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The evolution of analytical techniques has opened the possibilities of accurate analyte detection through a straightforward method and short acquisition time, leading towards their applicability to identify medical conditions. Surface-enhanced Raman spectroscopy (SERS) has long been proven effective for rapid detection and relies on SERS spectra that are unique to each specific analyte. However, the complexity of viruses poses challenges to SERS and hinders further progress in its practical applications. The principle of SERS revolves around the interaction among substrate, analyte, and Raman laser, but most studies only emphasize the substrate, especially label-free methods, and the synergy among these factors is often ignored. Therefore, issues related to reproducibility and consistency of results, which are crucial for medical diagnosis and are the main highlights of this review, can be understood and largely addressed when considering these interactions. Viruses are composed of multiple surface components and can be detected by label-free SERS, but the presence of non-target molecules in clinical samples interferes with the detection process. Appropriate spectral data processing workflow also plays an important role in the interpretation of results. Furthermore, integrating machine learning into data processing can account for changes brought about by the presence of non-target molecules when analyzing spectral features to accurately group the data, for example, whether the sample corresponds to a positive or negative patient, and whether a virus variant or multiple viruses are present in the sample. Subsequently, advances in interdisciplinary fields can bring SERS closer to practical applications.

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The phenomenon of compartmentalization is one of the key traits of life. Biological membranes and histohematic barriers protect the internal environment of the cell and organism from endogenous and exogenous impacts. It is known that the integrity of these barriers decreases with age due to the loss of homeostasis, including age-related gene expression profile changes and the abnormal folding/assembly, crosslinking, and cleavage of barrier-forming macromolecules in addition to morphological changes in cells and tissues. The critical molecular and cellular mechanisms involved in physiological barrier integrity maintenance and aging-associated changes in their functioning are reviewed on different levels: molecular, organelle, cellular, tissue (histohematic, epithelial, and endothelial barriers), and organ one (skin). Biogerontology, which studies physiological barriers in the aspect of age, is still in its infancy; data are being accumulated, but there is no talk of the synthesis of complex theories yet. This paper mainly presents the mechanisms that will become targets of anti-aging therapy only in the future, possibly: pharmacological, cellular, and gene therapies, including potential geroprotectors, hormetins, senomorphic drugs, and senolytics.

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Pectic polysaccharides have long been a challenging subject of research in the field of macromolecular science, given their complex structures and wide range of biological effects. However, the extensive exploration of pectic polysaccharides has been limited due to the intricacy of their structures. In this comprehensive review, we aim to provide a thorough summary of the existing knowledge on pectic polysaccharides, with a particular focus on aspects such as classification, extraction methodologies, structural analysis, elucidation of biological activities, and exploration of target molecules and signaling pathways. By conducting a comprehensive analysis of existing literature and research achievements, we strive to establish a comprehensive and systematic framework that can serve as a reference and guide for further investigations into pectic polysaccharides. Furthermore, this review delves into the applications of pectic polysaccharides beyond their fundamental attributes and characteristics, exploring their potential in fields such as materials, food, and pharmaceuticals. We pay special attention to the promising opportunities for pectic polysaccharides in the pharmaceutical domain and provide an overview of related drug development research. The aim of this review is to facilitate a holistic understanding of pectic polysaccharides by incorporating multifaceted research, providing valuable insights for further in-depth investigations into this significant polymer.

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Asthma is a major noncommunicable disease, affecting both children and adults, and represents one of the major causes leading to high health care costs due to the need for chronic pharmacological treatments. The standard gold therapy of inflammation in asthmatic patients involves the use of glucocorticoids even if their chronic use is often related to serious adverse effects. Growing evidence suggests the biological relevance of hydrogen sulfide (H2S) in the pathogenesis of airway diseases. Hence, aiming to associate the beneficial effects of steroidal anti-inflammatory drugs (SAIDs) to H2S biological activity, we designed and synthesized novel multi-target molecules by chemically combining a group of glucocorticoids, usually employed in asthma treatment, with an isothiocyanate moiety, well-known for its H2S releasing properties. Firstly, the synthesized compounds have been screened for their H2S-releasing profile using an amperometric approach and for their in vitro effects on the degranulation process, using RBL-2H3 cell line. The physicochemical profile, in terms of solubility, chemical and enzymatic stability of the newly hybrid molecules, has been assessed at different physiological pH values and in esterase-rich medium (bovine serum albumin, BSA). The selected compound 5c, through both its corticosteroid and H2S releasing component, has been evaluated in vivo in experimental model of asthma. The compound 5c inhibited in vivo all asthma features with a significative effect on the restoration of pulmonary structure and reduction of lung inflammation.

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In this study, highly sensitive flexible AuNPs@ polyimide SERS heating chips (APHC) were fabricated for in situ collecting and detecting TNT. Large-scale AuNPs arrays were synthesized by liquid-liquid interface self-assembly and transferred to polyimide heating film as SERS substrates. 4-ATP and AgNPs functionalized on APHC were used as capture means and signal amplifiers, combining with TNT to form the AuNPs-TNT-AgNPs "sandwich" structure. This flexible APHC chip showed high sensitivity as enhancement factor was 5.5×105, and good repeatability and stability (RSD<10%). It was applied to detect TNT solutions with a low concentration of 10-9 M, and showed a good linear response in the range from 10-5 to 10-9 M (R2 = 0.986). In addition, the detection method also had good selectivity and no response to various TNT analogs. More important, combing with the thermal enrichment strategy, TNT dispersed in environmental samples such as soil, fruit and clothing would be enriched as vapor then collected and detected by APHC. This APHC device shows great potential for in situ sensing platforms, due to its sensitivity, high efficiency, and excellent portability.

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Polymers are extensively used in food and beverage packaging to shield against contaminants and external damage due to their barrier properties, protecting the goods inside and reducing waste. However, current trends in polymers for food, water, and beverage applications are moving forward into the design and preparation of advanced polymers, which can act as active packaging, bearing active ingredients in their formulation, or controlling the head-space composition to extend the shelf-life of the goods inside. In addition, polymers can serve as sensory polymers to detect and indicate the presence of target species, including contaminants of food quality indicators, or even to remove or separate target species for later quantification. Polymers are nowadays essential materials for both food safety and the extension of food shelf-life, which are key goals of the food industry, and the irruption of smart materials is opening new opportunities for going even further in these goals. This review describes the state of the art following the last 10 years of research within the field of food and beverage polymer's applications, covering present applications, perspectives, and concerns related to waste generation and the circular economy.

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Nucleic-acid aptamers consisting in single-stranded DNA oligonucleotides emerged as very promising biorecognition elements for electrochemical biosensors applied in various fields such as medicine, environmental, and food safety. Despite their outstanding features, such as high-binding affinity for a broad range of targets, high stability, low cost and ease of modification, numerous challenges had to be overcome from the aptamer selection process on the design of functioning biosensing devices. Moreover, in the case of small molecules such as metabolites, toxins, drugs, etc., obtaining efficient binding aptamer sequences proved a challenging task given their small molecular surface and limited interactions between their functional groups and aptamer sequences. Thus, establishing consistent evaluation standards for aptamer affinity is crucial for the success of these aptamers in biosensing applications. In this context, this article will give an overview on the thermodynamic and structural aspects of the aptamer-target interaction, its specificity and selectivity, and will also highlight the current methods employed for determining the aptamer-binding affinity and the structural characterization of the aptamer-target complex. The critical aspects regarding the generation of aptamer-modified electrodes suitable for electrochemical sensing, such as appropriate bioreceptor immobilization strategy and experimental conditions which facilitate a convenient anchoring and stability of the aptamer, are also discussed. The review also summarizes some effective small molecule aptasensing platforms from the recent literature.

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Acute-on-chronic liver failure (ACLF) is a group of clinical syndromes related to severe acute liver function impairment and multiple-organ failure caused by various acute triggering factors on the basis of chronic liver disease. Due to its severe condition, rapid progression, and high mortality, it has received increasing attention. Recent studies have shown that the pathogenesis of ACLF mainly includes direct injury and immune injury. In immune injury, cytotoxic T lymphocytes (CTLs), dendritic cells (DCs), and CD4+ T cells accumulate in the liver tissue, secrete a variety of proinflammatory cytokines and chemokines, and recruit more immune cells to the liver, resulting in immune damage to the liver tissue, massive hepatocyte necrosis, and liver failure, but the key molecules and signaling pathways remain unclear. The "danger hypothesis" holds that in addition to the need for antigens, damage-associated molecular patterns (DAMPs) also play a very important role in the occurrence of the immune response, and this hypothesis is related to the pathogenesis of ACLF. Here, the research status and development trend of ACLF, as well as the mechanism of action and research progress on various DAMPs in ACLF, are summarized to identify biomarkers that can predict the occurrence and development of diseases or the prognosis of patients at an early stage.

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Based on the mechanism of neuropathic pain induction, a new type of bifunctional hybrid peptidomimetics was obtained for potential use in this type of pain. Hybrids consist of two types of pharmacophores that are connected by different types of linkers. The first pharmacophore is an opioid agonist, and the second pharmacophore is an antagonist of the pronociceptive system, i.e., an antagonist of the melanocortin-4 receptor. The results of tests in acute and neuropathic pain models of the obtained compounds have shown that the type of linker used to connect pharmacophores had an effect on antinociceptive activity. Peptidomimetics containing longer flexible linkers were very effective at low doses in the neuropathic pain model. To elucidate the effect of linker lengths, two hybrids showing very high activity and two hybrids with lower activity were further tested for affinity for opioid (mu, delta) and melanocortin-4 receptors. Their complexes with the target receptors were also studied by molecular modelling. Our results do not show a simple relationship between linker length and affinity for particular receptor types but suggest that activity in neuropathic pain is related to a proper balance of receptor affinity rather than maximum binding to any or all of the target receptors.

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Glucocorticoid-induced cataract (GIC)-associated biomarkers were screened by ceRNA network construction. The GIC samples' GSE3040 were obtained from the NCBI-GEO database. R's Limma package was used to identify differentially expressed RNAs (DERs) between the normal and GIC samples group (4- and 16-h). The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis for the mRNAs in the constructed GIC lncRNA-miRNA-mRNA ceRNA regulation network was implemented. A total of 1665 and 1443 DERs were obtained in the 4- and 16-h group, respectively. At two time points, 256 overlapping DERs were identified, of which 210 (17 lncRNAs and 203 mRNAs) had significant differential expression (4 down- and 206 up-regulated). A total of 534 co-expressed ligation pairs (all up-regulated) were obtained. A ceRNA regulation network was constructed. RPS6KA5, GAB1, CCR7, CCL2, COL4A4, and PPARG were obtained and significantly enriched in the 4 KEGG signaling pathways and were featured as GIC target molecules.

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BACKGROUND: Based on the encouraging results of phase III clinical trial of ß-Dmannuronic acid (M2000) (as a new anti-inflammatory drug) in patients with RA, in this study, we aimed to evaluate the effects of this drug on the expression of chemokines and their receptors in PBMCs of RA patients. METHODS: PBMCs of RA patients and healthy controls were separated and the patients' cells were treated with low, moderate and high doses (5, 25 and 50 µg/mL) of M2000 and optimum dose (1 µg/mL) of diclofenac, as a control in RPMI-1640 medium. Real-time PCR was used for evaluating the mRNA expression of CXCR3, CXCR4, CCR2, CCR5 and CCL2/MCP-1. Cell surface expression of CCR2 was investigated using flow cytometry. RESULTS: CCR5 mRNA expression reduced significantly, after treatment of the patients' cells with all three doses of M2000 and optimum dose of diclofenac. CXCR3 mRNA expression was downregulated significantly followed by the treatment of these cells with moderate and high doses of M2000 and optimum dose of diclofenac. CXCR4 mRNA expression declined significantly after the treatment of these cells with moderate and high doses of M2000. CCL2 mRNA expression significantly reduced only followed by the treatment of these cells with a high dose of M2000, whereas, mRNA and cell surface expressions of CCR2 diminished significantly followed by the treatment of these cells with a high dose of M2000 and optimum dose of diclofenac. CONCLUSION: According to our results, M2000 through the down-regulation of chemokines and their receptors may restrict the infiltration of immune cells into the synovium.

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PURPOSE OF REVIEW: This review a highlights that to use artificial intelligence (AI) tools effectively for hypertension research, a new foundation to further understand the biology of hypertension needs to occur by leveraging genome and RNA sequencing technology and derived tools on a broad scale in hypertension. RECENT FINDINGS: For the last few years, progress in research and management of essential hypertension has been stagnating while at the same time, the sequencing of the human genome has been generating many new research tools and opportunities to investigate the biology of hypertension. Cancer research has applied modern tools derived from DNA and RNA sequencing on a large scale, enabling the improved understanding of cancer biology and leading to many clinical applications. Compared with cancer, studies in hypertension, using whole genome, exome, or RNA sequencing tools, total less than 2% of the number cancer studies. While true, sequencing the genome of cancer tissue has provided cancer research an advantage, DNA and RNA sequencing derived tools can also be used in hypertension to generate new understanding how complex protein network, in non-cancer tissue, adapts and learns to be effective when for example, somatic mutations or environmental inputs change the gene expression profiles at different network nodes. The amount of data and differences in clinical condition classification at the individual sample level might be of such magnitude to overwhelm and stretch comprehension. Here is the opportunity to use AI tools for the analysis of data streams derived from DNA and RNA sequencing tools combined with clinical data to generate new hypotheses leading to the discovery of mechanisms and potential target molecules from which drugs or treatments can be developed and tested. Basic and clinical research taking advantage of new gene sequencing-based tools, to uncover mechanisms how complex protein networks regulate blood pressure in health and disease, will be critical to lift hypertension research and management from its stagnation. The use of AI analytic tools will help leverage such insights. However, applying AI tools to vast amounts of data that certainly exist in hypertension, without taking advantage of new gene sequencing-based research tools, will generate questionable results and will miss many new potential molecular targets and possibly treatments. Without such approaches, the vision of precision medicine for hypertension will be hard to accomplish and most likely not occur in the near future.

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Context: miR-146a, its targets (IRAK1, TRAF6) and NF-κB transcription factor play a fundamental role in rheumatoid arthritis (RA). Positive effects of drug ß-d-mannuronic acid (M2000) were proven on their expression in the HEK-Blue hTLR2 cell line, and results of its phase III clinical trial on RA patients were encouraging.Objective: This research aimed to investigate the effects of M2000 on expression of these genes and serum levels of IL-6 and TNF-α as pro-inflammatory cytokines in RA patients.Material and methods: In this study (Trial Registration Number: IRCT2017100213739N10), 12 RA patients (according to the American College of Rheumatology criteria) and 12 healthy subjects (as control group) were selected. The gene expression of miR-146a, IRAK1, TRAF6, and NF-κB were measured at the baseline and after 12 weeks M2000 therapy, using quantitative real-time PCR method. Moreover, the serum levels of IL-6 and TNF-α were evaluated at the similar times by ELISA method.Results: Our findings showed that the gene expression of miR-146a, IRAK1, TRAF6, and NF-κB significantly decreased after 12 weeks M2000 therapy in RA patients (0.81-, 0.68-, 0.79-, 0.82-fold, with p < .05, p < .01, p < .01, p < .05, respectively). Furthermore, the serum levels of IL-6 and TNF-α significantly reduced in these patients after 12 weeks M2000 therapy (both with p < .05).Conclusions: The present research results determined the part of molecular mechanisms of drug M2000 in RA treatment, based on the expression and function modification of miR-146a, IRAK1, TRAF6, NF-κB, IL-6 and TNF-α.

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The positive impacts of ß-d-mannuronic acid (M2000) on the gene expression of miR-155, its target molecules (SOCS1 and SHIP1), and NF-κB transcription factor were demonstrated in a study using the HEK293-TLR2 cell line. This new drug has been approved as a safe and effective medication by a randomized, multinational, phase III clinical trial on RA patients. The present study aimed to evaluate the oral administration effect of M2000 on the expression levels of the mentioned genes in RA patients. This research was conducted on 12 RA patients and 12 healthy individuals. After extraction of total RNA from PBMCs of patients and synthesis of cDNA, the expression levels of miR-155, SOCS1, SHIP1, and NF-κB genes were measured through quantitative Real-time PCR at baseline and after 12 weeks of M2000 therapy. Our findings showed that the miR-155 gene expression level significantly decreased in the M2000-treated patients compared with the baseline (0.76-fold, with p < .05). The expression levels of SOCS1 and SHIP1 genes significantly increased in the patients treated with M2000 compared with the before treatment (1.46-, 1.54-fold, with p < .01, p < .05, respectively). In addition, it was found that the gene expression level of the NF-κB transcription factor significantly reduced in M2000-treated patients compared with the baseline (0.81-fold, with p < .05). This study showed that the oral administration of M2000 was able to reduce the expression of the miR-155, increase the expression of SOCS1 and SHIP1, and decrease the NF-κB gene expression (Trial Registration Number: IRCT2017100213739N10).

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Diseases caused by bacterial infections, especially drug-resistant bacteria have seriously threatened human health throughout the world. It has been predicted that antimicrobial resistance alone will cause 10 million deaths per year and that early diagnosis and therapy will efficiently decrease the mortality rate caused by bacterial infections. Considering this severity, it is urgent to develop effective methods for the early detection, prevention and treatment of these infections. Until now, numerous efforts based on nanoparticles have been made to detect and kill pathogenic bacteria. Iron oxide-based magnetic nanoparticles (MNPs), as potential platforms for bacteria detection and therapy, have drawn great attention owing to their magnetic property. These MNPs have also been broadly used as bioimaging contrast agents and drug delivery and magnetic hyperthermia agents to diagnose and treat bacterial infections. This review therefore overviews the recent progress on MNPs for bacterial detection and therapy, including bacterial separation and enrichment in vitro, bacterial infection imaging in vivo, and their therapeutic activities on pathogenic bacteria. Furthermore, some bacterial-specific targeting agents, used to selectively target the pathogenic bacteria, are also introduced. In addition, the challenges and future perspective of MNPs for bacterial diagnosis and therapy are given at the end of this review. It is expected that this review will provide a better understanding toward the applications of MNPs in the detection and therapy of bacterial infections.

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The standard approach for quantitative estimation of genetic materials with qPCR is calibration with known concentrations for the target substance, in which estimates of the quantification cycle (Cq ) are fitted to a straight-line function of log(N 0), where N 0 is the initial number of target molecules. The location of Cq for the unknown on this line then yields its N 0. The most widely used definition for Cq is an absolute threshold that falls in the early growth cycles. This usage is flawed as commonly implemented: threshold set very close to the baseline level, which is estimated separately, from designated "baseline cycles." The absolute threshold is especially poor for dealing with the scale variability often observed for growth profiles. Scale-independent markers, like the first derivative maximum (FDM) and a relative threshold (Cr ) avoid this problem. We describe improved methods for estimating these and other Cq markers and their standard errors, from a nonlinear algorithm that fits growth profiles to a 4-parameter log-logistic function plus a baseline function. Further, by examining six multidilution, multireplicate qPCR data sets, we find that nonlinear expressions are often preferred statistically for the dependence of Cq on log(N 0). This means that the amplification efficiency E depends on N 0, in violation of another tenet of qPCR analysis. Neglect of calibration nonlinearity leads to biased estimates of the unknown. By logic, E estimates from calibration fitting pertain to the earliest baseline cycles, not the early growth cycles used to estimate E from growth profiles for single reactions. This raises concern about the use of the latter in lengthy extrapolations to estimate N 0. Finally, we observe that replicate ensemble standard deviations greatly exceed predictions, implying that much better results can be achieved from qPCR through better experimental procedures, which likely include reducing pipette volume uncertainty.

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Using in vitro procedures to prepare newly excysted metacercariae and gut-penetrated juvenile Fasciola gigantica, the ultrastructural features of the tegumental syncytium and perikarya of these ephemeral stages in the host-invasion process were compared. The T0-type tegumental cells in newly excysted metacercariae are packed with stored T0 granules which, following transport to the surface membrane of the syncytium, discharge by exocytosis to maintain the glycocalyx. The T0 cells become depleted of T0 granules during the penetration process, shrink in size, and initiate autophagy in the cytoplasm to facilitate metamorphosis from a storage function to active biosynthesis. The novel products appear to include lysosomes which contribute to the autophagosomes, and T1 granules, necessary for maintenance of the glycocalyx and immunoprotection, as the invasion process continues into the host liver. Residual bodies, the end-products of autophagy, are eliminated from the apical membrane of the tegumental syncytium into the host-parasite interface. There they may present a transient source of parasite-derived molecules, including lysosomal cathepsin-type proteases, with potential for interaction with the host's immune system, and so might be exploited as targets for vaccinal and immunomodulatory studies.

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