Proteases represent common targets in combating infectious diseases including COVID-19. The 3-chymotrypsin-like protease (3CLpro) is a validated molecular target for COVID-19 and it is key for developing potent and selective inhibitors for inhibiting viral replication of SARS-CoV-2. In this review, we discuss structural relationships and diverse subsites of 3CLpro, shedding light on the pivotal role of dimerization and active site architecture in substrate recognition and catalysis. Our analysis of bioinformatics and other published studies unveil a proposal of a novel catalytic mechanism for the SARS-CoV-2 polyprotein cleavage by 3CLpro, centering on the triad mechanism involving His41-Cys145-Asp187 and its indispensable role in viral replication. Recognizing Asp187 as a crucial component in the catalytic process underscores its significance as a fundamental pharmacophoric element in drug design. Next, we provide an overview of both covalent and non-covalent inhibitors, elucidating advancements in drug development observed in preclinical and clinical trials. By highlighting various chemical classes and their pharmacokinetic profiles, our review aims to guide future research directions toward the development of highly selective inhibitors, underscore the significance of 3CLpro as a validated therapeutic target, and propel the progression of drug candidates through preclinical and clinical phases.

We previously reported nano-pulse treatment (NPT), a pulsed power technology, resulted in 4T1-luc mammary tumor elimination and a strong in situ vaccination, thereby completely protecting tumor-free animals against a second live tumor challenge. The mechanism whereby NPT mounts effective antitumor immune responses in the 4T1 breast cancer predominantly immunosuppressive tumor microenvironment (TME) remains unanswered. In this study, orthotopic 4T1 mouse breast tumors were treated with NPT (100 ns, 50 kV/cm, 1000 pulses, 3 Hz). Blood, spleen, draining lymph nodes and tumors were harvested at 4-hour, 8-hour, 1-, 3-, 7-day. Additional studies were conducted over 3-month posttreatment intervals for the analysis of frequencies, death and functional markers of various immune cells in addition to suppressor function of regulatory T cells (Tregs). NPT was verified to elicit strong in situ vaccination (ISV) against breast cancer and promoted both acute and long-term T cell memory. NPT abolished immunosuppressive dominance systemically and in the TME by substantially reducing Tregs, myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs). NPT induced apoptosis in Tregs and TAMs. It also functionally diminished the Treg suppression capacity, likely explained by the downregulation of activation markers, particularly 4-1BB and TGFβ, and a phenotypic shift from predominantly activated (CD44+CD62L-) to naïve (CD44-CD62L+) Tregs. Importantly, NPT selectively induced apoptosis in activated Tregs and spared effector CD4+ and CD8+ T cells. These changes were followed by a concomitant rise in CD8+CD103+ tissue-resident memory T cells and TAM M1 polarization. These findings indicate that NPT effectively switches the TME and secondary lymphatic systems from an immunosuppressive to an immunostimulatory state allowing cytotoxic T-cell function and immune memory formation to eliminate cancer cells and account for the NPT in situ vaccination.

Graves' disease (GD) is an autoimmune disorder in which Thyrotropin Receptor Antibodies (TRAb) continuously stimulate thyroid receptors, leading to excessive production of thyroid hormones. TRAb also affect the orbital tissues, causing Graves' ophthalmopathy. Treatment to control Graves' disease consists of antithyroid drugs, radioiodine and thyroidectomy, and through such treatments, TRAb is reduced and the disease is alleviated. The mechanism by which TRAb, which play a critical role in the pathogenesis of Graves’ disease, decreases after GD treatment is still unknown. This paper presents a theoretical mechanism of how GD patients maintain a vicious cycle and how GD treatment can reduce the TRAb levels and breaks the cycle using stress-based ideas.

A novel interaction between the enzyme platelet-activating factor acetyl hydrolase (PAF-AH) and certain non-steroidal anti-inflammatory drugs (NSAIDs), such as sulindac, celecoxib, diclofenac and nimesulide, has been uncovered by this in-silico research. PAF-AH is known for its critical role in maintaining the fluidity and functionality of cell membranes by hydrolysing phospholipids and removing oxidized fatty acids. Since tumour microenvironments are largely marked by inflammation and oxidative stress, the discovery that these non-steroidal anti-inflammatory drugs can bind to the active pocket of PAF-AH. Suggests that they may be able to modulate its activity and thereby influence its role in cancer pathogenesis. Such modulation could lead to significant anti-tumour effects, including the reduction of inflammation, the inhibition of angiogenesis and the suppression of metastasis, particularly in cancers of the breast, colon, prostate, and lung. However, in certain con-texts, this interaction may cause the opposite effect, leading to cancer development. Therefore, this study is a gateway for the development of therapeutic strategies based on PAF-AH modulation and highlights the importance of the tumour microenvironment in the assessment of potential effects of NSAIDs. Furthermore, this finding may guide the selection of NSAIDs for the anti-inflammatory treatment of cancer patients, ruling out in-discriminate use of drugs that may promote neoplastic progression. This may also indicate the potential for repositioning specific NSAIDs within cancer treatment, thereby contributing to more precise and personalized therapeutic approaches.

The present study aims to evaluate the antibacterial activity of five commercially available essential oils (EOs): Lavender (LEO), Clove (CEO), Oregano (OEO), Eucalyptus (EEO), and Peppermint (PEO) against the most-known MDR Gram-positive and Gram-negative bacteria - Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC 27853) - alone and in various combinations. Gas Chromatography-Mass Spectrometry (GC-MS) analysis established their complex composition. Then, the antibacterial activity was investigated in vitro by diffusimetric antibiogram method, using sterile cellulose discs with Ø 6 mm impregnated with 10 µl of sample and sterile borosilicate glass cylinders loaded with 100 µl of sample; MIC (µg/mL) for each EO was calculated from IZD values (mm) measured after 24 hours. The following EO combinations were evaluated: OEO+CEO, CEO+EEO, CEO+PEO, LEO+EEO, and EEO+PEO. Then, the influence of each dual combination on 3 conventional antibacterial drugs – Neomycin (NEO), Tetracycline (TET), and Bacitracin (BAC) - activity was investigated. The most active EOs against S. aureus and E. coli were LEO and OEO (IZD = 40 mm). They were followed by the CEO and EEO (IZD = 20-27 mm); PEO exhibited the lowest antibacterial activity (IZD = 15-20 mm). EEO alone showed the highest inhibitory activity on P. aeruginosa (IZD = 25-35 mm). It was followed by the CEO, LEO, and EEO (IZD = 7-11 mm), while PEO proved no antibacterial action against it (IZD = 0 mm). Only one synergic action was recorded (OEO+CEO against P. aeruginosa); EEO+PEO revealed partial synergism against S. aureus and CEO+PEO additive behavior against E. coli. Two triple associations with TET showed partial synergism against E. coli, and the other 2 ones (with NEO and TET) evidenced the same behavior against S. aureus; all contained EEO+PEO or CEO+PEO. Most combinations reported indifference. However, numerous cases were of antagonism between constituents included in double and triple combinations, and EOs with the strongest antibacterial activities belong to the highest antagonistic combinations. A consistent statistical analysis supports our results, showing that EOs with moderate antibacterial activities could generate combinations with higher inhibitory effects based on synergistic or additive interactions.

The refractive index of a liquid serves as a fundamental parameter reflecting its composition, thereby enabling the determination of component concentrations in various fields such as chemical research, food industry, and environmental monitoring. Traditional methods for refractive index (RI) measurement rely on light deflection angles at interfaces between the liquid and a material of known refractive index. In this paper, the authors present a new differential refractometer for highly sensitive measurement of RI differences between two liquid samples. Using a configuration with two cells equipped with flat parallel plates as measuring elements, the instrument facilitates accurate analysis. Namely, the sensor signals from both the solution and the solvent cuvette are generated simultaneously with one laser pulse, reducing the possible fluctuations of the laser radiation intensity. Our evaluation shows the high sensitivity of RI measurements (< 7 · 106), so this differential refractometer can be proposed not only as a high-sensitivity sensing tool that can be used for mobile detection of nanoparticles in solution samples, but also to determine the level of environmental nano-pollution using water (including rain, snow) samples from various natural as well as industrial sources, thus helping to solve some important environmental problems.

.Various synthetic nematicides are currently used effectively in the control of plant parasitic nematodes. However, these nematicides have adverse effects on humans and the environment. Neem oil is eco-friendly alternatives to synthetic nematicides. The effectiveness of repeated neem oil application in suppressing the root-knot nematodes infestation in figs seedlings was therefore examined in this study, both in its natural form (10 ml/L) and in its nano-emulsion form (5 and 7 ml/L). The recorded reduction parameters of M. incognita were J2/250g soil, galls and egg masses / 5g roots of infected fig seedlings were measured at that time, and the effects of these natural additives were compared with the Fosthiazate (Krenkel 75%EC). The impact of such soil amendments on some typical plant parameters, the total microbial count of soil, and the overall enzymatic activity of the fig rhizosphere were also included. Obtained results revealed that the soil population density of root knot nematode suppressed by 80.3% , reduction of nematode egg masses (60.4%) due to the application of nano-emulsion of neem oil (at 7ml/L). Present work recommend the use of nano-emulsion of neem oil as one of the effective and eco-friendly means to reduce the root- knot nematode on fig .

In this study, the impact of the addition of high-aspect-ratio nano-ettringite to photocurable epoxy acrylate resin was explored, with a specific focus on the changes observed in viscosity, shrinkage, tensile strength, and elongation at the break of composites formed. Herein, the nano-ettringite samples were modified using KH-570. The 3 wt% or 6 wt% KH-570-modified and unmodified nano-ettringite were dispersed into the resin by ultrasonic treatment in conjunction with mechanical stirring. The grafting effects of nano-ettringite onto KH-570 were analyzed through scanning electron microscopy (SEM), X-ray diffraction (XRD), thermogravimetric (TG) analysis, and Fourier transform infrared spectroscopy (FTIR). The results demonstrate that increased dosages of unmodified and modified nano-ettringite led to increased viscosity of the composite while reducing shrinkage. At the same dosage, the photocurable resin with modified nano-ettringite demonstrated a lower shrinkage and a higher tensile strength. Notably, when the amount of modified nano-ettringite was 3 wt%, the highest tensile strength of the composite was 64.61 MPa, presenting a 72.57% increase compared to the blank sample. Furthermore, the incorporation of modified nano-ettringite as a filler provides a new perspective for improving the performance of photocurable epoxy acrylate resin composites.

Neurodegenerative diseases (NDs) are a set of progressive, chronic, and incurable diseases characterized by the gradual loss of neurons, culminating in the decline of cognitive and/or motor functions. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common NDs and represent an enormous burden both in terms of human suffering and economic cost. The available therapies for AD and PD only provide symptomatic and palliative relief for a limited period and are unable to modify the diseases’ progression. Over the last decades, research efforts have been focused on developing new pharmacological treatments for these NDs. However, to date, no breakthrough treatment has been discovered. Hence, the development of disease-modifying drugs able to halt or reverse the progression of NDs remains an unmet clinical need. This review summarizes the major hallmarks of AD and PD and the drugs available for pharmacological treatment. It also sheds light on potential directions that can be pursued to develop of new, disease-modifying drugs to treat AD and PD, thereby decreasing the social and economic burdens linked to these NDs.

The sound and heat insulation are among the most important concerns in modern life and nonwoven composite structures are highly effective in noise reduction and heat insulation. In this study, three layered nonwoven composite structures composed of recycled polyester (r-Pet) based thermo bonded nonwoven outer layer and meltblown nonwovens from PP and PBT as inner layers were formed to provide heat and sound insulation. Fiber fineness and cross section of thermo bonded outer layer, fiber type (PP/PBT), areal weight (100/200g/m2) and process conditions (calendared/non-calendared) of meltblown inner layer have changed systematically and the influence of these parameters on thickness, bulk density, air permeability, sound absorption coefficient and thermal resistance of composite structures were analyzed statistically. Also; the results were compared with composite structures including electrospun nano fiber web inner layer and with structures without inner layer. It was determined that sound absorption coefficients ranging between 0.77-0.98 for moderate sound frequencies and 0.99-1 for higher sound frequencies were acquired with developed nonwoven composite structures. Besides, higher sound absorption coefficients were obtained as 0.71 and 0.74 for low sound frequencies such as 800 and 1000Hz, respectively. As a result of this study it can be concluded that developed nonwoven composite structures that provides better sound absorption coefficients and similar thermal conductivity values compared to previous studies and materials in the market can be used as insulation material in required areas.

The electronic structure of 7/9-AGNR superlattices with up to eight unit cells has been studied by means of state of the art Density Functional Theory (DFT) and also by two model Hamiltonians, the first one including only local interactions (Hubbard model, Hu) while the second one is extended to allow long-range Coulomb interactions (Pariser, Parr and Pople model, PPP). Both are solved within mean field approximation. At this approximation level, our calculations show that 7/9 interfaces are better described by spin non-polarized solutions than by spin-polarized wavefunctions. Consequently, both Hu and PPP Hamiltonians lead to electronic structures characterized by a gap at the Fermi level that diminishes as the size of the system increases. DFT results show similar trends although a detailed analysis of the density of states around the Fermi level shows quantitative differences with both Hu and PPP models. Before improving model Hamiltonians, we interpret the electronic structure obtained by DFT in terms of bands of topological states: topological states localized at the system edges and extended bulk topological states which interact between them due to the long-range Coulomb terms of Hamiltonian. After careful analysis of the interaction among topological sates, we find that the discrepancy between ab initio and model Hamiltonians can be resolved considering a screened long-range interaction that is implemented adding an exponential cutoff to the interaction term of PPP model. In this way, an adjusted cutoff distance λ = 2 allows a good recovery of DFT results. In view of this, we conclude that the correct description of the density of states around the Fermi level (Dirac point) needs the inclusion of long-range interactions well beyond Hubbard model but not completely unscreened as is the case for the PPP model.

The prevalence of hepatitis B and delta viruses (HBV/HDV) among people who use drugs (PWUD) remains largely unknown. In the context of one Philadelphia-based harm reduction organization (HRO), this study aimed to assess HBV/HDV prevalence and facilitate linkage to care. Participants completed a demographic HBV/HDV risk factor survey and were screened for HBV and reflexively for HDV if positive for HBV surface antigen or isolated core antibody. Fisher’s exact tests and regression were used to understand relationships between risks and HBV blood markers. Of the 498 participants, 126 (25.3%) were susceptible to HBV, 52.6% had been vaccinated against HBV, and 17.9% had recovered from a past infection. Eleven (2.2%) participants tested positive for isolated HBV core antibody, 10 (2.0%) for HBV surface antigen, and one (0.2%) for HDV antibody. History of incarceration was associated with current HBV infection, while transactional sex and experience of homelessness were predictive of previous exposure. This study found high rates of current and past HBV infection, and a 10% HBV/HDV co-infection rate. Despite availability of vaccine, one quarter of participants remained vulnerable to infection. Findings demonstrate the need to improve low-threshold HBV/HDV screening, vaccination, and linkage to care among PWUD. The study also identified gaps in the HBV/HDV care cascade, including lack of point-of-care diagnostics and lack of support for HROs to provide HBV services.

Stem cell-based regeneration strategies have shown therapeutic efficacy in various fields of regenerative medicine. These include bone healing after bone augmentation, often complicated by pain, that is managed by using non-steroidal anti-inflammatory drugs (NSAIDSs). Information is limited about how NSAIDSs affect the therapeutic potential of stem cells. Therefore, we investigated the effects of ibuprofen and diclofenac in low and high therapeutic doses on the properties of human mesenchymal stromal cells isolated from the dental pulp (DPSCs) and cultured in vitro. Ibuprofen and diclofenac significantly reduced the viability of DPSCs, while the expression of mesenchymal stem cell surface markers was unaffected. Both ibuprofen and diclofenac treatment significantly upregulated the expression of HGF, while the expression of VEGFA remained unchanged. Ibuprofen significantly altered the expression of several apoptosis-related genes, including upregulation of CASP9 and BCL2, with decreased CASP3 expression. BAK, CASP3, CASP9, and BCL2 expressions were significantly increased in the diclofenac-treated DPSCs, while no difference was demonstrated in BAX expression. Our results suggest that concomitant use of the NSAIDSs ibuprofen or diclofenac with stem cell therapy may negatively impact cell viability and alter the expression of apoptosis-related genes, which can affect the efficacy of stem cell therapy.

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Over the past years, burgeoning insights into the gut microbiota have unveiled its pivotal role in human health, influencing everything from metabolism to immune function. This article comprehensively reviews literature from the last seven years to dissect the link between gut microbiota and gestational diabetes (GD), a condition of glucose intolerance manifesting during pregnancy with long-term implications for both mother and offspring. Through detailed analysis, we highlight how alterations in the composition and function of the gut microbiota may contribute to the development of GD by influencing insulin resistance and glucose homeostasis. The underlying pathophysiological mechanisms, including dysbiosis and its impact on systemic inflammation, as well as the interplay with genetic, epigenetic, and environmental factors, are discussed. Furthermore, we review current and potential microbiota-targeted interventions, such as probiotic use, and their capability to modify GD risk and management. With a focus on recent studies, this article underscores the significance of considering microbial health in the prevention and treatment of GD, offering insights into future research directions and clinical applications to improve maternal-infant health outcomes.

Abstract For the past 70 years, dopamine hypothesis has been the key working model in schizophrenia. This has contributed to the development of numerous inhibitors of dopaminergic signaling, antipsychotic drugs, which led to rapid symptom resolution but only marginal outcome improvement. Over the past decades, there was limited research on the quantifiable pathological changes in schizophrenia, including premature cellular/neuronal, senescence, brain volume loss, attenuation of gamma oscillations on electroencephalogram and oxidation of lipids in plasma and mitochondrial membranes. We surmise that aberrant activation of aryl hydrocarbon receptor by toxins derived from the gut microbes or the environment drives premature cellular, including neuronal, senescence, a hallmark of schizophrenia. Early brain aging promotes secondary changes, including impairment and loss of mitochondria, gray matter depletion, decreased gamma oscillations, and a compensatory metabolic shift to lactate and lactylation. The aim of this narrative review is twofold: 1. To summarize what is known about premature cellular/neuronal senescence in schizophrenia or schizophrenia-like disorders. 2. To discuss novel strategies for improving long-term outcome in severe mental illness with natural senotherapeutics, membrane lipid replacement, mitochondrial transplantation, microbial phenazines, novel antioxidant phenothiazines, inhibitors of glycogen synthase kinase-3 beta, and aryl hydrocarbon receptor.

Interest on psychosocial predictors of doping has been increasing as a way of finding new approaches to reduce use of performance-enhancing drugs. This investigation aimed to test the psychometric properties of an instrument to asses doping attitudes in Brazilian athletes. The PEAS was validated to Brazilian sports through a process of translation, back-translation and content validity assessment, presenting satisfactory evidences based on its content (CVC&gt;0.80). Then, 994 athletes, from different sexes, types of sports and competitive levels, answered to the Brazilian version of the PEAS. Results showed satisfactory evidences of validity based on its response process, internal structure [X2/df = 2.04; RMSEA = 0.032 (0.026-0.038); CFI = 0.96; TLI = 0.95] and reliability (Cronbach’s α, McDonald’s ω, and CR &gt; 0.70). Network analysis was also used to further explore PEAS’s internal structure. Overall results provide support for the adoption of the PEAS for Brazilian athletes and possibly other Portuguese-speaking countries.

Recently perovskite solar cells have been paying attention of researchers. This comes from their high efficiency and stability. In this work, the change of some Optical and Electrical Properties of BaxFe(1-x)TiO4 thin films due to the change of the nanocrystal spacing and size were studied. A simple theoretical model based on the string theory was utilized to explain some of these empirical relations. The empirical results obtained indicated that an increase in the efficiency of the nano solar cell requires the energy gap to be narrow. Decreasing the nanocrystal size and spacing caused the energy gap to become narrower. The energy gap decreases also upon increasing the absorption coefficient and decreasing the transmission. This also requires increasing the conductivity and the magnetic permeability. The increase of the nanocrystal spacing decreases the absorption coefficient, electrical conductivity, and magnetic permeability, while it causes the transmission to increase. All these changes are explained using a simple string model beside Newton's laws. The capability of the string theory to explain this Nano quantum behavior comes from the fact that the string theory, like quantum theory, recognizes both the particle and the wave nature of the Nano system.

Oral bone defects occur as a result of trauma, cancer, infections, periodontal diseases, and caries. Autogenic and allogenic grafts are the gold standard used to treat and regenerate damaged or defective bone segments. However, these materials do not possess the antimicrobial properties necessary to inhibit the invasion of the numerous deleterious pathogens present in the oral microbiota. In the present study poly(ε-caprolactone) (PCL), nano-hydroxyapatite (nHAp), and a commercial extract of Humulus lupulus L. (hops) were electrospun into polymeric matrices to assess their po-tential for drug delivery and bone regeneration. The fabricated matrices were analyzed by scanning electron microscopy (SEM), tensile analysis, thermogravimetric analysis (TGA), FT-IR assay, and in vitro hydrolytic degradation. The antimi-crobial properties were evaluated against the oral pathogens Streptococcus mutans, Porphyromonas gingivalis, and Aggregatibacter actinomycetemcomitans. The cytocompatibility was proved by the MTT assay. SEM analysis proved the nanostructured matrices have suitable fiber size. The present research provides new information about the interaction of natural compounds with ceramic and polymeric biomaterials. The hop extract and other natural or synthetic medicinal agents can be effectively loaded into PCL fibers and has the potential to be used in biomedical applications.

Curcumin, a polyphenol with a rich history spanning two centuries, has emerged as a promising therapeutic agent targeting multiple signaling pathways and exhibiting cellular-level activities that contribute to its diverse health benefits. Extensive preclinical and clinical studies have demonstrated its ability to enhance the therapeutic potential of various bioactive compounds. While its reported therapeutic advantages are manifold, predominantly attributed to its antioxidant and anti-inflammatory properties, its efficacy is hindered by poor bioavailability stemming from inadequate absorption, rapid metabolism, and elimination. To address this challenge, nano-delivery systems have emerged as a promising approach, offering enhanced solubility, biocompatibility, and therapeutic effects for curcumin. We have analyzed the knowledge on curcumin nano-encapsulation and its synergistic effects with other compounds, extracted from electronic databases. We discuss the pharmacokinetic profile of curcumin, current advancements in nano-encapsulation techniques, and the combined effects of curcumin with other agents across various disorders. By unifying existing knowledge, this analysis intends to provide insights into the potential of nano-encapsulation technologies to overcome constraints associated with curcumin treatments, emphasizing the importance of combinatorial approaches in improving therapeutic efficacy. Finally, this compilation of study data aims to inform and inspire future research into encapsulating drugs with poor pharmacokinetic characteristics and investigating innovative drug combinations to improve bioavailability and therapeutic outcomes.

Newcastle disease (ND) is a viral infection that affects domestic and wild type birds especially poultry and establishing serious economic costs for poultry industry. Newcastle disease virus’ (NDV) HN membrane receptor is attractive therapeutic candidate, contributes to pathogenicity with various functions such as fusion and prevent viral self-agglutination to permit viral spread. No validated HN inhibitor has been reported yet. However, the purpose of current study was to determine potential compounds via pharmacophore-based screening of natural molecules to inhibit HN receptor of NDV. Physicochemical characteristics and phylogenetic analysis were determined to elucidate structural information and phylogeny of target protein across different species as well as members of gene family. Fill missing residues of HN target protein and evaluated via PROCHECK and VERIFY 3D. We employed shape and feature-based pharmacophore model and screen natural compound’s library through numerous scoring schemes. Top 48 hits with 0.8860 pharmacophore fit score were subjected towards structure-based molecular docking. Top 9 compounds was observed witihin the range of -8.9 to -7.5 kcal/mol binding score. Five best-fitting compounds in complex with HN receptor were subjected to predict biological activity and ADMET analysis. Top two hits were selected for MD simulations to validate binding modes and structural stability. Upon scrutinization, A1 (ZINC05223166) emerges as potential HN inhibitor to treat ND, necessitating further validation via clinical trials.

The aim of this study is to solve the problems of complicated pretreatment and high analytical cost in the detection technology of trace drug toxicants in municipal wastewater. A high-performance magnetic sorbent was synthesized for enrichment of trace drug substances in wastewater to develop magnetic solid-phase extraction pretreatment combined with the acoustic ejection mass spectrometry (AEMS) analytical methods for the molecules in wastewater drug toxicants. The magnetic nanospheres was successfully prepared by magnetic nanoparticles modified with divinylbenzene and vinyl pyrrolidone.The results showed that the linear dynamic range of 17 drugs was 1-500 ng/L, the recovery was 43%-105%, the matrix effect was more than 67%, the limit of quantitative detection was 1-2 ng/L, and the detection time of each sample was 2.98s. It can be seen that the developed magnetic solid-phase extraction (MSPE) method is a good solution to the problem of complicated pre-treatment and analytical cost in the detection of drugs in wastewater. The developed magnetic material and acoustic excitation coupled mass spectrometry analysis method can realize the low-cost, efficient enrichment and fast analysis of different kinds of drug molecules in urban sewage.

Alcoholic liver disease (ALD) is a major cause of chronic liver disease. This term covers a broad spectrum of liver lesions, from simple steatosis to alcoholic hepatitis and cirrhosis. The patho-genesis of ALD is multifactorial and not fully elucidated due to complex mechanisms related to direct ethanol toxicity with subsequent hepatic and systemic inflammation. The accumulation of pro-inflammatory cytokines and the reduction of anti-inflammatory cytokines promote the development and progression of ALD. To date, there are no targeted therapies to counteract disease progression and prevent acute liver failure. Corticosteroids reduce mortality by acting on the hepatic-systemic inflammation. On the other hand, several studies analyzed the effect of the inhibition of pro-inflammatory cytokines and the stimulation of anti-inflammatory cytokines as potential therapeutic targets in ALD. This narrative review aims to clarify the role of the cy-tokines in the pathogenesis and treatment of ALD.

In vitro fertilization (IVF) has revolutionized the field of assisted reproductive technologies (ART) by offering hope to individuals and couples struggling with infertility. Nevertheless, traditional IVF methods are not exempt from drawbacks, such as suboptimal success rates, intrusive procedures, and ethical considerations. The introduction of micro/nanorobotics in IVF offers a revolutionary chance to tackle these difficulties. This paper presents a short review of the utilization of micro/nanorobotics in IVF, investigating progress in the manipulation of sperm, retrieval of oocytes, culture of embryos, and potential future developments in this fast progressing area. In this discussion, we explore the fundamental concepts, advantages, difficulties, and possible influence of micro/nanorobotics in transforming IVF processes and enhancing patient outcomes.

Preventing the occurrence of secondary caries serves as one of the significant issues in dental clinic, thus make it indispensable to improving the properties of conventional composite resin (CR) by developing a novel CR. In present study, two groups of experimental CRs loaded with different contents of fluoride-doped nano-zirconia fillers (25 wt% and 50 wt%) were fabricated. The surface topography, mechanical performance, fluoride release, antibacterial effect, aging property and cytotoxicity of the experimental CRs were evaluated subsequently. A uniform distribution of the F-zirconia fillers over the whole surface of resin matrix could be observed. The experimental CRs showed continuous fluoride release within 28 days, which was positively correlated with the content of F-zirconia fillers. Moreover, the amount of fluoride release increased in the acidic buffer. Addition of F-zirconia fillers could improve the color stability, wear resistance and microhardness of the experimental CRs, without reducing the flexure strength. Furtherly, the fluoride ions released continuously from the experimental CRs resulted in effective contact and antibacterial properties, while they showed no cytotoxicity. As a consequence, considerations can be made to employ this new kind of composite resin loaded with fluoride-doped nano-zirconia fillers to meet clinical requirements when the antimicrobial benefits are desired.

Coccomyxa subellipsoidea KJ (C-KJ) is a green alga with unique immunoregulatory characteristics. Here, we investigated the mechanism underlying the modification of T cell function by C-KJ components. The water-soluble extract of C-KJ was fractionated into protein (P) and sugar (S) fractions [acidic (AS), basic (BS), and neutral (NS)]. These fractions were used for the treatment of peripheral blood mononuclear cells stimulated with toxic shock syndrome toxin-1. Transcriptome analysis revealed that both P and AS enhanced the expression of the genes encoding metallothionein (MT) family proteins, inflammatory factors, and T helper (Th) 17 cytokine and suppressed that of those encoding Th2 cytokines in stimulated T cells. The kinetics of MT1 and MT2A gene expression showed a transient increase in MT1 and maintenance of MT2A mRNA after T cell stimulation in the presence of AS. The kinetics of Th17-related cytokine secretion in the early period were comparable to those of MT2A mRNA. Furthermore, our findings revealed that static, a STAT-3 inhibitor, significantly suppressed MT2A gene expression. These findings suggest that the expression of MTs is involved in the immune regulatory function of C-KJ components, which is partially regulated by Th17 responses, and may help develop innovative immunoregulatory drugs or functional foods.

The swift progress in low-dimensional nanocarbons, specifically in the realm of the authentic one-dimensional carbon chain featuring sp¹ hybridization, has unveiled exciting prospects for integrating them into cutting-edge technologies across diverse industries. To fully harness their potential, precise control over the growth process is necessary to obtain desired nanostructure and functionality. However, optimizing properties through traditional approaches has been challenging due to complex interactions. To address this, we implement a focused data-driven strategy for nanocarbon inverse design by leveraging a state-of-the-art data-driven nanocarbon genome approach (NCGA). By uncovering relationships between growth parameters and resultant traits, this serves as an expedient catalyst in engineering nanostructures with tailored attributes. We introduce an extensive array of technological approaches aimed at precisely controlling the growth process. These methods encompass stimulating and precisely adjusting synergistic effects, coordinating atomic vibrations at a collective level through the implementation of multilayer nano-interfaces, harnessing the potential of active screen plasma surface engineering, utilizing nano-patterning and allotropic phase transformations, incorporating heteroatom doping, and effectively directing self-assembly. These aim to unlock nanomaterials' latent potential and reveal novel neural pathways within the data-driven NCGA, enhancing its predictive capabilities. Specifically, triggering self-organization during growth can potentially unlock previously unexplored neural pathways. The data-driven NCGA offers a paradigm shift, accelerating discovery and design of nanocarbons with optimized, application-specific properties.

Micro nano bubbles (MNBs) can generate ·OH in situ, which provides a new idea for the safe and efficient removal of pollutants in water supply systems. However, the difficulty in obtaining stable MNBs causes the low efficiency of ·OH generation, which makes the inability to guarantee the removal efficiency of pollutants. This paper reviews the application research of MNBs technology in water security from three aspects: the generation process of MNBs in water, the generation rule of ·OH during MNBs collapse, and the control mechanism of MNBs on pollutants and biofilms. We found that MNBs generation methods are divided into chemical and mechanical (about 10 kinds) categories, and the instability of bubble size restricts the application of MNBs technology. The generation of ·OH by MNBs is affected by pH, gas source, bubble size, temperature, external stimulation. And pH and external stimulus have more influence on ·OH generation in situ than other factors. Adjusting pH to alkaline or acidic conditions and selecting ozone or oxygen as the gas source can promote the ·OH generation. MNBs’ collapse also releases a large amount of energy, which the temperature and pressure can reach 3000K and 5Gpa respectively, making it efficient to remove ≈90 % of pollutants (i.e., trichloroethylene, benzene, and chlorobenzene). The biofilm can also be removed by physical, chemical, and thermal effect. MNBs technology also has great application potential in drinking water, which can be applied to improve water quality, optimize household water purifiers, and enhance the taste of bottled water. Under the premise of safety, let people of different ages taste, finding that compared with ordinary drinking water, 85.7 % of people think MNBs water is softer, 73.3 % of people think MNBs water is sweeter. This further proves that MNBs water has a great prospect in the drinking water application. This review provides innovative theoretical support for solving the problem of drinking water safety.

The present minireview assessed the benefits of using artificial intelligence applications in healthcare at predicting the targets of bioactive small molecules in human. Method. The tool is a tuned algorithm, with novel data in web interface. Results. We used tables to order the information of Swiss Target Prediction that allow predictions on combination of chemotherapies and probable side effects. This tool is useful to understand the molecular mechanisms underlying a given phenotype or bioactivity, to rationalize possible favorable or unfavorable side effects and to predict off-targets of known molecules as well as to clear the way for drug repurposing. Predictions are done using a ligand-based approach to compare the similarity between a query molecule and the known ligands of a large collection of protein targets. Conclusion. This study allowed us to formulate recommendations for the use of some of the chemotherapeutic agent groups in cancer patients at a low cost. It is very important and beneficial for patients that take medicine for a longer period and on whose lives depend on such treatment.

Two pilot scale desalination system employing carbon modified nano-sized, zero valent metals (n-ZVM) were maufactured and tested to determine (1) the degree to which high salt water (20 to 130 mS) could be desalinated and (2) if this degree of desalination could be maintained throughout an extended treatment period. Two pilot systems were tested (referred to as Generation 1 and Generation 2) consisting of parallel lines of 4 individual reactors in series, a settling tank and an activated carbon cell at the end of each reactor line. The system capacity was 300 gal in Generation 1 and 600 gal in Generation 2 total with a total hydraulic residence time of 6 hours per reactor line (one hour per cell/tank). A slurry of n-ZVM was introduced in the first reactor on each line to yield approximately 5 to 45 grams of nano-metal per 100 L of influent salt water. The n-ZVM slurry was made from mixing tea extract with metal salts (eg ferrous sulfate, ferric chloride) to produce the carbon modified metal slurry. Initial runs focused on dosing required to achieve maximum salt removal at each of three influent salt contents, 28 mS, 44 mS and 123 mS. Once dosing was set, continuous runs (14 days, 23 days and 9 days) were carried out to (1) examine the ability of the pilot to maintain the removal efficiency over an extended period, (2) to determine the weaknesses inherent in the pilot systems, and (3) to begin to develop CAPEX and OPEX estimates for the pilot and pre-design full scale mobile desalination unit (MDU) system. Results demonstrated that maximum removal occurred with 10 g/100L of salt for the 30 mS salt solution,16 g/100 L of salt for the 40 mS influent water and 40 g/100 L for the 130 mS influent. Salt removal (expressed as Na and Cl removed) approached 78% for the 30 mS influent and 41 mS influent respectively while removal for the highest salt influent (130 mS) approached 81 %. Addition of greater amounts of carbon modified slurry than those described resulted in a pH less than 6 which inhibits continued salt removal and would require addition of calcium or magnesium oxides/hydroxides or bicarbonate solutions at the influent side to achieve greater salt removal and of course greater cost per gallon. Continuous operation over the extended time-period showed no significant decrease in salt removal with typical day to day variation of no more than 10% suggesting that this approach to desalination could rapidly provide usable water from saline aquifers, seawater or even produced water. Treatment of saline waters at 30 mS or less yields effluent water in the range necessary for irrigation use of many crops while treatment of seawater or produced water levels of salt (40 mS or higher) yields effluent in the range of 8 to 10 mS a range ideal for RO influent that would prevent the production of large volumes of brine. Pilot testing continues with seawater extracted from Puget Sound, Seattle WA and higher levels of salt to better represent produced water.

Patient access to new oncology drugs in Canada is only possible after navigating multiple sequential systemic checkpoints for national regulatory approval, health technology assessment (HTA) and collective government price negotiation. These steps delay access and prevent health care providers from being able to prescribe optimal therapy. Eighteen Canadian oncology clinicians from the medicine, nursing and pharmacy professions met to develop consensus recommendations for defining reasonable government performance standards around process and timeliness to improve Canadian cancer patients’ access to best care. A modified Delphi methodology was used to confirm strong consensus on 30 questions involving five themes: accountability, disparities, endpoints, timeliness, and cost-effectiveness. It was agreed that greater transparency is required across regulatory and HTA processes. Health professionals in oncology are frustrated for their patients because they are unable to deliver the modern guideline-supported therapies they want to provide due to delays in approval or funding. Canadian patients and their health care providers request improvements in timely access to life-saving therapeutics in line with other countries. Clinicians expect urgent improvements in our health systems to give our patients their best chance of survival.

Heel pain in the “funnel-shaped” space between the calcaneus, talus, and talocalcaneonavicular and subtalar joints may be representative of Sinus Tarsi syndrome. The pain is often characterized by a burning, numbness, or tingling sensation that can stem from strains and tears on the ligaments in that area. Injury treatment typically includes balance training, muscle exercises, bracing, foot orthosis, and non-steroidal anti-inflammatory drugs (NSAIDs). This study presents Wharton Jelly (WJ) tissue allografts as an alternative intervention for patients who fail standard-care treatments. WJ targets tissue defects, unlike other therapies, which aim to reduce swelling and symptomatic pain. This study includes five female patients who have previously failed standard-of-care treatment. Each received extracorporeal pulse-activated therapy (EPAT), WJ, laser therapy, and an orthotic. After an average of 80 days, the cohort had an overall 85.29% improvement in pain. The study's limitations include a small cohort size and a non-blinded design. Given the significant improvement in pain, WJ tissue allograft, combined with other techniques, presents an optimal patient care plan for tissue defects associated with Sinus Tarsi syndrome when standard-of-care treatments fail. These results provide evidence for a more extensive, randomized study to define dosage protocols further and confirm safety and efficacy.

This work is concerned with studying the change of some Optical and Electrical Properties of Ba_xFe_(1-x)TiO₄ thin films due to the change of the nano crystal size. Simple theoretical explanation based on the string theory was developed. The empirical results obtained indicated that the absorption coefficient, electrical conductivity, and the magnetic permeability increase upon decreasing the nano crystal size. However, the transmission coefficient, and the refractive index increase upon increasing the nano crystal size. All these changes are explained using a simple string model with the aid of Newton's laws. The capability of the string theory to explain this nano quantum behavior comes from the fact that the string theory recognize both the particle and the wave nature of the nano system. This is similar of course to the quantum approach which is based mainly on the dual wave particle nature of atomic systems and entities.

This study describes the synthesis, and characterization of lead-free organic ferroelectric perovskite N-methyl-N’-diazabicyclo[2.2.2]octonium)-ammonium trichloride (MDABCO-NH4Cl3). The electrospinning technique was employed to obtain nanofibers embedded with this perovskite into PVC polymer for hybrid fiber production. The dielectric, piezoelectric and pyroelectric properties of these fibers were carefully examined. From measurements of the dielectric permittivity temperature and frequency dependence, together with the pyroelectric results, a transition from a high temperature paraelectric to a ferroelectric phase that remained down to room temperature, was found to occur at 438 K. A pyroelectric coefficient as high as 290 C K-1 m-2value obtained is within the same order of magnitude as that reported for MDABCO-NH4I3 and the semiorganic ferroelectric triglycine sulfate (TGS). The hybrid nanofibers exhibited good morphological characteristics and demonstrated very good piezoelectric properties. Specifically, a piezoelectric coefficient of 42 pC/N was obtained when a periodical force of 3 N was applied. The performance of these fibers is on par with materials discussed in the existing literature for fabrication of nano energy harvesting generators. Importantly, the perovskite nanocrystals within the fibers not harmed by oxidation, making them a promising environmentally friendly platform for flexible energy harvesting.

With the increasing demand for energy worldwide, researchers from different fields have been striving to improve the sustainability and proper utilization of energy resources. Passive radiative cooling, as a natural energy transport method, can achieve cooling without additional external energy input. This review provides a comprehensive examination of passive radiative cooling, including its fundamental theories and latest development. A particular emphasis is placed on the diverse range of fields where passive radiative cooling has been applied, notably including but not limited to construction and architecture. The current state of applications, potential challenges that may arise with wider adaption and promising research directions for each field are thoroughly discussed. This review underscores the universal applicability and feasibility of passive radiative cooling and contributes to its future development by identifying promising areas for further exploration.

A new method is proposed for performance assessment of lubricating compositions based on industrial lubricants that contain nano-additives of different chemical composition for higher wear resistance of heavy-loaded steel friction pairs. The method is based on the joint analysis of the experimental data on the wear kinetics, change of the relative hardness, and damage in the surface layers of the metal of friction pairs. The level of structural damage to the materials in the contact zone is determined by using the statistical parameters of dispersion of the hardness values. The paper investigates the known experimental results of assessment of the level of damage to structural materials of various grades under the conditions of long-term, cyclic, static loading, and lubricated friction. It is demonstrated that the structural changes occurring in the materials during loading correlate to the changes in the statistical dispersion characteristics of hardness measurement results. Experimental substantiation of the method is carried out for steel friction pairs using lubricating compositions based on industrial oil Greaseline Lithium BIO Rail 000 by AIMOL and nano-additives of copper of M2 grade, magnesium alloy of MA2 grade, aluminum alloy of Al-Mg system, graphite of medium carbon steel grades, i.e. rail and industrial. Under system of indicators presented in the paper, the highest efficiency in terms of increase in the wear resistance of steel friction pairs is demonstrated by the lubricating composition based on industrial lubricant with the additive of nano-powder made of rail steel, as it provided the optimum value of friction coefficient, minimum damage and wear of friction surface.

Avian Influenza viruses (AIVs) has posed a significant pandemic threat since their discovery. This review mainly focuses on the epidemiology, virology, and pathogenesis, and treatments of avian influenza viruses. We delve into the global spread, past pandemics, clinical symptoms, severity, and immune response related to AIVs. The review also discusses various control measures, including antiviral drugs, vaccines, and potential future directions in influenza treatment and prevention. Lastly, by summarizing the insights from the previous pandemic control, this review aims to direct effective strategies for managing future influenza pandemics.

Endocrine-disrupting chemicals (EDCs) may impact the development of Prostate Cancer (PCa) by altering the steroid metabolism. Although their exact mechanism of action in controlling tumor growth is not known, EDCs may inhibit steroidogenic enzymes such as CYP17A1 or CYP19A1 involved in the production of androgens or estrogens. High levels of circulating androgens are linked to PCa in men and Polycystic Ovary Syndrome (PCOS) in women. Essential Oils or their metabolites like lavender oil and tea tree oil have been reported to act as potential EDCs and contribute towards sex steroid imbalance in case of prepubertal gynecomastia in boys and premature thelarche in girls due to the exposure to lavender-based fragrances. We screened a range of EO components to determine their effects on CYP17A1 and CYP19A1. Computational docking was performed to predict the binding of Essential oils with CYP17A1 and CYP19A1, and functional assays were done using the radiolabeled substrates or Liquid Chromatography high‑resolution Mass Spectrometry and cell viability assays were carried out in LNCaP cells. Many of the tested compounds bind close to the active site of CYP17A1, and (+)-Cedrol had the best binding with CYP17A1 and CYP19A1. Eucalyptol, Dihydro-β-Ionone & (-)-α-pinene showed 20% to 40% inhibition of dehydroepiandrosterone production; and some compounds also effected CYP19A1. Extensive use of these Essential oils in various beauty and hygiene products is common, but only a limited knowledge about their potential detrimental side effects exists. Our results suggest that prolonged exposure to some of these essential oils may result in steroid imbalances. On the other hand, due to their effect on lowering androgen output, ability to bind at the active site of steroidogenic cytochrome P450s, these compounds may provide design ideas for the novel compounds against hyperandrogenic disorders such as PCa and PCOS.

This paper introduces an innovative nanotechnology-based approach that provides a pathway to enhance the energy release efficiency of nanoenergetic materials (nEMs) by harnessing self-synchronized collective atomic vibrations and phonon wave resonance within the transition domains between nanocomponents, without altering the material composition. The key innovation involves incorporating finely-tuned 2D-ordered linear-chain carbon-based multilayer nano-enhanced interfaces as programmable nanodevices into the transition domains using advanced multistage processing and assembly techniques. These programmable nanodevices enable precise control over self-synchronized collective atomic vibrations and phonon wave propagation, leading to synergistic effects. To activate and optimize these effects, a combination of various methods is employed, including energy-driven initiation of allotropic phase transformations, surface acoustic wave-assisted micro/nano-manipulation, heteroatom doping, directed self-assembly using high-frequency electromagnetic fields, and data-driven inverse design approaches. By leveraging a data-driven inverse design strategy and uncovering hidden structure-property relationships, we maximize energy release efficiency using the carbon nano-materials genome approach derived from multifactorial neural network-based predictive models. This approach not only unlocks new functionalities in nEMs but also improves environmental performance and safety levels. By pioneering transformative pathways for nEMs through harnessing phonon wave resonance in low-dimensional nanocarbon transition interfaces, this research brings significant advancements in the field.

Brain-stimulation reward, also known as intracranial self-stimulation (ICSS), is a commonly used procedure for studying brain reward function and drug reward. In electrical ICSS, an electrode is surgically implanted into the medial forebrain bundle in the lateral hypothalamus or the ventral tegmental area in the midbrain. Operant lever responding leads to the delivery of electrical pulse stimulation. The alteration in the stimulation frequency-lever response curve is used to evaluate the impact of pharmacological agents on brain reward function. If a test drug induces a leftward or upward shift in the ICSS response curve, it implies a reward-enhancing or abuse-like effect. Conversely, if a drug causes a rightward or downward shift in the functional response curve, it suggests a reward-attenuating or aversive effect. A significant drawback of electrical ICSS is the lack of cellular selectivity in understanding the neural substrates underlying drug reward versus aversion. Excitingly, recent advancements in optical ICSS (oICSS) have facilitated the development of at least three cell type-specific oICSS models – dopamine-, glutamate-, and GABA-dependent oICSS. In these new models, a comparable frequency-rate response curve has been established and employed to study the substrate-specific mechanisms underlying brain reward function and a drug's rewarding versus aversive effects. In this review article, we summarize recent progress in this exciting research area. The findings in these new behavioral models have not only increased our understanding of the neural mechanisms underlying drug reward and addiction but have also introduced a novel experimental approach in preclinical medication development for treating substance use disorders.

This review summarises the complex relationship between medications used to treat type 2 diabetes, and bone health. T2DM patients face an increased fracture risk despite higher bone mineral density, thus we analysed the impact of key drug classes, including Metformin, Sulphonylureas, SGLT-2 inhibitors, DPP-4 inhibitors, GLP-1 agonists, and Thiazolidinediones. Metformin, despite promising preclinical results, lacks a clear consensus on its role in reducing fracture risk. Sulphonylureas present conflicting data, with potential neutral effects on bone. SGLT-2 inhibitors seem to have a transient impact on serum calcium and phosphorus, but evidence on their fracture association is inconclusive. DPP-4 inhibitors emerge as promising contributors to bone health, as well as GLP-1 agonists exhibit positive effects on bone metabolism, reducing fracture risk. Thiazolidinediones, however, demonstrate adverse impacts on bone, inducing loss through mesenchymal stem cell effects. Insulin presents a complex relationship with bone health. While it has an anabolic effect on bone mineral density, its role in fracture risk remains inconsistent. In conclusion, a comprehensive understanding of diabetes medications' impact on bone health is crucial. Further research is needed to formulate clear guidelines for managing bone health in diabetic patients, considering individual profiles, glycemic control and potential medication-related effects on bone.

Evidence from large epidemiological studies has shown that obesity may predispose to increased Th2 inflammation and increase the odds of developing asthma. On the other hand, there is growing evidence suggesting that metabolic dysregulation that occurs with obesity, and more specifically hyperglycemia and insulin resistance, may modify immune cell function and in some degree systemic inflammation. Insulin resistance seldom occurs on its own, and in most cases constitutes a clinical component of metabolic syndrome, along with central obesity and dyslipidemia. Despite that, in some cases, hyperinsulinemia associated with insulin resistance has been proven a stronger risk factor than body mass in developing asthma. This finding has been supported by recent experimental studies showing that insulin resistance may contribute to airway remodeling, promotion of airway smooth muscle (ASM) contractility and proliferation, increase of airway hyper-responsiveness and release of pro-inflammatory mediators from adipose tissue. All these effects indicate the potential impact of hyperinsulinemia on airway structure and function, suggesting the presence of a specific asthma phenotype with insulin resistance. Epidemiologic studies have found that individuals with severe and uncontrolled asthma have a higher prevalence of glycemic dysfunction, whereas longitudinal studies have linked glycemic dysfunction to an increased risk of asthma exacerbations. Since the components of metabolic syndrome interact with one another so much, it is challenging to identify each one's specific role in asthma. This is why, over the last decade, additional studies have been conducted to determine whether treatment of type 2 diabetes mellitus affects comorbid asthma as shown by the incidence of asthma, asthma control and asthma-related exacerbations. The purpose of this review is to present the mechanism of action, and existing preclinical and clinical data, regarding the effect of insulin resistance in asthma.

Transcranial direct current stimulation (tDCS) is acknowledged for its non-invasive modulation of neuronal activity in psychiatric disorders. However, its application in insomnia research yields varied outcomes depending on different tDCS types and patient conditions. Our primary objective is to elucidate its efficiency and uncover the underlying mechanisms in insomnia treatment. We hypothesized that anodal prefrontal cortex stimulation activates glutaminergic projections from the infralimbic cortex (IL) to ventrolateral preoptic area (VLPO) to promote sleep. After administering 0.06 mA of electrical currents for 8 minutes, our results indicate significant non-rapid eye movement (NREM) enhancement in naïve mice within the initial 3 hours post-stimulation, persisting up to 16-24 hours. In the insomnia group, tDCS enhanced NREM sleep bout numbers during acute stress response and improved NREM and REM sleep duration in subsequent acute insomnia. Sleep quality, assessed through NREM delta powers, remains unaffected. Interference of the IL-VLPO pathway, utilizing designer receptors exclusively activated by designer drugs (DREADDs) with the cre-DIO system, partially blocked tDCS's sleep improvement in stress-induced insomnia. This study elucidated that the activation of the IL-VLPO pathway mediates tDCS's effect on stress-induced insomnia. These findings support the understanding of tDCS effects on sleep disturbances, providing valuable insights for future research and clinical applications in sleep therapy.

Metformin is an oral antidiabetic agent with antimicrobial properties, excreted in an active and unmetabolized form. Like some non-antibiotic drugs, subinhibitory concentrations of metformin may contribute to the expression of microbial resistance in wild-type strains. This work aimed to evaluate the biofilm formation of Pseudomonas aeruginosa TGC04 exposed to 100 and 200 µg/mL of metformin, varying the Chemical Oxygen Demand (COD) and flow regime. Biofilms were quantified after 2 and 24 hours, observing reductions and increases in biofilm growth around 13 and 64%, respectively. The greatest biofilm growth occurred in cells exposed to 200 µg/mL of metformin. Both the flow regime and COD concentration were important for the development of the biofilm, whose cells were mostly weakly to moderately adhered. The study provides evidence that in polluted aquatic systems with turbulent regimes, the inhibitory concentration of metformin promoted the least disturbances to the biofilm.

With the COVID-19 pandemic behind us, the U.S. Food and Drug Administration (FDA) has approved 55 new drugs in 2023, a figure consistent with the number authorized in the last five years (53 per year on average). Thus, 2023 is the second-best FDA harvest after 2018 (59 approvals) in all the series. Monoclonal antibodies (mAbs) continue to be the class of drugs with most approvals, with an exceptional 12, a number that makes it the most outstanding year for this class. As in 2022, five proteins/enzymes have been approved in 2023. However, no antibody–drug conjugate (ADC) has been released onto the market. With respect to TIDES (peptides and oligonucleotides), 2023 has proved a spectacular year, with a total of nine approvals, corresponding to five peptides and four oligonucleotides. Natural products continue to be the best source of inspiration for drug development, with 10 new products on the market. Three drugs in this year’s harvest are pegylated, which may indicate the return of pegylation as a method to increase the half-lives of drugs, after the withdrawal of peginesatide from the market in 2013. Following the trends of recent years, two bispecific drugs have been authorized in 2023. As in preceding years, fluorine and/or N-aromatic heterocycles are present in most of the drugs. Herein, the 55 new drugs approved by the FDA in 2023 are analyzed exclusively on the basis of their chemical structure. They are classified as the following: biologics (antibodies, proteins/enzymes); TIDES (peptide and oligonucleotides); combined drugs; pegylated drugs; natural products; nitrogen aromatic heterocycles; fluorine-containing molecules; and other small molecules.

Monomeric Ubiquitin (Ub) is a 76-amino acid highly conserved protein found in eukaryotes. The first described biological activity of Ub in the 1970s was extracellular, but it quickly gained relevance due to its intracellular role, i.e., post-translational modification of intracellular proteins (ubiquitination) that regulate numerous eukaryotic cellular processes. In the following years, the extracellular role of Ub was relegated to the background, until a correlation between higher survival rate and increased serum Ub concentrations in patients with sepsis and burns was observed. Although the mechanism of action (MoA) of extracellular ubiquitin (eUb) is not yet well understood, further studies have shown that it may ameliorate the inflammatory response in tissue injury and multiple sclerosis diseases. These observations compounded with the high stability and low immunogenicity of eUb due to its high conservation in eukaryotes have made this small protein a relevant candidate for biotherapeutic development. Here, we review the in vitro and in vivo effects of eUb on immunologic, cardiovascular, and nervous systems, and discuss the potential MoAs of eUb as an anti-inflammatory, antimicrobial, cardio- and brain-protective agent.

Numerous structures at the nano- and microscale manifest distinctive properties with far-reaching implications across diverse fields, including electronics, electricity, medicine, and surface engi-neering. Established methods such as nanoimprint lithography, photolithography, and self-assembly play crucial roles in the fabrication of nano- and microstructures; however, they exhibit limitations in generating high-aspect-ratio structures when utilizing high-viscosity pho-tocurable resins. In response to this inherent challenge, we propose a highly cost-effective ap-proach facilitating the direct replication of high-aspect-ratio structures, specifically nanowires, through the utilization of anodized aluminum substrates. This study elucidates the streamlined fabrication process for multiscale porous surfaces achieved through the evaporation-induced in-tegration of solid nanowires printed with high-viscosity photocurable resin.

Power sources that can consistently deliver high levels of energy over extended periods are crucial for various space applications. Among the many methods of energy generation, direct heat-to-electricity conversion without intermediate steps or moving components shows particular promise but also presents significant challenges. The aim of this research is to address these challenges by enhancing the energy efficiency of thermionic conversion, which transforms thermal energy into electrical energy, through the development and utilization of a novel class of emission nanomaterials known as multilayer carbyne-enriched 3D-shaped nano-interfaces. By manipulating the topological, physicochemical, and functional characteristics of these interfaces, we seek to optimize their thermionic conversion capabilities. Building on the recent discovery of collective atomic vibrations called phonon waves within transition domains of multilayer nanostructures, we have devised a new approach to enhance the efficiency of thermionic energy converters. This involves unlocking the predictive functionality of 2D-ordered linear-chain carbon-based multilayer emitters through the excitation and fine-tuning of collective atomic vibrations and nanoarchitecture. To achieve this, we propose employing a combination of techniques that leverage interface effects, enable phonon wave propagation, facilitate energy exchange, and capitalize on synergistic effects offered by the multilayer nano-enhanced interfaces. The resulting devices for thermionic energy conversion have the potential to significantly surpass the efficiency of existing plasma thermionic converters by several orders of magnitude. Moreover, these electricity-generating sources based on thermionic conversion represent fundamental options for the advancement of Lunar and Martian research missions, opening up possibilities for sustainable energy production in extraterrestrial environments.

Currently, the use of medications during pregnancy in Latin America is common; studies with Latin American samples find that nearly 90% of pregnant women use some medication at least once during pregnancy. Furthermore, approximately 21% of the respondents self-medicated. Worldwide, the prevalence of this disease is 32%. The most common medications are nonsteroidal anti-inflammatory drugs and analgesics. Many of these drugs are available over the counter without a prescription. For this reason, a systematic review of the literature on the adverse effects on the woman and the fetus was performed. Objective: To determine the adverse effects associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) on pregnant women and fetuses during pregnancy. Methods: Systematic literature review. The following search strategy was used for the databases: Science Direct, PubMed, Scopus and Web of Science, through September 3, 2022. The population of pregnant women without previous comorbidities was defined. The intervention of interest was the use of NSAIDs during pregnancy. The outcomes of interest were adverse effects for the mother or fetus (weight of the newborn, congenital malformations present in the fetus, systemic effects in the pregnant woman during her gestation period). The types of studies included clinical trials, cohort studies and case‒control studies. Results: 1 study included 2,985 pregnant women without previous comorbidities. The use of aspirin more frequently during pregnancy stands out. The adverse effects on the fetus were preterm birth <37 weeks, low birth weight < 2500 g and increased admission to the neonatal intensive care unit. No adverse effects were found for the mother. Conclusions: There are not enough data indicating that the use of NSAIDs during pregnancy is safe. Some studies show that the use of NSAIDs during pregnancy could be related to problems in the development and growth of the fetus and health effects for the mother during pregnancy, so it is advisable to use these drugs under medical prescription and for the shortest possible time. in the gestation stage.

In recent years, extensive research has delved into the pathophysiology of local reactions triggered by Bothrops snake venoms. Even though antivenom works well at reducing death and systemic effects, it is still not very effective in treating local reactions because the venom works so quickly, and antivenom cannot fix injuries that have already been triggered. This might be attributed to certain molecules amplifying the venom-induced innate response. While evidence suggests endogenous mediators at the venom site play a role in this envenomation, in Brazil, concurrent use of anti-inflammatories or other drugs associated with the antivenom remains uncommon. The aim of this study was to determine how various inflammatory mediators affected the leukocyte-endothelium interaction (LEI) following a B. jararaca bite. According to our findings, nitric oxide and cyclooxygenase pathway eicosanoids significantly contribute to alteration of LEI induced by B. jararaca venom. Conversely, lipoxygenase-mediated eicosanoids, histamine, or serotonin had minimal participation. Markedly, treatment with dexamethasone alongside antivenom mitigated alterations of LEI induced by the B. jararaca snake venom. The limited efficacy of the antivenom in managing Bothrops venom-induced local reactions emphasizes the critical need for supplementary treatments to enhance therapeutic outcomes.

Recent advances in nanomaterials have been heavily influenced by low-dimensional nanocarbon allotropes. In particular, carbyne has attracted attention for its potential as a true one-dimensional carbon chain with sp1 hybridization. To maximize the capabilities of this material, we employ a focused data-driven inverse design approach based on the carbon nanomaterials genome concept. This involves using deep learning neural network models to identify key descriptors tied to desired properties, enabling property prediction and reverse engineering of nanocarbons. Our iterative approach entails: (i) gathering growth/property data on nanostructures; (ii) identifying informative numerical/categorical predictors; (iii) developing deep learning models mapping descriptors to properties; (iv) refining models with new insights; (v) determining required descriptors/conditions for target properties via inverse mapping; (vi) validating models by synthesizing predicted nanostructures; and (vii) enhancing models with validation data. This allows uncovering hidden growth-property connections, precisely tuning nanocarbons for desired attributes. We introduce new methodologies including exciting synergistic effects, synchronizing atomic vibrations, active screen plasma, energy-driven transformations, surface acoustic micro/nano-manipulation, doping and directed self-assembly to expose relationships and integrate insights into the inverse design flow. This research promises to accelerate discovery of next-generation low-dimensional nanocarbons with exceptional properties and applications.

The application of dry lubrication in rolling contacts is challenging due to wear. In previous studies graphene platelets applied as dry lubricants on the surfaces of angular contact ball bearings demonstrated superior properties. These specific bearings, experiencing both rolling and spinning motion, create more severe conditions for dry lubricants. The applied graphene platelets have a thickness of few graphene layers in the nm range and a diameter in the µm range. Such platelets can be produced by mechanical exfoliation from graphite. To delve deeper into the lubrication effects, investigations were carried out using a milli tribometer. In the tests, a fixed steel ball is sliding against an oscillating counterpart under defined load. During the measurements, the applied load and tangential forces on the ball are recorded to calculate the friction. In our case, a steel ball with a diameter of 6 mm was used against graphene-based films on flat bearing surfaces (axial bearing washer). Comparative investigations included nano graphite particles and fullerene as dry lubricants, in addition to graphene platelets of various staple thicknesses. To increase the adhesion of the films to the surfaces, a pre-rolling process was implemented. Afterwards, the friction on the compressed films was measured. The results indicate that the pre-rolling process effectively reduces the friction of the system. After testing, the surfaces underwent analysis using laser scanning microscopy to assess the formed films, wear, and material transfer. It has been demonstrated that the pre-rolling process leads to the formation of a very thin compacted film with surface protective properties. On the ball as counterpart, the graphene platelets generate a transfer film on the contacting surface.

Soil salinity is seen as a major restriction for crop production, and with water scarcity this problem becomes more complicated. Mulching is crucial to salinity dynamics management by decreasing evaporation with improving the soil’s characteristics. Using chitosan as an eco-friendly biostimulant can enhance plant defense genes during different abiotic stresses. Recently, agricultural research has recognized nanoparticles as a pioneer material due to their distinctive physicochemical features. Therefore, a lysimeter experiment was conducted to investigate the interactive effects of mulching (UNM: un-mulched, WPM: white plastic, RSM: rice straw and SDM: sawdust) and chitosan foliar application (Ch0: control, Ch1: 250 mg chitosan L-1, Ch2: 125 mg nano chitosan L-1, and Ch3: 62.5 mg nano chitosan L-1) on the biochemical soil characteristics and common beans productivity under salt affected soil conditions. Organic mulching (RSM and SDM) treatments significantly improved the soil's organic carbon, available nutrient content, and total count of bacteria. WPM treatment lowered soil EC to 6.63 dS m-1 and increased soil water content to 34.13%. The application of Ch3 caused considerable increases in the plant height, shoot dry weight, root dry weight, grain yield, and nutrient content in the seed. The total fungi count in the soil and Na% in the seed was significantly decreased due to chitosan foliar applications. Moreover, the interactive effect of different mulch materials plus foliar by chitosan applications gave a statistically similar seed yield in both seasons. Overall, this study revealed the potential of the mulching treatments and foliar application of nano chitosan in improved biochemical soil characteristics and common bean productivity under saline soil conditions.

Nano-drugs and nano-delivery systems are rapidly evolving, with new strategies emerging in the current practices. The evolution of these technologies began with modifying the chemical structure, progressing to supramolecular ionic complexes, and culminating in elegant ad hoc delivery systems. Nanoparticles have numerous benefits as a carrier system for delivering therapeutic agents to intra-arterial sites. These benefits include their subcellular size, targeted surfaces, good suspensibility, and uniform dispersity, making them an ideal choice for catheter-based delivery. Despite the advancements made in the field of nano-drugs and nano-delivery systems, there are still some hurdles to overcome in terms of their commercial availability.The current review presents an updated summary of recent advancements in nano-drugs and nano-delivery systems, including their commercial availability. We aim to discuss the present challenges and prospects of commercially available nano-drugs and nano-delivery systems. Here, we provide a precise and informative overview of the current state of these technologies and underscore the potential they hold for future developments. Further, we have categorized commercially available modifications, name, parent company and their main applications in nano-drugs.

Over recent years, nanocarriers have played an ever-increasing role in clinical and biomedical applications owing to their unique physicochemical properties and surface functionalities. Lately, much effort has been directed towards the development of smart, stimuli-responsive nanocarriers that are capable of releasing their cargos in response to specific stimulus. These intelligent-responsive nanocarriers can be further surface-functionalized so as to achieve active tumor targeting in a sequential manner, which can be simply modulated by the stimuli. By applying this methodological approach, these intelligent-responsive nanocarriers can be directed to different target-specific organs, tissues or cells, and exhibit on-demand controlled drug release that may enhance therapeutic effectiveness and reduce systemic toxicity. Light, an external stimulus, is one of the most promising triggers for use in nanomedicine to stimulate on-demand drug release from nanocarriers. Light-triggered drug release can be achieved by light irradiation at different wavelengths, either in UV, visible or even NIR region, depending on the photophysical properties of the photo-responsive molecule embedded in the nanocarrier system, the structural characteristics and material composition of the nanocarrier system. In this review, we highlighted the emerging functional role of light in nanocarriers, with emphasis on light-responsive liposomes and dual-targeted stimuli-responsive liposomes. Moreover, we provided the up-to-date phototriggered targeting strategies and mechanisms of light-triggered drug release from liposomes and NIR-responsive nanocarriers. Lastly, we addressed the current challenges, advances, and future perspectives for the deployment of light-responsive liposomes in targeted drug delivery and therapy.

In this computational study, we investigate the electronic properties of zigzag graphene nano-parallelograms (GNPs), which are parallelogram-shaped graphene nanoribbons of various widths and lengths, using thermally-assisted-occupation density functional theory (TAO-DFT). Our calculations reveal a monotonic decrease in the singlet-triplet energy gap as the GNP length increases. The GNPs possess singlet ground states for all the cases examined. With the increase of GNP length, the vertical ionization potential and fundamental gap decrease monotonically, while the vertical electron affinity increases monotonically. Besides, as the GNP length increases, the symmetrized von Neumann entropy increases monotonically, denoting an increase in the degree of multi-reference character associated with ground-state GNPs. The occupation numbers and real-space representation of active orbitals indicate that there is a transition from the nonradical nature of the shorter GNPs to the increasing polyradical nature of the longer GNPs. In addition, the edge/corner localization of active orbitals is found for the wider and longer GNPs.

In this paper, an intelligent blind guide system based on 2D LiDAR and RGB-D camera sensing is proposed, and the system is mounted on the smart cane. The intelligent guide system relies on 2D LiDAR, RGB-D camera, IMU, GPS, Jetson nano B01, STM32 and other hardware. The main advantage of the intelligent guide system proposed by us is that the distance between the smart cane and obstacles can be measured by 2D LiDAR based on Cartographer algorithm, thus achieving Simultaneous localization and mapping (SLAM). At the same time, through the improved yolov5 algorithm, pedestrians, vehicles, pedestrian crosswalks, traffic lights, warning posts, stone piers, tactile paving and other objects in front of the visually impaired can be quickly and effectively identified. Laser SLAM and improved yolov5 obstacle identification tests were carried out inside a teaching building on the campus of Hainan Normal University and on a pedestrian crossing on Longkun South Road in Haikou City, Hainan Province. The results show that the intelligent guide system developed by us can drive the wheels and omnidirectional wheels at the bottom of the smart cane, and give the smart cane a self-leading blind guide function like a "guide dog", which can effectively guide the visually impaired to avoid obstacles and reach the predetermined destination, and can quickly and effectively identify the obstacles on the way out. The laser SLAM speed of this system is 25~31FPS, which can realize the short-distance obstacle avoidance and navigation function both in indoor and outdoor envionments. The improved yolov5 helps to identify 86 types of objects, the recognition rate for pedestrian crosswalks and for vehicles are 84.6% and 71.8%, respectively; the overall recognition rate for 86 types of objects is 61.2%, and the obstacle recognition rate of the intelligent guide system is 25-26FPS.

Despite recent improvements in the methods used to eradicate and minimize mosquito populations, they still pose severe threats to human health. This study aimed to investigate the Larvicidal potentials of silver nanoparticles of Ocimum gratissimum on wild Anopheles larvae from Lagos. The plant used in this study was collected from the southeastern part of Nigeria, Ibite-Olo in Ezeagu Local Government Area of Enugu State. Wild Anopheles mosquito larvae were collected from a field at Kosofe Local Government Area of Lagos State, Nigeria where resistant Anopheline populations have been reported in and around Lagos State were brought to the laboratory and kept under standard insectary conditions (25–29 °C;78–82% relative humidity). Aqueous extract of Ocimum gratissimum was made and subsequently into the silver nanoparticles. A bioassay test was performed according to WHO guidelines, with six different concentrations to assess the larvicidal activity and values obtained were subjected to log prohibit regression analysis to obtain LC₅₀ and values with 95% confidence limit. The results of the larvicidal activities of the silver nanoparticles of Ocimum gratissimum showed that the mortality rate was dose-dependent with the percentage mortality increasing at a direct proportional rate as with dose and time of exposure. Ocimum gratissimum gave LC₅₀ at 0.5 ppm and LC₉₅ at 2.5 ppm respectively. The biosynthesized silver nanoparticles augmented the larvicidal activity of the silver nanoparticles of Ocimum gratissimum on wild Anopheles larvae from Lagos. Therefore, this study showed that the silver nanoparticles of Ocimum gratissimum have the potency to be used against an insecticide-resistant mosquito vector and are a suitable candidate for the development of novel natural insecticides.

Drug resistance in tumor cells is a significant roadblock in the clinical management of advanced or recurrent diseases in endometrial cancers. As a part of the tumor-stromal ecosystem, tumor cells are ecologically connected to the cancer-associated fibroblasts (CAFs), which form contributory elements of the tumor microenvironment (TME). We recently reported a novel model of patient-derived CAF-based 2-cell Hybrid Co-Culture (HyCC) to evaluate CAFs' role in developing drug resistance and understanding personalized tumor cell-CAF dialogue. Using our 2-cell HyCC model of patient-derived endometrial CAFs, we present data to demonstrate the direct counter-inhibitory effect of CAFs to combinations of cytotoxic and targeted drugs in developing drug resistance. CAFs derived from resected endometrial tumor samples were first passage-wise characterized before and after freeze-thaw for their positive and negative CAF markers expression pattern. Paclitaxel and its combination with copanlisib, TAK228, lenvatinib, and trametinib were used to test the 3D clonogenic growth of endometrial AN3CA cells on endometrial CAFs. We demonstrate that CAF-mediated resistance to antitumor drugs occurs via direct and indirect contact with CAFs in HyCC. Our data established the strength of the 2-cell HyCC model of patient-derived CAFs in solid tumors and provided a model of resistance to antitumor drugs tailored on a patient-to-patient basis.

Both the use of plastic and its decomposition products lead to the distribution of plastic all over the earth and finally to the uptake by all kind of living beings including humans. Still, it is widely unknown what risks harbor the widespread uptake of plastics for human health, espe-cially regarding contributing factors like size, shape and surface composition. We assessed the uptake of polymethylmethacrylate (PMMA)-nano- and microbeads for HEK293-, A549- and MRC5 cells. Via confocal microscopy, we localized multiple PMMA-beads inside the cytosol of cells. Uptake of PMMA-beads did not alter cell growth and cell division, implying no short-term toxicity towards human cells. Further, we used a cAMP response element binding protein (CREB)-mediated reporter assay to assess whether internalized PMMA-nanobeads alter cell-signaling pathways. In contrast to the in vitro transcription, where the addition of PMMA-nanobeads abolished the transcription, no changes regarding CREB-mediated cell sig-naling are given in HEK293-cells. Our data led to the assumption that PMMA-nano-and mi-crobeads are internalized via endocytosis and end up as lysosomes within the cells cytosol. Therefore, we concluded differences regarding the surface composition of the PMMA-nanobeads mainly affect its potential to alter cell signaling. These findings emphasize the key role the sur-face composition plays regarding microplastic and its risks for human health.

Onchocerciasis treatment and control relies mainly on the use of ivermectin which has high activity against the microfilarial stage of Onchocerca volvulus but limited activity against the long lived, tissue dwelling adult nematodes. As this neglected tropical disease has now been targeted for elimination there is an urgent need for new drugs to combat these parasites, ideally with macrofilaricidal activity. In this study we have examined the anti-Onchocerca activity of a range of existing FDA approved drugs with a view to repurposing, which can lead to rapid and relatively inexpensive development. From the Pharmakon-1600 library, 106 drugs were selected and tested against O. gutturosa adult male parasites using a concentration of 1.25 x 10-5 M in an in vitro 5-day standard assay to assess motility and viability (using MTT/formazan colorimetry). The findings revealed that 44 drugs produced marginal/moderate activity (50-99% motility and/or MTT reductions) including cefuroxime sodium, methenamine, primaquine phosphate, rivastigmine tartrate, while 23 drugs produced good activity (100% motility reductions and significant MTT reductions), including atovaquone, isradipine, losartan, rifaximin, cefaclor and pyrantel pamoate. Although this study represents only a first step, some of the identified hits indicate there are potential anti-Onchocerca drug candidates worthy of further investigation.

Musculoskeletal infections (MIs) are among the most difficult-to-treat staphylococcal diseases. The limited availability of effective antibiotics has encouraged the development of innovative strategies such as combinatory therapy to combat MI. The aim of this study was to investigate the in vitro antistaphylococcal activity of anti-inflammatory and the antimicrobial combinatory effect of celecoxib with oxacillin. The minimum inhibitory concentrations (MICs) of 17 anti-inflammatory drugs were determined for standard strains and clinical isolates of S. aureus strains, counting methicillin-resistant strains (MRSA), by the broth microdilution method. The fractional inhibitory concentration indices (FICIs) were evaluated by the checkerboard assays. Celecoxib produced the most potent antistaphylococcal effect against all the tested strains (MIC ranging from 32 to 64 mg/mL), followed by diacerein against MRSA3 and MRSA ATCC 33592 (MIC 64 mg/mL). Several synergistic effects were observed for tested S. aureus strains, including MRSA (FICI ranging from 0.087 to 0.471). The strongest synergistic interaction (FICI 0.087) was obtained against MRSA ATCC 33592 at a celecoxib concentration of 2 mg/mL with a 19-fold oxacillin MIC reduction (from 512 to 26.888 mg/mL). This is the first report on the antistaphylococcal combinatory effect of celecoxib with oxacillin. Our findings suggest celecoxib and its combination with oxacillin as perspective agents for research focused on the development of novel therapies for MI caused by S. aureus. Thus, this study presents novel findings that celecoxib could, in some cases, resensitise MRSA strains to become susceptible to certain β-lactams (e.g., oxacillin) not previously tested.

In order to investigate both the physiological and molecular mechanisms underlying the impacts of organic selenium and nano-selenium on drought stress of Pak Choi (Brassica chinensis var. pekinensis. cv. ‘Suzhouqing’), we measured photosynthetic pigment, antioxidant, nutritional quality, and performed transcriptome sequencing of leaves using RNA-seq technology. Under drought conditions, the beneficial effects of organic selenium and nano-selenium on weight and quality of ‘Suzhouqing’ were primarily manifested in the following aspects. Firstly, there was an enhancement in photosynthetic capacity through upregulation of light-trapping pigment proteins: Lhca1, Lhca2, Lhca3, Lhca4, Lhcb1, Lhcb2, Lhcb3, Lhcb4 and Lhcb5. Secondly, effective regulation of reactive oxygen species homeostasis was achieved by activating the antioxidant system via up-regulation of glutathione S-transferase. Thirdly, water homeostasis was maintained through glutathione oxidase activity. Lastly, increased expression levels of ABC transporter, adenylate kinase and cysteine desulphurase contributed to elevated total selenium content. In addition, we screened hub core genes related to the above key metabolic pathways through Weighted Gene Co-expression Network Analysis. Since the results were consistent with the up-regulated genes identified in the Kyoto Encyclopedia of Genes and Genomes pathway of differentially expressed genes by transcriptome sequencing analysis, this confirms the accuracy and reliability of the transcriptome sequencing data.

Antiviral drugs cannot treat dengue fever, a serious medical disease spread by the Aedes aegypti and Aedes albopictus mosquitoes. One important arbovirus disease is dengue fever. Safe, affordable and effective drugs that inhibit dengue virus (DENV) are needed to control dengue worldwide. Medicinal plants have long been considered an important alternative in the treatment of various diseases, including dengue fever. The aim of this study was to use databases PubMed, Google Scholar and Research Gate to identify plants of different tribes from different places that can be used for the treatment of DENV infection and open supportive care for dengue. Previous studies have shown antiviral activity of medicinal plants against DENV. The aim of the present study is to discover plants from different tribes from different places that can be used to treat DENV infection and provide open supportive care against dengue. The recommended reporting guidelines for systematic reviews and meta-analyses (PRISMA statement) were followed in the search and selection of articles using the PubMed database, Google Scholar and Research Gate. The final selection was made after careful consideration and up to 85 publications that met the inclusion criteria. It is said that different plants from different tribes and geographical locations can be used to treat DENV infection.

Protein–nanoparticle hybridization can ideally lead to novel biological entities characterized by emerging properties, which can sensibly differ from those of the parent components. Herein, the effect of ionic strength on the biological functions of recombinant, His-tagged spermine oxidase (i.e., SMOX) was studied for the first time. Moreover, SMOX was integrated to colloidal surface active maghemite nanoparticles (SAMNs) by direct self-assembly, leading to a biologically active nano-enzyme (i.e., SAMN@SMOX). The hybrid was subjected to an in-depth chemical-physical characterization highlighting that protein structure was perfectly preserved. The catalytic activity of the nanostructured hybrid (SAMN@SMOX) was assessed by extracting kinetics parameters using spermine as substrate and compared to the soluble enzyme as a function of ionic strength. Results revealed that the catalytic function was dominated by electrostatic interactions and that they were drastically modified upon hybridization with colloidal ɣ-Fe2O3. Noteworthy, the affinity of SMOX toward spermine was significantly higher for the nanohybrid at low salinity. The present study supports the vision of using protein–nanoparticle conjugation as a mean for modulating biological functions.

The new coronavirus SARS-CoV-2 is the cause of the COVID-19 pandemic, which has created an incomparable global health problem. PLpro is a key protein involved in viral polyprotein processing and immune system evasion, making it a prime target for the development of antiviral drugs to combat COVID-19. The review begins by elucidating the functional and structural properties of SARS-CoV-2 PLpro, underscoring its significance in viral pathogenicity and replication. Employing homology modeling, a tertiary structure model of PLpro is constructed, laying the groundwork for subsequent investigations. To expedite the search for potential therapeutic candidates, the study harnesses computational methodologies. Molecular docking techniques are employed to explore binding sites for antiviral drugs within the catalytic region of PLpro. This computational approach not only aids in drug development but also provides crucial preliminary data before experimental research commences. The stability of drug-PLpro complexes is assessed through comprehensive all-atom molecular dynamics (MD) simulations, affording dynamic insights into drug-PLpro interactions. By evaluating binding energy estimates from MD simulations, stable drug-PLpro complexes with potential antiviral properties are identified. However, it is emphasized that experimental validation is imperative to confirm these computational findings, necessitating in vitro and in vivo tests to assess safety and efficacy. This pivotal stage bridges the computational realm with real-world clinical applications. The review emphasizes the imperative need for enhancements in the existing PLpro-targeting drugs currently on the market. Their actions are insufficient for clinical use and necessitate thorough characterization and improvement. The Supervised Molecular Dynamics (SuMD) simulation technique reveals critical information about drug unbinding pathways, shedding light on opportunities for refinement. In addition to optimizing existing drugs, the investigation of sub-structurally similar molecules emerges as a promising avenue for drug development. In conclusion, the review underscores the pivotal role of targeting SARS-CoV-2 PLpro in the ongoing battle against COVID-19. By integrating molecular dynamics simulations, structural modeling, and computational insights, a robust foundation is established for identifying promising antiviral drug candidates. The continual need for improvement in existing drugs and the exploration of novel compounds remain paramount in the global effort to combat COVID-19. The evolution and management of COVID-19 hinge on the symbiotic relationship between computational insights and experimental validation, illustrating the interdisciplinary synergy crucial to this endeavor.

The human body contains 60-70% of water, depending on age. As a body fluid, it is not only a medium in which physical and chemical processes take place, but it is also one of the active mediators. Water is the richest substance with non-covalent hydrogen bonds. Water molecules, by themselves (in vacuum), are diamagnetic, but when organized into clusters, become diamagnetic or paramagnetic. Also, biomolecules (DNA, collagen, clathrin, and other proteins) have non-covalent hydrogen bonds in their structure. The interaction, as well as signal transmission, between water and biomolecules is achieved through the vibrations of covalent and non-covalent hydrogen bonds, which determine the state and dynamics of conformational changes of biomolecules. Disruptive conformational changes of biomolecules, cells, and tissues lead to their dysfunctionality, so they are a frequent cause of many disorders and diseases. For example, the rearrangement of hydrogen bonding due to mitochondrial disease mutation in cytochrome bc1 disturbs heme bH redox potential and spin state. In order to prevent and repair the dysfunctional conformational changes, a liquid substance was developed based on the second derivative of the C₆₀ molecule (SD-C₆₀), which has classical and quantum properties. Characterization of SD-C₆₀ by UV-VIS-NIR, FTIR, TEM, and AFM/MFM was done and it is shown that SD-C₆₀ water layers generate vibrations with near-zero phase dispersion which are transmitted through the Fibonacci’s water chains to biomolecules. In comparison to previously published SD-C₆₀ derivate (3HFWC, size until 10 nm, and 1-5 water layers), improved formulation (3HFWC-W, size 10-25 nm, and 6-9 water layers) showed multiplied cytotoxic activity against melanoma cell lines of different aggressiveness. Apart from this, the mode of action was preserved and based on induction of senescence rather than cell death. Importantly, high selectivity toward malignant phenotype was detected. Observed effects can be ascribed to a machinery of hydrogen bonds, which are generated in SD-C₆₀ and transmitted through water to biomolecules. This approach may open a new field in science and healthcare - a “water-based nanomedicine”.

Plastic poses a significant threat to the environment, polluting land, water, and air. It is a broad term encompassing a variety of polymers. In the form of microplastics and nanoplastics, it can induce toxicity in water bodies. Plastic debris not only physically pollutes freshwater, but also chemically, undergoing changes over time due to hydroclimatic effects. Rivers serve as conduits, transporting plastics from minor tributaries to major rivers and ultimately into the ocean, endangering marine life. India, as a developing country with the largest population and numerous rivers, generates a significant amount of plastic waste, a substantial portion of which finds its way into rivers, leading to alarming rates of plastic accumulation in the ocean. Previously, policymakers focused primarily on landfills for plastic waste, neglecting the pollution of water bodies. The consequences of this neglect are evident, with major rivers in the country severely affected by plastic waste, necessitating advanced, efficient, and sustainable solutions. This study aims to establish a comprehensive framework for managing plastic waste, understanding its transport mechanisms to the ocean, and recognizing the threats it poses to life. It also expounds on harmful plastic pollutants in water, globally adopted technologies, and emphasizes the need for further research and data collection in this field. The primary concluding point is to prevent plastics from entering waterways and to actively collect river and marine plastic pollution. Banning single-use plastics and implementing efficient collection methods are crucial in containing plastic pollution. Effluents from industries should not be overlooked, as they often contain harmful micro and nanoplastics with ecotoxicological effects. The innovative concept of the "4Rs" - Refuse, Reduce, Reuse, and Recycle - stands as the cornerstone for safeguarding the environment against plastic pollution.

A healthy cornea is a nonvascularized, transparent tissue. It is nourished by diffusion through the tear film, aqueous fluid and neurotrophins supplied by the corneal innervation. The cornea is devoid of both blood and lymphatic vessels, which makes it an immunologi-cally privileged tissue. Corneal neovascularization develops due to an imbalance between angiogenic and anti-angiogenic factors and can lead to a significant decrease in visual acui-ty. It may cause scarring, lipid keratopathy, and corneal edema. The resulting pathological vascularization of the cornea reduces its immune privilege and significantly worsens the prognosis after subsequent penetrating keratoplasty, increasing the risk of rejection of the transplanted flap. Neovascularization is favored by many disease processes, including auto-immune diseases, viral inflammations, mainly herpes and varicella-zoster, and blepharitis [1]. There are several options to treat corneal neovascularization, both pharmacological and surgical. Angiostatic treatment involves inhibiting the growth of new vessels by suppressing inflammatory responses. VEGF inhibitors, steroids, cyclosporine A, and amniotic membrane grafts secured to the cornea work this way. VEGF inhibitors are the agents with the direct and most potent angiostatic effect. Angioregressive treatment, on the other hand, results in the regression of already existing pathological vessels. This therapy is also based on VEGF inhibitors, which, however, have the most potent effect on newly formed and small vessels but are less effective in reducing large-caliber and mature vessels. A more effective method for such vessels is ablation, which involves surgical closure. The most commonly used an-gio-occlusive method is needle diathermy and argon or yellow laser therapy. In advanced corneal neovascularization, corneal transplant surgery may be necessary. It is best performed after pretreatment with anti-VEGF preparations, often continued after corneal transplanta-tion to reduce the risk of transplant rejection [2]. This paper discusses the pathogenesis of corneal neovascularization and the current and future trends in its treatment.

In this paper we introduce the concept of Nano Beta Closure, Nano Beta Interior and study the relationship between them also study some of their properties. Based on these notions we introduced the topological Approach to Decision Making and Its Application in the Medical Field" which describes the use of topological methods in decision-making, specifically through the utilization of nano beta closure and nano beta interior. These mathematical tools are applied in the medical field to improve diagnostic accuracy and aid in treatment planning. The authors demonstrate the effectiveness of this approach through a case study on the diagnosis of Chronic Kidney. The results show that the topological approach using nano beta closure and nano beta interior provides a reliable and accurate method for medical decision-making. Finally, we introduce a medical application for disease groups patients of with chronic kidney. To identify the main causative agent of kidney disease. where using this approach, the medical team can identify the specific areas of the kidney that are affected by the infection, as well as the extent of damage and any potential complications. This information is used to create an individualized treatment strategy that is customized to meet the specific requirements of the patient. and medical history. We write an algorithm that can be a helpful tool for doctors to utilize in diagnosing infection disease Chronic Kidney infections. By utilizing this approach, clinicians can provide accurate diagnoses, develop effective treatment plans, and ultimately improve patient outcomes. finally, we show that fractals hold significant importance in future nano topological generation of the human factor. Their unique properties and self-similar patterns offer insights into the complex organization of biological systems and provide a foundation for designing advanced Nanosystems.

In this study, sodium alginate (SA) was oxidized with potassium periodate to produce an alginate-based tanning agent. Using OSA as a biodegradable tanning agent and a nano-hydroxyapatite (nano-HAp) low concentration suspension to give flame retardancy to leather, eco-design concepts were applied to establish a chrome-, aldehyde-, and phenol-free tanning process. Micro-DSC, 1H NMR, attenuated total reflection mode Fourier transform infrared spectroscopy (FTIR-ATR), and scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDS) were used to investigate the complex matrix collagen-OSA-nano-HAp. Micro-differential scanning calorimetry (micro-DSC) was used to assess OSA's ability to interact with collagen and stabilize the collagen-OSA matrix, while 1H unilateral nuclear magnetic resonance (NMR) was used to investigate the aqueous environment and limitations around collagen molecules caused by their association with OSA and nano-HAp. Industrial standard tests were used to assess mechanical properties and fire resistance of the new leather prototype. The findings reported here indicate that both OSA and nano-HAp are suitable alternatives for cleaner tanning technologies and more sustainable leather.

Fibrosis is the end result of persistent inflammatory responses induced by a variety of stimuli, including chronic infections, autoimmune reactions, and tissue injury. Fibrotic diseases affect all vital organs and are characterized by a high rate of morbidity and mortality in the developed world, although currently there are no approved antifibrotic therapies. In recent years, high levels of interleukin-17 (IL-17) have been associated with chronic inflammatory diseases with fibrotic complications, that culminate in organ failure. In this review, we provide an update on the role of IL-17 in fibrotic diseases, with particular attention to the most recent lines of research in the therapeutic field represented by the epigenetic mechanisms that control IL-17 levels in fibrosis. A better knowledge of the IL-17 signalling pathway implications in fibrosis could design new strategies for therapeutic benefits.

Rhabdomyosarcoma is a cancer arising from arrested myogenic differentiation, seen mainly in children or adolescents. Metastatic rhabdomyosarcoma is often fatal even with aggressive cytotoxic chemotherapies, surgery, and irradiation. SALIQ is an acronym for a multidrug augmentation regimen designed as an adjunct to current rhabdomyosarcoma chemotherapies. SALIQ uses five common non-oncology drugs, repurposed from general medicine use, to promote malignant clone maturation and inhibit rhabdomyosarcoma growth. The five drugs are: the cholesterol lowering drug simvastatin, the acne medicine tretinoin (ATRA), the psychiatric drug lithium carbonate, the antifungal drug itraconazole, and the food supplement quercetin. All five drugs are in common use for non-cancer conditions, are cheap, have an eminently safe side effect profile, and all five have preclinical evidence and good rationale for inhibiting rhabdomyosarcoma growth.

Multiple drugs administration is a common practice in hospitals and clinics. This is the case when heavy pathologies are treated. In this context, frequently, antivirals and antibiotics are co-administrated either simultaneously or sequentially ignoring potential incompatibilities. In this study, we focused on an antiviral (Acyclovir) and an antibiotic (Ciprofloxacin) compatibility/incompatibility when they co-administrated with special interest on the effect of drugs ratio, pH and delay. By implementing robust HPLC method, we determined the main factors leading to potential modification of concentration of one of the two drugs in the mixture. The results showed that acyclovir is quantitatively recovered in all conditions related to pH, concentration and time (up to 24 hours). However, ciprofloxacin is strongly altered in acidic and basic conditions, the quantity of ciprofloxacin and time after mixing the two drugs. The most valuable piece of information is that the ratio of acyclovir/ciprofloxacin is crucial. The latter should be calculated and managed to provide at least two fold quantity of acyclovir versus ciprofloxacin in order to maintain the administrated doses and warrant efficient therapeutic effect.

Optimizing input parameters not only improves production efficiency and processing quality but also plays a crucial role in the development of green manufacturing engineering practices. The aim of the present study is to conduct a comparative evaluation at cutting performance and machinability process during the turning of AISI 4340 steel under different cooling conditions. The study analyses cutting operations during turning using dry, minimum quantity lubrication (MQL), and nano-MQL. As control parameters in the experiments, three different cooling types, cutting speed (100, 150, 200 m/min), and feed rate (0.1, 0.15, 0.20 mm/rev) levels were applied. The experiment results present that the optimal output values are found as Vb=0.15 mm, Ra=0.81µm, 88.1 dB for sound intensity, and I=4.18 A for current. Moreover, variance analysis (ANOVA) was performed to determine the effects of input parameters on response values. Under dry, MQL, and nano-MQL processing conditions, parameters affecting tool wear, surface roughness, current by the motor shaft, and sound level were examined in detail, along with the chip morphology. The responses obtained were optimized according to the Taguchi S/N method. As a result of optimization, it was concluded that the optimum values for cutting conditions (A3B1C1) were nano-MQL cooling and V=100 m/min, f=0.1 mm/rev cutting. Last but not least, it was observed that there was a 13% improvement in tool wear, 7% in current, 9% in surface roughness, and 8% in sound intensity compared to the standard conditions. In conclusion, it was determined that nano-MQL and the lowest level of cutting and feed rate values provided the optimum results.

This study investigates the contribution of nano-alumina (nA: 1-3wt.% binder) to the performance of silica fume (SF-10%) blended mortar in ternary blended mortar. The fresh (workability, setting time) and hardened properties (compressive strength and thermal resistance (300 °C for 1 h)), were examined. Nano alumina (nA) contributed positively to the consistency of SF blended mortar such that similar workability could be achieved with OPC when 3% nA was added. The initial and final setting time of 180 and 220 mins were recorded in SF blended mortar and reduced by 18.4 and 21.8%, respectively by adding 3%nA. The optimum mixture that contained 10%SF and 2%nA had 3-d and 28-d compressive strengths of 28 and 43.2 MPa. In the absence of nA, this reduced by 14.3% and 29.4% while it reduced by 25.2% and 16.7%, respectively in OPC mortar. The main products characterizing SF-nA ternary blended binder with dense microstructural density were nepheline and tobermorite. Besides, it is more susceptible to carbonation despite its superior performance in thermal resistance when compared to SF blended and OPC mortars.

Pregestational and gestational diabetes mellitus are relevant complications of pregnancy and antidiabetic drugs are prescribed to obtain glycemic control and improve perinatal outcomes. The objective of this study was to highlight the prescription pattern of antidiabetics before, during and after pregnancy in Italy and to evaluate its appropriateness. A multi-database cross sectional population study using a Common Data Model was performed. In a cohort of about 450,000 women, the prescribing profile of antidiabetics seemed to be in line with the Italian standards for the treatment of GDM which currently do not recommend the use of oral antidiabetics and non-insulin injection, even if a small share of new users (up to 3.8% in the third trimester) used oral antidiabetics. A substantial variability in the prescription pattern was observed among the Italian regions considered: the highest increase was registered in Tuscany (4.2%), Umbria (3.5%) and Emilia-Romagna (2.6%) while the lowest in Lombardy (1.5%), Veneto (1.7%) and Apulia (1.7%). Analysing the prevalence of use of antidiabetics between foreign women we observed that the consumption during pregnancy was higher than Italians (second trimester: 1,8% vs 0,9%, third trimester: 3,6% vs 1,8%).

In recent years, frequent occurrences of low temperature disasters due to global climate change have significantly impacted the normal growth of crops. Research has indicated that inorganic selenium (which is more toxic) can not only enhance the effects of low temperature stress but also increase selenium content on plants; however, there is a scarcity of studies investigating the impacts of organic selenium and nano-selenium on crops. In order to investigate whether organic selenium and nano-selenium can enhance low-temperature tolerance and increase selenium content in pak choi (Brassica chinensis var. pekinensis. cv. ‘Suzhouqing’), different concentrations (0, 5, 10, 20 mg L-1) of exogenous selenium were applied in this experiment to assess their effects on plant growth, nutritional quality and antioxidant properties. RNA-Seq technology was used to sequence the transcriptome of the leaves. Based on the transcriptome data, a Weighted Gene Co-expression Network Analysis (WGCNA) was employed to construct a network that associates with physiological traits related to stress resistance. Two highly correlated gene co-expression modules were identified, and within them, nine hub genes associated with endocytosis, antioxidant stress, absorption, transport, and metabolism of selenium were discovered. The results indicated that the beneficial effects on yield and total selenium content under low temperature were attributed to (1) protection of photosynthetic pigments for enhancing photosynthetic capacity by the up-regulation of LHca2, LHcb1, LHca1, LHcb4 in KEGG pathway: photosynthesis-antenna proteins; (2) activation of antioxidant system for efficient ROS homeostasis such as SOD, POD and CAT by the genes such as Superoxide dismutase, Monodehydroascorbate and (3) selenium absorption by endocytosis, seleninum transportation by ABC transporter gene family and selenium metabolism related genes such as Cysteine synthase, Glutaredoxin. These findings provide a foundation for further investigation into the molecular mechanisms underlying the effects of organic selenium and nano-selenium on cyanochloride production at low temperatures.

Recent media reports commented about a possible antidiabetics’ misuse issue related to molecules promoted as a weight-loss treatment in non-obese people. We evaluated here available pharmacovigilance misuse/abuse signals related to semaglutide, a glucagon-like peptide-1 (GLP-1) analogue, in comparison to other GLP-1 receptor agonists (albiglutide; dulaglutide; exenatide; liraglutide; lixisenatide; tirzepatide) and the phentermine-topiramate combination. To that aim, we analysed the Food and Drug Administration-FDA Adverse Events Reporting System (FAERS) dataset, performing a descriptive analysis of adverse event reports (AER) and calculating related pharmacovigilance measures, including the reporting odds ratio (ROR) and the proportional reporting ratio (PRR). During January 2018-December 2022, a total of 31,542 AER involving the selected molecules were submitted to FAERS; most involved dulaglutide (n=11,858; 37.6%) and semaglutide (n=8,249; 26.1%). In comparing semaglutide vs the remaining nolecules, the AER ‘drug abuse’, ‘drug withdrawal syndrome’, ‘prescription drug used without a prescription’ and ‘intentional product use issue’ respective PRR values were 4.05, 4.05, 3.60 and 1.80 (all<0.01). The same comparisons of semaglutide vs the phentermine-topiramate combination were not associated with any significant differences. To the best of our knowledge, this is the first study documenting the misusing/abusing potential of semaglutide in comparison with other GLP1 analogues and the phentermine-topiramate combination. Current findings will need to be confirmed by further empirical investigations to fully understand the safety profile of those molecules.

The effective treatment of human immunodeficiency virus (HIV), also known as acquired immunodeficiency syndrome (AIDS), has transformed a highly lethal disease into a chronic and manageable condition. However, better methods need to be developed for eliminating the virus from reservoirs, enhancing patient access and adherence to therapy, and improving treatment in the long term to reduce adverse effects. From the perspective of drug discovery, one promising strategy is the development of anti-HIV prodrugs. This approach aims to enhance the efficacy and safety of treatment, promoting the development of more appropriate and convenient systems for patients. In this review, we discussed the use of the prodrug approach for HIV antiviral agents and emphasized nucleoside reverse transcriptase inhibitors. We comprehensively described various strategies that are used to enhance factors such as water solubility, bioavailability, pharmacokinetic parameters, permeability across biological membranes, chemical stability, drug delivery to specific sites/organs, and tolerability. These strategies might help researchers conduct better studies in this field. We also reported successful examples from the primary therapeutic classes while discussing the advantages and limitations. In this review, we highlighted the key trends in the application of the prodrug approach for treating HIV/AIDS..

Anthocyanins (ACNs) have attracted considerable attention for their potential to modulate the immune system. Research has revealed their antioxidant and anti-inflammatory properties, which play a crucial role in immune regulation by influencing key immune cells such as lymphocytes, macrophages, and dendritic cells. Moreover, ACNs contribute to maintaining a balance between proinflammatory and anti-inflammatory cytokines, thus promoting immune health. Beyond their direct effects on immune cells, ACNs significantly impact gut health and the microbiota, essential factors in immune regulation. Emerging evidence suggests that they positively influence the composition of the gut microbiome that enhance the immunomodulatory effects of ACNs. Furthermore, these compounds synergize with other bioactive substances, such as vitamins and minerals, further enhancing their potential as immune-supporting dietary supplements. However, detailed clinical studies must fully validate these findings and determine safe dosages for different populations. Incorporating these natural compounds into functional foods or supplements can revolutionize the management of immune-related conditions. Personalized nutrition and healthcare strategies can be developed to enhance overall well-being and immune resilience by fully understanding the mechanisms underlying their actions. Recent advancements in delivery methods have focused on improving the bioavailability and effectiveness of ACNs, providing promising avenues for future applications.

Drought is one of the leading abiotic factors limiting morphological and physiological activities in blackberry cultivation. We investigated the effect of silver nanoparticles (AgNPs) on morphological and physiological processes in the boysenberry crop (Rubus ursinus Chamisso &amp; Schlenhtendal) under drought stress. The experiment was performed with three drought stress levels (0% PEG, 4% PEG and 8% PEG) and three AgNPs treatments (0, 0.1, 0.2 mg L−1) invitro conditions. The results showed that drought stress induced by PEG, reduced root and shoot development of boysenberry plants grown invitro. The addition of AgNPs is significantly alleviated the adverse effect of drought stress and increased the plant growth parameters. Antioxidant activity of SOD and CAT enzymes increased in boysenberry leaves when treated with AgNPs under drought conditions, while the amount of MDA decreased. Therefore, the results obtained in this study suggest that 0.1 mg L-1 AgNPs added to the medium improve the growth and development of invitro boysenberry plants under drought stress.

Generally, mineral fillers are added to thermoplastic polymers to reduce cost and improve performance. However, properly selected mineral fillers can also improve thermal conductivity and deformation behavior, shrinkage, impact strength, dimensional stability, and molding cycle time in thermoset polymers. This study focused on the preparation and microscopic and spectroscopic characterization of various hybrid composites using pumice as primary filler and gypsum, kaolin and hollow glass sphere as secondary fillers, as well as examining some of their mechanical properties and thermal conductivities. For this, first of all, surface modification of the clay was carried out by intercalation method from solution using raw Montmorillonite, cationic surfactant and long chain hydrocarbon material, and then organo-clay melamine formaldehyde nanocomposite was prepared by in situ synthesis using organo clay and melamine formaldehyde pre-polymer. Finally, non-ionic surfactant, foaming agent and glycerin were added to the prepared nano-composite at approximately 90°C, mixed mechanically and then pumice was added. The processes at this stage were repeated while preparing hybrid composites with pumice and other mineral additives. For curing and molding, the composite was first subjected to microwave irradiation for 5 minutes followed by thermal treatment at 140°C for 60 min. Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD) spectra and Scanning electron microscope (SEM) and High resolution transmission electron microscope (HRTEM) images were taken for morphological and textural characterization for raw clay (MMT), organo clay (OMMT) and pure polymer with prepared hybrid composites. In addition, some mechanical properties such as bending strength, elasticity modulus and screw holding resistance, as well as thermal conductivity coefficients of the hybrid composites were determined according to the relevant standards and the obtained results were evaluated. Spectroscopic and microscopic analyzes have shown that effective adhesion interactions occur between polymer-clay nanocomposite particles and filler grains, thus resulting in textural arrangements with different properties. Mechanical and thermal conductivity test results showed that melamine formaldehyde-organo-clay nano composite foam and hybrid composite containing hollow glass sphere are highly qualified materials in terms of thermal insulation and mechanical strength.

Preterm infants often experience frequent intermittent hypoxia (IH) episodes which is associated with neuroinflammation. We tested the hypotheses that early caffeine and/or non-steroidal in-flammatory drugs (NSAIDs) confer superior therapeutic benefits for protection against IH-induced neuroinflammation than late treatment. Newborn rats were exposed to IH or hy-peroxia (50% O2) from birth (P0) to P14. For early treatment, the pups were administered: 1) dai-ly caffeine citrate (Cafcit, 20 mg/kg IP loading on P0, followed by 5 mg/kg from P1-P14); 2) ke-torolac topical ocular solution in both eyes from P0 to P14; 3) ibuprofen (Neoprofen, 10 mg/kg loading dose on P0 followed by 5 mg/kg/day on P1 and P2); 4) caffeine+ketorolac co-treatment; 5) caffeine+ibuprofen co-treatment; or 6) equivalent volume saline. On P14, animals were placed in room air (RA) with no further treatment. For late treatment, pups received similar treatments from P15-P21 (caffeine and/or ketorolac), or P15-P17 (ibuprofen). RA control were similarly treated. At P21, whole brains were assessed for histopathology, apoptosis, mye-lination, and biomarkers of inflammation. IH caused significant inflammation, reduced mye-lination, and apoptosis in preterm rat brains, an effect that was improved predominantly with combined caffeine/NSAID early treatment. Early caffeine/NSAID co-treatment confers syner-gistic neuroprotection against IH-induced damage.

Diabetes mellitus is a cluster of metabolic diseases characterized by hyperglycemia. Since this epidemic growing worldwide, the usage of phototherapeutics to manage diabetes is vital. Coccinia grandis (Aka ivy gourd) belongs to cucumber family is identified as a most effective herb, especially for diabetes and many other disease conditions. Hence, an instant herbal porridge cube incorporating Coccinia grandis leaf powder was produced and sensory acceptability of the porridge was evaluated using trained panelists. The bioactive activity of Coccinia grandis leaf powder showed that 66.77±0.74 mg/g GAE of Total Phenolic Content, 27.65±6.79% of DPPH radical scavenging activity, 5.72% of alpha-amylase inhibition activity and 59.64% of alpha-glucosidase inhibition activity. The effect on postprandial blood sugar levels after consuming the developed porridge was measured using healthy adults and it was observed there was no blood sugar elevation during the 2 hours of time. As a further development, Coccinia grandis leaf extract was nano-encapsulated with food grade Sodium alginate and it was incorporated into the same porridge as a safe delivery method of bioactive compounds. In-vitro digestion assay was conducted and the results show that alpha-amylase inhibition activity for the gastric phase and alpha-glucosidase inhibition activity for the intestinal phase was higher in nano-encapsulated porridge. The study concludes that, consuming nano-encapsulated Coccinia grandis leaf extract with porridge is more beneficial for diabetic patients.

Cancer is amenable to low-cost treatments, given that it has a significant metabolic component, which can be effected through diet and lifestyle change at minimal cost. The Warburg hypothesis states that cancer cells have altered cell metabolism towards anaerobic glycolysis. Given this metabolic reprogramming in cancer cells, it is possible to target cancers metabolically by depriving them of glucose. In addition to dietary and lifestyle modifications which work on tumors metabolically, there are a panoply of nutritional supplements and repurposed drugs associated with cancer prevention, and better treatment outcomes. These interventions and their evidentiary basis are covered in the latter half of this review to guide future cancer treatment.

The creation of nano-zero-valent iron (nZVI) by implementing plant extracts is an environmentally friendly process. High antioxidant capacity and phenol content indicated the possibility of oak-nZVI synthesis using oak leaf extract as a stable material with minimal agglomeration. Simultaneously removal of Cd and phosphates and Ni and phosphates was optimized by a statistically designed experiment with a definitive screening design. In terms of significance, 4 input parameters on process productivity were monitored: initial metal concentration (1 - 9 mgL-1), initial ion concentration (1- 9 mgL-1), pH value (2 - 10) and oak-nZVI dosage (2 - 16 ml). Phosphate removal efficiency, in the presence of cadmium, was the most influenced by oak-nZVI dose and cadmium concentration, while pH gave three statistically significant interactions with oak-nZVI dosage, cadmium concentration, and phosphate concentration. Phosphate removal efficiency, in the presence of Ni, is the most influenced by nickel concentration, phosphate concentration, pH, two-factor interaction between nZVI dose and Ni concentration, and quadratic phosphate interaction. The process optimization yielded the highest simultaneous removal efficiency of 98.99% and 87.30% for cadmium and phosphate ions, respectively. Also, the highest simultaneous removal efficiency of nickel and phosphates ion was 93.44% for 96.75%, respectively. The optimization process fits into the confidence intervals, confirming the assumption that the adopted regression model describes the process well. This work demonstrated an enormous potential and prosperous application for the Cd(II), Ni(II), and phosphate removal from water matrices.

Non-systemic oral drugs, which do not get absorbed through the gastrointestinal membrane, are an important group of compounds for targeting diseases residing within the gastrointestinal lumen. However, they require a set of design principles not sufficiently covered by traditional druglikeness metrics, such as Lipinski’s Rule of 5. These druglikeness metrics fail to accurately identify true negative outcomes; such is the requirement for novel cheminformatic based approaches for the discovery of non-systemic small molecules. One such example of these newer metrics is the fraction of SP3-hybridised carbon atoms (fSP3) which has shown promising application as an identifier of poor oral-bioavailability. Herein, we discuss the application of fSP3 in the drug discovery process in a number of case studies, including our own work discovering non-systemic fructose scavengers for the treatment of fructose malabsorption.

For several millennia, doctors and healers used therapeutic ingredients extracted from minerals, plants, and animals. Among the active remedies derived from animals, the placenta was among the most popular ones. The use of placenta-based remedies has retained its significance in our time. The placenta-based therapeutics are indicated for stimulating immunity, wound healing, reduction of skin pigmentation, treatment of various patients suffering from gynecological disorders, etc. By the beginning of the 21st century, the majority of specific functions and chemical ingredients of the placenta were identified and described. However, only now active proteins and peptides with molecular weight of about ten kDa were revealed. Presumably, they play an essential role during the therapeutic application of placental extract. Hopefully, this discovery will start a new era in the research and clinical application of organotherapeutic remedies, including placenta.

This study explored the potential synergism within chlorhexidine-silver nanoparticles conjugates against Influenza type A, Staphylococcus aureus, Escherichia coli, and Candida albicans. Silver nanoparticles (SN) were obtained by the reduction of silver ions with green tea total phenolic extract and conjugated with chlorhexidine (Cx). The particles were characterized by UV-Vis and FTIR spectroscopies, dynamic light scattering, X-ray diffraction, and transmission electron microscopy. A stable negatively-charged nano-silver colloid (ζ=-50.01) was obtained with an average hydrodynamic diameter of 92.34 nm. In the presence of chlorhexidine, the spectral data and the shift of the zeta potential to positive values (ζ=+44.59) revealed the successful sorption of the drug onto the silver surface. The conjugates (SN-Cx) demonstrated potentiation in the effects against S. aureus and C. albicans, and synergism against E. coli with minimal inhibitory concentrations of SN 5.5 µg/mL+Cx 8.8 µg/mL. The SN showed excellent, increasing with time, virucidal properties, and low toxicity. The coupling of the cationic chlorhexidine with nano-silver, however, did not reduce its intrinsic cytotoxicity on various cell lines (MDCK, BJ, and А549). The newly-synthesized antimicrobial agent presented with an extended and promising therapeutic spectrum and needs to be further evaluated on relevant to the designated route of administration three-dimensional cell models (e.g., nasal, bronchial, dermal, ocular, etc.).

Poor interlaminar fracture toughness has been a major issue in glass fiber-reinforced epoxy resin (GF/EP) laminate composites. In this paper, soft carboxy-terminated liquid nitrile (CTBN) rubber particles and rigid nano-SiO2 are used to toughen the epoxy resin (EP) matrix to improve the interlayer properties of GF/EP laminate composites. The effects of adding two toughening agents on the mechanical and interlayer properties of GF/EP laminates were studied. The results showed that adding the two kinds of particles improved the mechanical properties of the epoxy matrix. When the additional amount of flexible CTBN rubber particles was 8wt%, and the rigid nano SiO2 was 0.5wt%, the fracture toughness of the matrix resin was increased by 215.8%, and the tensile strength was only decreased by 2.3% compared with the pure epoxy resin. On this basis, the effects of two kinds of particles on the interlayer properties of GF/EP composites were studied. Compared with the unmodified GF/EP laminates, the interlayer shear strength and mode Ⅰ interlayer fracture toughness is significantly improved by toughening agent, and the energy release rate GIC of interlayer shear strength and interlayer fracture toughness is increased by 109.2%, and 86.8%, respectively.

Nano-titanium has excellent corrosion resistance and can be widely used in the field of corrosion resistant coatings. This paper introduces nano-weight titanium modified phenolic resin coatings and their anti-corrosion properties to explore the principle of nano-titanium modification and the mechanism of anti-corrosion to further develop more advanced corrosion resistant coatings. The article uses scanning electron microscopy, Fourier transform infrared spectroscopy, Raman spectroscopy and UV-Vis spectrophotometer to characterise the morphology and structure of the nano-titanium modified phenolic resin coatings and to determine the corrosion resistance properties of the modified phenolic resin coatings. The results show that the 4% nano-titanium modified phenolic resin coating, nano-titanium powder and phenolic resin will maximize the dispersion and combination, and the structure is good; nano-titanium grafted on phenolic resin, the successful preparation of nano-titanium modified phenolic resin; modified nano-titanium added to improve the coating's ability of UV absorption. The corrosion resistance of the coating is much better than that of the unmodified phenolic resin coating.

In the field of clinical medicine, the real-time monitoring of carbon dioxide gas exhaled by the human body is of great significance. At present, the detection devices in the market are mainly detected by sucking a small amount of gas in the nasal cavity to the detection device, and there are some problems such as too long sampling tubes, easy blockage or distortion, and abnormal gas dispersion. In this paper, a micro-nano optical fiber sensor that can directly detect the concentration of end-tidal carbon dioxide is proposed. The measurement is achieved by using the principle of high evanescent field absorption, and the operating band is 2.004 μm. The sensor uses micro-nano optical fiber as the sensing area, and then detects the presence of carbon dioxide gas exhaled by human body through optical power attenuation. The function of micro-nano fiber is to realize the transmission of signal light and also serve as the absorption medium of the gas to be measured. In addition, the variation of light power also reflects the respiratory cycle of the human body. The sensor can realize rapid real-time response to carbon dioxide gas detection, with small size, low cost, and easy to replace. It has great application potential in clinical scenarios such as Gastrointestinal Endoscopes that require real-time monitoring of human respiration.

Accumulation of proteins in filter membranes limits the efficiently of filtering technologies for cleaning wastewater. Efforts are ongoing to coat commercial filters with different materials (such as titanium-dioxide, TiO2) in order to reduce the fouling of the membrane. Beyond monitoring the desired effect of retention of biomolecules, it is demanding to understand what are the biophysical changes in water-soluble proteins caused by interacting with the new coated filter membranes, an aspect that has received little attention so far. Using spin label electron paramagnetic resonance (EPR), aided with native fluorescent spectroscopy and dynamic light scattering (DLS), here we report the changes in the structure and dynamics of bovine serum albumin (BSA) exposed to TiO2 (P25) nanoparticles or passing through commercial polyvinylidene fluoride (PVDF) membranes coated with the same nanoparticles. We have found that the filtering process and prolongued exposure to TiO2 nanoparticles had significant effects on different regions of BSA, and denaturation of the protein was not observed, neither with TiO2 nanoparticles nor by pressing through TiO2-coated filter membranes.

The molecular structure and vibrational spectra of six 1,2,3-triazoles-containing molecules with possible anticancer activity were investigated. In two of them, the optimized geometry was determined in the monomer, cyclic dimer and staking forms using the B3LYP, M06-2X and MP2 methods. The effect of the para-substitution in the aryl ring was evaluated based on the changes in the molecular structure and atomic charge distribution of the triazole ring. Several relationships were obtained that could facilitate the selection of the substituents on the triazole ring for their further synthesis. The observed IR and Raman bands in the solid state of two of these compounds were accurately assigned according to the functional calculations on the monomer and dimer forms, together with the polynomic scaling equation procedure (PSE).

Pulmonary hypertension (PH) is a severe vascular complication of connective tissue diseases (CTD). Patients with CTD may develop PH belonging to different groups: 1) pulmonary arterial hypertension (PAH), 2) PH secondary to lung disease and/or hypoxia, 3) PH due to left heart disease, and 4) chronic thromboembolic pulmonary hypertension (CTEPH). PAH most often develops in systemic scleroderma (SSc), mostly in its limited variant. PAH-CTD is a progressive disease characterized by poor prognosis, therefore the early diagnosis should be established A specific treatment for PAH-CTD is currently available and recommended: prostacyclin derivative (treprostinil, epoprostenol, iloprost, selexipag), nitric oxide and natriuretic pathway: stimulators of soluble guanylate cyclase (sGC: riociguat) and phosphodiesterase 5 inhibitors (PDE5i: sildenafil, tadalafil), endothelin receptor antagonists (ERA: bosentan, macitentan, ambrisentan). Moreover, novel drugs e.g. sotatercept are intensively investigated in the clinical trials. The aim of this paper is to review the literature on the recent advances in treatment strategy and prognosis of patients with PAH-CTD.

This study introduces an innovative integration of hyperbolic metamaterials (HMMs) and photonic crystals (PtCs), each possessing unique dispersion properties that effectively manipulate the propagation of light. We present a PtC waveguide consisting of arrays of HMM nanorods, denoted as HMM PtCs. This waveguide configuration enables the realization of a high figure of merit (FOM) nano-sensor. By modifying the refractive indices of the surrounding materials, the PtC waveguide exhibits alterations in absorption and transmission, allowing for the detection of temperature, pressure, and material variations. Numerical methods were employed to demonstrate the remarkable efficiency of this proposed system, achieving a sensitivity of 324.16 nm/RIU (refractive index unit) and an impressive FOM of 469.58 RIU−1. These results signify a substantial improvement over surface plasmonic sensors, which typically exhibit limited FOMs. As a consequence, the HMM PtC waveguide sensor emerges as an exceptionally appealing option for photonic sensing applications. The proposed HMM PtC waveguide holds vast potential across diverse fields, including biology, medicine, and clinics, representing an exciting advancement for both industry and scientific research.

Organophilic nano clay is the composition of mostly clay and organic molecules designed to improve various materials' physical and chemical properties. Permanent deformation in asphalt pavements is primarily the result of inadequate compaction, excessive loading, and high temperatures. Rutting can result in aquaplaning, leading to accidents and costly maintenance and rehabilitation works that drain the economy. Such behavior of asphalt pavements may be attributable to poor selection of aggregate, asphalt binder, or substandard asphalt binders. This study used different percentages of organophilic nano clay ranging from 3.0% - 5.0% with two penetration grade bitumen, i.e., N.R.L 60-70 &amp; N.R.L 80-100. Adding organophilic nano clay to asphalt binder significantly reduced the rutting potential under cyclic loading at high temperatures (55 °C). Ten modified formulations and two virgin bitumen specimens were prepared. The modified binders' viscosity and rutting were tested using the Rotational Viscometer and Wheel Tracker Test (W.T.T.), respectively. The results were analyzed using software for Statistical Analysis. It was recorded that organophilic nano clay-modified bitumen significantly affected rutting to interpret the results. The results indicated that rutting decreased and viscosity increased in all nano clay-modified bitumen samples, with a 4.5% O.N.C modified binder showing the most significant improvement.

High mobility group box 1 (HMGB1) is secreted from activated immune cells, necrotic cells, and certain cancers. Previous studies have reported that different patterns of post-translational modification, particularly acetylation and oxidation, mediate HMGB1 release and confer distinct extracellular HMGB1 signaling activity. Here we report that cisplatin but not carboplatin induces secretion of HMGB1 from human A549 non-small cell lung cancer (NSCLC) cells. Cisplatin-mediated HMGB1 secretion was dose-dependent and was regulated by nuclear exportin 1 (XPO1) also known as chromosomal maintenance 1 (CRM1) rather than adenosine diphosphate (ADP)-ribosylation, acetylation, or oxidation. HMGB1, as well as lysine acetylation and cysteine disulfide oxidation of secreted HMGB1, were monitored by sensitive and specific assays using immunoprecipitation, stable isotope dilution, differential alkylation, and nano liquid chromatography parallel reaction monitoring/high-resolution mass spectrometry (nano-LC-PRM/HRMS). A major fraction of the HMGB1 secreted by low dose cisplatin treatment of A549 NSCLC cells was found to be in the fully reduced form. In contrast, mainly oxidized forms of HMGB1 were secreted by dimethyl sulfoxide (DMSO)-mediated apoptosis. These findings suggest that inhibition of XPO1 could potentiate the anti-tumor activity of cisplatin by increasing the nuclear accumulation of HMGB1 protein, an inhibitor of cisplatin DNA-adduct repair. Furthermore, low-dose cisplatin therapy could modulate the immune response in NSCLC through the established chemokine activity of extracellular reduced HMGB1. This could potentially enhance the efficacy of subsequent immunotherapy treatment.

Premenstrual syndrome is characterized by pain and symptoms affecting the women´s quality of life. We aimed to evaluate the safety and effectiveness of an oral fixed dose combination containing naproxen 220 mg + paracetamol 300 mg + pamabrom 25 mg tablet (Analgen Fem®) during the routine clinical practice. A prospective, open-label, multicenter, observational post-marketing study was conducted from December 2017 to December 2019 including 270 women older than 18 years. Primary endpoint was the proportion of adverse events, meanwhile the pain intensity, premenstrual syndrome symptoms, and patient proportion with a pain score reduction by at least 50% were secondary endpoints. The mean age of population was 28.9 ± 8.8 years. Among the 270 women, 8 (3%) experienced 10 adverse events. These were headache (5/8), gastritis (2/8) dyspepsia (1/8), diarrhea (1/8) and nausea (1/8). The investigator discontinued the study medication in 3/8 patients because of adverse events. The median of differences between the pain intensity at baseline and at last observation (-4.5, 95%CI; -5, -4) demonstrated that naproxen 220 mg + paracetamol 300 mg + pamabrom 25 mg fixed dose combination reduced pain intensity (p<0.001). In addition, the proportion of patients with pain reduction by at least 50% at the end of the treatment was 70.7%. The study demonstrated that this drug represents a safe and tolerated treatment, reducing pain intensity and premenstrual symptoms.