Alveolar Rhabdomyosarcoma (ARMS), an invasive subtype of Rhabdomyosarcoma (RMS), is associated with chromosomal translocation events resulting in one of two oncogenic fusion genes PAX3-FOXO1 or PAX7-FOXO1. ARMS patients exhibit an overexpression of the pleiotropic cytokine Transforming growth factor beta (TGF-β). This overexpression of TGF-β1 causes an increased expression of a downstream transcription factor called SNAIL, which promotes Epithelial to Mesenchymal Transition (EMT). Overexpression of TGF-β also inhibits myogenic differentiation, making ARMS patients highly resistant to chemotherapy. In this review, we first describe different types of RMS and then focus on ARMS and the impact of TGF-β in this tumor type. We next highlight current chemotherapy strategies including a combination of FDA approved drugs vincristine, actinomycin D, and cyclophosphamide (VAC), Cabozantinib, Bortezomib, Vinorelbine, AZD 1775 and cisplatin. Lastly, we discuss chemotherapy agents that target the differentiation of tumor cells in ARMS which include all trans retinoic acid (ATRA) and 5-Azacytidine. Improving our understanding of the role of signaling pathways, such as TGF-β1, in the development of ARMS tumor cells differentiation will help inform more tailored drug administration in the future.

Glutathione (GSH) is an antioxidant that our cells utilize to prevent damage done by reactive oxygen species, free radicals, peroxides, lipid peroxides, and heavy metals [1]. Due to its immune role in tuberculosis (TB), GSH is hypothesized to play an important part in the immune response against M. tb. Furthermore, one of the hallmark structures of TB is granuloma formation, which involves many types of immune cells. T cells specifically are a major component and are involved in the release of cytokines and activation of macrophages. GSH acts as an important function in macrophages, natural killer cells, and T cells in modulating their activation, their metabolism, the proper cytokine release, the proper redox activity, and free radical levels. For more susceptible patients with HIV and Type 2 Diabetes, the demand for higher GSH levels is increased. This review compiles reports demonstrating the benefits of GSH in improving the immune cell responses against M. tb infection and the use of GSH as adjunctive therapy for TB.

FoxP3 is a transcription factor essential for the differentiation and function of T regulatory cells (Tregs). There are two major subsets of Tregs: natural Tregs (nTregs) generated in thymus and inducible Tregs (iTregs) produced in peripheral immune system. It has been documented that iTreg development is dependent on soluble mediators including interleukin 2 (IL2), transforming growth factor β (TGFβ) and all-trans-retinoic acid (ATRA). In our experiments we performed a gene expression array, followed by Real-time PCR experiments, to study the expression of genes regulated by 1,25-dihydroxyvitamin D (1,25D) or ATRA in cells of myeloid origin. Our experiments revealed that ATRA alone, but also a cocktail of mediators consisting of IL2, TGFβ and ATRA, upregulate the expression of FOXP3 gene in lymphoid cells, but also in normal and leukemic myeloid cells. The FoxP3 expression is followed by a phenotypic changes in cells of myeloid origin. Our results indicate that signaling pathways which are used in the late stages of T cell differentiation, are also active in the cells of myeloid lineage

Streptococcus mutans (S. mutans) is the main etiological bacteria present in the oral cavity that leads to dental caries. All of the S. mutans in the oral cavity form biofilms that adheres to the surfaces of teeth. Dental caries are infections facilitated by the development of biofilm. An esterified derivative of epigallocatechin-3-gallate (EGCG), epigallocatechin-3-gallate-sterate (EGCG-S) was used in this study to assess its ability to inhibit the growth and biofilm formation of S. mutans. The effect of EGCG-S on bacterial growth was evaluated with colony forming units (CFU) and log reduction; biofilm formation was qualitatively determined by Congo red assay, and quantitatively determined by crystal violet assay, fluorescence-based LIVE/DEAD assays to study the cell viability, and scanning electron microscopy (SEM) was used to evaluate the morphological changes. The results indicated that EGCG-S was able to completely inhibit growth and biofilm formation at concentrations of 250 µg/ml. Its effectiveness was also compared with a commonly prescribed mouthwash in the United States, chlorhexidine gluconate. EGCG-S was shown to be equally effective in reducing S. mutans growth as chlorhexidine gluconate. In conclusion, EGCG-S is potentially a natural anticariogenic agent by reducing bacterial presence in the oral cavity.

The incremental sheet forming represents a relatively recent technology that guarantees high customization, thanks to the layered manufacturing principle typical of rapid prototyping, and cost-effectiveness, because it does not require dedicated equipment. Research has initially shown that this process is effective in metal materials capable of withstanding plastic deformation but, in recent years, the interest in this technique has been increasing for the manufacture of complex polymer sheet components as an alternative to the conventional technologies, based on heating-shaping-cooling manufacturing routes. Conversely, incremental formed polymer sheets can suffer from some peculiar defects, for example twisting. To reduce the risk of this phenomenon and the occurrence of failures, a viable way is to choose toolpath strategies that make the tool/sheet contact conditions less severe, and this represents the main goal of the present research. Polycarbonate sheets were worked by incremental forming; in detail, cone frusta with a fixed wall angle were manufactured with a reference and a stair toolpath strategy, and both the forming forces and the twist angle were monitored. The analysis of the results highlighted that a stair toolpath involving an alternation of diagonal up and vertical down steps represents a useful strategy to mitigate the forming forces and, with them, the occurrence of the twisting phenomenon in incremental formed thermoplastic sheets.

A novel process design for damage-free and highly accurate positional integration of an optical multi-axial force sensor into a hollow tube by means of rotary swaging is introduced. Numerical simulations reveal relevant process phenomena of thin disc joining inside a pre-toothed hollow tube and help to find an optimal process design. Experimental trials show a significant effect of axial material flow and the number of tools in a rotary swaging process. By taking these effects into account, a successful form- and force-fit joining of the sensor carrying discs into the tube can be achieved. A successful joining of an optical sensor for bending forces and torque measurement shows hysteresis-free sensory behavior and thus backlash-free joining of the sensor carrier discs. The paper finishes with presenting an approach for closed-loop position controlling during the joining process and numerically investigation of the process design.

The limited information available on the structure of complexes involving transcription factors and cognate DNA response elements represents a major obstacle in the quest to understand their mechanism of action at the molecular level. We implemented a concerted structural proteomics approach, which combined hydrogen-deuterium exchange (HDX), quantitative protein-protein and protein-nucleic acid cross-linking (XL), and homology analysis, to model the structure of the complex between the full-length DNA binding domain (DBD) of FOXO4 and its DNA binding element (DBE). The results confirmed that FOXO4-DBD assumes the characteristic forkhead topology shared by these types of transcription factors, but its binding mode differs significantly from those of other members of the family. The results showed that the binding interaction stabilized regions that were rather flexible and disordered in the unbound form. Surprisingly, the conformational effects were not limited only to the interface between bound components but extended also to distal regions that may be essential to recruiting additional factors to the transcription machinery. In addition to providing valuable new insights into the binding mechanism, this project provided an excellent evaluation of the merits of structural proteomics approaches in the investigation of systems that arematerial not directly amenable to traditional high-resolution techniques.

In the last decades, intensive crop management has involved excessive use of pesticides or fertilizers, compromising environmental integrity and public health. Accordingly, there has been worldwide pressure to find an eco-friendly and safe strategy to ensure agricultural productivity. Recently, Plant Growth-Promoting (PGP) rhizobacteria are receiving increasing attention as suitable biocontrol agents against agricultural pests. In the present study, 22 spore-forming bacteria were selected among a salt-pan rhizobacteria collection for their PGP traits and their antagonistic activity against the plant pathogen fungus Macrophomina phaseolina. Based on the higher antifungal activity, strain RHFS10, identified as Bacillus vallismortis, was furtherly examined and cell-free supernatants assays, column purification, and tandem mass spectrometry employed to purify and preliminarily identify the antifungal metabolites. Interestingly, the minimum inhibitory concentration assessed for the fractions active against M. phaseolina, resulted 10 times lower and more stable than the one estimated for the commercial fungicide pentachloronitrobenzene. These results suggest the use of B. vallismortis strain RHFS10 as a potential Plant Growth Promoting Rhizobacteria to efficiently control phytopathogenic fungus M. phaseolina, in alternative to chemical pesticides.

The use of biodegradable materials has a growing field of application due to environmental concerns, however, scientific research on incremental forming using biomaterials is scarce. Thus, this study focuses on the single point incremental forming (SPIF) process applied to a composite sheet that combines a biodegradable thermoplastic matrix (Solanyl) reinforced with natural fibres (flax). The influence of the process parameters on the final geometry is determined, evaluating the effect of the following factors: step depth, wall angle and temperature reached during the process. Additionally, a heated aqueous medium is incorporated which facilitates the formability of the composite sheets. This method is especially useful for materials that have poor formability at room temperature. The benefits of using controlled heat include the reduction of formation forces applied to the plate, improved accuracy due to the reduction of elastic recovery, and the manipulation of the samples remarkably close to the glass transition temperatures. Through this experimental study with the variables analysed, a maximum shaping depth of 310 mm is obtained. These results confirm that the single point shaping used with bioplastic materials is possible and has positive outcomes for incremental forming.

In this paper, we dive into the exciting world of wireless communication, focusing on how millimeter-wave technology and Multiple-Input Multiple-Output phased array antennas are shaping the future of 5G and the upcoming 6G technologies. We cover the latest advancements in millimeter-wave and beam-forming technologies, emphasizing their role in enhancing network security and efficiency in automotive vehicles through dual radar communication. Our discussion spans the benefits, applications, challenges, and solutions of these technologies individually from millimeter-wave to beam-forming technology and joint radar communications, alongside a look at their theoretical and practical implementations. We emphasize the integration of beam-forming technology in joint radar communications for future automotive vehicles and its impact on automotive systems, smart cities, and the Internet of Things (IoT). Looking ahead, we discuss the potential of these technologies to transform future tech landscapes, while also addressing the security implications of merging communication and radar capabilities. This paper aims to provide a clear view of the advancements and prospects of millimeter-wave, beam-forming, and dual radar communication technologies.

A proposed low-temperature forging method aims to enhance stainless steel bearings by creating a martensitic subsurface layer, significantly boosting bearing fatigue life due to increased surface hardness. This technique induces beneficial residual stresses, particularly in axial bearings, streamlining their construction and improving machine elements. Challenges persist, especially with radial bearings, but simplicity in axial bearing forging promotes compact, resource-efficient facility construction. Future research will focus on applying this technique to axial bearing washers, potentially replicating success in other bearing components. Despite the energy ex-penditure for cooling during forging, the substantial increase in bearing fatigue life offsets this, enhancing overall longevity and reliability of critical machine components. Integration of this forging technique into bearing fabrication appears seamless, offering a promising trade-off be-tween energy use and enhanced performance.

The coevolution of species drives diversity in animals and plants and contributes to natural selection, whereas in host–parasite coevolution, a parasite may complete an incomplete evolutionary/developmental function by utilizing the host cell’s machinery. Analysis of related older data suggests that Plasmodium falciparum (P. falciparum), the pathogen of malaria tropica, cannot survive outside its human host because it is unable to perform the evolutionarily first protein glycosylation of serologically A-like, O-GalNAcα1-Ser/Thr-R, Tn antigen (“T nouvelle”) formation, owing to its inability for synthesizing the amino sugar N-acetyl-d-galactosamine (GalNAc). This parasite breaks the species barrier via hijacking the host's physiological A-like/Tn formation through abundantly expressing serine residues and creating hybrid A-like/Tn structures, which in the human blood group O(H) are attacked by the germline-encoded nonimmune polyreactive immunoglobulin M (IgM), exerting the highly anti-A/B/H-aggressive isoagglutinin activities. These activities physiologically undergo the ABO(H) blood group phenotype formation, occurring on the surfaces of red blood cells (RBC), epithelial and endothelial cells and on plasma proteins by identical glycosylation, performed by the ABO(H)-allelic glycotransferases, phenotypically downregulating the anti-A/B/H-reactive IgM (isoagglutinin) activities in the non-O blood groups. ABO(H) phenotype diversity, this way glycosidically linked and molecularly connected to humoral immunity, becomes exposed to the evolution.

The picornavirus genome encodes a large single polyprotein that is processed by viral proteases to form an active replication complex. The replication complex is formed with the viral genome, host proteins, and viral proteins that are produced/translated directly from each of the viral genomes (cis-provided viral proteins). Efficient complementation in vivo of replication complex formation by trans-provided viral proteins, thus exogenous or ectopically expressed viral proteins, remains to be demonstrated. Here we report an efficient trans-complementation system for the replication of defective poliovirus (PV) mutants by a viral polyprotein precursor in HEK 293 cells. Viral 3AB in the polyprotein, but not 2BC, was processed exclusively in cis. Replication of a defective PV replicon mutant, with a disrupted cleavage site for viral 3Cpro protease between 3Cpro and 3Dpol (3C/D[A/G] mutant) could be rescued by a trans-provided viral polyprotein. Only a defect of 3Dpol activity, of the replicon could be rescued in trans; inactivating mutations in 2CATPase/hel, 3B, and 3Cpro of the replicon completely abrogated the trans-rescued replication. An intact N-terminus of the 3Cpro moiety, of the trans-provided 3CDpro, was essential for the trans-rescue activity. By using this trans-complementation system, a high-titer defective PV pseudovirus (> 107 infectious units per mL) could be produced with the defective mutants, whose replication was completely dependent on trans-complementation. This work reveals potential roles of exogenous viral proteins in PV replication and offers insights into protein/protein and protein/RNA interactions during picornavirus infection.

Following the era of GWAS studies, efforts are being made to identify genes underlying complex traits by merging eQTL and GWAS data and assessing the colocalization of eQTLs and GWAS signals. A problem that sometimes occurs in this context is the observation of association between several genes in a genomic region with a trait. This happens because genes in a region could be under the regulatory impact of common elements and coexpress. As such, computational approaches that rely on cis-eQTL information can not exactly pinpoint the causal gene. Here, I report an alternative solution, based on trans-eQTLs to test the association between a gene and a trait. Through the analyses applied to adjacent genes that coexpress and concordantly impact blood traits, I provide evidence that trans-eQTLs can resolve the problem of coexpression-causality without the interference of shared cis-regulatory SNPs.

The first diastereoselective synthesis of (–)-1-epi-lentiginosine stars from a common chiral trans-epoxyamide derived from 2-pyridincarbaldehyde is reported. This methodology involves a sequential oxirane ring opening and intramolecular 5-exo-tet cyclization of tosylate tras-epoxyalcohol to afford a diastereomeric mixture of indolizinium salts in a one-pot fashion, followed by regio- and diastereospecific pyridinium ring reduction.

Introduction: Spinal epidural arteriovenous fistulas (SEDAVFs) are extremely rare and the pathological process still remains unclear. Nevertheless, neurofibromatosis, surgery, as well as trauma have been implicated as causes. Nevertheless, long standing chronic vertebral compression fractures (VCFs) as a cause of SEDAVFs has not been reported in literature. Case Presentation: Our cases comprised of a male and female with ages 67 and 62 year respectively. They presented with weakness of bilateral lower extremities and back pain. Their symptoms deteriorated into mild recto-bladder dysfunction as well as hypoesthesia of lower limbs. They both had history of road traffic accidents (RTAs) prior to their symptomatology. In both cases, Magnetic resonance imaging (MRI) revealed VCFs prior to the above symptomatology. Spinal digital subtraction angiography (DSA) was used to confirm SEDAVFs in both cases. We utilized the trans-arterial route with Onyx embolization agent to obliterate both fistulae and their symptom resolved after the embolization. Two-years follow-ups revealed no recurrence of their fistulae. Conclusion: The initial long standing VCFs caused by trauma resulted in perforation of the dorsal somatic branches of the radicular artery leading to the occurrences of SEDAVFs in our cases.

The electronic transport stability in nanodevices composed by metal/trans-polyacetylene /metal with different long length has contributed greatly for performance, homogeneity, stability, organization of the chains, reproducibility and higher conductivity. In this paper, we present an analytical study of the electronic transport characteristics from dimerized trans-polyacetylene (trans-PA) molecules containing an odd-even number of sites coupled to metal leads (left and right) in T-shaped geometry using the extended Su-Schrieffer-Heeger (SSH) model based on tight-binding Hamiltonian with the Non-Equilibrium Green´s Function (NEGF) via Heisenberg´s equation of motion and the Keldysh´s formalism. Due to the complexity of the T-shaped odd-even chain, our proposal was to test the effects on the finite-length network for three, four, five sites and furthermore foresee for 17-sites. We show how to tune dimerization strength () coupling to the parameters and T-shaped geometry of the device to which it affects the overlap integral localized at the three endpoints of the T-shaped system, making both the odd and even chains to undergo a metal-insulator transition in their electronic behavior. The results reached through control parity of the chain plane of the parameters governing () the electronic and experimental tunneling allow a better understanding of the subject.

Multilayered metallic sheets fabricated by hot metal forming processes are attractive structural components in the aerospace and automobile industry. The strength of the mechanical bond between the different layers is critical to the applicability of such components in load bearing applications. While it is well understood that the process conditions such as temperature, deformation and rate of deformation influence the bond strength, a clear functional relationship between these conditions and the bond strength has yet to be established. The objective of the current study is to investigate the joining of Aluminum-6061 alloy specimens by hot compression bonding. Hot compression tests of beam specimen pairs were conducted at different temperatures (300-500℃), with different strains and strain rates (10-2-10-1 [1sec]). Coupled thermo-mechanical finite element models were utilized to compute the time dependent thermo-mechanical fields that develop along the specimen interface. The computed values were used to map the spatial distribution of a scalar parameter J which is hypothesized to govern bond formation. Mechanical tensile tests were used to determine the bond strength and expose the bonded surfaces. It is demonstrated that the computed J distribution can be correlated well with SEM observations of the debonded surface. It is also shown that the actual bonded area can be predicted from the computations for a certain range of critical J values.

While the angiotensin converting enzyme 2 (ACE2) protein is defined as the primary severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor, the viral serine molecule might be mobilized by the host's transmembrane protease serine subtype 2 (TMPRSS2) enzyme from the viral spike (S) protein and hijack the host’s N-acetyl-D-galactosamine (GalNAc) metabolism. The resulting hybrid, serologically A-like/Tn (T-nouvelle) structure potentially acts as a host–pathogen functional molecular bridge. In humans, this intermediate structure will hypothetically be replaced by ABO(H) blood group-specific, mucin-type structures, in the case of infection hybrid epitopes, implicating the phenotypically glycosidic accommodation of plasma proteins. The virus may, by mimicking the synthetic pathways of the ABO(H) blood groups, bind to the cell surfaces of the blood group O(H) by formation of a hybrid H-type antigen as the potential precursor of hybrid non-O blood groups, which does not affect the highly anti-glycan aggressive anti-A and anti-B isoagglutinin activities, exerted by the germline-encoded nonimmune immunoglobulin M (IgM). In the non-O blood groups, which have developed from the H-type antigen, these IgM activities are downregulated by phenotypic glycosylation, while adaptive immunoglobulins might arise in response to the hybrid A and B blood group structures, bonds between autologous carbohydrates and foreign peptides, suggesting the exertion of autoreactivity. The non-O blood groups thus become a preferred target for the virus, whereas blood group O(H) individuals, lacking the A/B phenotype-determining enzymes and binding the virus alone by hybrid H-type antigen formation, have the least molecular contact with the virus and maintain the critical anti-A and anti-B isoagglutinin activities, exerted by the ancestral IgM, which is considered the humoral spearhead of innate immunity.

We continue our recent endeavor in which a time-dependent black hole solution of a one-loop quantum-corrected Einstein-scalar system was obtained and its near-horizon behavior was analyzed. The energy analysis led to a trans-Planckian scaling behavior near the event horizon. In the present work the analysis is extended to a rotating black hole solution of an Einstein-Maxwell-scalar system with a Higgs potential. Although the analysis becomes much more complex compared to that of the previous, we observe the same basic features, including the quantum-gravitational trans-Planckian energy near the horizon.

This study analyzed the technical efficiency of barley production by smallholder farmers in Meket district, Amhara National Regional State, Ethiopia. A cross sectional data from a sample of 123 barley producers during the 2016/17 production season was collected by applying two stage random sampling. To address the objective of the study, both descriptive statistics and econometric models were used to analyze the data. The trans-log functional form of the production function simultaneously with single stage estimation approach was used to estimate the production of barley output and technical inefficiency factors. The estimated stochastic production frontier model indicated that input variables such as fertilizer, human labor and oxen power were the significant variables to increase the quantity of barley output while, barley seed had a negative effect. The estimated mean levels of technical efficiency of the sample farmers were about 70.9% which revealed that, presence of a room to increase their technical efficiency level on average by 29.1% with the existing resources. The discrepancy ratio gamma indicated that 63% of the total variation from the frontier comes due to technical inefficiency while, the remaining 37% comes due to factors outside the control of farmers. Among the hypothesized factors that affect technical inefficiency; education level, extension contact and number of barley plots significantly and negatively affected technical inefficiency score. Besides, practice of crop rotation, distance of residence from the nearest main market, total expenditure and soil fertility was found to have a positive and significant effect. Hence, emphasis should be given to decrease the inefficiency level of those more inefficient farm households via experience sharing among the farmers and usage of improved or certified barley seed. Besides to this, policies and strategies of the government should be directed towards increasing farmers’ education, improve the system of input distributions and institutional facilities.

For deep-penetrating geochemistry, there is a frontier issue as to how to explore ore-bearing information deep in covered areas, while it is, too, important to investigate the geochemical migration of ore-forming elements for the development of exploration geochemistry. In this study, a 380-day migration column experiment was conducted with surface soil and pure Cu powder collected from the Yujiashan study area in Wuhan City, Hubei Province taken as the object of research to simulate the migration process of ore-forming elements under natural conditions. The results showed obvious vertical migration of the ore-forming elements and conversion of mobile metal forms in the process; further, according to 6 groups of simulation experiments that took 45 days to conduct on migration column samples and the surface oil and Cu powder collected from the Pulang mining area in Yunnan Province, the vertical migration of the ore-forming element was still visible, and the exogenous substance (pure Cu powder) could enhance the anomaly without changing the basic migration mechanism. This indicates that Cu might migrate in a stable manner in soil cover in the Pulang mining area, and its migration was mostly driven by the transformation of Fe-Mn oxide bound state and organic bound state; finally, a multifractal analysis was conducted, revealing that the ore-forming elements presented a nonlinear and complex structure during their upward migration, which caused anomalies in the covered area, and multiple parameters exerted a certain indicative effect on different source intensities and properties of soil. In this study, laboratory simulations were performed to summarize the active-state evolution pattern and migration mechanism of ore-forming elements with a view to providing technical support and theoretical guidance for geochemical prospecting in the covered region.

Pore Forming Toxins (PFTs), formed mainly by virulence factors of bacteria, belongs to Pore Forming Protein (PFP) family. Secreted as soluble monomers, they bind specific targets in membranes where their oligomerization and insertion place. Lysenin, a member of the PFTs, forms and oligomer after sphingomyelin binding, the so-called prepore, which become inserted forming a pore after a conformational change triggered by a pH decrease. In crowded conditions, oligomers tends to stay in prepore form because the prepore-to-pore transition is sterically blocked. In this study, we investigate the effect of calcium ions in those crowded conditions, finding that calcium act as a trigger for lysenin insertion. We localize the residues responsible for calcium sensitivity in a small α-helix. Our results are not only one of the few complete structural descriptions of prepore-to-pore transitions but the very first that involves a calcium triggering mechanism. The presence of glutamic or aspartic acids in the insertion domains could be an indication that calcium may be a general trigger for PFTs and more generally PFP.

The plant Allium hookeri, belonging to the Allium genus, has a history of being used both as a common food ingredient and in herbal medicine. It has recently been reported to have anti-oxidant and anti-inflammatory effects. A. hookeri has been also shown to exhibit neuroprotective and anti-neuroinflammatory activities, but the active compounds responsible for these effects have not been identified in previous studies. This study aimed to perform a metabolite profiling using an HRESI-qTOF MS/MS-based molecular networking approach and identify the active compounds from A. hookeri that target senescent cell-associated secretory phenotype (SASP) inhibitory effects, which contribute to neuroprotective activities. As a result, ten compounds, including one new flavonoid (2) and nine known compounds (1 and 3–10), were identified, and their biological activity was tested. The most potent compound was N-trans-feruloyltyramine (7), which inhibited SASP markers and contributed to the senomorphic activities of A. hookeri. These findings suggest that the phenolamides from A. hookeri could be a promising source of bioactive compounds for preventing senescence-associated diseases.

A facile solid-phase synthetic method for incorporating the imidazoline ring motif, a surrogate for a trans peptide bond, into bioactive peptides is reported. The example described is the synthesis of an imidazoline peptidomimetic analog of an insect pyrokinin neuropeptide via a cyclization reaction of an iminium salt generated from the preceding amino acid and 2,4-diaminopropanoic acid (Dap).

Genes encoding regulatory RNAs known as short RNAs (sRNAs) or non-coding sRNAs (ncRNAs), modulate physiological responses through different mechanisms, through RNA-RNA interaction or RNA-protein interaction. These molecules transcribed in trans and in cis relative to the target RNA. They are located between the coding regions of proteins, i.e., in the intergenic regions of the genome and show signals of promoters and termini sequences generally Rho-independent. The size of the ncRNAs genes ranges from ~ 50 to ~ 500 nucleotides and several transcripts are processed by RNase with smaller end products, which modulate physiological responses through different mechanisms, by RNA-RNA interaction or RNA-protein interactions and some interactions may be stabilized by the Hfq chaperone. The Riboswitches constitute another class of ncRNAs, located in the 5'UTR region of an mRNA that promote transcriptional regulation through their interaction with a linker molecule. Recently, in prokaryotes, CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) regions have described, which repeats of sequences of palindromic bases are. Each replicate consists of short segments of "spacer DNA" from exposures prior to a bacteriophage virus or exogenous plasmid. The CRISPR system consists of an immune system of resistance to exogenous molecules.

The principal main of this research work was the study the influence of Cu addition on the wear behavior (WB) of eutectic Al-12.6Si alloy developed by spray forming (SF) method and compared with as-cast (AC) alloys. The phases of chemical compositions and microstructure were studied by optical microscopy, energy dispersive spectroscopy (EDS) and Scanning Electron Microscopy (SEM). The microstructure of SFAl-12.6Si (SF1) alloy reside — of fine primary and eutectic Si phases evenly distributed in the equiaxed α-Al matrix and SF Al-12.6Si-2Cu (SF2) alloy lie of uniformly distributed fine eutectic Si particulates and spherical form θ-Al2Cu precipitates in α-Al matrix. On other hand, the AC Al-12.6Si alloy (AC1) alloy involve of eutectic Si needles in the dendrite α-Al matrix, whereas AC Al-12.6Si-2Cu (AC2) alloy consisted of eutectic Si needles and Chinese script form θ phase distributed randomly in the α-Al matrix. The microhardness and wear properties were analyzed using Vickers hardness (VH) and dry sliding WT. The SF alloys exhibit superior hardness compared to the AC alloys. The wear properties of SF alloys exhibited significantly superior compared to the AC alloys. The SF2 alloy showed high wear resistance (WR) than the SF1 alloy in the entire sliding velocities and applied loads. The results indicate that the spray deposited alloys have a lower coefficient of friction (CF(µ)) than the AC alloys under varying load and sliding velocity conditions. The high WR in the SF alloy was due to microstructural modification during SF and precipitation of fine Al2Cu intermetallic and solid solubility effects. The SF2 depicts increased transition from oxidative to abrasive. In other ways, AC alloys demonstrate wear mechanisms that change from oxidative to abrasive and delamination with an increase in sliding velocity and load.

Glycans play important roles as recognition molecules on cell surfaces in living organisms due to their remarkable structural diversity. Carbohydrates exist in numerous isomeric forms and can adopt diverse structures through various branching patterns. Despite their relatively small molecular weights, they exhibit extensive structural diversity. On the other hand, lectins, also known as carbohydrate-binding proteins, not only recognize and bind to the diverse structures of glycans but also induce various biological reactions based on structural differences. Initially discovered as hemagglutinins in plant seeds, lectins have been found to play significant roles in cell recognition processes in higher vertebrates. However, our understanding of lectins in marine animals, particularly marine invertebrates, remains limited. Recent studies have revealed that marine animals possess novel lectins with unique structures and glycan recognition mechanisms not observed in known lectins. Of particular interest is their role as pattern recognition receptors in the innate immune system, where they recognize glycan structures of pathogens. Furthermore, lectins serve as toxins for self-defense against foreign enemies. Recent discoveries have identified various pore-forming proteins containing lectin domains in fish venoms and skins. These proteins utilize lectin domains to bind target cells, triggering oligomerization and pore formation in the cell membrane. These findings have spurred research into the new functions of lectins and lectin domains. In this review, we present recent findings on the diverse structures and functions of lectins in marine animals.

Advanced manufacturing techniques, aimed at implants with high dependability, flexibility, and low manufacturing costs, are crucial in meeting the growing demand for high-quality products like biomedical implants. Incremental sheet forming is a promising flexible manufacturing approach for rapidly prototyping sheet metal components using low-cost tools. Titanium and its alloys are used to shape most biomedical implants because of its superior mechanical qualities, biocompatibility, low weight, and great structural strength. The poor formability of titanium sheets at room temperature, however, limits their widespread use. The goal of this research is to show that gradual sheet formation of a titanium biomedical implant is possible. The possibility of creative and cost-effective concepts for the manufacturing of such complicated shapes with significant wall angles is explored in this study. A numerical simulation based on finite element modeling as well as a design process tailored to metal forming is used to complete the development. The mean of uniaxial tensile tests with a constant strain rate was used to study the flow behavior of the studied material. To forecast the crack, the obtained flow behavior was modeled using the behavior model and failure model.

To improve the effect of multi-point stretch forming of sheet metal, it is proposed in this paper to replace fixed ball head with swinging ball head. According to the multi-point dies with different arrangements, this research establishes the finite element models of the following stretch forming, i.e. fixed ball heads with conventional arrangement, swinging ball heads with conventional arrangement, swinging ball heads with declining staggered arrangement, and swinging ball heads with parallel staggered arrangement and then numerical simulation is performed. The simulation results show that by replacing fixed ball head with swinging ball head, the surface indentation of the formed part was effectively suppressed, the stress and tension strain distribution of the formed part was improved and the forming quality was improved; that the thickness of the elastic pad was reduced, the springback was reduced and the forming accuracy was improved; and that when the ball head was applied to multi-point die with staggered arrangement, better forming result was achieved, where the best forming result was achieved in combining the swinging ball heads with the multi-point die with parallel staggered arrangement. The forming experiments were carried out, and the experimental results were consistent with the trend of numerical simulation results, which verified the correctness of the numerical simulation.

Stess in laser cladding coating is an important factor affecting the safe operation of remanufacturing components. Ultrasonic testing has become a hot direction in nondestructive evaluation of stress, because it has the advantages of safety, non-destructive and on-line detection. This paper provides a review of ultrasonic testing for stress in remanufacturing laser cladding coating. It summarizes the recent research outcomes on ultrasonic testing for stress, analyzes mechanism of ultrasonic testing for stress. Remanufacturing laser cladding coating shows typical anisotropic behaviors, the ultrasonic testing signal in laser cladding coating is influenced by many complex factors, such as microstructure, defect, temperature and surface roughness, etc. At present, ultrasonic testing for stress in laser cladding coating can only be done roughly. The paper discusses active mechanism of micro / macro factors to the reliability of stress measurement and the impact of stress measurement to the quality and safety of remanufacturing components. Base on the discussion, the paper proposes strategies for acquisition of nondestructive, rapid and accurate measurement of stress in remanufacturing laser cladding coating.

Acidic ostreolysin A/pleurotolysin B (OlyA/PlyB, formerly known as ostreolysin (Oly), and basic 20 kDa equinatoxins (EqTs) are cytolytic proteins isolated from the edible mushroom Pleurotus ostreatus and the sea anemone Actinia equina, respectively. Both toxins, although from different sources, share many similar biological activities: (i) colloid-osmotic shock by forming pores in cellular and artificial membranes enriched in cholesterol and sphingomyelin; (ii) increased vascular endothelial wall permeability in vivo and perivascular oedema; (iii) dose-dependent contraction of coronary vessels; (iv) haemolysis with pronounced hyperkalaemia in vivo; (v) bradycardia, myocardial ischemia and ventricular extrasystoles accompanied by progressive fall of arterial blood pressure and respiratory arrest in rodents. Both types of toxins are haemolytic within nanomolar range concentrations, and it seems that hyperkalaemia plays an important role in toxin cardiotoxicity. However, it was observed that the haemolytically more active EqT III is less toxic than EqT I, the most toxic and least haemolytic EqT. In mice, EqT II is more than 30 times more toxic than OlyA/PlyB when applied intravenously. These observations imply that haemolysis with hyperkalaemia is not the sole cause of the lethal activity of both toxins. Additional mechanisms responsible for lethal action of the two toxins are direct effects on heart, coronary vasoconstriction and related myocardial hypoxia. In this review, we appraise the pathophysiological mechanisms related to the chemical structure of OlyA/PlyB and EqTs, as well as their toxicity.

Previous high throughput screening studies indicated trans-eQTLs tend to be tissue specific. In this study, I probed if this feature can be used to identify tissue-specific gene regulatory networks. eQTL data (P<5e-8) for 16,259 genes were identified and their summary association statistics were obtained from the eQTLGene database. Next, eQTLs that display both cis and trans regulatory effects were selected and the association between their corresponding genes were examined using Mendelian randomization. A total of 169 genes that exerted trans-regulatory impacts on 692 genes were identified. 90% of the genes (N=749) aggregated into a gene regulatory network significantly enriched in hemo-immune processes. The robustness of finding was confirmed through simulation. The identified network displayed the scale-free topology. This provided the reason to examine the association of the network’s hub genes with the phenome. The outcome of analyses revealed GSDMB and ORMDL3 impact several disorders of immune origin and ALDH2 overexpression contributes to obesity. This study reports trans-eQTLs can be used to identify tissue-specific gene regulatory networks and describes a workflow to achieve this purpose. The network identified in this study showed scale-free topology indicating the hub genes of a GRN could be targeted to prevent disease outcomes.

Neurotoxicity belongs to the leading factors inducing neurodegeneration-related diseases, such as Alzheimer’s (AD) and Parkinson’s disease. In particular, accumulation of β-amyloid proteins in the brain, a hallmark in AD, induces oxidative stress and neurotoxicity. The use of antioxidants in AD is not sufficiently effective and other pharmacological approaches tested failed to cure, prevent or retard the progression of the disease. Clinical studies indicated that several medicinal plants display beneficial effects by improving memory and cognitive functions of patients with mild and moderate AD. In this study, the potential antioxidant and neuroprotective properties of Olea europea, Crocus sativus and Salvia spp extracts, as well as their main active compounds on cell viability was evaluated using an in vitro model of AD, the differentiated human SH-SY5Y neuroblastoma cells to cholinergic neurons. Their effects were assessed against the H2O2- and β-amyloid- induced cell toxicity using the MTS test. Current findings indicated that Salvia fruticosa, S. officinalis, S. argentea leaf extracts and the active compounds, oleuropein, trans-crocin-3 and -4 display significant dose-dependent antioxidant and neuroprotective properties. It is of note though that the total phenolic fragment of Olea europea leaf extract includes several toxic compounds, such as oleocanthal, that markedly reduce cell viability and exacerbate the H2O2- and Aβ-induced cell toxicity. In addition, the Crocus sativus hydrophilic and diethyl ether extracts and all their active compounds tested markedly increased the H2O2-induced cell toxicity. In conclusion, the medicinal plants tested contain several compounds displaying dose-dependent effects against H2O2- and Aβ-induced neurotoxicity and could be used in AD, but they also contain several neurotoxic agents.

Circular RNAs (circRNAs), which are a class of non-coding RNA with covalently closed loops, play important roles in epigenetics regulation of gene expression at both the transcriptional and post-transcriptional level. Accumulating evidence demonstrated that numerous circRNAs were abnormally expressed in tumors and their dysregulation was involved in the tumorigenesis and metastasis of cancer. Although the functional mechanisms of many circRNAs have been revealed, why circRNAs are dysregulated in cancer remains elusive. CircRNAs are generated by a “backsplicing” process, which is regulated by different cis-regulatory elements and trans-acting proteins. Therefore, how these cis- and trans-elements change during tumorigenesis and how they regulate the biogenesis of circRNAs in cancer are two questions that interest us. In this review, we summarized the pathways for the biogenesis of circRNAs; and then illustrated why circRNAs dysregulated in cancer by discussing the changes of cis-regulatory elements and trans-acting proteins that related to circRNA splicing and maturation in cancer.

The lipid fraction of margarines and fast-food French-fries, two types of foods traditionally high in trans fatty acids (TFA), is assessed. TFA data reported worldwide during the last 20 years have been gathered, and show that some countries still report high TFA amounts in these products. The content of TFA was analysed in margarines (2 store and 4 premium brands) and French-fries from fast-food restaurants (5 chains). Margarines showed mean values of 0.68% and 0.43% (gTFA/100g fat) for store and premium brands, respectively. French-fries values ranged from 0.49% to 0.89%. All samples were lower than the 2% set by some European countries as the maximum legal content of TFA in fats, and contained less than 0.5g/serving, so they could also be considered “trans free products”. This work confirmed that the presence of TFA is not significant in the two analysed products and contributes to update food composition tables, key tools for epidemiological and nutrition studies.

The 1060 aluminium alloy is widely applied to electronic industry, construction area, aerospace field, traffic engineering, decoration and consumption goods market for its good chemical, physical and mechanical properties. In general, excellent processing property is necessary and important for manufacturing of complicated panels. In this paper, a special 2D ultrasonic vibration incremental forming method is designed to improve its plasticity and mechanical properties. Three kind of processing methods including traditional single point incremental forming, longitudinal ultrasonic vibration incremental forming and 2D ultrasonic vibration incremental forming are conducted for flexible manufacture of conical parts of 1060 aluminium alloy sheet. Then micro-hardness tests, residual stress tests and scanning electron microscopy tests are carried out to probe its revolution of micro-structure and mechanical properties and to analysis the effects of different types of ultrasonic vibration on plasticity and fracture characteristic of 1060 aluminium alloy. It is proved that 2D ultrasonic vibration is facilitated to improvement of plasticity and surface qualities of 1060 aluminium alloy than the other two processing methods. So, the novel 2D ultrasonic vibration incremental forming possesses substantial application values on flexible and rapid manufacturing of complicated thin-walled component of aluminium alloy.

Recent developments in artificial nucleic acid and drug delivery systems (DDS) present possibilities for the symbiotic engineering of oligonucleotide therapeutics, such as antisense oligonucleotides (ASOs), and small interfering RNA (siRNA). These technologies can also be applied for triplex-forming oligonucleotides (TFOs) to develop symbiotic genome-targeting tools and a new class of oligonucleotide drugs. Many reports have described the functionalization of TFOs and the enhancement of TFO activities. In particular, the tethering of crosslinking groups to TFOs enables irreversible triplex formation and is frequently exploited for antigene and genome-editing experiments. These crosslinkable TFOs have shown considerable potential for therapeutic application. In this review, we revisit these crosslinking techniques and explore the combination of these techniques with recent artificial oligonucleotide and DDS technologies.

The use of metal oxide nanoparticles as an alternative antimicrobial agent has gained attention due to the increasing problem of antibiotic resistance. Understanding its properties and potential benefits can contribute to the development of more effective and sustainable treatments in veterinary medicine. The aim of this study was to characterize TiO2-NP formulations and evaluate their antibacterial and wound healing abilities. The diameters and zeta potentials were determined using the Zetasizer in conjunction with dynamic light scattering. The agar-well diffusion method, time-kill kinetic assay and crystal violet assay were used to evaluate their antimicrobial activities. Wound healing assays were conducted both in-vitro and in-vivo. The study demonstrated that TiO2-NP formulations exhibit significant antimicrobial properties against various bacterial strains such as S. aureus and E. coli. No measurable E. coli growth was observed within a 15-mins period following exposure to TiO2-NP formulations. The TiO2-NP formation can improve wound healing by enhancing cell migration and collagen formation in both in-vitro and in-vivo conditions. In summary, our study suggests that TiO2-NP has the potential for use as an antimicrobial agent for animal wound treatment due to its ability to suppress bacterial growth and biofilm formation, as well as to enhance wound healing.

Bio-based packaging materials and efficient drug delivery systems are gaining attention, carboxymethyl cellulose (CMC) is one of the most soluble cellulose derivatives, is a good candidate material due to its biocompatibility, biodegradability, and reproducibility. However, CMC-based films are lack of sufficient mechanical properties, limiting its widespread application. In this paper, the molecular interactions between CMC and additives with different molecular structures have been studied with rheological method. The additives are chitosan and cellulose derivatives including O-carboxymethylated chitosan (O-CMCh), N-2-hydroxypropyl-3-trimethylammonium-O-carboxymethyl chitosan (HTCMCh), hydroxypropyltrimethyl ammonium chloride chitosan (HACC), cellulose nanofibers (CNC), and cellulose nanofibers (CNF). The influencing factors, such as molecular structure, concentration of additives and temperature on the rheological properties were studied, which results revealed the information intermolecular interactions. Based on the rheological properties, several systems were selected to prepare films, which show very good transparency, wettability, mechanical properties, biodegradability, and cytotoxicity. These good characteristics of the selected films also proved the good biocompatibility of CMC and chitosan and cellulose derivatives. This work will provide an idea to prepare CMC-based food packaging and effective drug delivery materials with specific properties.

Artificial membrane systems can serve as models to investigate molecular mechanisms of different cellular processes, including transport, pore formation, and viral fusion. However, the current simulacrums such as SUVs, GUVs, and the supported lipid bilayers suffer from issues, namely high curvature, heterogeneity, and surface artefacts, respectively. Freestanding membranes provide a facile solution to these issues, but current systems developed by various groups use silicon or aluminium oxide wafers for fabrication that involves access to a dedicated nanolithography facility and high cost while conferring poor membrane stability. Here, we report the development, characterization and applications of an easy-to-fabricate suspended lipid bilayer (SULB) membrane platform leveraging commercial track-etched porous filters (PCTE) with defined microwell size. Our SULB system offers a platform to study the lipid composition-dependent structural and functional properties of membranes with exceptional stability in a high throughput fashion. With dye entrapped in PCTE microwells by SULB, we show that sphingomyelin significantly augments the activity of pore-forming toxin, Cytolysin A (ClyA) and the pore formation induces lipid exchange between the bilayer leaflets. Further, we demonstrate high efficiency and rapid kinetics of membrane fusion by dengue virus in our SULB platform. Our suspended bilayer membrane mimetic offers a novel platform to investigate a large class of biomembrane interactions and processes.

This study investigated the breakdown trend in an automated production with an aim to recommend the application of Reliability-centered maintenance (RCM) for an improved productivity via a new preventive maintenance (PM) program. Individual Section-forming machine (ISM): a glass blowing machine for making glass bottles was used as the case study of an automated production system. The machine parts and the working mechanisms were analysed with a special focus on methods of processes and procedures that will enable the ISM maintenance department run more effective and achieve its essential goal of ensuring effective machine operation and reducing machine downtime. In this work, information is provided on the steps and procedures to identify critical components of the ISM using Failure Modes and Effect Analysis (FMEA) as a tool to develop an optimal maintenance program based on the reliability data of the equipment’s functional components. A relationship was established between the failure rate of the machine components and the maintenance costs such that using the recommended PM program, an evidence of improvement in the machine’s availability, safety and cost-effectiveness will result into an increase in the company’s profit margin.

Among all the processing technologies of heat-treatable aluminum alloys like 2219 aluminum alloy, using friction stir welding (FSW) as the joining technology and using electromagnetic forming (EMF) for plastic forming technology both have obvious advantages and successful applications. Therefore, there is a broad prospect for the compound technologies which can be used on the 2219 aluminum alloy to manufacture the large-scale thin-wall parts in the astronautic industry. The microstructure and mechanical properties of 2219 aluminum alloy under the process compounded of FSW, heat treatment, and EMF were investigated by means of tensile test, optical microscope (OM), and scanning electron microscope (SEM). The results show that the reduction of strength, which was caused during the FSW process, can be recovered effectively by the post-welding heat treatment composed of solid solution and aging, while the ductility was still reduced after heat treatment. Under the compound technology of FSW, heat treatment, and EMF, the forming limit of 2219 aluminum alloy decreased distinctly due to the poor ductility of the welding joint. A ribbon-pattern, which was formed due to the banded structure caused by FSW process, was found on the fracture surface of welded 2219 aluminum alloy after EMF treatment. During the EMF process, because of the effects of induced eddy current, a unique structure, which was manifested as a molted-surface appearance under the SEM observation, was formed as the material fractured.

The paper presents the numerical and experimental results of research aimed at determining the influence of hardness in the range of 50-90 Shore A of layered tools made of elastomeric materials on the possibility of forming Inconel 625 nickel-based alloy sheets. A stamping die made of 90MnCrV8 steel (hardness 60HRC) was designed for forming embosses in drawpieces, ensuring various stress states on the cross-section of the formed element. The principle of operating the stamping die was based on the Guerin method. Finite element-based numerical modelling of the forming process for various configurations of polyurethane inserts was also carried out. The drawpieces obtained by sheet forming were subjected to geometry tests using optical 3D scanning. The results confirm that in the case of forming difficult-to-deform Inconel 625 Ni-based alloy sheets, the hardness of the polyurethane inserts significantly affects the geometric quality of the obtained drawpieces. The assumptions made in numerical simulations were verified in experimental studies. Based on the test results, it was concluded that the selection of polyurethane hardness should be determined by the shape of the formed element. Significant non-uniform sheet metal deformation was also found, which may pose a problem in the process of designing forming tools and technology of plastic forming of Inconel 625 Ni-based alloy sheets.

Transdermal drug delivery (TDD) is one of the key approaches for treating diseases, avoiding first-pass effects, reducing systemic adverse drug reactions and improving patient compliance. Microneedling, iontophoresis, electroporation, laser ablation and ultrasound facilitation are often used to improve the efficiency of TDD. Among them, microneedling is a relatively simple and efficient means of drug delivery. Microneedles usually consist of micron-sized needles (50-900 μm in length) in arrays that can successfully penetrate the stratum corneum and deliver drugs in a minimally invasive manner below the stratum corneum without touching the blood vessels and nerves in the dermis, improving patient compliance. Hydrogel-forming microneedles (HFMNs) are safe, non-toxic, no residual matrix material, high drug loading capacity, controlled drug release and are suitable for long-term, multiple drug delivery. This work reviewed the characteristics of skin structure and transdermal drug delivery; introduced TDD strategies based on hydrogel microneedles; summarised the characteristics of HFMNs TDD systems and the evaluation methods of HFMNs; and the application of HFMNs drug delivery systems in disease treatment. The HFMNs drug delivery system has a wide scope for development, but the translation to clinical application still has more challenges.

The development of numerical simulations is potentially useful in predicting the most suitable manufacturing process and ultimately improving product quality. Seamless pipes are manufactured by rotary piercing process in which round bars are fed between two rolls and pierced by a stationary plug. During this process, the material undergoes severe deformation which renders it impractical to be modelled and analysed with conventional finite element methods. In this paper, three dimensional numerical simulations of the piercing process are performed with Arbitrary Lagrangian-Eulerian (ALE) Formulation in LS DYNA software. Details about the material model as well as the elements formulations are elaborated here and mesh sensitivity analysis was performed. The results of the numerical simulations are in good agreement with experimental data found in the literature and the validity of the analysis method is confirmed. The effects of varying workpiece velocity, process temperature, and wall thickness on the maximum stress levels of the product material/pipes are investigated by performing simulations of sixty scenarios. Three dimensional surface plots are generated which can be utilized to predict the maximum stress value at any given combination of the three parameters.

The possibility of using additive manufacturing (AM) in the medicine area has created a new opportunities in health care. This has contributed to a sharp increase in demand for 3D printers, their systems and materials that are adapted to strict medical requirements. We described herein a medical-grade thermoplastic polyurethane (S-TPU), which was developed and then formed into a filament for Fused Deposition Modeling (FDM) 3D printers during a melt-extrusion process. S-TPU consisting of aliphatic hexamethylene 1,6-diisocyanate (HDI), amorphous α,ω-dihydroxy(ethylene-butylene adipate) (PEBA) and 1,4 butandiol (BDO) as a chain extender, was synthesized without the use of a catalyst. The filament properties were characterized by rheological, mechanical, physico-chemical and in vitro biological properties. The tests showed biocompatibility of the obtained filament as well as revealed no significant effect of the filament formation process on its properties. This study may contribute to expanding the range of medical-grade flexible filaments for standard low-budget FDM printers.

To study the fermentation process of biocatalyzing decanoic acid to synthesize trans-2-decenoic acid, this study was based on the engineering E.coli constructed in the laboratory in the early stage and studied the effect of seed liquid culture time, culture temperature, inoculum amount, induction temperature, dissolution effects of substrate solvent, metal ions, and substrate loading on the yield of trans-2-decenoic acid. Based on single-factor experimental optimization, the Box–Behnken design was used to conduct response surface testing using the substrate feeding concentration, inducer concentration, and MnCl2 concentration as response variables and trans-2-decenoic acid production as the response value. The optimal fermentation process was determined through experiments: seed culture time 20 h, culture temperature 37°C, inoculation amount 1%, induction temperature 30°C, substrate flow amount 0.15 g/L, inducer concentration 5.60 g/L, MnCl2 concentration was 0.10 mM. Under these conditions, the average production of trans-2-decenoic acid was 1.982 ± 0.110 g/L. Compared with the basic LB medium, the production of trans-2-decenoic acid increased by 1.042 g/L; compared with the previous period, the yield of trans-2-decenoic acid studied increased by 1.501 ± 0.110 g/L, which provides a reliable basis for further research on the fermentation process of biocatalytic decanoic acid synthesis of trans-2-decenoic acid.

Brain stem cells (neural stem cells or NSCs) and neurons of a chosen kind reprogramming is a potential technique for cell therapy. It is possible to reprogram non-neuronal cells, for example, by using a predetermined group of factors, nuclear transfer, and the induced transcriptional factors (TFs) expression in a related lineage of cells, and non-coding microRNAs (miRNAs). Researchers have additionally been attempting to improve reprogramming methods, whether it is by employing unique sets of biomolecules and particular TFs or by delivering relevant miRNA and Biomolecules. The technique of miRNA mediated is intriguing for its capability to quickly create a range of biologically desirable cell types for therapy from different lineages of cells. Current findings have made significant advancements towards changing the somatic cells to diverse particular neuronal subgroups with greater efficiency, using reprogramming of miRNA-mediated neural cells, despite the fact that the precise processes need to be discovered. To further understand how miRNAs might direct somatic cells to become neural, we need to look at the latest research on their function in neural reprogramming over the differentiated cells. Recent findings on the role of miRNAs in the initiation of cell reprogramming and the determination of the neuronal subtype's destiny are the primary focus of this comprehensive overview. Furthermore, we cover the far more latest results concerning certain miRNAs' activity in controlling different phases of neuronal differentiation, which contributes in comprehending the interaction network of miRNAs and their receptors.

Excessive intake of fat and fatty acids is associated with major health hazards such as obesity or chronic diseases. The aim of this study was to provide the first data on total fat, saturated fatty acids (SFA) and trans fatty acids (TFA) intakes and their major food sources in Tunisian children. A total of 1200 children, aged 3 to 9 years old (yo), were randomly selected from primary schools and kindergarten under a cross-sectional design. The 24-hour recall method and food frequency questionnaire were used to assess dietary intake. The energy percentages of total fat, SFA and TFA in Tunisian children were respectively 29.6, 11.4 and 0.15. No sex differences were found. The WHO recommendations for total fat, SFA and TFA were adopted by 58 %, 39 % and 89 % of the study population, respectively. The leading food groups of fat and fatty acids were ultra-processed foods, breakfast cereals and dairy products. The meat, fish, eggs and fish alternatives were the fifth main contributors to the total fat and SFA intakes in Tunisian children. The implementation of a relevant strategy for fat reduction, especially from ultra-processed foods, considered as low nutrient energy-dense products, is needed to promote health among children and prevent diet-related chronic diseases.

In gravity theory, there is a well-known trans-Planckian problem, which is that general relativity theory leads to a shorter than Planck length and shorter than Planck time in relation to so-called black holes. However, there has been little focus on the fact that special relativity also leads to a trans-Planckian problem, something we will demonstrate here. According to special relativity, an object with mass must move slower than light, but special relativity has no limits on how close to the speed of light something with mass can move. This leads to a scenario where objects can undergo so much length contraction that they will become shorter than the Planck length as measured from another frame, and we can also have shorter time intervals than the Planck time. The trans-Planckian problem is easily solved by a small modication that assumes Haug's maximum velocity for matter is the ultimate speed limit for something with mass. This speed limit depends on the Planck length, which can be measured without any knowledge of Newton's gravitational constant or the Planck constant. After a long period of slow progress in theoretical physics, we are now in a Klondike "gold rush" period where many of the essential pieces are falling in place.

This experimental study probes the dynamic behaviour of a 3mm ABS sheet during positive mould vacuum-assisted thermoforming. In this process, the sheet undergoes large and fast deformations, caused by the applied vacuum and mechanical stretching by the mould. The objective is to elucidate the complexities of these large, rapid and non-isothermal deformations. The non-isothermal conditions are caused by the radiative heating of the sheet, convective heat loss to the surrounding air and conductive heat transfer from the sheet to the mould. Utilizing stereo Digital Image Correlation (DIC) in tandem with thermal imaging, the present study accurately maps the occurring displacement, strain and strain rate field in relation to real-time temperature variation of the material. The study progresses to observe the ABS material from the moment it contacts the mould until it conforms to a positive 250mm diameter semi-sphere cast aluminium mould. The DIC methods are validated by comparing thickness values derived from DIC’s principal strain directions to ultrasonic thickness gauge readings. This knowledge not only broadens the understanding of the thermo-mechanical behaviour of the material but also aids in optimizing process parameters for improved thickness uniformity in thermoformed products.

Orogenic antimony-gold deposits contribute significantly to the global antimony resource base. China's orogenic antimony-gold deposits are primarily in southern Tibet. Investigations indicate that antimony combines and migrates with sulfur hydroxides in ore-forming fluids. Previous research on fluid inclusions in orogenic antimony-gold ores with sedimentary rock accommodation revealed the presence of organic inclusions, including liquid hydrocarbons, alongside common components such as CO2, H2O, CH4, and NaCl. However, the impact of liquid hydrocarbons on antimony migration and mineralization is still de-batable. To investigate the transportability of antimony by liquid hydrocarbons in orogenic antimony ores, we selected n-dodecanethiol and n-dodecane as the subjects. We measured the solubility and occurrence form of antimony in these compounds at various temperatures and durations. The results indicate that after 5 and 10 days of reaction at 100 °C, the antimony concentrations in the n-dodecanethiol and n-dodecane groups were 67.44±7.62 ppm, 75.15±16.74 ppm, 1.40±1.02 ppm, and 3.02±3.09 ppm, respectively. At 150 °C for 5 and 10 days, the respective concentrations were 50.58±5.39 ppm, 77.26±45.20 ppm, 2.66±3.08 ppm, and 2.41±2.03 ppm. At 200 °C for 5 and 10 days, the corresponding concentrations were 339.76±71.94 ppm, 218.97±25.03 ppm and 6.53±7.17 ppm, 2.27±0.82 ppm (n=3). The measured solubility of antimony in the n-dodecanethiol group increased gradually with rising temperature. The solubility of antimony in the n-dodecane group was low and notably inferior to that observed in the n-dodecanethiol group. X-ray photoelectron spectroscopy (XPS) analysis demonstrated a distinct thiol (R-SH) peak at 163.31 eV and compound peaks of antimony reacting with thiols at 162.06 and 160.87 eV. This suggests that antimony predominantly forms complexes with thiols for migration. Our findings suggest that specific liquid hy-drocarbon components, predominantly thiols, can interact with antimony at metallogenic temperatures and persist in ore-forming fluids, facilitating migration and mineral enrichment. Earlier experimental studies on gold and crude oil have indicated that liquid hydrocarbons also play an essential role in the transportation and enrichment of gold during the formation of gold deposits, thus indicating that liquid hydrocarbons possess the considerable potential to act as an ore-forming fluid during orogenic antimony-gold deposit formation in southern Tibet.

The Colony-Forming Unit (CFU) counting problem remains a complex issue without a universal solution in biomedical and food safety domains. A multitude of sophisticated heuristics and segmentation-driven approaches have been proposed by numerous researchers. Among those, U-Net is the most frequently cited and popular Deep Learning method. The latter approach provides a segmentation output map and requires an additional counting procedure which accounts for unique segmented regions and detected microbial colonies. However, because of pixel-based targets it tends to generate irrelevant artifacts or errant pixels, leading to inaccurate and mixed post-processing results. In response to these challenges, we propose a novel hybrid counting approach, incorporating a multi-loss U-Net reformulation and a post-processing Petri dish localization algorithm. First of all, our unique innovation lies in the multi-loss U-Net reformulation. We introduce an additional loss term at the bottleneck U-Net layer, focusing on delivering an auxiliary signal indicating where to look for distinct CFUs. Second, our novel localization algorithm accurately incorporates an agar plate and its bezel into the CFU counting routines. Finally, our proposition is further enhanced by the integration of a fully automated solution. This comprises a specially designed uniform Petri dish illumination system and a counting web application. The latter application is capable of directly receiving images from the camera, which are subsequently processed, and the segmentation results are sent back to the user. This feature provides an opportunity to correct the CFU counts, offering a feedback loop that contributes to the continued development of the Deep Learning model. Through extensive experimentation, we have found that all probed multi-loss U-Net architectures incorporated in our hybrid approach consistently outperform their single-loss counterparts which utilize exclusively the combination of Tversky and Cross-Entropy training losses at the output U-Net layer. We report further significant improvements by the means of our novel localization algorithm. This reaffirms the effectiveness of our proposed hybrid solution in addressing contemporary challenges of the precise in-vitro CFU counting.

Use of rhizosphere microorganisms provides an alternative or supplement to conventional plant breeding to improve water deficit tolerance of tomato plants. Experiment was carried out to explore the effect of two microbial species, AMF (Rhizophagus irregularis) and Bacillus subtilis, in single and co-application, on growth, colonization, and molecular aspects of tomato plants under drought stress. Co-inoculated plants showed less reduction in growth traits, photosynthetic pigments, colonization rate, and increased compatible solutes like proline which help in sustaining relative water content than non-inoculated plants. Inoculation considerably enhanced proline dehydrogenase activity, and significantly reduced both Δ1-pyrroline-5-carboxylate reductase Δ1-pyrroline-5-carboxylate synthetase activity causing lower proline accumulation in inoculated plants under drought stress. Co-inoculated plants showed obvious upregulation of antioxidant system, thus facilitating amelioration of oxidative stress through exclusion of reactive oxygen species. No inoculation under drought stress upregulated abscisic acid related genes expression but have no effect in plants inoculated either sole or mixed inoculation. Expression of aquaporin genes was upregulated in plants co-inoculated and with AMF alone under normal condition. However the expression of aquaporin genes were decreased or unaffected in plants inoculated with Bacillus subtilis but increased in non-inoculated plants. Co-applied AMF and bacillus subtilis substantially increase drought tolerance by upregulating proline metabolism, antioxidant enzymes and aquaporin genes. Therefore our results suggest that co-inoculation mediated drought tolerance is linked with increased proline accumulation, enhanced antioxidant enzyme activities and differential regulation of ABA biosynthetic and aquaporin genes, which is vital for osmotic adjustment of host plant.

K417G Ni-based superalloy is widely used in aeroengine turbine blade for its excellent properties. However, the aeroengine rotor blade zigzag crown appears early failure frequently, which is because of the wear problems occurring in the working process. Laser forming repairing (LFR) is a promising technique to repair these damaged blades. Unfortunately, the laser formed Ni-based superalloys with high content of (Al + Ti) have a high cracking sensitivity. In this paper, the crack characterization of the LFRed K417G, the microstructure, microhardness and tribological properties of the coating before and after laser remelting are presented. The results show that the microstructure of as-deposited K417G consists of γ phase, γ′ precipitated phase, γ + γ′ eutectic and carbide. Cracking mechanisms including solidification cracking, liquation cracking and ductility dip cracking are proposed based on the composition of K417G and processing characteristics to explain the cracking behavior of the K417G superalloy during LFR. After laser remelting, the microstructure of the coating has been refined, and the microhardness and tribological properties has been improved. Laser remelting can decrease the size of the cracks in the LFRed K417G but not the number. Therefore, laser remelting can be applied as an effective method for strengthening coating and as an auxiliary method for controlling cracking.

Fiber-metal laminates (FMLs) such as Kevlar reinforced aluminum laminate (ARALL), Carbon reinforced aluminum laminate (CARALL), and Glass reinforced aluminum laminate (GLARE) offer great potential for weight reduction applications in automobile and aerospace construction. In order to investigate the feasibility for utilizing such materials in the form of laminates, sheet hydro-bulging tests are studied under the condition of uniform blank holder force for three-layered aluminum and aluminum-composite laminates using orthogonal carbon and Kevlar as well as glass fiber in the middle. The experimental results validate the finite element results and they exhibited that the forming limit of glass fiber in the middle is the highest among the studied materials, while carbon fiber material performs the worst. Furthermore, the crack modes are different for the three kinds of fiber materials investigated in the research. This study provides fundamental guidance for the selection of multi-layer sheet materials in the future manufacturing field.

From grape cultivation to ripening and harvest timing to processing, each step can be a critical point when it comes to wine quality and phenolic composition. In this study, the influence of winemaking technology on resveratrol and quercetin content, as well as other polyphenolic compounds, was investigated. Resveratrol is a non-flavonoid polyphenolic stilbene synthesized by grape skin when damaged by infectious diseases or ionizing radiation. Quercetin is a phenol found in grape skins and stems and is produced to protect grapes from UV light damage. Trans-resveratrol and quercetin are known to act as antioxidants, reduce the risk of atherosclerosis and type 2 diabetes, inhibit the growth of cancer cells, and prevent the release of allergic and inflammatory molecules. However, the question was whether red wine could be enriched with these phenols using an innovative winemaking technology. The innovative idea was to completely replace the cold maceration process with maceration with the addition of wild yeast (Torulaspora delbrueckii, Td). Maceration with the addition of wild yeast (Td) offers the following advantages over traditional cold maceration: (1) higher concentrations of trans-resveratrol (>35-40%) and quercetin (>35-40%) in the final wine, (2) the new wine has a higher potential for human health, (3) the wine has a better aroma and stability due to the higher mannoprotein content, and (4) the better energy efficiency in the production process. The study of stability during storage and aging also included derivatives of benzoic acid and hydroxycinnamic acid, piceid, catechin, naringenin, rutin, kaempherol, hesperetin, and anthocyanins. The study found that younger wines had higher phenolic content, while storage of the wine resulted in a decrease in total phenolic content, especially monomeric stilbenes and quercetin.

Abstract The hallmark of acute promyelocytic leukemia (APL) is the presence of the characteristic fusion transcript of the promyelocytic leukemia gene with the retinoic acid receptor α gene (PML::RARA), which is a molecular target for all-transretinoic acid (ATRA) and arsenic trioxide (ATO). Therapies with ATRA plus ATO have excellent outcomes in terms of complete remission rate, overall survival, and achievement of a deep and durable molecular response with a very low incidence of relapse. However, although the combination of ATRA and ATO has lower hematologic toxicity than standard chemotherapy, its use is associated with a spectrum of unique toxicities, such as hepatic toxicity, QTc (QT interval corrected) prolongation, neurotoxicity, and differentiation syndrome. Hematologists treating patients with acute promyelocytic leukemia should be aware of possible early-complications of the ATRA plus ATO regimen and aim to balance treatment-related adverse events and efficacy. Careful follow-up of the patient’s clinical course is essential to identify and treat each complication. This study focused on treatment-related complications during induction and consolidations in patients with APL who received ATRA plus ATO. We retrospectively analyzed 26 adult patients diagnosed with APL between 2019 and 2022 at our center to identify the incidence rate, severity and time of onset of short-term non-hematologic adverse events relative to the initiation of the ATRA and ATO regimen. Additionally, we review the existing literature regarding the toxic side effects of ATO in APL and discuss how its most frequent toxicities should be managed. The median follow-up of our patients was 21.5 months (range, 1-48 months) and the most common adverse events were hepatic toxicity (69.2%), infections (46.1%), differentiation syndrome(23%) and QT prolongation (11.5%). All patients experienced at least one adverse event and grade 3 and 4 toxicities occurred in 57.6 % patients; these generally consisted of liver enzyme elevations, QTc prolongation, but also some rare manifestations such as musculoskeletal pain syndrome (1 patient) and ATO-related pancreatitis (1 patient). Most patients developed side-effects during induction. This is the first study about Romanian patients diagnosed with APL. Our results suggest that all treatment-related adverse events, except for differentiation syndrome are manageable, self-limiting and reversible. All patients, except for two (one died during induction and one died during consolidation), were able to complete the treatment consolidation with ATO and ATRA.

Background: Trans-septal endocardial left ventricle lead placement is an alternative technique used capture the left ventricular endocardially but it is use is limited due lack of evidence, practice uptake and clinical trials. we evaluated the efficiency of the procedure, post procedural complication rate, rate of thromboembolic events as well as changes in echocardiographic parameters, brain natriuretic peptide (BNP) level and the New York Heart Association (NYHA) class. Results: TSLV lead implant is safe, improves ejection fraction, LVEDV, LVESV, LVIDd. Significantly reduces NTproBNP levels and NYHA class. Stroke rate was reported only in one patient (9%), noticeably, this particular patient was on DOAC rather than anti-vitamin K antagonists. In this group, patients, who were on Warfarin , were not reported to have any thrombo-embolic events. Discussion: Trans-septal endocardial LV lead implant in patients with a failed CS approach remains a viable alternative however, there is a higher risk of stroke amongst these patients, as well as more procedure related risk of complications compared to conventional CRT. The data analysis demonstrates that patients undergoing a TSLV lead implant due to a failed trans-venous approach have more advanced heart failure, defined by their higher NYHA class compared to conventional trans-venous CRT implant groups. Their pre TSLV implant, echocardiographic parameters are also worse compared to trans-venous CRT implant group

(1) Background: Treatment of male stress incontinence in patients with prostate cancer treated with radical prostatectomy and adjuvant pelvic radiation is a therapeutic challenge. The efficacy and safety of the adjustable trans-obturator male system (ATOMS) in these patients is not well established, despite the general belief that outcomes are worse than in patients without radiation. (2) Methods: Retrospective multicenter study evaluating patients treated with silicone-covered scrotal port (SSP) ATOMS implant after radical prostatectomy and radiotherapy in nine different institutions between 2016 and 2022. The primary endpoint was dry patient rate, defined as pad-test ≤20 mL/day. The secondary endpoints were complication rate (defined using Clavien-Dindo classification), device removal and self-perceived satisfaction using the Patient Global Impression of Improvement (PGI-I) scale. Wilcoxon rank sum test, Fisher’s exact test and logistic regression were performed using stepwise method with a 0.15 entry and 0.1 stay criteria. (3) Results: 223 patients fulfilled criteria for inclusion, 12 (5.4%) had received salvage prostatectomy after radiation and 27 (12.1%) previous devices for stress incontinence. After ATOMS adjustment, 95 patients (42.6%) were dry and 36 (16.1%) had complications of any grade (grade I, n=20; grade II, n=11; grade III, n=5) during the first 3 months postoperatively. At a mean 36 ± 21 months follow-up the device was explanted in 26 (11.7%) patients. Regarding self-perceived satisfaction with the implant, 105 of 125 patients (84%) considered themselves satisfied (PGI-I 1 to 3). In univariate analysis dryness was associated to younger age (p=.06), primary prostatectomy (p=.08), no previous incontinence surgery (p=.02), absence of overactive bladder symptoms (p=.04), absence of bladder neck stricture (p=.001), no need of surgical revision (p=.008) and lower baseline incontinence severity (p=.0003). Multivariate analysis identified absence of surgical revision (p=.018), absence of bladder neck stricture (p=.05), primary prostatectomy (p=.07) and baseline incontinence severity (p&lt;.0001) were independent predictors of dryness. A logistic regression model was proposed and internally validated. (4) Conclusions: ATOMS is an efficacious and safe alternative to treat male incontinence after radical prostatectomy and adjuvant radiotherapy. Factors predictive of dryness are identified in this complex scenario to allow better patient selection.

This paper investigates the use of contactless power ultrasonic excitation to decrease the electrical impedance of the weld in laser welding. The literature extensively documents the impact of em-ploying contact power ultrasonic excitation on the microstructure morphology and refinement of grain in the weld. This study involves characterizing an industrial High Power Ultrasound Transducer (HPUT) by determining the optimal distance and angle for contactless excitation of the fusion zone in the weld, aiming to achieve the maximum amplitude. Subsequently, the transducer is integrated into the laser welding system, resulting in the creation of an ultrasonic-assisted welding system. To find the improvement due to the contactless vibration assistance, the welding area was char-acterised by an impedance ohmmeter device. The results indicate an approximately 6 % im-provement in the welding quality in terms of the impedance value, an important parameter for battery pack welding. In response to the issue of overheating in the industrial transducer during prolonged welding operations, an alternative transducer was proposed to overcome this challenge. Further investigations are carried out by the alternative transducer to find the effect of different wave types, namely, shear and compressional waves, on the welding quality. The contact vibration can excite the plate approximately 50 times higher in acceleration amplitude than contactless ex-citation. Nevertheless, enhancements of 10% and 6% are observed in the impedance value when utilising compressional and shear waves, respectively, as compared to the results obtained with contactless vibration.

Background Due to the Covid-19 pandemic and the strict national policies regarding social distancing behavior in Europe, America and Australia, people became reliant on social media as a means for gathering information and a tool for staying connected to family, friends and work. This is the first trans-national study exploring the qualitative experiences and challenges of using social media while in lockdown or shelter in place during the current pandemic. Methods This study was part of a wider cross-sectional online survey conducted in Norway, UK, USA and Australia during April/May 2020. The manuscript reports on the qualitative free text component of the study asking about the challenges of social media users during the Covid-19 pandemic in UK, USA and Australia. 1991 responses were included in the analysis. Thematic analysis was conducted independently by two researchers. Results Three overarching themes identified were: Emotional/Mental Health, Information and Being Connected. Participants experienced that using social media during the pandemic amplified anxiety, depression, fear, panic, anger, frustration and loneliness. They felt that there was information overload and social media was full of misleading or polarized opinions from which was difficult to switch off. Nonetheless, participants also thought that there was an urge for connection and learning which was positive and stressful and the same time. Conclusion Using social media while in shelter in place or lockdown could have a negative impact on the emotional and mental health of some of the population. To support policy and practice in strengthening mental health care in the community, social media could be used to deliver practical advice on coping and stress management. Communication with the public should be strengthened by unambiguous and clear messages and clear communication pathways. We should be looking at alternative ways of staying connected.

One of the important features of polymethine (cyanine) dyes is isomerization around one of C–C bonds of the polymethine chain. In this review, spectral properties of the isomers, photoisomerization and thermal back isomerization of carbocyanine dyes, mostly meso-substituted carbocyanine dyes, are considered. meso-Alkyl-substituted thiacarbocyanine dyes are present in polar solvents mainly as cis isomers and, hence, exhibit no photoisomerization, whereas in nonpolar solvents, in which the dyes are in the trans form, photoisomerization takes place. In contrast, the meso-substituted dyes 3,3′-dimethyl-9-phenylthiacarbocyanine and 3,3′-diethyl-9-(2-hydroxy-4-methoxyphenyl)thiacarbocyanine occur as trans isomers and exhibit photoisomerization in both polar and nonpolar solvents. The behavior of these dyes may be explained by the fact that the phenyl ring of the substituent in their molecules can be twisted at some angle, removing the substituent from the plane of the molecule and reducing its steric effect on the conformation of the trans isomer. In some cases, photoisomerization of cis isomers of meso-substituted carbocyanine dyes is also observed (for some meso-alkyl-substituted dyes complexed with DNA and chondroitin-4-sulfate; for 3,3′-diethyl-9-methoxythiacarbocyanine in moderate polarity solvents). The cycle photoisomerization–thermal back isomerization of cyanine dyes can be used in various systems of information storage and deserves further investigation using modern research methods.

Maintenance of intestinal barrier integrity is crucial for preventing inflammatory bowel diseases (IBDs) onset and exacerbations. In this work we study the effect of a fixed combination of Lactobacillus reuteri and Lactobacillus acidophilus and herbal extracts in an in vitro inflammation experimental model. Caco-2 cell monolayer was exposed to INF-γ+TNF-α or to LPS; Trans Epithelial Electrical Resistance (TEER) and paracellular permeability were investigated. ZO-1 and occludin tight junctions (TJs) were also investigated by mean of immunofluorescence. The pre-treatment with the fixed combination of probiotics and herbal extracts prevented the inflammation-induced TEER decrease, paracellular permeability increase and TJs translocation. In summary the fixed combination of probiotics and herbal extracts investigated in this research was found to be an interesting candidate for targeting the re-establishment of intestinal barrier function in IBDs conditions.

High-entropy alloys (HEAs) are of great interest in the field of materials science and engineering. Unlike conventional alloys, which contain a maximum of two base metals, this new category of materials consists of multi-principle elements and the possible number of alloy compositions, in case of HEAs, is outstandingly higher than that for conventional alloys. Here, a review on the high-entropy alloys, has been provided, on the issue whether the earliest definition of High- Entropy alloys, proposed in 2004^{[2, 4]}, is consistent with one of the four-component equiatomic Compositionally complex alloys exhibiting a “High-entropy” effect.

The formability and failure behavior of TRIP steel blanks were investigated through various stress states. The forming limit diagram (FLD) at fracture is constructed both experimentally and numerically. Numerical studies are performed to evaluate the applicability of different damage criteria in predicting the FLD as well as complex cross-die deep drawing process. The fracture surface and numerical results revealed that the material failed in a different mode for different strain path. Therefore, Tresca model which is based on shear stress accurately predicted the conditions where shear had the profound effect on the damage initiation, whereas Situ localized necking criterion was able to calculate the conditions which localization was dominant.

Ferrite body is the origin of crack and corrosion initiation of steels. Distribution and density of ferrite in seven steel ingots were examined by light optical microscopy and computational modeling in the study to explore the correlation of ferrite formation to chemical composition and mushy zone temperature in ingot forming. The central segregation phenomenon in ferrite distribution was observed in all the examined steel specimens except 0Cr17Ni4Cu4Nb stainless steel. No significant difference was found in distribution and density of ferrite amongst zones of the surface, ½ radius and core in neither risers nor tails of 0Cr17Ni4Cu4Nb ingots. Additionally, fewer ferrite was found in 0Cr17Ni4Cu4Nb compared to other examined steels. The difference of ferrite formation in 0Cr17Ni4Cu4Nb elicited a debate on the traditional models explicating ferrite formation. Considering the compelling advantages in mechanical strength, plasticity and corrosion resistance, further investigation on the unusual ferrite formation in 0Cr17Ni4Cu4Nb would help understand the mechanism to improve steel quality. In summary, we observed that ferrite formation in steel was correlated with mushy zone temperature. The advantages of 0Crl7Ni4Cu4Nb in corrosion resistance and mechanical stability could be resulted from that fewer ferrites formed and distributed in a scattered manner in microstructure of the steel.

The leaves of Ligustrum robustum have been applied as Ku-Ding-Cha, a functional tea to clear heat and remove toxins; and served as a folk medicine to deal with diabetes, obesity, and hypertension. Trans-p-hydroxycinnamic acid and its esters, which were isolated from the leaves of L. robustum, might be a new resource to prevent diabetes and its complications because of their strong -glucosidase and fatty acid synthase (FAS) inhibitory activities and antioxidant effect. However, the quantitative analytical method for trans-p-hydroxycinnamic acid and its esters in the leaves of L. robustum hasn’t been reported so far. In addition, it was difficult and troublesome to analyze no less than 34 trans-p-hydroxycinnamic acid esters by usual HPLC. Therefore, a new HPLC-UV method using hydrolyzation with sodium hydroxide for quantitation of trans-p-hydroxycinnamic acid and its esters in the leaves of L. robustum was developed in the present study. The optimal hydrolyzation conditions were as follows: 1 mL sodium hydroxide aqueous solution (1 M) was added into 1 mL the extract of L. robustum and incubated at 80 °C for 2 h , and then 1 mL hydrochloride (1 M) solution was added. HPLC analysis was performed in reverse phase mode using a C-18 column, eluting with methanol-0.1% acetic acid aqueous solution (40:60, v/v) in isocratic mode at a flow rate of 1.0 mL/min, and detecting at 310 nm. The analytical method was simple and rapid, which simplified greatly the analytical process. The method was validated in terms of linearity, limit of detection (LOD), limit of quantification (LOQ), precision, and accuracy. High linearity was demonstrated with correlation coefficient of 1.000 for trans-p-hydroxycinnamic acid. The LOD and LOQ values were 1.55 and 4.69 μg/mL, respectively. The relative standard deviations (RSD) of intra-day and inter-day variabilities for trans-p-hydroxycinnamic acid were less than 2%. The percentage recovery of trans-p-hydroxycinnamic acid was 101.2% ± 0.8%. Finally, the proposed method was applied successfully to the determination and comparison of the contents of trans-p-hydroxycinnamic acid and its esters in various extracts of the leaves of L. robustum. The 60%-70% ethanol extracts of L. robustum showed the highest contents of free trans-p-hydroxycinnamic acid (3.96-3.99 mg/g), and the 50%-80% ethanol extracts of L. robustum displayed the highest contents of trans-p-hydroxycinnamic acid esters (202.6-210.6 mg/g). The method can be applied also to the quality control of the products of L. robustum.

Curcumin and trans-cinnamaldehyde are acrolein-based Michael acceptor compounds that are commonly found in domestic condiments, and known to cause cancer cell death via redox mechanisms. Based on the structural features of these compounds we designed and synthesized several 2-cinnamamido-N-substituted-cinnamamide (bis-cinnamamide) compounds. One of the derivatives, (Z)-2-[(E)-cinnamamido]-3-phenyl-N-propylacrylamide 1512 showed a moderate antiproliferative potency (HCT-116 cell line inhibition of 32.0 µM), good selectivity profile (no inhibition of normal cell lines), and proven cellular activities leading to apoptosis. SAR studies led to more than 10-fold increase in activity. Our most promising compound, [(Z)-3-(1H-indol-3-yl)-N-propyl-2-[(E)-3-(thien-2-yl)propenamido)propenamide] 4112 killed colon cancer cells at IC50 = 0.89 µM (Caco-2), 2.85 µM (HCT-116) and 1.65 µM (HT-29), while exhibiting much weaker potency on C-166 and BHK normal cell lines (IC50 = 71 µM and 77.6 µM, respectively). Cellular studies towards identifying the compounds mechanism of cytotoxic activities revealed that apoptotic induction occurs in part as a result of oxidative stress. Importantly, the compounds showed inhibition of cancer stem cells that are critical for maintaining the potential for self-renewal and stemness. The results presented here show discovery of covalently-acting Michael addition compounds that potently kill cancer cells by a defined mechanism, with minimal effect on normal noncancerous cell.

Conjugation is a bacterial mechanism for DNA transfer from a donor cell to a wide range of recipients, including both prokaryotic and eukaryotic cells. In contrast to conventional DNA delivery techniques, such as electroporation and chemical transformation, conjugation eliminates the need for DNA extraction, thereby preventing DNA damage during isolation. While most established conjugation protocols allow for DNA transfer in liquid media or on a solid surface, we developed a procedure for conjugation within solid media. Such a protocol may expand conjugation as a tool for DNA transfer to species that require semi-solid or solid media for growth. Conjugation within solid media could also provide a more stable microenvironment in which the conjugative pilus can establish and maintain contact with recipient cells for the successful delivery of plasmid DNA. Furthermore, transfer in solid media may enhance the ability to transfer plasmids and chromosomes greater than 100 kbp. Using our optimized method, plasmids of varying sizes were tested for transfer from E. coli to S. cerevisiae. We demonstrated that there was no substantial decrease in conjugation frequency as plasmid size increased—up to 138.5 kbp in length. Finally, we established an efficient PCR-based synthesis protocol to generate custom conjugative plasmids

In order to improve real-time performance of gesture recognition by micro-Doppler map of mmWave Radar, the point cloud based gesture recognition for mmWave Radar is proposed in this paper.Two steps are carried out for mmWave Radar based gesture recognition. The first step is to estimate the point cloud of the gestures by 3D-FFT and the peak grouping. The second step is to train the TRANS-CNN model by combining the multi-head self-attention and the 1D-convolutional network, so as to extract the features in the point cloud data at a deeper level to categorize the gestures. In the experiments, TI mmWave Radar sensor IWR1642 is used as benchmark to evaluate the feasibility of the proposed approach. The results show that the accuracy of the gesture recognition reaches 98.5%. In order to prove the effectiveness of our approach, a simply 2Tx2Rx Radar sensor is developed in our lab and the accuracy of recognition reaches 97.1%. The results show that our proposed gesture recognition approach achieves the best performance in real-time with limited training data, in comparison with the existing methods.

In the modern power grid, characterized by the increased penetration of power electronics and extensive utilization of renewable energy, inverters-based power plants play a pivotal role as the principal interface of renewable energy sources (RESs) and the grid. Considering the stability characteristics of grid-following (GFL) inverters when the grid is relatively weak, the application of grid-forming (GFM) controls becomes imperative to enhance the stability of the entire power plant. Thus, there is an urgent need for suitable and effective models to study the interaction and stability of the paralleled inverters employing GFL and GFM controls. Thus, the small-signal modeling with full-order state space model and eigenvalues analysis is presented in this paper. First, the small-signal state-space model of the individual GFL and GFM inverters is obtained considering the control loop, interaction, reference frame, transmissions, and time delays. Then, the models of the individual inverter are extended to the hybrid inverters to study the effects of the GFM inverters on the small- signal stability of the entire system. And, the impacts of the inertia and damping are analyzed by the eigenvalues of the state-transition matrix. Case comprising three parallel GFL inverters and two GFL inverters with one GFM inverter, respectively, are studied to examine the effectiveness and accuracy of the model. Finally, the stability margin obtained from the eigenvalue analysis of the entire system is verified by time-domain simulations.

Antimicrobial peptides (AMPs) have emerged as a promising solution to tackle bacterial infections and combat antibiotic resistance. However, their clinical application has been hindered by their vulnerability to protease degradation and toxicity towards mammalian cells. To overcome these challenges, our study aims to develop a method to enhance the stability and safety of AMPs, applicable to effective drug-device combination products. KR12 antimicrobial peptide was chosen and in order to further enhance its delivery and efficacy, HIV TAT protein-derived cell-penetrating peptide (CPP) was fused to form CPP-KR12. A new product, CPP-KR12@Si, was developed by forming silica nanoparticles with self-entrapped CPP-KR12 peptide using the biomimetic silica precipitability due to its cationic nature. Peptide delivery from CPP-KR12@Si to bacteria and cells was delivered at a slightly delayed rate with improved stability against trypsin treatment and a reduction in cytotoxicity over CPP-KR12. Finally, the antimicrobial potential of CPP-KR12@Si/bone graft substitute (BGS) combination product was demonstrated, which is coated with CPP-KR12 in the form of nanoparticles on the surface of BGS. Self-entrapped AMP in silica nanoparticles is a safe and effective AMP delivery method that will be useful for developing a drug/device combination product for tissue regeneration.

Cardiovascular disease (CVD) comprises a group of heart and circulatory disorders, which are regarded as a global medical issue with high prevalence and mortality rates. Currently, vascular regenerative surgery represents the most employed therapeutic option to treat ischemic disorders, even though not all the patients are amenable to surgical revascularization. Therefore, more efficient therapeutic approaches are urgently required to promote neovascularization. Therapeutic angiogenesis represents an emerging strategy that aims at reconstructing the damaged vascular network by stimulating local angiogenesis and/or promoting de novo blood vessel formation according to a process known as vasculogenesis. Circulating endothelial colony forming cells (ECFCs), in turn, represent truly endothelial precursors able to aggregate into bidimensional tube networks and to originate patent vessels. Accordingly, ECFCs provide the most rationale and promising cellular candidate for therapeutic purposes. The current review provides a brief outline on the origin and characterization of ECFCs and a summary of the progress in preclinical studies aiming at assessing their efficacy in a variety of ischemic disorders, including AMI, PAD, ischemic brain disease and retinopathy. We also describe how to enhance the vasoreparative potential of ECFCs by boosting specific pro-angiogenic signalling pathways either pharmacologically or through gene manipulation. Taken together, these observations suggest that ECFCs represent a useful strategy to treat ischemic diseases.

The viability, productivity and survival of higher plants under the adverse factors influence are largely determined by the functional activity of the antioxidant system. The aim of our work was to investigate changes in formation of high-molecular (superoxide dismutase and peroxidase) and low-molecular (phenolics, including flavanols and proanthocyanidins) antioxidants in callus culture of Camellia sinensis under influence of phenolic precursors (L-phenylalanine – 3 mM, trans-cinnamic acid – 1 mM, naringenin – 0.5 mM). According to the data obtained, precursors effect on tea callus cultures did not lead to significant increasing of superoxide dismutase and peroxidase activity in most cases. However, it led to the increased accumulation of the total phenolics content, as well as flavanols and proanthocyanidins contents. For C. sinensis callus cultures, the most promising regulator of phenolic compounds was L-phenylalanine, in the presence of which its content increased almost twice. Thus, the exogenous effect of various precursors is possible to use for the targeted regulation of the certain phenolics classes accumulation in plant cells.

Biofilms are communities of microorganisms that can colonize biotic and abiotic surfaces playing a significant role in the persistence of bacterial infection and antibiotic resistance. About 65% and 80% of microbial and chronic infections are produced by biofilm formation. The increase in infections by multi-resistant bacteria draws attention to the discovery of new drugs based on natural inhibitory molecules. The inhibition of diguanylate cyclases (DGCs), the enzyme implicated in the synthesis of the second messenger, cyclic diguanylate (c-di-GMP), involved the biofilm formation, represents a potential method for preventing the biofilm development. It has been extensively studied using PleD protein as a model of DGC for in silico studies as virtual screening and as a model for in vitro studies in biofilms formation. In the present study 224205 molecules from natural products database, ZINC15 has been evaluated through molecular docking and molecular dynamic simulation, our result suggests trans-Aconitic acid (TAA) as a possible starting point for hit-to-lead methodologies to obtain new molecules capable of inhibiting the PleD protein and hence blocking the biofilm formation.

The article features the structure and functions of plant synthetic promoters frequently exercised to precisely regulate complex regulatory routes. The composition of plant native promoters together with interacting proteins is presented to provide a better understanding of tasks associated with synthetic promoter development. The production of synthetic promoters is conferred on relatively small libraries produced generally by basic molecular or genetic engineering methods such as cis-element shuffling or domain swapping. Moreover, the preparation of large-scale libraries supported by synthetic DNA fragments, directed evolution, and machine or deep learning methodologies is presented. A particularly interesting group of synthetic promoters are bidirectional forms that enable the putative expression of up to 6–8 genes by one regulatory element. The introduction and controlled expression of several genes after one transgenic event strongly decreases the frequency of such problems as complex segregation patterns and random integration of multiple transgenes. These complications are commonly observed during transgenic crop development through traditional, multistep transformation by genetic constructs containing a single gene. Another path to solving problems associated with the low complexity and homology of already tested DNA fragments is through orthogonal expression systems composed of synthetic promoters and trans-factors that do not occur in nature or arise from different species. Their structure, functions, and applications are rendered in the article.

In response to a perceived epidemic of coronary heart disease, Ancel Keys introduced the lipid-heart hypothesis in 1953 which asserted that high intakes of total fat, saturated fat, and cholesterol lead to atherosclerosis and that consuming less fat and cholesterol, and replacing saturated fat with polyunsaturated fat, would reduce serum cholesterol and consequently the risk of heart disease. Keys proposed an equation that would predict the concentration of serum cholesterol (DChol.) from consumption of saturated fat (DS), polyunsaturated fat (DP), and cholesterol (DZ): ΔChol. = 1.2(2ΔS − ΔP) + 1.5ΔZ. However, the Keys equation conflated natural saturated fat and industrial trans-fat into a single parameter and considered only linoleic acid as the polyunsaturated fat. This ignored the widespread consumption of trans-fat and its effects on serum cholesterol and promoted an imbalance of omega-6 to omega-3 fatty acids in the diet. Numerous observational, epidemiological, interventional, and autopsy studies have failed to validate the Keys equation and the lipid-heart hypothesis. Nevertheless, these have been the cornerstone of national and international dietary guidelines which have focused disproportionately on heart disease and much less so on cancer and metabolic disorders, which have steadily increased since the adoption of this hypothesis.

Geminiviruses possess single-stranded, circular DNA genomes, and control the transcription of their late genes, including BV1 of many bipartite begomoviruses, through transcriptional activation by the early expressing AC2 protein. DNA binding by AC2 is not sequence-specific, hence the specificity of AC2 activation is thought to be conferred by plant transcription factors (TFs) recruited by AC2 in infected cells. However, the exact TFs AC2 recruits are not known for most viruses. Here we report a systematic examination of the BV1 promoter (PBV1) of mungbean yellow mosaic virus (MYMV) for conserved promoter motifs. We found that MYMV PBV1 contains three abscisic acid (ABA)-responsive elements (ABREs) within its first 70 nucleotides. Deleting these ABREs, or mutating them all via site-directed mutagenesis, abolished the capacity of PBV1 to respond to AC2-mediated transcriptional activation. Furthermore, ABRE and other related ABA-responsive elements were prevalent in more than a dozen Old World begomoviruses we inspected. Together these findings suggest that ABA-responsive TFs may be recruited by AC2 to BV1 promoters of these viruses to confer specificity to AC2 activation. These observations are expected to guide the search for the actual TF(s), furthering our understanding of the mechanism of AC2 action.

Hemolysin II (HlyII) – one of the pathogenic factors of Bacillus cereus, a pore-forming β-barrel toxin – possesses a C-terminal extension of 94 amino acid residues, designated as the C-terminal domain of HlyII (HlyIICTD), which plays an important role in the functioning of the toxin. Our previous work described a monoclonal antibody (HlyIIC-20), capable of strain-specific inhibi-tion of hemolysis caused by HlyII, and demonstrated the dependence of the efficiency of hemol-ysis on the presence of proline at position 324 in HlyII outside the conformational antigenic de-terminant. In this work, we studied 16 mutant forms of HlyIICTD. Each of the mutations, ob-tained by multiple site-directed mutagenesis leading to the replacement of amino acid residues lying on the surface of the 3D structure of HlyIICTD, led to a decrease in the interaction of HlyIIC-20 with the mutant form of the protein. Changes in epitope structure confirm the high conformational mobility of HlyIICTD required for the functioning of HlyII. Comparison of the effect of the introduced mutations on the effectiveness of interaction between HlyIICTD and HlyIIC-20 and a control antibody recognizing a non-overlapping epitope enabled identifying the amino acid residues N339, K340 included in the conformational antigenic determinant rec-ognized by HlyIIC-20.

Almost contact complex Riemannian manifolds, known also as almost contact B-metric manifolds, are in principle equipped with a pair of mutually associated pseudo-Riemannian metrics. Each of these metrics is specialized here as a Yamabe almost soliton with a potential collinear to the Reeb vector field. The resulting manifolds are then investigated in two important cases with geometric significance. The first is when the manifold is of Sasaki-like type, i.e. its complex cone is a holomorphic complex Riemannian manifold (also called a Kähler–Norden manifold). The second case is when the soliton potential is torse-forming, i.e. it satisfies a certain recurrence condition for its covariant derivative with respect to the Levi-Civita connection of the corresponding metric. The studied solitons are characterized. In the three-dimensional case, an explicit example is constructed and the properties obtained in the theoretical part are confirmed.

Trans fatty acids (TFA) are a concern for public health due to their negative impact on cardiovascular health. This study aimed to assess the levels of TFA and other fatty acids in popular edible oils and fried foods commonly consumed in Tanzania. A total of 57 samples from 38 brands of edible oils and 20 samples of fried street foods and fast foods were collected in Dar es Salaam, Tanzania. Capillary gas chromatography was used to determine TFA levels, while nutritional labeling and other fatty acid classes were also evaluated. Among the analyzed edible oils, 21% exceeded the recommended TFA levels, primarily found in popular brands of margarine, industrially refined sunflower oils, animal butter, and peanut butter. Only two food items surpassed the 2% TFA limit, but a majority of the foods had high levels of saturated fatty acids and a fatty acid profile similar to palm oil. Additionally, only 22% of the edible oils provided TFA content information. These findings indicate the persistence of TFA levels beyond recommended limits and inadequate TFA nutritional labeling in Tanzanian food products. Urgent interventions are necessary to reduce TFA levels and improve nutritional labeling practices to safeguard public health.

Vitamins are essential compounds obtained through diet that are necessary for normal devel-opment and function in an organism. One of the most important vitamins for human physiology is Vitamin A, a group of retinoid compounds and carotenoids which generally function as a mediator for cell growth, differentiation, immunity, and embryonic development, as well as serving as a key component in the phototransduction cycle in vertebrate retina. For humans, vitamin A is obtained through the diet, where provitamin A carotenoids like β-carotene, or preformed vitamin A such as retinyl esters are absorbed into the body via the small intestine and converted into all-trans retinol within the intestinal enterocytes. Specifically, once absorbed, carotenoids are cleaved by carote-noid cleavage oxygenases (CCOs), such as BCO1, to produce all-trans retinal that subsequently gets converted into all-trans retinol. CRBP2 bound retinol is then converted into retinyl esters (REs) by the enzyme lecithin retinol acyltransferase (LRAT) in the endoplasmic reticulum, which is then packaged into chylomicrons and sent into the bloodstream for storage in hepatic stellate cells in the liver or for functional use in peripheral tissues such as the retina. All-trans retinol also travels through the bloodstream bound to retinol binding protein 4 (RBP4), where it enters cells with the assistance of the transmembrane transporters, stimulated by retinoic acid 6 (STRA6) in peripheral tissues or retinol binding protein receptor 2 (RBPR2) in systemic tissues (e.g. in the retina and the liver respectively). Much is known about the intake, metabolism, storage, and function of vitamin A compounds, especially with regard to its impact on eye development and visual function in the retinoid cycle. However, there is much to learn about the role of vitamin A as a transcription factor in development and cell growth, as well as how peripheral cells signal hepatocytes to secrete all-trans retinol into the blood for peripheral cell use. This article aims to review literature re-garding the major known pathways of vitamin A intake from dietary sources into hepatocytes, vitamin A excretion by hepatocytes, as well as vitamin A usage within the retinoid cycle in the RPE and retina to provide insight on future directions of novel membrane transporters for vitamin A in retinal cell physiology and visual function.

Dietary vitamin A/all-trans retinol/ROL plays a critical role in human vision. ROL circulates bound to the plasma retinol-binding protein (RBP4) as RBP4-ROL. In the eye, the STRA6 membrane receptor binds to circulatory RBP4 and internalizes ROL. STRA6 is however not expressed in systemic tissues, where there is high-affinity RBP4 binding and ROL uptake. We tested the hypothesis, that the second retinol-binding protein 4 receptor 2 (Rbpr2) which is highly expressed in systemic tissues of zebrafish and mouse, contains a functional RBP4 binding domain, critical for ROL transport. As for STRA6, modeling and docking studies confirmed three conserved RBP4 binding residues in zebrafish Rbpr2. In cell culture studies, disruption of the RBP4 binding residues on Rbpr2 almost completely abolished uptake of exogenous vitamin A. CRISPR generated rbpr2-RBP4 domain zebrafish mutants showed microphthalmia, shorter photoreceptor outer segments, and decreased opsins, that were attributed to impaired ocular retinoid content. Injection of WT-Rbpr2 mRNA into rbpr2 mutant or all-trans retinoic acid treatments rescued the mutant eye phenotypes. In conclusion, zebrafish Rbpr2 contains a putative extracellular RBP4-ROL ligand-binding domain, critical for yolk vitamin A transport to the eye for ocular retinoid production and homeostasis, for photoreceptor cell survival.

A new pathway leading to the n-10 fatty acid series has been recently evidenced, starting from sapienic acid - a monounsaturated fatty acid (MUFA) resulting from the transformation of palmitic acid by delta-6 desaturase. Sapienic acid attracts attention as novel marker of cancer cell plasticity. Here, we analyzed fatty acids including the n-10 fatty acid contents, and compared for the first time cell membranes and the corresponding extracellular vesicles (EV) of two human prostatic adenocarcinoma cell lines of different aggressiveness (PC3 and LNCaP). The n-10 components were 9-13% of the total fatty acids in both cancer cell lines and EVs, with total MUFA levels significantly higher in EVs of the most aggressive cell type (PC3). High sapienic/palmitoleic ratios indicated the preference for delta-6 vs. delta-9 desaturase enzymatic activity in these cell lines. The expressions analysis of enzymes involved in desaturation and elongation by qRT-PCR showed a higher desaturase activity in PC3 and a higher elongase activity toward polyunsaturated fatty acids than toward saturated fatty acids, compared to LNCaP cells. Our results improve the present knowledge in cancer fatty acid metabolism and lipid phenotypes, highlighting EV lipidomics to monitor positional fatty acid isomer profiles and MUFA levels in cancer.

Dunaliella salina is a rich source of 9-cis β-carotene, which has been identified as important in the treatment of retinal dystrophies and other diseases. We previously showed that chlorophyll absorption of red light photons in D. salina is coupled to oxygen reduction and phytoene desaturation and increases the pool size of β-carotene [1]. Here we show for the first time that growth under red light also controls conversion of extant all-trans β-carotene to 9-cis β-carotene by β-carotene isomerases. Cells illuminated with red light from a light emitting diode (LED) during cultivation contained a higher 9-cis β-carotene content compared to cells illuminated with white or blue LED light. The 9-cis/all-trans β-carotene ratio in red light treated cultures reached >2.5:1 within 48 hours and was independent of light intensity. Illumination using red light filters that eliminated blue wavelength light also increased the 9-cis/all-trans β-carotene ratio. With norflurazon, a phytoene desaturase inhibitor which blocked downstream biosynthesis of β-carotene, extant all-trans β-carotene was converted to 9-cis β-carotene during growth with red light and the 9-cis/all-trans β-carotene ratio was ~2:1. With blue light under the same conditions, 9-cis β-carotene was likely destroyed at a greater rate than all-trans β-carotene (9-cis/all-trans ratio 0.5:1). Red light perception by the red light photoreceptor, phytochrome, may increase the pool size of anti-oxidant, specifically 9-cis β-carotene, both by upregulating phytoene synthase to increase the rate of biosynthesis of β-carotene and to reduce the rate of formation of reactive oxygen species (ROS), and by upregulating β-carotene isomerases to convert extant all-trans β-carotene to 9-cis β-carotene.

In order to study the petrogenesis and tectonic setting of Permian A-type granites and their relationships with hydrothermal mineralization along the Hegenshan-Heihe suture zone (HHSZ) in northeastern China, we select the newly discovered Hongyan Cu-polymetallic deposit in the northeastern part of the HHSZ that develops three stages of mineralization associated with the Shanshenfu alkali-feldspar granite (SAFG). The zircon U-Pb dating and whole rock geochemistry suggest that the SAFG is a typical A-type granite formed in the Early Permian. The zircon Hf isotopes and trace elements suggest that the SAFG has high Ti-in-zircon temperature (721–990℃), high magmatic oxygen fugacity and largely positive εHf(t) (+6.0 to +9.9). Therefore, we propose that the SAFG was derived from the crustal assimilation and fractional crystallization of the charnockitized juvenile crust. The high oxygen fugacity favors the chalcophile elements (e.g., Cu, Au, Ag) of the source region enriched in the fluid phases after magmatic fractional crystallization, consequently facilitating subsequent hydrothermal mineralization, which is also consistent with the characteristics of ore-forming fluids that changed from the initial high temperature, high salinity, high fO2 and CO2-rich magmatic-hydrothermal fluids of stage I to CO2-poor, dilute, and cooling meteoric fluids of stage III. Combined with regional geological background, the Permian A2-type granites along the HHSZ can be formed in post-collisional slab break-off process. In subsequent exploration for hydrothermal deposits along the HHSZ, the Permian A-type granites with arc-related juvenile crustal source and high fO2 have great potential and need more attention.

The classification of tumors in subtypes, characterized by phenotypes determined by specific differentiation pathways, aids diagnosis and directs therapy towards targeted approaches. However, with the advent and explosion of next-generation sequencing, cancer phenotypes are turning out to be far more heterogenous than initially thought, and the classification is continually being updated to include more subtypes. Tumors are indeed highly dynamic and they can evolve and undergo various changes in their characteristics during disease progression. The picture becomes even more complex when tumor responds to a therapy. In all these cases, cancer cells acquire the ability to trans-differentiate, changing subtype, and adapt to changing microenvironments. These modifications affect the tumor's growth rate, invasiveness, response to treatment, and overall clinical behavior. Studying tumor subtype transitions is crucial for understanding tumor evolution, predicting disease outcomes, and developing personalized treatment strategies. We discuss this emerging hallmark of cancer and the molecular mechanisms involved at the crossroads between tumor cells and their microenvironment, focusing on four different human cancers in which tissue plasticity causes a subtype switch: breast cancer, prostate cancer, glioblastoma and pancreatic adenocarcinoma.

Debris-covered glaciers are a notable feature in the greater Himalaya, and their ongoing mass loss under changing climate will affect the water resources of over a billion people. The current knowledge of the mass balance of Himalayan glaciers is restricted by the paucity of in-situ measurements of glaciers in both space and time, as well as the resolution of satellite remote sensing imageries. Recently, the use of Unmanned Aerial System (UAS) imagery has shown the potential to bridge this gap by enabling very detailed monitoring of inaccessible glacial areas. UAS imagery-based monitoring of Himalayan glaciers has so far been limited to a single glacier in the entire Himalaya, providing a limited understanding of spatial variability in glacier mass balance and driving factors. In the first UAS based glacial mass change estimation in the trans-Himalaya, we conducted two Unmanned Aerial System (UAS) surveys (May and November 2019) over the debris-covered Annapurna III glacier in the Himalaya. We performed Structure-from-Motion (SfM) analysis and utilized differential GPS field observations to derive geometrically accurate point clouds, ortho-mosaics and digital surface models (DSMs). The glacial volumetric loss was estimated from DSM differencing, and the magnitude and spatial variability of glacier surface change was derived from 3-D differencing of point clouds. Results revealed a heterogeneous glacial melt pattern, with an average elevation loss of 0.89 m during the monitored time period. The majority of the glacial tongue exhibited surface lowering except the area above and around the glacial snout that surprisingly exhibited significant elevation gain. Both the highest magnitude of mass loss and the highest spatial variability in mass change was observed in areas with exposed ice-cliffs and supraglacial ponds. Glacial surface velocity derived from manual feature tracking showed velocity ranging from 0-4.1 m. A detailed evaluation of specific areas allowed an improved understanding of the complex interplay of factors leading to observed surface change. Our findings expand the extent of UAS based monitoring of debris-covered glaciers in the Himalaya and conclude that UAS derived 3D topographic products will become increasingly important for monitoring of thinning debris-covered glaciers.

A paper impregnated with silver nanoparticles (AgNPs) has been prepared. For the preparation of the substrates, aqueous suspensions of pulp fines, a side product from the paper production, have been mixed with Ag nanoparticles (AgNP) suspensions. The nanoparticle synthesis thereof was carried out via laser ablation of pure Ag in water. After the sheet formation process, the leaching of the AgNPs was determined to be low while the sheets exhibited antimicrobial activity towards E. Coli.

It is introduced and studied para-Ricci-like solitons with potential Reeb vector field on almost paracontact almost paracomplex Riemannian manifolds. The special cases of para-Einstein-like, para-Sasaki-like and having a torse-forming Reeb vector field have been considered. It is proved a necessary and sufficient condition the manifold to admit a para-Ricci-like soliton which is the structure to be para-Einstein-like. Explicit examples are provided in support of the proven statements.

Photophysical properties of a series of bis(arylydene)cycloalkanone dyes with various donor substituentns are studied by quantum chemistry. Their capacity for luminescence and nonradiative relaxation through trans-cis isomerization is related to their structure, in particular, to the donor capacity of the substituents and the degree of conjugation due to the central cycloalkanone moiety. It is shown that cyclohexanone central moiety introduces distortions and disrupts the conjugation, thus leading to a nonmonotonic change in their properties. The increasing donor capacity of the substituents causes increase in the HOMO energy (raise of the oxidation potential) and decrease in the HOMO-LUMO gap, which results in the red shift of the absorption spectra. The ability of the excited dye to relax through fluorescence or through trans-cis isomerization is governed by the height of the barrier between the Franck–Condon and S1-S0 conical intersection regions on the potential energy surface of the lowest π-π* excited state. This barrier also correlates with the donor capacity of the substituents and the degree of conjugation between the central and donor moieties. The calculated fluorescence and trans-cis isomerization rates are in good agreement with the observed fluorescence quantum yields.

Deuterostomes make a sudden appearance in the fossil record during the Early Cambrian. Two deuterostome groups, the chordates and the vetulicolians, are of particular interest for understanding the evolutionary dynamics of the Cambrian evolutionary event. Lagerstätten in China and elsewhere have dramatically improved our understanding of the range of variation in these ancient animals. Cephalochordate and vertebrate body plans are well established at least by Cambrian Series 2. Taken together, roughly a dozen chordate genera and fifteen vetulicolian genera document an explosive radiation of deuterostomes at the base of the Cambrian. A new vetulicolian (••• nov. gen. nov. sp.) with a polygonal anterior section and a narrow, unsegmented posterior region (‘tail’) bearing possible myotomes provides new insight into the affinities of the various body plans that emerged during the Early Cambrian. It seems clear that the advent of deuterostomes near the Cambrian boundary involved both a reversal of gut polarity and a two-sided retinoic acid gradient, with a gradient discontinuity at the midpoint of the organism that is reflected in the sharp division of vetulicolians into anterior and posterior sections.

Spectrally weighed irradiance on the corneal plane is often used to determine the visual and non-visual potency of light. Spectral irradiance or illuminance is measured with a diffuser in the so-called 2π geometry (i.e., a hemispheric measurement). Due to anatomical conditions, the human binocular field of view (FOV) does not correspond to a hemisphere but is occluded upwards and downwards. FOV-restricted measurements are scarce, however, and thus the error when using hemispheric measurements is yet to be determined. For our study, we designed and 3D printed FOV occlusions as attachments to spectral measurement devices. Measurements with and without the occlusion were taken in different lighting situations in the laboratory (light from different directions) and in real-world conditions (light typically from above). Our measurements show a reduction of visual and melanopic values due to the FOV occlusion ranging from negligible to over 60% for realistic scenarios. Further, the reduction was comparable for visual and melanopic parameters, as the distribution of light in the FOV was generally spectrally homogeneous. In the case of an exemplary and artificial laboratory situation, however, the melanopic daylight (D65) efficacy ratio changed by more than a factor of 2 only due to the FOV occlusion. Finally, head orientation showed a marked impact on all quantities. Our results reveal the potential for considerable error when just evaluating and comparing vertical, hemispheric measurements in experiments and non-visual lighting design projects. We thus encourage the (additional) use of a FOV occlusion for eye-level measurements in typical viewing directions and provide open-source 3D-print files.

A generalization of $\eta$-Ricci solitons is considered involving an additional metric and functions as soliton coefficients. The soliton potential is torse-forming and orthogonal to the contact distribution of the almost contact B-metric manifold. Then such a manifold can also be considered as an almost Einstein-like manifold, a generalization of an $\eta$-Einstein manifold with respect to both B-metrics and functions as coefficients. Necessary and sufficient conditions are found for a number of properties of the curvature tensor and its Ricci tensor of the studied manifolds. Finally, an explicit example of an arbitrary dimension is given and some of the results are illustrated.

Hypercholesterolemia accelerates atherosclerosis, and extensive research has been undertaken to ameliorate this abnormality. Plant sterols have been shown to inhibit cholesterol absorption and lower plasma cholesterol level since the 1950s. This ingredient has recently been reappraised as a food additive that can be taken daily in a preclinical period to prevent hypercholesterolemia, considering that cardiovascular-related diseases are the top cause of death globally even with clinical interventions. Intestinal cholesterol handling is still elusive, making it difficult to clarify the mechanism for plant sterol-mediated inhibition. Notably, although the small intestine absorbs cholesterol, it is also the organ that excretes it abundantly, via trans-intestinal cholesterol efflux (TICE). In this review, we show a model where the brush border membrane (BBM) of intestinal epithelial cells stands as the dividing ridge for cholesterol fluxes, making cholesterol absorption and TICE inversely correlated. With this model, we tried to explain the plant sterol-mediated inhibitory mechanism. As well as cholesterol, plant sterols diffuse into the BBM but are effluxed back to the lumen rapidly. We propose that repeated plant sterol shuttling between the BBM and lumen promotes cholesterol efflux, and plant sterol in the BBM may disturb the trafficking machineries that transport cholesterol to the cell interior.

Various factors, such as uncertainty of component parameters and uncertainty of sensor meas-urement values, contribute to the difficulty of fault detection in the landing gear retrac-tion/extension hydraulic system. In this paper, we introduce linear fractional transformation technology and uncertainty analysis theory for the construction of the diagnostic bond graph of the landing gear retraction/extension hydraulic system. In this way, interval analytical redundancy relations and fault signature matrix can be derived. Using the fault signature matrix, existing faults of the system can be preliminarily detected and isolated. Additionally, interval analytical re-dundancy relations can be used to detect system faults in detail, and cases analysis can be carried out to determine if the actuator is externally or internally leaky, and if the landing gear selector valve is reversing stuck. Compared to the traditional analytical redundancy relations, this method takes into account the negative factors of uncertainty; and compared to the traditional absolute diagnostic threshold, the interval diagnostic threshold is more accurate and sensitive.

Melting phase relations of the diamond-forming system olivine (Ol) – jadeite (Jd) – diopside (Di) – (Mg, Fe, Ca, Na)-carbonates (Carb*) – (C-O-H-fluid) are studied in experiments at 6.0 GPa in the polythermal section Ol74Carb*18.5(C-O-H)7.5 - Omp74Carb*18.5(C-O-H)7.5, where Ol = Fo80Fa20, Omp (omphacite) = Jd62Di38 and Carb* = (MgCO3)25(FeCO3)25(CaCO3)25(Na2CO3)25. Peritectic reaction of olivine and jadeite-bearing melt with formation of garnet has been determined as a physico-chemical mechanism of ultrabasiс-basiс evolution of the diamond-forming system. In the process CO2-component of the supercritical C-O-H-fluid can react with silicate components to form additional carbonates of Mg, Fe, Ca and Na. Solidus temperature of the diamond-forming system is depressed to 1000-1020°C by joint effect of the H2O-fluid and carbonate constituents thereof. The experimentally recognized peritectic mechanism of ultrabasiс-basiс evolution of the diamond-forming system explains the origin of the associated paragenetic inclusions of peridotite and eclogite minerals in diamonds as well as the xenoliths of diamond-bearing peridotites and eclogites of the kimberlitic deposits of diamond. The diamond-forming systems have formed with the use of material of the upper mantle native peridotite rocks. In this case the capacity of the rocks to run the peritectic reaction of olivine was transmitted with silicate components to the diamond-forming systems.

Inflammatory bowel diseases, which consist of chronic inflammatory conditions of the colon and the small intestine, are considered a global disease of our modern society. Recently, the interest toward the use of herbal therapies for the management of inflammatory bowel diseases has increased because of their effectiveness and favorable safety profile, compared to conventional drugs. Boswellia serrata Roxb. and Curcuma longa L. are amongst the most promising herbal drugs, however, their clinical use in inflammatory bowel diseases is limited and little is known on their mechanism of action. The aim of this work was to investigate the effects of two phytochemically characterized extracts of B. serrata and C. longa in an in vitro model of intestinal inflammation. Their impact on cytokine release and reactive oxygen species production, as well as the maintenance of the intestinal barrier function and on intestinal mucosa immune cells infiltration, has been evaluated. The extracts showed a good protective effect on the intestinal epithelium at 1 µg/ml, with TEER values increasing by approximately 1.5 fold, compared to LPS-stimulated cells. C. longa showed an anti-inflammatory mechanism of action, reducing IL-8, TNF-α and IL-6 production by approximately 30%, 25% and 40%, respectively, compared to the inflammatory stimuli. B. serrata action was linked to its antioxidant effect, with ROS production being reduced by 25%, compared to H₂O₂-stimulated Caco-2 cells. C. longa and B. serrata resulted to be promising agents for the management of inflammatory bowel diseases by modulating in vitro parameters which have been identified in the clinical conditions.