientific opinion has prioritised the hypothesis that the most important parameter determining cellular behaviour has been intensity, ignoring the other exposure parameters (frequency, time, mode, waveform). This has been reflected in the methodologies of the in vitro articles published and the reviews in which they are included. A scope review was carried out, grouping a total of 79 articles that met the proposed inclusion criteria and studying the effects of the different experiments on viability, proliferation, apoptosis, oxidative stress and the cell cycle. These results have been divided and classified by frequency, intensity, exposure time and exposure mode (continuous/intermittent). The results obtained for each of the processes according to the exposure parameter used are shown graphically to highlight the importance of a good methodology in experimental development and the search for mechanisms of action that explain the experimental results, considering not only the criterion of intensity. The consequence of this is a more than necessary revision of current exposure protection regulations for the general population based on the reductionist criterion of intensity. [ABSTRACT FROM AUTHOR]

Block copolymer (BCP) surfaces permit an exquisite level of nanoscale control in biomolecular assemblies solely based on self-assembly. Owing to this, BCP-based biomolecular assembly represents a much-needed, new paradigm for creating nanobiosensors and nanobiomaterials without the need for costly and time-consuming fabrication steps. Research endeavors in the BCP nanobiotechnology field have led to stimulating results that can promote our current understanding of biomolecular interactions at a solid interface to the never-explored size regimes comparable to individual biomolecules. Encouraging research outcomes have also been reported for the stability and activity of biomolecules bound on BCP thin film surfaces. A wide range of single and multicomponent biomolecules and BCP systems has been assessed to substantiate the potential utility in practical applications as next-generation nanobiosensors, nanobiodevices, and biomaterials. To this end, this Review highlights pioneering research efforts made in the BCP nanobiotechnology area. The discussions will be focused on those works particularly pertaining to nanoscale surface assembly of functional biomolecules, biomolecular interaction properties unique to nanoscale polymer interfaces, functionality of nanoscale surface-bound biomolecules, and specific examples in biosensing. Systems involving the incorporation of biomolecules as one of the blocks in BCPs, i.e., DNA–BCP hybrids, protein–BCP conjugates, and isolated BCP micelles of bioligand carriers used in drug delivery, are outside of the scope of this Review. Looking ahead, there awaits plenty of exciting research opportunities to advance the research field of BCP nanobiotechnology by capitalizing on the fundamental groundwork laid so far for the biomolecular interactions on BCP surfaces. In order to better guide the path forward, key fundamental questions yet to be addressed by the field are identified. In addition, future research directions of BCP nanobiotechnology are contemplated in the concluding section of this Review. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a highly desmoplastic and extreme immunosuppressive tumor microenvironment (TME), which underlines the chemoresistant mechanism in PDAC. The TME components contain actionable targets for drug development. The aim of this review is to discuss the complexity of the TME, highlighting actionable drug targets that have been identified and targeted in preclinical studies and clinical trials. Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with a very poor prognosis. Despite advancements in treatment strategies, PDAC remains recalcitrant to therapies because patients are often diagnosed at an advanced stage. The advanced stage of PDAC is characterized by metastasis, which typically renders it unresectable by surgery or untreatable by chemotherapy. The tumor microenvironment (TME) of PDAC comprises highly proliferative myofibroblast-like cells and hosts the intense deposition of a extracellular matrix component that forms dense fibrous connective tissue, a process called the desmoplastic reaction. In desmoplastic TMEs, the incessant aberration of signaling pathways contributes to immunosuppression by suppressing antitumor immunity. This feature offers a protective barrier that impedes the targeted delivery of drugs. In addition, the efficacy of immunotherapy is compromised because of the immune cold TME of PDAC. Targeted therapy approaches towards stromal and immunosuppressive TMEs are challenging. In this review, we discuss cellular and non-cellular TME components that contain actionable targets for drug development. We also highlight findings from preclinical studies and provide updates about the efficacies of new investigational drugs in clinical trials. [ABSTRACT FROM AUTHOR]

The relevance of this study is conditioned by the widespread use of stem cells in veterinary medicine, a wide range of studies and ambiguous data on the oncoprotective properties of stem cells of different origins. In this regard, the purpose of this study was to investigate the course of the tumour process in Lewis lung carcinoma and the specific features of the effect of allogeneic mesenchymal stem cells of red bone marrow culture on it. The leading approach to investigating this problem was the method of modelling Lewis lung carcinoma in C57BL6 mice and the use of stem cells. The use of allogeneic mesenchymal stem cells from the bone marrow culture of C57BL6 mice with transplanted epidermoid metastatic carcinoma of the Lewis lung contributed to the activation of the tumour process. Under the influence of allogeneic mesenchymal stem cells of red bone marrow culture from Day 14 to Day 24 of the study, the body weight of mice decreased by 7.0-12.1% (P < 0.05) compared to the control, the diameter of the primary tumour increased by 1.43-1.51 times (P < 0.05), which is conditioned by the activation of primary tumour growth. The number of lymphocytes as producers of vascular growth factor in primary tumour tissue under the influence of allogeneic mesenchymal stem cells of red bone marrow culture significantly increased by 1.47 and 1.52 times on Day 18 of the experiment compared to animals of the control group and placebo (P < 0.05), respectively. This promoted angiogenesis in the primary tumour node and metastasis through the circulatory system. After administration allogeneic mesenchymal cells of red bone marrow culture to mice, a larger volume of lung metastases was recorded, which was 41.52 ± 7.9 mm3 compared to the values in the control and placebo groups, respectively, 17.94 ± 6.59 and 16.43 ± 5.32 mm3. The morphological picture of the histological sections of the primary tumour of Lewis lung carcinoma confirms all the signs of qualitative and quantitative indicators of its progression. The findings obtained are of both theoretical and practical value for clinical veterinary medicine on the use of allogeneic bone marrow mesenchymal stem cells in tumour processes. [ABSTRACT FROM AUTHOR]

Similar to invasive breast cancer, ductal carcinoma in situ is also going through a phase of changes not only from a technical but also a conceptual standpoint. From prescribing radiotherapy to everyone to personalized approaches, including radiotherapy omission, there is still a lack of a comprehensive framework to guide radiation oncologists in decision making. Many pieces of the puzzle are finding their place as high-quality data mature and are disseminated, but very often, the interpretation of risk factors and the perception of risk remain very highly subjective. Sharing the therapeutic choice with patients requires effective communication for an understanding of risks and benefits, facilitating an informed decision that does not increase anxiety and concerns about prognosis. The purpose of this narrative review is to summarize the current state of knowledge to highlight the tools available to radiation oncologists for managing DCIS, with an outlook on future developments. [ABSTRACT FROM AUTHOR]

Simple Summary: The prevalence of drug resistance has become a global concern, impacting the effectiveness of various cancer treatments. One of the mechanisms of drug resistance involves cellular stress response, in which stress granules (SGs) form against pharmacological stress. Recent research pointed out that an SGs component, DEAD-box helicase 3 X-linked (DDX3X) protein, is upregulated in multiple cancers, but its role in cancer drug resistance has yet to be fully understood. This review aims to describe the relationship among DDX3X, SGs, and drug resistance in depth. The DEAD (Asp-Glu-Ala-Asp)-box helicase 3 X-linked (DDX3X) protein participates in many aspects of mRNA metabolism and stress granule (SG) formation. DDX3X has also been associated with signal transduction and cell cycle regulation that are important in maintaining cellular homeostasis. Malfunctions of DDX3X have been implicated in multiple cancers, including brain cancer, leukemia, prostate cancer, and head and neck cancer. Recently, literature has reported SG-associated cancer drug resistance, which correlates with a negative disease prognosis. Based on the connections between DDX3X, SG formation, and cancer pathology, targeting DDX3X may be a promising direction for cancer therapeutics development. In this review, we describe the biological functions of DDX3X in terms of mRNA metabolism, signal transduction, and cell cycle regulation. Furthermore, we summarize the contributions of DDX3X in SG formation and cellular stress adaptation. Finally, we discuss the relationships of DDX3X, SG, and cancer drug resistance, and discuss the current research progress of several DDX3X inhibitors for cancer treatment. [ABSTRACT FROM AUTHOR]

Background: The effects of laser therapy on normal cells are well known and accepted, but the impact of this therapy on malignant cells are not yet fully understood. This review aims to map and outline what the scientific literature addresses on the effects of laser therapy on malignant cells. Methods: This review article followed the guidelines of the PRISMA‐ScR protocol, being all the search, analysis, and selection of articles based on it. Results: After all application of the predetermined criteria, five studies were included, dated between the years 2013 and 2021. With the complete reading of the selected studies, 100% of the articles were classified as category III of the Agency for Healthcare as Research and Quality classification. Similar themes among the papers included were investigated and compared. In these five studies, the visible red and near infrared wavelengths were used, and energy densities varied between 1 and 5 J/cm2. It was observed that low‐level laser could alter the expression of cell proliferation and migration proteins, such as cyclin D1, E‐cadherin, and β‐catenin. In addition, changes related to increased cell viability and metabolism were also identified. Conclusion: The low‐level laser seems to positively regulate the proliferative, migratory, and viability capacity of neoplastic cells, depending on the protocol used. All these studies included in the review are equivalent to in vitro studies; the cells are not in such a complex environment as is an organized tissue, making it necessary to carry out more complex tests, such as in vivo research. [ABSTRACT FROM AUTHOR]

Cell regulatory networks are the determinants of cellular homeostasis. Any alteration to these networks results in the disturbance of cellular homeostasis and induces cells towards different fates. Myocyte enhancer factor 2A (MEF2A) is one of four members of the MEF2 family of transcription factors (MEF2A-D). MEF2A is highly expressed in all tissues and is involved in many cell regulatory networks including growth, differentiation, survival and death. It is also necessary for heart development, myogenesis, neuronal development and differentiation. In addition, many other important functions of MEF2A have been reported. Recent studies have shown that MEF2A can regulate different, and sometimes even mutually exclusive cellular events. How MEF2A regulates opposing cellular life processes is an interesting topic and worthy of further exploration. Here, we reviewed almost all MEF2A research papers published in English and summarized them into three main sections: 1) the association of genetic variants in MEF2A with cardiovascular disease, 2) the physiopathological functions of MEF2A, and 3) the regulation of MEF2A activity and its regulatory targets. In summary, multiple regulatory patterns for MEF2A activity and a variety of co-factors cause its transcriptional activity to switch to different target genes, thereby regulating opposing cell life processes. The association of MEF2A with numerous signaling molecules establishes a central role for MEF2A in the regulatory network of cellular physiopathology. [ABSTRACT FROM AUTHOR]

Morbidity and mortality from ischaemic heart disease (IHD) and heart failure (HF) remain significant in Europe and are increasing worldwide. Patients with IHD or HF might benefit from novel therapeutic strategies, such as cell-based therapies. We recently discussed the therapeutic potential of cell-based therapies and provided recommendations on how to improve the therapeutic translation of these novel strategies for effective cardiac regeneration and repair. Despite major advances in optimizing these strategies with respect to cell source and delivery method, the clinical outcome of cell-based therapy remains unsatisfactory. Major obstacles are the low engraftment and survival rate of transplanted cells in the harmful microenvironment of the host tissue, and the paucity or even lack of endogenous cells with repair capacity. Therefore, new ways of delivering cells and their derivatives are required in order to empower cell-based cardiac repair and regeneration in patients with IHD or HF. Strategies using tissue engineering (TE) combine cells with matrix materials to enhance cell retention or cell delivery in the transplanted area, and have recently received much attention for this purpose. Here, we summarize knowledge on novel approaches emerging from the TE scenario. In particular, we will discuss how combinations of cell/bio-materials (e.g. hydrogels, cell sheets, prefabricated matrices, microspheres, and injectable matrices) combinations might enhance cell retention or cell delivery in the transplantation areas, thereby increase the success rate of cell therapies for IHD and HF. We will not focus on the use of classical engineering approaches, employing fully synthetic materials, because of their unsatisfactory material properties which render them not clinically applicable. The overall aim of this Position Paper from the ESC Working Group Cellular Biology of the Heart is to provide recommendations on how to proceed in research with these novel TE strategies combined with cell-based therapies to boost cardiac repair in the clinical settings of IHD and HF. [ABSTRACT FROM AUTHOR]

In this issue we highlight three recent papers that demonstrate new strategies to extend the capabilities of paper microfluidics. Paper (a mesh of porous fibers) has a long history as a substrate to perform biomolecular assays. Traditional lateral flow immunoassays (LFAs) are widely used for rapid diagnostic tests, and perform well when a yes or no answer is required and the analyte of interest is at relatively high concentrations. High concentrations are required because usually only a small volume of analyte-containing fluid flows past the detection region, leading to a limited signal. Further, the small pores within paper matrices prevent the use of paper to control the flow of larger particles and cells, limiting the use of paper microfluidics for cell-based diagnostics. The work we highlight addresses these important unmet challenges in paper microfluidics: enriching low concentration analytes to a higher concentration in a smaller volume that can be processed effectively, and using paper to pump flows in larger channels amenable to cells. Applying these new approaches may allow diagnosis of disease states currently technically unachievable using current LFA systems, while maintaining many of the “un-instrumented” advantages of an assay on self-wicking paper. [ABSTRACT FROM AUTHOR]

Atomic Force Microscopy (AFM) is a powerful tool enabling the mechanical characterization of biological materials at the nanoscale. Since biological materials are highly heterogeneous, their mechanical characterization is still considered to be a challenging procedure. In this paper, a new approach that leads to a 3-dimensional (3D) nanomechanical characterization is presented based on the average Young's modulus and the AFM indentation method. The proposed method can contribute to the clarification of the variability of the mechanical properties of biological samples in the 3-dimensional space (variability at the x–y plane and depth-dependent behavior). The method was applied to agarose gels, fibroblasts, and breast cancer cells. Moreover, new mathematical methods towards a quantitative mechanical characterization are also proposed. The presented approach is a step forward to a more accurate and complete characterization of biological materials and could contribute to an accurate user-independent diagnosis of various diseases such as cancer in the future. [ABSTRACT FROM AUTHOR]

Simple Summary: This scoping review of systematic reviews aims to accurately assess the degree of existing scientific evidence on the cancer hallmarks proposed in 2011 by Hanahan and Weinberg, in the form of systematic reviews and meta-analyses, applied to oral potentially malignant disorders, oral cavity and oropharyngeal squamous cell carcinomas, in order to point out gaps in evidence and lines of research that should be implemented in the future to improve the malignant transformation prediction, diagnosis and/or prognosis of these diseases. In 2000 and 2011, Hanahan and Weinberg published two papers in which they defined the characteristics that cells must fulfil in order to be considered neoplastic cells in all types of tumours that affect humans, which the authors called "hallmarks of cancer". These papers have represented a milestone in our understanding of the biology of many types of cancers and have made it possible to reach high levels of scientific evidence in relation to the prognostic impact that these hallmarks have on different tumour types. However, to date, there is no study that globally analyses evidence-based knowledge on the importance of these hallmarks in oral and oropharyngeal squamous cell carcinomas. For this reason, we set out to conduct this scoping review of systematic reviews with the aim of detecting evidence gaps in relation to the relevance of the cancer hallmarks proposed by Hanahan and Weinberg in oral and oropharyngeal cancer, and oral potentially malignant disorders, and to point out future lines of research in this field. [ABSTRACT FROM AUTHOR]

Characterization of a newly developed class of passive nonreciprocal acoustic metamaterials is presented in an attempt to quantify their ability of controlling the flow and distribution of acoustic energy in acoustic cavities and systems. The proposed nonreciprocal acoustic metamaterial (NAMM) cell consists of a one-dimensional acoustic cavity provided with piezoelectric flexible boundaries connected to an array of anti-parallel diodes to introduce the nonlinear damping effect that tends to break the reciprocity of the energy flow through the NAMM cell. A comprehensive experimental characterization of prototypes of the NAMM cells is presented here in order to investigate the effect of various anti-parallel diode arrangements on the nonreciprocal behavior of the cell. Furthermore, the experimental characterization aims also at demonstrating the effectiveness of the proposed NAMM in tuning the directivity, flow, and distribution of acoustic energy propagating through the metamaterial. [ABSTRACT FROM AUTHOR]

Background: Encephalitis caused by dengue virus (DENV) is considered a manifestation of severe dengue. Tanreqing injection (TRQ) is a well-known Chinese patented medicine, which has been used to treat brain-related disorders by inhibiting inflammation. Nevertheless, the effects of TRQ on DENV encephalitis have not been studied. The aim of this study was to evaluate the effects of TRQ on DENV encephalitis and to explore its potential mechanisms. Methods: The cytotoxicity of TRQ was examined by MTT assay, and the anti-DENV activities of TRQ in BHK-21 baby hamster kidney fibroblast were evaluated through CCK-8 and plaque assays. The expression levels of NO, IL1B/IL-1β, TNFα and IL6 were measured by qRT‒PCR and ELISA in the BV2 murine microglial cell line. The inhibitory effects of TRQ on NLRP3 inflammasome activation in BV2 cells were examined by Western blotting, qRT‒PCR and ELISA. The effects of TRQ on HT22 mouse hippocampal neuronal cells were examined by CCK-8 assay, morphology observation and flow cytometry. Moreover, a DENV-infected ICR suckling mouse model was developed to investigate the protective role of TRQ in vivo. Results: TRQ decreased the release of NO, IL6, TNFα and IL1B from BV2 cells and inhibited the activation of NLRP3. The presence of the NLRP3 agonist nigericin reversed the anti-inflammatory activities of TRQ. Furthermore, TRQ inhibited the death of HT22 cells by decreasing IL1B in DENV-infected BV2 cells. In addition, TRQ significantly attenuated weight loss, reduced clinical scores and extended the survival in DENV-infected ICR suckling mice. Critically, TRQ ameliorated pathological changes in ICR suckling mice brain by inhibiting microglia and NLRP3 activation and decreasing the production of inflammatory factors and the number of dead neurons. Conclusion: TRQ exerts potent inhibitory effects on dengue encephalitis in vitro and in vivo by reducing DENV-2-induced microglial activation and subsequently decreasing the inflammatory response, thereby protecting neurons. These findings demonstrate the potential of TRQ in the treatment of dengue encephalitis. [ABSTRACT FROM AUTHOR]

Simple Summary: Radiation therapy is widely applied to treat and alleviate cancers. However, it may lead to acute and chronic side effects in adjacent normal organs. Therefore, it is imperative to develop effective strategies for the radiological protection of the normal organs and immune system of patients during radiotherapy. In this context, we investigated a mitochondria-targeted nitronyl nitroxide radical with a tri-phenylphosphine ion (TPP-NIT) and its nanoparticles (NPs-TPP-NIT) with minimal toxicity. Through in vitro and in vivo experimental studies, we found that NPs-TPP-NIT display a protective effect against oxidative damage caused by X-ray irradiation. These findings reveal that NPs-TPP-NIT may be promising radioprotectors and could therefore be applied to protect healthy tissues and organs from radiation during the treatment of cancer with radiotherapy. Radiotherapy is a non-invasive method that is widely applied to treat and alleviate cancers. However, radiation-induced effects in the immune system are associated with several side effects via an increase in oxidative stress and the inflammatory response. Therefore, it is imperative to develop effective clinical radiological protection strategies for the radiological protection of the normal organs and immune system in these patients. To explore more effective radioprotective agents with minimal toxicity, a mitochondria-targeted nitronyl nitroxide radical with a triphenylphosphine ion (TPP-NIT) was synthesized and its nanoparticles (NPs-TPP-NIT) were prepared and characterized. The TPP-NIT nanoparticles (NPs-TPP-NIT) were narrow in their size distribution and uniformly distributed; they showed good drug encapsulation efficiency and a low hemolysis rate (<3%). The protective effect of NPs-TPP-NIT against X-ray irradiation-induced oxidative damage was measured in vitro and in vivo. The results show that NPs-TPP-NIT were associated with no obvious cytotoxicity to L-02 cells when the concentration was below 1.5 × 10−2 mmol. NPs-TPP-NIT enhanced the survival rate of L-02 cells significantly under 2, 4, 6, and 8 Gy X-ray radiation exposure; the survival rate of mice was highest after 6 Gy X-ray irradiation. The results also show that NPs-TPP-NIT could increase superoxide dismutase (SOD) activity and decrease malondialdehyde (MDA) levels after the L-02 cells were exposed to 6.0 Gy of X-ray radiation. Moreover, NPs-TPP-NIT could significantly inhibit cell apoptosis. NPs-TPP-NIT significantly increased the mouse survival rate after irradiation. NPs-TPP-NIT displayed a marked ability to reduce the irradiation-induced depletion of red blood cells (RBCs), white blood cells (WBCs), and platelets (PLTs). These results demonstrate the feasibility of using NPs-TPP-NIT to provide protection from radiation-induced damage. In conclusion, this study revealed that NPs-TPP-NIT may be promising radioprotectors and could therefore be applied to protect healthy tissues and organs from radiation during the treatment of cancer with radiotherapy. [ABSTRACT FROM AUTHOR]

Background: The placement of liners near the pulp area is essential for therapeutic effects and maintaining pulp health while stimulating the formation of tertiary dentin. This in vitro study aimed to evaluate the calcium release, pH, biocompatibility, solubility, and bioactivity of three resin-modified calcium hydroxide cavity liners. Methods: The disc specimens of each cavity liner were prepared using polyethylene molds of 7 mm in diameter and 2 mm in height (n = 10). Three light-cure liners evaluated include Ultra-Blend Plus (UB), Base-it (BI), and Master Dent (MD). The samples were then immersed in flasks containing 10 mL of distilled water. Calcium ion release, pH, and solubility were evaluated in two weeks of incubation. The cytotoxicity of extracts adjacent to the specimens was evaluated by MTT assay using NIH/3T3 cells after 1, 3, and 7 days of incubation. The ability to induce the nucleation of calcium phosphates (CaPs) after 28-day immersion in a simulated body fluid was investigated by SEM-EDX analysis. Statistical analysis was performed using ANOVA, Kruskal-Wallis, and repeated measures tests at the significant level of 0.05. Results: There was a significant difference in the release of calcium ions among the three liners investigated on days 1, 7, and 14 (p < 0.05). UB liners exhibited a significantly higher amount of calcium release than the other two liners, followed by BI, and MD. On day 1, there was no significant difference in the average pH among the three liners. However, after day 7, the MD liner showed a significant decrease in pH compared to the other two liners. BI liner demonstrated the highest level of biocompatibility, followed by the MD and UB liners. UB showed a high calcium release, solubility with no alkalizing activity, and the formation of more mature Ca-rich apatite deposits than the other two liners. Conclusion: Based on the results of this study, the cavity liner material's performance is material dependent. It can impact ion release, biocompatibility, and bioactivity which are important factors to consider in clinical practice. Further studies are needed to investigate the long-term effects of different liner materials on oral tissues. [ABSTRACT FROM AUTHOR]

This paper presents a review of the space exploration for life signature search with a special focus on the fluorescence microscope we developed for the life signature search on Mars and in other sites. Considering where, what, and how to search for life signature is essential. Life signature search exploration can be performed on the Mars surface and underground, on Venus' cloud, moon, asteroids, icy bodies (e.g., moons of Jupiter and Saturn), and so on. It is a useful strategy to consider the targeted characteristics that may be similar to those of terrestrial microorganisms, which are microorganisms with uniform spherical or rod structures with approximately 1 μm diameter surrounded by a membrane having a metabolic activity and mainly made of carbon-based molecules. These characteristics can be analyzed by using a fluorescence microscope and a combination of fluorescence pigments with specific staining characteristics to distinguish the microorganism characteristics. Section 1 introduces the space exploration for life signature search. Section 2 reviews the scientific instruments and achievements of past and ongoing Mars exploration missions closely related to astrobiology. Section 3 presents the search targets and analysis of astrobiology. Section 4 discusses the extraterrestrial life exploration methods that use a microscope together with other methods (based on mass spectrometry, morphology, detection of growth, movement, and death, etc. for microscopic and macroscopic organism). Section 5 expounds on the life signature detection fluorescence microscope, for which we have manufactured a bread board model and tested for extraterrestrial life exploration. [ABSTRACT FROM AUTHOR]

This paper proposes a resonant switching cell model to analyze and design the single-ended resonant dc–dc converters. The single-ended zero-voltage switching (ZVS) converters such as the Class E converter are efficient for megahertz switching because they feature low turn-on and turn-off switching losses. Also, they use only a ground-referenced switch, allowing a simple gate drive circuit. In this paper, we investigate the single-ended resonant converter with the small input inductance, whereas the conventional Class E converter has a large input inductance. The main contribution of this paper is to propose the resonant switching cell as an analytic model that simplifies the analysis and the design of the resonant dc–dc converters. Furthermore, this paper presents the design method of the resonant switching cell model for minimizing the resonant current magnitude and conduction loss while the converter maintains ZVS property. The experimental results from a 10-MHz GaN-based prototype demonstrate the feasibility and effectiveness of the analysis and design based on the proposed resonant switching cell model. [ABSTRACT FROM AUTHOR]

This is a broad overview and critical review of a particular group of closely related ex vivo and in vitro metabolic NMR spectroscopic methods. The scope of interest comprises studies of cultured cells and excised tissue, either intact or after physicochemical extraction of metabolites. Our detailed discussion includes pitfalls that have led to erroneous statements in the published literature, some of which may cause serious problems in metabolic and biological interpretation of results. To cover a wide range of work from relevant research areas, we consider not only the most recent achievements in the field, but also techniques that proved to be valid and successful in the past, although they may not have generated a very significant number of papers more recently. Thus, this comparative review also aims at providing background information useful for judiciously choosing between the metabolic ex vivo/in vitro NMR methods presented. Finally, the methods of interest are discussed in the context of, and in relation to, other metabolic analysis protocols such as HR-MAS and cell perfusion NMR, as well as the mass spectrometry approach. [ABSTRACT FROM AUTHOR]

Cardiac remodelling refers to changes in left ventricular structure and function over time, with a progressive deterioration that may lead to heart failure (HF) development (adverse remodelling) or vice versa a recovery (reverse remodelling) in response to HF treatment. Adverse remodelling predicts a worse outcome, whilst reverse remodelling predicts a better prognosis. The geometry, systolic and diastolic function and electric activity of the left ventricle are affected, as well as the left atrium and on the long term even right heart chambers. At a cellular and molecular level, remodelling involves all components of cardiac tissue: cardiomyocytes, fibroblasts, endothelial cells and leucocytes. The molecular, cellular and histological signatures of remodelling may differ according to the cause and severity of cardiac damage, and clearly to the global trend toward worsening or recovery. These processes cannot be routinely evaluated through endomyocardial biopsies, but may be reflected by circulating levels of several biomarkers. Different classes of biomarkers (e.g. proteins, non‐coding RNAs, metabolites and/or epigenetic modifications) and several biomarkers of each class might inform on some aspects on HF development, progression and long‐term outcomes, but most have failed to enter clinical practice. This may be due to the biological complexity of remodelling, so that no single biomarker could provide great insight on remodelling when assessed alone. Another possible reason is a still incomplete understanding of the role of biomarkers in the pathophysiology of cardiac remodelling. Such role will be investigated in the first part of this review paper on biomarkers of cardiac remodelling. [ABSTRACT FROM AUTHOR]

In this paper, an automatic vision-guided micromanipulation approach to facilitate versatile deployment and portable setup is proposed. This paper is motivated by the importance of micromanipulation and the limitations in existing automation technology in micromanipulation. Despite significant advancements in micromanipulation techniques, there remain bottlenecks in integrating and adopting automation for this application. An underlying reason for the gaps is the difficulty in deploying and setting up such systems. To address this, we identified two important design requirements, namely, portability and versatility of the micromanipulation platform. A self-contained vision-guided approach requiring no complicated preparation or setup is proposed. This is achieved through an uncalibrated self-initializing workflow algorithm also capable of assisted targeting. The feasibility of the solution is demonstrated on a low-cost portable microscope camera and compact actuated microstages. Results suggest subpixel accuracy in localizing the tool tip during initialization steps. The self-focus mechanism could recover intentional blurring of the tip by autonomously manipulating it 95.3% closer to the focal plane. The average error in visual servo is less than a pixel with our depth compensation mechanism showing better maintaining of similarity score in tracking. Cell detection rate in a 1637-frame video stream is 97.7% with subpixels localization uncertainty. Our work addresses the gaps in existing automation technology in the application of robotic vision-guided micromanipulation and potentially contributes to the way cell manipulation is performed. Note to Practitioners—This paper introduces an automatic method for micromanipulation using visual information from microscopy. We design an automatic workflow, which consists of: 1) self-initialization; 2) vision-guided manipulation; and 3) assisted targeting, and demonstrate versatile deployment of the micromanipulator on a portable microscope camera setup. Unlike existing systems, our proposed method does not require any tedious calibration or expensive setup making it mobile and low cost. This overcomes the constraints of traditional practices that confine automated cell manipulation to a laboratory setting. By extending the application beyond the laboratory environment, automated micromanipulation technology can be made more ubiquitous and expands readily to facilitate field study. [ABSTRACT FROM AUTHOR]

MCL, Mincle and Dectin‐2 are C‐type lectin receptors expressed by subsets of myeloid cells, and their genes cluster together in the APLEC/Dectin‐2 gene complex. We have previously shown that MCL and Mincle form a heterodimer in the rat, and others have shown that MCL and Dectin‐2 form a heterodimer in the mouse. In the rat, Dectin‐2 is a pseudogene, but here, we examine the association of the three receptors in human. In co‐transfection experiments analyzed with flow cytometry and immunoprecipitation, we here show that human MCL and Mincle form a disulphide‐linked heterodimer that associates with the signalling adaptor molecule FcεRIγ, in accordance with our previous findings in the rat. In contrast to previous findings in the rat, data in this paper indicate a direct association of MCL with FcεRIγ, as previously shown for mouse MCL. We were unable to demonstrate the formation of a heterodimer between human MCL and Dectin‐2. Thus, despite similarities, there may be important differences in the conformation of these receptors between rat, mouse and human, and this may have functional consequences. [ABSTRACT FROM AUTHOR]

Objective: To explore the impacts of bone marrow mesenchymal stem cells (BMSCs) intervention on the neuronal withering and autophagy in rats after subarachnoid hemorrhage (SAH) in rats and its process. Methods: forty-eight SD rats (males), were randomly assigned to the followings: sham surgery (Sham) group, modeling (SAH) group, modeling group + bone marrow mesenchymal stem cells (BMSCs) group, the modeling group + BMSCs + AMPK inhibitor (Compound C) group, twelve rats in each group. Except Sham group, other groups formed SAH samples with intravascular points. Separate groups Compound C and BMSCs, respectively Compound C and 10 µL of normal saline were injected into the left lateral ventricle of rats using a stereoscope brain machine 30 minutes before modeling, and 2 µL concentration is 1x108/mL cell suspension was injected into the ventricles of the brain 1 hour after the model was established. Observe whether the rats have severe brain swelling. Garcia were used to test the neural function of rats. TUNEL staining was used to monitor neuronal apoptosis in the rat hippocampal gyrus. Immunohistochemical fluorescence reflected the expression of two proteins, LC3-II and Beclin-1, in rat hippocampal gyrus. Western blotting is applied to measure the expressions of autophagy-associated proteins in the AMPK pathway. Results: Compared with the group undergoing sham-surgery, brain edema worsened in the model group, neuronal apoptosis rate was increased, neural function was weakened, Protein granules decreased (P<0.05) and expression levels of p-AMPK and other proteins decreased (P<0.05); brain swelling and neuronal apoptosis were reduced in the BMSCs group by comparison with the modeling group's, with substantial elevation in the expression of proteins comprising LC3-II, Beclin-1, and p-AMPK. And the standard of p-mTOR protein expression was considerably lessened (P<0.05); rats belonging to group compound C showed increased brain swelling which is relative to that of BMSCs group, increased neuronal apoptosis, decreased neuronal function (P<0.05), increased p-AMPK protein expression, and decreased LC3-II, Beclin-1, and p-mTOR protein expression (P<0.05). Conclusion: BMSCs transplantation can reduce neuronal apoptosis after SAH; its principle may be to activate AMPK/mTOR pathway, strengthen autophagy of neurons, and thus inhibit their transformation to apoptosis. [ABSTRACT FROM AUTHOR]

Tumours do not exist in isolation from the organism; their growth, proliferation, motility, and immunosuppressive response are intricately connected to the tumour's microenvironment. As tumour cells and the microenvironment coevolve, an inflammatory microenvironment ensues, propelling the phenomenon of inflammation-cancer transformation—an idea proposed by modern medicine. This review aims to encapsulate the array of representative factors within the tumour's inflammatory microenvironment, such as interleukins (IL-6, IL-10, IL-17, IL-1β), transforming growth factor-beta (TGF-β), interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMPs). Moreover, drawing upon research in traditional Chinese medicine (TCM) and pharmacology, we explore the delicate interplay between these factors and tumour-associated inflammatory cells: tumour-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), tumour-associated neutrophils (TANs) and dendritic cells (DCs). By analyzing the tumour-promoting effects of these entities, we delve into the connotations of Academician Tong Xiao-lin's novel model of "state-target differentiation" and its application in the diagnosis and treatment of tumours. Our aim is to enhance the precision and targeting of tumour treatment in clinical practice. Delving deeper into our understanding of tumour pathogenesis through the lens of modern medicine, we discern the key etiology and pathogenesis throughout the entire developmental stage of tumours, unveiling the evolutionary patterns of Chinese Medicine (CM) states: heat state → phlegm state → stagnation state → deficiency state. Building upon this foundation, we devised a state-regulating formula. Simultaneously, drawing on pharmacological research in traditional Chinese medicine (TCM), we meticulously identified a range of targeted drugs that effectively modulate the aforementioned tumour-related mediators. This comprehensive strategy—a harmonious integration of state identification, target recognition, and simultaneous regulation—aims to elevate clinical efficacy. The fusion of TCM with Western medicine in tumour treatment introduces novel dimensions to the precise and refined application of TCM in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Although clinically, Alzheimer's disease (AD) and vascular dementia (VaD) are the two major types of dementia, it is unclear whether the biophotonic activities associated with cognitive impairments in these diseases share common pathological features. Methods: We used the ultraweak biophoton imaging system (UBIS) and synaptosomes prepared by modified percoll method to directly evaluate the functional changes in synapses and neural circuits in AD and VaD model animals. Results: We found that biophotonic activities induced by glutamate were significantly reduced and spectral blueshifted in synaptosomes and brain slices. These changes could be partially reversed by pre-perfusion of the ifenprodil, a specific antagonist of the GluN2B subunit of N-methyl-D-aspartate receptors (NMDARs). Conclusion: Our findings suggest that AD and VaD pathology present similar but complex changes in biophotonic activities and transmission at synapses and neural circuits, implying that communications and information processing of biophotonic signals in the brain are crucial for advanced cognitive functions. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]