Blood Concentrates (BCs) are autologous non-transfusional therapeutical preparations with biological properties applied in tissue regeneration. These BCs differ in the preparation method, in fibrin network architecture, growth factors release as well as in platelet/cell content. Methodological changes result in distinct matrices that can compromise their clinical effectiveness. The present study evaluated the influence of different g-forces and types of tubes in the release of vascular endothelial growth factor (VEGF) from platelet-rich fibrin (PRF) as a function of time. The PRF-like samples were obtained with three g-forces (200, 400, and 800 x g) for 10 minutes in pure glass tubes or in polystyrene-clot activator tubes. Scanning and Transmission electron microscopy was used to morphometric analyzes of PRF’s specimens and flow cytometry was used to quantify VEGF slow release until 7 days. Our results showed that platelets were intact and adhered to the fibrin network, emitting pseudopods and in degranulation. The fibrin network was rough and twisted with exosomic granulations impregnated on its surface. An increase in the concentration of VEGF in the PRF supernatant was observed until 7 days for all g forces (200, 400 or 800 x g), with the highest concentrations observed with 200 x g, in both tubes, glass or plastic. Morphological analyzes showed a reduction in the diameter of the PRF fibers after 7 days. Our results showed that g-force interferes with the shape of the fibrin network in the PRF, as well as affect the release of VEGF stored into platelets. This finding may be useful in applying PRF to skin lesions, in which the rapid release of growth factors can favor the tissue repair process. Our observations point to a greater clarification on the methodological variations related to obtaining PRF matrices, as they can generate products with different characteristics and degrees of effectiveness in specific applications.

Immunoglobulin G (IgG) adopts a modular multidomain structure that mediates antigen recognition and effector functions, such as complement-dependent cytotoxicity. IgG molecules are self-assembled into a hexameric ring on antigen-containing membranes, recruiting the complement component, C1q. To provide deeper insights into the initial step of the complement pathway, we report a high-speed atomic force microscopy study for quantitative visualization of the interaction between IgG and the C1 complex composed of C1q, C1r, and C1s. Results showed that C1q in the C1 complex is restricted regarding internal motion and has a stronger binding affinity for on-membrane IgG assemblages than C1q alone, presumably because of smaller conformational entropy loss upon binding. Furthermore, we visualized a 1:1 stoichiometric interaction between C1/C1q and an IgG variant that lacks the entire CH1 domain in the absence of antigen. In addition to the canonical C1q-binding site on Fc, their interactions are mediated through a secondary site on the CL domain that is cryptic in the presence of the CH1 domain. Our findings offer clues for novel-modality therapeutic antibodies.

Background: The fascial system provides an environment that enables all body systems to operate in an integrated manner and is capable of modifying its tensional state in response to the stress applied to it. Recent in vitro, animal and cadaveric studies have shown that “myofascial force transfer” (MFT) has the potential to play a major role in musculoskeletal function and dysfunction.Objective: Human evidence for the existence of invivo MFT is scarce. This scoping review attempts to gather and analyse the available evidence of the in-vivo human MFT studies in order to sustain and facilitate further research and evidence based practice in this field.Methods: A search of most major databases was conducted with relevant keywords that yielded 238 articles as of August 2020. A qualitative analysis of the studies was conducted after rating it with Oxford’s Center for Evidence –based Medicine (CEBM) scale.Result: Nineteen studies ranging from randomized controlled trials to case studies covering 540 patients were included in this review. The analysed studies were highly heterogeneous and of lower methodological quality meddling with the quantitative analysis. Ten studies are confirming a ‘most likely’ existence of MFT, eight studies confirming it as ‘likely’ and one study couldn’t confirm any MFT existence in this review.Conclusion: Findings from in vivo human studies supports the animal and cadaveric studies claiming the existence of MFT which need to be corroborated by the future high quality studies. Forthcoming studies on MFT may give answers and solutions to many of the human musculoskeletal mysteries or dysfunctions.

G-quadruplex, a unique secondary structure in nucleic acids found throughout human genome elicited widespread interest in the field of therapeutic research. Being present in key regulatory regions of oncogenes, G-quadruplex structure regulates transcription, translation, splicing, telomere stability etc. Changes in its structure and stability lead to differential expression of oncogenes causing cancer. Thus, targeting G-Quadruplex structures with small molecules/ other biologics has shown elevated research interest. Covering previous reports, in this review we try to enlighten the facts on the structural diversity in G-quadruplex ligands aiming to provide newer insights to design first-in-class drugs for the next generation cancer treatment.

Nucleobase-containing molecules are compounds essential in biology due to the fundamental role of nucleic acids, and in particular G-quadruplex DNA and RNA in life. Moreover, some molecules different from nucleic acids isolated from different vegetal sources or microorganisms show nucleobase moieties in their structure. Nucleoamino acids and peptidyl nucleosides belong to this molecular class. Closely related to the above, nucleopeptides also known as nucleobase-bearing peptides are chimeric derivatives of synthetic origin and more rarely isolated from plants. Herein the self-assembly properties of a vast number of structures, belonging to the nucleic acid and nucleo amino acid/nucleopeptide family, is explored in the light of the recent scientific literature. Moreover, several technologically relevant properties such as the hydrogelation ability of some of the nucleobase-containing derivatives are reviewed in order to open the door to future experimental investigations of newly-inspired nucleobase-driven hydrogels. Nucleobase-containing molecules, such as mononucleosides, DNA, RNA, quadruplex (G4)-forming oligonucleotides and nucleopeptides, are paramount in gel and hydrogel formation owing to their distinctive molecular attributes and ability to self-assemble in biomolecular nanosystems with the most diverse applications in different fields of biomedicine and nanotechnology. In fact, these molecules and their gels present numerous advantages, underscoring their significance and applicability in both material science and biomedicine. Their versatility, capability for molecular recognition, responsiveness to stimuli, biocompatibility, and biodegradability collectively contribute to their prominence in modern nanotechnology and biomedicine. In this review, we emphasize the critical role of nucleobase-containing molecules of different nature in pioneering novel materials with multifaceted applications highlighting their potential in therapy, diagnostics, and new nanomaterials fabrication as required in order to address the numerous current biomedical and nanotechnological challenges.

An effective approach to fabricate large-scale of conducting polyaniline (PANI) by an in situ anodic electrochemical polymerization on the nickel foam, which coated by a novel aryl diazonium salt (ADS)-functionalized graphene (ADS-G). In present work, ADS-G was used as a high surface area support material for electrochemical polymerization of PANI. Electrochemical performances of the ADS-G/PANI composites exhibited better suitability as supercapacitor electrode materials than that of the PANI. The ADS-G/PANI composites achieved the specific capacitance of 528 F g-1, which was higher than that of PANI (266 F g-1) due to the excellent electrode-electrolyte interaction and synergistic effect of electrical conductivity between ADS-G and PANI in the composites. These findings suggested that the ADS-G/PANI composites were a suitable composite for the potential supercapacitor applications.

The spin magnetic moments and spin g factors (g_s = -2) of electron, muon and tau are explained based on the electric charges (EC) and lepton charges (LC) in terms of the three-dimensional quantized space model. The spin g factors of electron, muon and tau are g_s = -2 which is the sum of the EC g factor (g_EC = -1) and the LC g factor (g_LC = -1). The spin g factor (g_s = -2) of the electron is predicted by the Dirac’s equation. The orbit g factors of electron, muon and tau are g_L = g_EC = -1 from the EC g factor (g_EC = -1) without the contribution of the LC g factor (g_LC = -1). The spin g factors of the elementary fermions are calculated from the equation of g_s = g_EC + g_LC + g_CC where g_EC = EC/|EC|, g_LC = LC/|LC| and g_CC = CC/|CC|. For example, the spin g factors of the neutrinos and dark matters are g_s = -1. The spin g factors of the u and d quarks are g_s = 0 and g_s = -2, respectively. The g factor problem of neutrinos with the non-zero LC charges are solved by the LC Coulomb force of F_c(LC) ≈0. It is, for the first time, proposed that the binary motion (fluctuations) of the m_EC and m_LC masses for the electron, muon and tau leptons make the anomalous g factor. This binary motion could be originated from the virtual particle processes including the photons. Also, the weak force (beta) decay is closely related to the binary motion of the m_EC and m_LC for the electron, muon and tau leptons.

Performance of the overhead squat may affect golf swing mechanics associated with golf-related low back pain. This study investigates the difference in lumbar kinematics and joint loads during the golf downswing between golfers with different overhead squat abilities. Based on the per-formance of the overhead squat test, 21 golfers aged 18 to 30 years were divided into the highest-scoring group (HS, N=10, 1.61 ± 0.05 cm, and 68.06 ± 13.67 kg) and lowest-scoring group (LS, N=11, 1.68 ± 0.10 cm, and 75.00 ± 14.37 kg). Data collection used a motion analysis system, two force plates, and TrackMan. OpenSim software was used to simulate the joint loads for each lum-bar joint. An independent t-test was used for statistical analysis. Compared to golfers demonstrat-ing limitations in the overhead squat test, golfers with better performance in the overhead squat test demonstrated significantly greater angular extension displacement on the sagittal plane, smaller lumbar extension angular velocity, and smaller L4-S1 joint shear force. Consequently, the overhead squat test is found to be a useful index to reflect lumbar kinematics and joint loading patterns during the downswing, and provides a good training guide reference for reducing the risk of a golf-related low back injury

The Casimir–Lifshitz friction force and the heating rates of two metal plates with a narrow vacuum gap between them during nonrelativistic motion of one of them are calculated analytically and numerically within the framework of fluctuation electrodynamics. Changes in material properties are taken into account using the Bloch-Grüneisen and modified Bloch-Grüneisen (with finite residual resistance) resistivity models within the Drude approximation. It is shown that identical plates with the same initial temperature have the same heating rate, determined by the power of the friction force, and the possibility of measuring the friction force from the heating kinetics of nonmagnetic metal plates with temperatures of 1–10 K is substantiated.

In this study, the preparation of the composite 3% Au/graphite-C3N4 (3% Au/g-C3N4) sensing material was prepared by doping 3% Au onto the surface of graphitic carbonitride (C3N4) for detection pimobendan. By the way of sensing materials characterization, the X-ray diffraction analysis (XRD) and transmission electron Microscope (TEM) were performed. The cyclic voltammetry (CV) was used to measure the concentration and redox properties of pimobendan. It can be seen that when the voltage value is 0.05 V, and a reduction peak was appeared and the pimobendan concentration (0 to 55 μM) has a relationship with the reduction current value. At low concentrations of pimobendan concentration from 0.0 to 0.8 μM, the linearity R2 = 0.9642 with a detection limit of 0.28 μM. A possible pimobendan sensing mechanism on 3% Au/g-C3N4 was proposed.

Telomeres are crucial structures that preserve genome stability. Their progressive erosion over rounds of DNA duplication determines senescence of cells and organisms. Telomere length homeostasis is critical for cancer development then telomere maintenance mechanisms are established targets in cancer treatment. Besides telomere elongation, telomere’s dysfunction impinges on intracellular signalling pathways, in particular DNA damage signalling and repair affecting cancer cell survival and proliferation. This review summarizes and discusses about the recent findings in anti-cancer drug development targeting different “telosome” components.

The vomeronasal system serves as a pivotal element in mammalian sensory biology, allowing the perception of chemical signals essential for social communication via the activation of two main receptor families, V1R and V2R. The expression of V1Rs and V2Rs is linked with that of the G-protein alpha-subunits, Gαi2 and Gαo, respectively. The exploration of the evolutionary pathways of V1Rs and V2Rs across all mammalian species remains a main challenge, juxtaposing available genomic data against emerging immunohistochemical evidence. However, recent investigations, in contrast to what is predicted by the currently annotated genomic sequences, have revealed the expression of Gαo in the vomeronasal neuroepithelium of wild canids, including wolves and foxes. In the present study, the employment of a specific antibody raised against the mouse V2R2, member of the C-family of vomeronasal receptors, V2Rs, has confirmed the expression of this receptor in the fox and wolf, but it has revealed the lack of expression in the dog. This may reflect the impact of domestication on the regression of the VNS in this species, in contrast to their wild counterparts, and underscores the effects of artificial selection on sensory functions. Thus, these findings suggest a more refined chemical detection capability in wild species.

Low separation efficiency of photogenerated carriers and inefficient utilization of visible light limit the application of g-C3N4 nanosheets (CNNs) in the field of photocathodic protection (PCP). Therefore, this work considered indium zinc sulfide (ZnIn2S4, ZIS) as a visible photosensitizer and an electronic donor to promote its PCP performance. ZIS nanolayers with nano-leaf structures were fabricated on CNNs by a simple hydrothermal method. The synthesized 30% ZIS@CNNs composites significantly enhanced the PCP performance for 316 stainless steel (SS) compared with pure CNNs. Under visible light illumination, the 30% ZIS@CNNs photoelectrode exhibited the largest photoinduced current density of 17.30 μA cm−2 and a photoinduced potential drop of 0.37 V, which was approximately 4 and 7.5 times higher than that of pure CNNs, respectively. The improved protection performance may be attributed to the significant increase in visible light absorption and the great enhancement in the separation efficiency of

Mobile robots need an environmental perception ability in order to interact with the surrounding environment. In this paper we present the G-SLAM method, where the map is consisted of a cloud of scattered points in the continuous space and each point is accompanied by an obstacle existence probability. On the other hand the robot's pose (and trajectory) is estimated by an particle filters while the cloud of points is estimated by an adaptive recursive algorithm which is presented. Main feature of the presented method is the adaptive repositioning of the scattered points and their convergence around obstacles. In addition to our previous publications, In this paper a mathematical derivation of the method is presented and real case scenarios are discussed, presented and compared with other methods.

Water and sanitation facilities in sub-Saharan Africa and Africa in general are appalling and for the most part absent. Progress continues with respect to the development of plant materials as potent adsorbents, disinfectants, coagulants, flocculants, wetland species and lots more as substitutes for the dangerous chemical disinfectants. This research presents the potential of phyto-active components of Zanthoxylum zanthoxyloides and Gongronema latifolium as effective biocides against water microbial contaminants. Dry powder of Zanthoxylum zanthoxyloides and Gongronema latifolium were extracted and prepared into different concentrations with ethyl acetate and chloroform, ranging from 25 to 500 mg/ml. These fractions were then examined for antimicrobial activities against inherent bacterial and fungal water contaminants using disc diffusion assay. Fractions were afterwards screened for phytochemical active compounds using standard methods. Crude extracts of the different plant examined selectively comprise saponins, tannins, reducing sugars, anthraquinones, flavonoids, terpenoids, phlobatanins and alkaloids. All plant extracts showed broad spectrum antibiosis against selected gram positive and gram negative bacteria including E. coli, P. aeruginosa, Klebsiella sp, S. pneumoniae and B. cereus, as well as tested fungi, including A. niger, A. flavus, Trichoderma sp and Candida sp. While all extracts exhibited maximum antibiosis at 500 mg/ml, the chloroform extracts compared well than ethyl acetate extracts. The overall results revealed that antimicrobial activities of the plant extracts are dose dependent with comparative activity greater than that of commercial antibiotics at the concentration of extracts tested. E.coli was the most susceptible microbial isolate tested and represents the potential of the extract against a group of coliform which are important indicators of microbial pollution in water. Other microbial isolates also recorded sensitivity to extracts tested at varying degrees. The findings indicate that microbes tested were mostly susceptible to chloroform extract of Z. zanthoxyloides and G. latifolium except for the activity of ethyl acetate extract of Z. zanthoxyloide against E.coli. Results of phytochemical screening of the extract also showed the varied presence of alkaloids, saponins, tannins, flavonoids, terpenoids and anthraquinones The results indicated that plant materials investigated can be developed as effective biocides against water microbial contaminants

This paper proposes a contact force controller for a constrained flexible manipulator in three-dimensional motion. This controller used the conversion formula obtained empirically and experimental results showed the effectiveness of the proposed contact force controller. First, the manipulator was operated with the tip of the second link restrained, then, time response of the root strain, joint angles and contact force were used to derive the relational between the three quantities. The effectiveness of the relational expression was verified by conducting a target contact force tracking experiment by inputting the angle from the relational expression. The contact force control using the strain feedback method was proposed with the strain amount estimated from the target contact force as the target value, and its effectiveness was verified by experiments. From the results obtained, controller using the strain feedback method was designed for the purpose of controlling the contact force at the tip of a flexible manipulator with two links and three degrees of freedom that performs three-dimensional spatial motion, and its effectiveness was shown by comparison with the contact force feedback method.

We proposed a so-called Beta Kumaraswamy Burr Type X distribution which gives the extension of the Kumaraswamy-G class of family distribution. Some properties of this proposed model were provided, like: the expansion of densi- ties and quantile function. We considered the Bayes and maximum likelihood methods to estimate the parameters and also simulate the model parameters to validate the methods based on dierent set of true values. Some real data sets were employed to show the usefulness and exibility of the model which serves as generalization to many sub-models in the elds of engineering, medical, survival and reliability analysis.

We proposed a so-called Beta Kumaraswamy Burr Type X distribution which gives the extension of the Kumaraswamy-G class of family distribution. Some properties of this proposed model were provided, like: the expansion of densities and quantile function. We considered the Bayes and maximum likelihood methods to estimate the parameters and also simulate the model parameters to validate the methods based on different set of true values. Some real data sets were employed to show the usefulness and flexibility of the model which serves as generalization to many sub-models in the field of engineering, medical, survival and reliability analysis.

The thesis proposes a argument that a mass point moving in a horizontal circle on the Earth's surface can generate a radial centrifugal force of the Earth's center of mass, thus realizing an unconventional anti-gravity path. And through the theoretical analysis of the difference in the distribution of gravitational acceleration at different latitudes caused by the rotation of the earth, and the centrifugal force of a mass point moving in a horizontal circle on the earth's surface is analyzed, the validity of the argument is demonstrated. At the same time, the paper puts forward two possible basic principles, and makes theoretical analysis and demonstration. Conceive of the concrete experimental verification of principle two is proposed. Four technical schemes for antigravity ascent are proposed and basic analysis is made. On the premise of not fully considering the practical technical ability, it is theoretically proved that three of them have realistic operability and development potential. In theory, this paper opens up a different way of anti-gravity for human beings, which will bring new ideas and prospects for human beings to get rid of the bondage of gravity.

The manual muscle test (MMT) is a flexible diagnostic tool, which is used in many disciplines, applied in several ways. The main problem is the subjectivity of the test. The MMT in the version of a “break test” depends on the tester’s force rise and the patient’s ability to resist the applied force. As a first step, the investigation of the reproducibility of the testers’ force profiles is required for valid application. The study examined the force profiles of n=29 testers (n=9 experiences (Exp), n=8 little experienced (LitExp), n =12 beginners (Beg)). The testers performed 10 MMTs according to the test of hip flexors, but against a fixed leg to exclude the patient’s reaction. A handheld device recorded the temporal course of the applied force. The results show significant differences between Exp and Beg concerning the starting force (padj=0.029), the ratio of starting to maximum force (padj=0.005) and the normalized mean Euclidean distances between the 10 trials (padj=0.015). The slope is significantly higher in Exp vs. LitExp (p=0.006) and Beg (p=0.005). The results also indicate that experienced testers show inter-tester differences and partly even a low intra-tester reproducibility. That highlights the necessity of an objective MMT-assessment. Furthermore, an agreement on a standardized force profile is required – a suggestion is given.

The sulfated polysaccharide (SP) was extracted from Gracilaria edulis and tested for its ability to protect against carbon tetrachloride (CCl4)-induced liver injury in Wistar rats. The chemical composition of the sulfated polysaccharide, documented 12.90% of yield, 83.07% of carbohydrate, 0% of protein, 15.02% of ash, and 2.09% of moisture, and the carbon, hydrogen, nitrogen, and sulfur content were 25.90%, 4.28%, 2.65%, and 3.61%. SP has a molecular weight of 41kDa. The monosaccharide and structural properties of SP were investigated using GC-MS, FT-IR, and 1H-NMR spectral analysis. In rats, CCl4 produced hepatotoxicity, as evidenced by an increase in serum ALT, AST, and ALP levels and a decrease in ALB levels. The SP treated showed decreases in ALT, AST and ALP levels, as well as an increase in ALB levels. SOD, catalase, GPx, and GSH levels were suggestively lower in CCL4-induced rats compared to normal control rats. SOD, catalase, GPx and GSH levels in the SP-treated rats, on the other hand, improved to normal levels. The rat liver tissue treated with SP recovered well from hepatic injury. SP can be considered an alternative in the treatment of liver injury or as preventive medicine.

In this study, we reported that novel single-chain fusion-proteins linked thromboxane A2 (TXA2) receptor (TP) to a selected G-protein α-subunit q (SC-TP-Gαq), or s (SC-TP-Gαs) could be stably expressed in megakaryocytes (MK). We tested the MK-released platelet-linked particles (PLPs) to be used as a vehicle to deliver the over-expressed SC-TP-Gαq), or s (SC-TP-Gαs) to regulate human platelet function. To understand how the single-chain TP-Gα fusion proteins could regulate opposite platelet activities by an identical ligand TXA2, we used dual-binding domains linked to different signaling pathways within a single polypeptide chain using a 3D structural model. The immature MKs were cultured and transfected with cDNAs constructed from structural models of the individual SC-TP-Gαq and SC-TP-Gαs, respectively. After transient expression was identified, the immature MKs stably expressing SC-TP-Gαq or SC-TP-Gαs (stable cell lines) were selected. The stable cell lines were induced into mature MKs which released PLPs. Western blot analysis confirmed that the released PLPs were carrying the recombinant SC-TP-Gαq or SC-TP-Gαs. Flow cytometry analysis showed the PLPs carrying SC-TP-Gαq were able to perform the activity by promoting platelet aggregation. In contrast, PLPs carrying SC-TP-Gαs reversed Gq to Gs signaling to inhibit platelet aggregation. This is the first time demonstrating that SC-TP-Gαq and SC-TP-Gαs were successfully overexpressed in MK cells and released as PLPs with proper folding. This bio-engineering led to the formation of two sets of biologically active PLP forms, which mediate calcium and cAMP signaling, respectively. As a result, these PLPs are able to bind to identical endogenous TXA2 with opposite activities, inhibiting and promoting platelet aggregation as required for therapeutic process.The results also demonstrated the nucleus-free PLPs could be used to deliver recombinant membrane-bound GPCRs to regulate cellular activity in general.

Enzyme immobilization is known to enhance polypeptide resistance towards environmental changes, particularly in terms of their stability. The Y509E mutant of β-xylosidase from Geobacil-lus stearothermophilus (XynB2Y509E) (which also bears xylanase activity) has been immobilized in chitosan spheres through either entrapment or covalent bond formation methods. In the immo-bilization by entrapment, besides observing a total loss of xylanase activity, it was found that chitosan concentration affects the process efficiency. Additionally, the maturation time of the spheres and the alkaline pH used to precipitate the spheres affect the β-xylosidase activity of the enzyme. In covalent bond immobilization, it was found that the pH during the modification with glutaraldehyde, as well as the subsequent protein binding, were key factors in preserving the dual enzymatic activity. The activity expressed after immobilization by covalent bonding was 23% higher compared to the activity expressed following entrapment immobilization, with values of 122.3 and 99.4 U. g-1, respectively. Both biocatalysts showed increased thermal and pH stability, along with an improved storage capacity, as they retained 40% and 88% of their activi-ty after being stored at 4 C for two months. Moreover, XynB2Y509E immobilized by covalent binding also exhibited outstanding reusability, retaining a 92% of activity after ten cycles of re-use.

HLA-G is an immune checkpoint molecule with immunosuppressive and anti-inflammatory activities, and its expression and level of its soluble form (sHLA-G) may play an important role in tumor prognosis. The HLA-G 14 bp ins/del polymorphism and the plasma level of soluble HLA-G (sHLA-G) were investigated by a polymerase chain reaction and ELISA, respectively, in 59 glioma patients. A significantly higher proportion of glioma patients had the 14 nt insert in both homozygous and heterozygous states compared to the control group. Glioma patients had also higher plasma levels of sHLA-G. Patients with methylated MGMT promoter had lower levels of sHLA-G than those with unmethylated MGMT promoter. Level of sHLA-G negatively correlated with the overall survival of patients. Glioblastoma patients who survived more than one year after diagnosis had lower levels of sHLA-G than those surviving less than one year. Patients with sHLA-G levels below the cut off value 40 U/mL survived significantly longer than patients with sHLA-G above 40 U/mL. The levels of sHLA-G also negatively correlated with the level of IL-6 (P=0.0004) and positively with IL-10/IL-6 (P=0.046). Conclusion: The presence of 14 nt insert in both homozygous and heterozygous states of the HLA-G 14 bp ins/del polymorphism is more frequent in glioma patients and the elevated plasma levels of sHLA-G are negatively associated with their survival.

Graphite carbon nitride (g-C3N4) supported PtNi alloy nanoparticles (NPs) were fabricated via a facile and simple impregnation and chemical reduction method and explored their catalytic performance towards hydrogen evolution from ammonia borane (AB). Interestingly, the resultant Pt_0.5Ni₀.5/g-C₃N₄ catalyst affords superior performance, including 100% conversion, 100% H₂ selectivity, yielding the extraordinary initial total turnover frequency (TOF) of 250.8 mol_H2 min^-1 (mol_Pt)^-1 for hydrogen evolution from AB at 10 °C, a relatively low activation energy of 38.09 kJ mol⁻¹, and a remarkable reusability (at least 10 times), which surpass most of the noble metal heterogeneous catalysts. This notably improved activity is attributed to the charge interaction between PtNi NPs and g-C₃N₄ support. Especially, the nitrogen-containing functional groups on g-C₃N₄, serving as the anchoring sites for PtNi NPs, may be beneficial for becoming a uniform distribution and decreasing the particle size for the NPs. Our work not only provides a cost-effective route for constructing high-performance catalysts towards the hydrogen evolution of AB but also prompts the utilization of g-C₃N₄ in energy fields.

The potential to affect gene expression via G-quadruplex stabilization has been extended to all domains of life, including viruses. Here, we investigate the polymorphism and structures of G-quadruplexes of the human papillomavirus type 52 with UV, CD and NMR spectroscopy and gel electrophoresis. We show that oligonucleotide with five G-tracts folds into several structures and that naturally occurring single nucleotide polymorphisms (SNPs) have profound effects on the structural polymorphism in the context of G-quadruplex forming propensity, conformational heterogeneity and folding stability. With help of SNP analysis, we were able to select one of the predominant forms, formed by G-rich sequence d(G3TAG3CAG4ACACAG3T). This oligonucleotide termed HPV52(1-4) adopts a three G-quartet snap back (3+1) type scaffold with four syn guanine residues, two edgewise loops spanning the same groove, a no-residue V loop and a propeller type loop. The first guanine residue is incorporated in the central G-quartet and all four-guanine residues from G4 stretch are included in the three quartet G-quadruplex core. Modification studies identified several structural elements that are important for stabilization of the described G-quadruplex fold. Our results expand set of G-rich targets in viral genomes and address the fundamental questions regarding folding of G-rich sequences.

A simple, effective and environmental-friendly method was adopted for enhancing the photocatalytic activity of g-C3N4 in the reduction of aqueous Cr(Ⅵ) under visible-light irradiation. The enhancement was achieved via treatment of g-C3N4 in organic solvent with addition of NaOH particles by ultrasonic process for two hours. The results demonstrated that the treated g-C3N4 exhibited much higher photocatalytic activity than pristine g-C3N4 in the reduction of Cr(VI) . Under visible light irradiation for 120 min, the reduced ratios of Cr(VI) with the initial concentration of 50 mg/L in the presence of the treated g-C3N4and pristine g-C3N4 were 100% and 37.1%, respectively. With the addition of fulvic acid, Cr(VI) was efficiently removed at 40 min. Based on the characterization results of the structures and other physiochemical properties of the treated g-C3N4 and pristine g-C3N4 by X-ray diffraction, scanning electron microscopy, transmission electron microscopy and UV Vis diffuse reflectance, the possible reasons responsible for the enhanced photocatalytic activity of the treated g-C3N4 were proposed. The yield and mechanism of different exfoliation methods were compared by semi-quantitative method.

Atomic force microscopes are used, beside their principal function as surface imaging tools, in surface manipulation and measurement of interfacial properties. In particular, they can be modified to measure lateral friction forces that occur during the sliding of the tip against the underlying substrate. However, the shape, size, and deformation of the tips profoundly affect the measurements in a manner that is difficult to predict. In this work, we investigate the contribution of these effect to the magnitude of the lateral forces during sliding. The surface substrate is chosen to be few-layer AB-stacked graphene surface whereas the tip is initially constructed from face-centered cubic gold. In order to separate the effect of deformation from shape, rigid tips of three different shapes were considered first, namely a cone, a pyramid and a hemisphere. The shape was seen to dictate all aspects of the interface during sliding, from temperature dependence to stick-slip behavior. Deformation was investigated next by comparing a rigid hemispherical tip to one of identical shape and size but with all but the top three layers of atoms free to move. The deformation, as also verified by an indentation analysis, occurs by means of the lower layers collapsing on the upper ones, thereby increasing the contact area. This collapse mitigates the friction force and decreases it with respect to the rigid tip for the same vertical distance. Finally, the size effect is studied by means of calculating the friction forces for a much larger hemispherical tip whose atoms are free to move. In this case, the deformation is found to be much smaller but the stick-slip behavior is much more clearly seen.

Temperature dependent entropic force acting between the straight direct current I and the linear system (string with length of L) of N elementary non-interacting magnets/spins μ is reported. The system of elementary magnets is supposed to be in the thermal equilibrium with the infinite thermal bath T. The entropic force at large distance from the current is given by Fmagnen=Nμ02μ2I24π2kBTr3 , where r is the distance between the edge of the string and the current I, and kB is the Boltzmann constant; (r≫L is adopted). The entropic magnetic force is the repulsion force. The entropic magnetic force scales as Fmagnen~1T , which is unusual for entropic forces. The effect of “entropic pressure” is predicted for the situation when the source of the magnetic field is embedded into the continuous media, comprising elementary magnets/spins.

This paper proposes a multi-terminal adaptive collaborative operation method to solve the problem of unstable internal force tracking in clamping and handling unknown objects by multi-terminal robots. In the proposed method, the internal command force changes the complex internal force control problem into an internal force tracking problem from multi-slave to master. Moreover, we develop an algorithm for multi-slave setups to estimate object stiffness and motion uncertainty in the direction of the internal command force according to Lyapunov theory. Finally, the impedance control generates a reference trajectory for the multi-slave to maintain the desired internal force and track the master’s motion. Several experiments are conducted on a self-made robot equipped. The experimental results show that the oscillation amplitude of each slave end is less than 1 mm, the directional oscillation amplitude is less than 1 degree during the tracking of the desired commanded internal force. For objects with low stiffness, the error of the commanded internal force is less than 1 N (6%) per slave. The error in tracking the commanded internal force for objects with high stiffness is less than 2 N (8%). The results prove the feasibility and effectiveness of the proposed method.

The translocator protein (TSPO) is a transmembrane protein present in the three domains of life. Its functional quaternary structure consists of one or more subunits. In mouse, the dimer-to-monomer equilibrium is shifted in vitro towards the monomer by adding cholesterol, a natural component of mammalian membranes. Here, we present a coarse-grained molecular dynamics study on the mouse protein in the presence of a physiological content and of an excess of cholesterol. The latter turns out to weaken the interfaces of the dimer by clusterizing mostly at the inter-monomeric space and pushing the contact residues apart. It also increases the compactness and the rigidity of the monomer. These two factors might play a role for the experimentally observed incremented stability of the monomeric form with increased content of cholesterol. Comparison with simulations on bacterial proteins suggests that the effect of cholesterol is much less pronounced for the latter than for the mouse protein.

Force reduction is one of the most important benefit of applying ultrasonic vibration on milling. However, most of studies so far are limited to experimental investigation. In the current study, an analytical predictive model on cutting forces in ultrasonic vibration-assisted milling is proposed. The three types of tool-workpiece criteria are considered based on the instantaneous position and velocity of tool center. Type I criterion indicates that there is no contact if the instantaneous velocity is opposite to tool rotation direction. Type II criterion checks whether the vibration displacement is larger than the instantaneous uncut chip thickness. Type III criterion considers the overlaps between current and previous tool paths due to vibration. If none of these criteria is satisfied, milling forces are nonzero. Then the calculation is performed by transforming milling and tool geometry configuration to orthogonal cutting at each instant. The orthogonal cutting forces are predicted through the exhaustive search of shear angle and calculation of shear flow stress on tool-chip interface. The axial force is then calculated based on tool geometry, and the milling forces in feed, cutting, and axial directions are calculated after coordinate transformation. The proposed predictive force model in ultrasonic vibration-assisted milling is validated through comparison to experimental measurements on Aluminum alloy 2A12. The predicted values are able to match the measured milling forces with high accuracy of average difference of 13.6% in feed direction and 13.8% in cutting direction.

In this work, oxygen-doped g-C3N4 mesoporous nanosheets (O-CNS) were synthesized via a facile recrystallization method with the assistance of H2O2. The crystal phase, chemical composition, morphological structure, optical property, electronic structure and electrochemical property of the prepared O-CNS samples were well investigated. The morphological observation combining with nitrogen adsorption-desorption results demonstrated that the prepared O-CNS samples possessed nanosheets-like morphology with porous structure. The O doping into g-C3N4 resulted in the augment of specific surface area, which could provide more active sites for photocatalytic reaction. Simultaneously, the visible-light absorption capacity of O-CNS samples was boosted owing to the regulation of O doping. The built energy level induced by the O doping could accelerate the migration rate of photoinduced carriers, and the porous structure was most likely to speed up the release of hydrogen during photocatalyic hydrogen process. Resultantly, the photocatalytic hydrogen production rate of the optimized oxygen-doped g-C3N4 nanosheets reached up to 2012.9 μmol•h-1•g-1, which was 13.4 times higher than that of bulk g-C3N4. Thus, the significantly improved photocatalytic behavior was imputed to the porous structure, the augment of active sites, and the enhancement of visible light absorption and charge separation efficiency.

Generally, stochastic functional differential equations (SFDEs) pose a challenge as they often lack explicit exact solutions. Consequently, it becomes necessary to seek certain favorable conditions under which numerical solutions can converge towards the exact solutions. This article aims to delve into the convergence analysis of solutions for stochastic functional differential equations by employing the framework of G-Brownian motion. To establish the goal, we find a set of useful monotone type conditions and work within the space Cr((−∞,0];Rn). The investigation conducted in this article confirms the mean square boundedness of solutions. Furthermore, this study enables us to compute both LG2 and exponential estimates.

Background: Night-migratory birds sense the Earth´s magnetic field by an unknown molecular mechanism. Theoretical and experimental evidence support the hypothesis that light-induced formation of a radical-pair in European robin cryptochrome 4a, ErCry4a, is the primary signalling step in the retina of the bird. In the present work, we investigated a possible route of cryptochrome signalling involving the α-subunit of the cone specific heterotrimeric G protein from European robin. Methods: Protein-protein interaction studies include surface plasmon resonance, pulldown affinity binding and Förster resonance energy transfer. Results: Surface plasmon resonance studies showed direct interaction revealing high to moderate affinity for binding of non-myristoylated and myristoylated G protein to ErCry4a, respectively. Pulldown affinity experiments confirmed this complex formation in solution. We validated these in vitro data by monitoring the interaction between ErCry4a and G protein in a transiently transfected neuroretinal cell line using Förster resonance energy transfer. Conclusions: Our results suggest that ErCry4a and the G protein also interact in vivo and might constitute the first biochemical signalling step in radical-pair-based magnetoreception.

Despite a large amount of data on the association of folate metabolism disturbances with different aspects of schizophrenia, the role of the MTHFD1 1958 G>A polymorphism in this disorder is barely studied. The aim of this study was to assess the distribution of alleles and genotypes frequencies of MTHFD1 1958 G>A in patients with schizophrenia and healthy controls and to study the association of allele/genotype carriage of this SNP with biochemical markers of one-carbon metabolism and with the severity of schizophrenia symptoms. Methods: In 57 patients with schizophrenia and 37 healthy volunteers the carriage of alleles/genotypes of the MTHFD1 1958 G>A and biochemical markers of folate metabolism disturbances were evaluated. Clinical symptoms of schizophrenia and the severity of extrapyramidal side effects of therapy were assessed in patients. Results: an association of the wild GG genotype with schizophrenia was shown (GG versus AG / AA: χ2 = 7.31; p = 0.007). The serum folate level in carriers of the wild genotype GG is lower (in all participants p = 0.024, in patients p = 0.10), and the level of cobalamin in this subgroup is higher (in all participants p = 0.047, in patients p = 0.091) than in carriers of other genotypes. Patients carrying the G allele had less severe negative symptoms (p = 0.0041) and extrapyramidal side effects of antipsychotics (p = 0.054), than patients with AA genotype. The age of psychosis manifestation is the later, the more wild alleles G are present in the genotype (p = 0.00195).

Steroidal anti-inflammatory drugs are widely used for treatment of chronic cutaneous inflammation, such as atopic dermatitis, although it remains unknown how they modulate cutaneous mast cell functions. Murine connective tissue-type mast cells, which were sensitive to mast cell secretagogues, such as compound 48/80 and substance P, were generated by co-culture of bone marrow-derived mast cells with Swiss 3T3 fibroblasts in the presence of stem cell factor. This process was accompanied by up-regulation of a subunit of a trimeric G protein, G_i1, and several Mas-related G protein-coupled receptor (Mrgpr) subtypes. Secretagogue-induced degranulation and up-regulation of these genes were suppressed when they were cultured in the presence of a synthetic glucocorticoid, dexamethasone. The profiles of granule constituents were drastically altered by dexamethasone. Several Mrgpr subtypes were found to be expressed in the cutaneous tissues and their expression levels were decreased in response to topical application of dexamethasone. The numbers of degranulated cutaneous mast cells in response to compound 48/80 were decreased in mice treated with dexamethasone. These results suggest that mast cell-mediated IgE-independent cutaneous inflammation could be suppressed by steroidal anti-inflammatory drugs through down-regulation of G_ai1 and several Mrgpr subtypes in mast cells.

We present a Quantum Space Model (QSM) of cosmic evolution based on the theory that space consists of energy quanta which participates in the evolution of the universe. It shows that Dark Energy is the energy of space which causes its accelerating expansion. We used the Friedmann equations to trace the history of the cosmos from a time before the Big Bang to its ultimate end. The universe started from a quantum size volume of space with high energy density.Quantum fluctuations triggered the release of energy in a Big Bang at very high temperature and pressure. It then expanded and cooled undergoing phase transitions to radiation, fundamental particles, and matter. Matter grew into galaxies, and was further consolidated by gravity into Dark Energy Stars/Black Holes, ending in a Big Crunch at about 1.380 trillion years, thus bringing the universe back to its initial state. It can stay in a Deep Feeeze inside a Black Hole and through fluctuations or other mechanism may start a new cycle in its life with a new Bang. If the Law of Conservation of Energy is universal, then the cosmos is eternal. Space and energy are equivalent just as matter and energy are. This is well founded in Planck’s energy equation. They are the two most fundamental quantities in the universe that govern cosmic evolution. The two principal long range forces are the gravitational force and the space force.The latter could be the fifth force in the universe. They may provide the clockwork mechanism that operates our eternal cyclic universe.

The material flow dynamic and velocity distribution on the melted domain surface play a crucial role on the joint quality and formation of welding defects. In this study, authors investigated the effects of the low and high currents of plasma arc welding on the material flow and thermodynamics of molten pool and its relationship to the welding defects. The high-speed video camera (HSVC) was used to observe the convection of the melted domain and welded-joint appearance. Furthermore, to consider the Marangoni force activation, the temperature on the melted domain was measured by a thermal HSVC. The results revealed that the velocity distribution on the weld surface was higher than that inside the molten weld pool due to the difference of the massive density between the air and the steel. Moreover, in the case of low welding current (80A) the convection speed of molten was faster than that of the high welding current case (160A) owing to the difference of main driving forces direction and strength, which leading to undercut and humping defects on the weld surface and excessive convex (burn-through) defect at the bottom weld side, respectively. The medium welding current (120A) had two convection patterns with the main flow in backward direction, which resulted in better welding quality without defect. The interaction between the shear force and Marangoni force played a solid state on the convection and heat transportation processes in the plasma arc welding process.

Many studies discuss carbon-based materials because of the versatility of its element. They include different opinions for scientific problems and discuss fairly at convincing and compelling levels within the scope and application. A gas-state carbon atom converts into various states depending on its conditions of processing. The electron transfer mechanism in the gas-state carbon atom is responsible to convert it into various states, namely, graphite, nanotube, fullerene, diamond, lonsdaleite and graphene. The shape of ‘energy trajectory’ enables transferring electrons from the left- and right-sides of an atom is like a parabola. That ‘energy trajectory’ is linked to states (filled state and suitable nearby unfilled state) where force-exertion along the poles of transferring electrons is remained balance. So, the mechanism of originating different states of a gas-state carbon atom is under the involvement of energy first. This is not the case for atoms executing confined inter-state electron-dynamics as the force is involved first. Graphite-, nanotube- and fullerene-state atoms ‘partially evolve partially develop’ (form) their structures. These possess one-dimensional, two-dimensional and four-dimensional ordering of atoms, respectively. Their structural formation also comprises ‘energy curve’ having a shape-like parabola. Transferring suitable filled state electron to suitable nearby unfilled state is under a balance force exerting along the poles. The graphite structure under only attained-dynamics of atoms can also be formed but in two-dimension. Here, binding energy between graphite-state carbon atoms is for a small difference of exerting forces along their opposite poles. Structural formation in diamond, lonsdaleite and graphene atoms involve energy to gain required infinitesimal displacements of electrons through which they maintain orientationally-controlled exerting forces along dedicated poles. In this study, the growth of diamond is found to be south to east-west (ground) where atoms bound ground to south. Thus, diamond atoms merge for a tetra-electron ground to south topological structure. Lonsdaleite atoms merge for a bi-electron ground to just-south topological structure. The growth of graphene is found to be north to ground where atoms bound ground to north. Thus, graphene atoms merge for a tetra-electron ground to north topological structure. Glassy carbon exhibits layered-topological structure where, tri-layers of gas-, graphite- and lonsdaleite-state atoms successively bind in repetitive order. Nanoscale hardness is also sketched based on different force-energy behaviors of different state carbon atoms. Here, structure evolution in each carbon state atom explores its own science.

STRAS (Single access Transluminal Robotic Assistant for Surgeons) is a flexible robotic system based on the Anubis® platform of Karl Storz for application to intra-luminal surgical procedures. It consists of three cable-driven systems, one endoscope serving as guide and two inserted instruments. The flexible and bendable instruments have three degrees of freedom and can be teleoperated by a single user via two specially designed master interfaces. In this research, a pair of specific sensor gloves, which ergonomically fit to the master handles of the system was designed and the forces applied by one expert and one novice user during system-specific task execution in a simulator task (4-step-pick-and-drop) were compared. The results show that user expertise is not only reflected by shorter task execution times but also, more importantly, by specific differences in handgrip force profiles for specific sensor locations on anatomically relevant parts of the fingers and hand controlling the surgical instruments of the robotic master/slave system.

Polyvinyl Alcohol (PVA)/ Graphene Quantum Dots (GQDs) polymer nanocomposite films have been prepared, and the relationship between their structural, thermal and nanoscale morphologi-cal properties, and their photoluminescent response, has been investigated. Although according to X-ray Diffraction (XRD), Fourier-Transform Infrared Spectroscopy (FT-IR) and Differential Thermal Analysis (DTA) the incorporation of GQDs does not significantly affect the percentage crystallinity of the PVA matrix, for a range of added GQD concentrations, Atomic Force Micros-copy (AFM) showed the formation of islands with apparent crystalline morphology on the surface of the PVA/GQD films, with GQD presumably acting as a nucleating agent for island growth. The incorporation of GQD also led to the formation of characteristic surface pores with increased stiffness and frictional contrast, according to Ultrasonic Force Microscopy (UFM) and Frictional Force Microscopy (FFM) data. The photoluminescence (PL) spectra of the films were found to de-pend both on the amount of GQD incorporated and on the film morphology. For GQD loads > 1,2wt%, a GQD-related band was observed at ~ 1650 cm-1 in FT-IR, along with an increase in the PL band at lower energy. For a load of ~2wt% GQD, the surface morphology was characterized by extended cluster aggregates with lower stiffness and friction than the surrounding matrix, and the PL signal decreased.

Temperature-responsive separation membranes can significantly change their permeability and separation properties in response to changes in their surrounding temperature, improving efficiency and reducing membrane costs. This study focuses on the modification of commercial polyvinylidene fluoride (PVDF) membranes with amphiphilic temperature-responsive copolymer and inorganic nanoparticles. We prepared an amphiphilic temperature-responsive copolymer which the hydrophilic poly(N-isopropyl acrylamide) (PNIPAAm) was side-linked to a hydrophobic polyvinylidene fluoride (PVDF) skeleton. Subsequently, PVDF-g-NIPAAm polymer and graphene oxide (GO) blended with PVDF to prepare temperature-responsive separation membranes. The results showed that temperature-responsive polymers with different NIPAAm grafting ratios were successfully prepared by adjusting the material ratio of PVDF to NIPAAm. PVDF-g-NIPAAm was blended with PVDF with different grafting ratios to obtain separate membranes with different temperature responses. GO and PVDF-g-NIPAAm formed a relatively stable hydrogen bond network, which improved the internal structure and mechanical properties of the membrane without affecting the temperature response, thus extending the service life of the membrane.

The therapeutic effectiveness of current neurodegenerative diseases treatments is still under debate because of problems with bioavailability and a range of side effects. Fungi, which are increasingly recognized as sources of natural antioxidants and AChE enzyme inhibitors, may thus serve as potent neuroprotective agents. Previous studies have associated the anti-AChE and antioxidant activities of fungi mostly with polysaccharides and phenolic compounds, while other secondary metabolites such as polyamines (PAs) have been neglected. This study aimed to investigate eight edible and medicinal fungi from Serbia, marking the initial investigation into the neuroprotective capabilities of Postia caesia, Clitocybe odora, Clitopilus prunulus, and Morchella elata. Neuroprotective activity was examined using Ellman assay, while antioxidant capacity was tested by conducting DPPH, NO, ABTS and FRAP tests. PAs levels were determined by HPLC coupled with fluorescent detection. Ganoderma applanatum and Lepista nuda exhibited the most robust anti-AChE (98.05 ± 0.83% and 99.94 ± 3.10%, respectively) and antioxidant activities attributed to the synergistic effects of total protein, total phenolic and PAs levels. Furthermore, P. caesia displayed significant AChE inhibition (88.21 ± 4.76%), primarily linked to elevated SPD (62.98 ± 3.19%) and PUT levels (55.87 ± 3.16%). Our results highlight the need of thorough research to comprehend the intricate relationships between distinct fungus species and AChE inhibition. However, it's important to recognize that more research is required to identify the precise substances causing the reported inhibitory effects.

This study assessed the impacts of genotypes, environments, and their interaction on the performance of elite cowpea lines for key adaptive, grain yield, and associated traits across different locations. A total of 42 elite genotypes were evaluated in five Nigerian environments, representing various savanna ecologies during the 2021 growing season. The experimental design employed was an alpha lattice arrangement, replicating each genotype three times. The results revealed significant differences among genotypes, environments, and genotype-by-environment interaction for most traits, including days to maturity, 100 seed weight, and grain yield. GGE biplot showed G21 (IT14K-2111-2) and G25 (IT15K-2386-1) as the most stable genotypes across the five environments, G41(IT1K-61-82) was best adapted to Ibadan and Shika, G5 (245-1) was best adapted to Bagauda and Gumel while G30 (IT16K-2365-1) was best adapted to Bauchi. G21 and G25 could be recommended across the five test environments while G41, G30 and G5 are specific to the adapted environments.

At the level of the 50 U.S. states, an interconnected nexus of well-being variables exists. These variables have been shown to strongly correlate with estimates of state IQ in interesting ways. But the state IQ estimates (McDaniel 2006) are now more than 16 years old, and the state well-being estimates (Pesta et al., 2010) are over 12 years old. Updated state IQ and well-being estimates are therefore needed. I thus first created new state IQ estimates by analyzing scores from both the Program for the International Assessment of Adult Competency (for adults), and the National Assessment of Educational Progress (for fourth and eighth grade children) exams. I also created new global well-being scores by analyzing state variables from the following four well-being subdomains: crime, income, health, and education. When validating the nexus, several interesting correlations existed among the variables. For example, state IQ most strongly predicted FICO credit scores, alcohol consumption (directly), income inequality, and state temperature. Interestingly, state IQ derived here also correlated .58 with state IQ estimates from over 100 years ago. Global well-being likewise correlated with many old and new variables in the nexus, including a correlation of .80 with IQ. In sum, at the level of the U.S. state, a nexus of important, strongly correlated variables exists. These variables comprise well-being, and state IQ is a central node in this network.

The mammalian/mechanistic target of rapamycin complex 1 (mTORC1) is activated by the small G-protein, RHEB-GTPase. On lysosome, RHEB activates mTORC1 by binding the domains of N-heat, M-heat, and FAT, which allosterically regulates ATP binding in the active site for further phosphorylation. The crucial role of RHEB in regulating growth and survival through mTORC1, makes it a targetable site for anti-cancer therapeutics. However, the binding kinetics of RHEB to mTORC1 is still unknown at the molecular level. Therefore, we studied the kinetics by in vitro and in-cell protein-protein interaction (PPI) assays. For this, we used the split-luciferase system (NanoBiT®) for in-cell studies, and prepared proteins for the in vitro measurements. Consequently, it was shown that RHEB binds to the whole mTOR both in the presence or absence of GTPɣS, with five-fold weaker affinity in the presence of GTPɣS. Also, RHEB bound to the truncated mTOR fragments of N-heat domain (60-167) and M-heat domain (967-1023) in a GTP independent manner. Furthermore, RHEB bound to the truncated kinase domain (2148-2300) with higher affinity also in GTP independently. In conclusion, RHEB binds two different binding sites of mTOR, which probably regulates the kinase activity of mTOR through multiple different molecular mechanisms.

Adrenergic receptor β3 (ADRβ3) is a member of the rhodopsin-like G protein-coupled receptor family. The binding of the ligand to ADRβ3 activates adenylate cyclase and increases cAMP in the cells. ADRβ3 is highly expressed in white and brown adipocytes and controls key regulatory pathways of lipid metabolism. Trp64Arg (W64R) polymorphism in the ADRβ3 has been associated with the early development of type 2 diabetes mellitus, lower resting metabolic rate, abdominal obesity, and insulin resistance. It is unclear how the substitution of W64R affects the functioning of ADRβ3. This study was initiated to functionally characterize this obesity-linked variant of ADRβ3. We evaluated in detail the expression, subcellular distribution, and post-activation behavior of the WT and W64R ADRβ3 using a single cell quantitative fluorescence microscopy. When expressed in HEK 293 cells, ADRβ3 shows a typical distribution displayed by other GPCRs with a predominant localization at the cell surface. Unlike Adrenergic receptor β2 (ADRβ2), agonist induced desensitization of ADRβ3 does not involve loss of cell surface expression. WT and W64R variant of ADRβ3 displayed comparable biochemical properties and there was no significant impact of the substitution of Tryptophan with Arginine on the expression, cellular distribution, signaling, and post-activation behavior of ADRβ3. The obesity-linked W64R variant of ADRβ3 is indistinguishable from the WT ADRβ3 in terms of expression, cellular distribution, signaling, and post-activation behavior.

In this paper, the modification of two synthetic steps to obtain EMICORON, with respect to the usual protocol, is reported. EMICORON is a benzo[ghi]perylen-diimmide which was synthesized the first time in our laboratory in 2012 and showed to have in-vivo antitumor activities interfering with tumor growth and development by a multi-target mechanism of action. The provided modifications regarded the reaction times and the reaction conditions as well as the work-up procedures and allowed to increase the global yield of the process from 28% to about 40%. Thus, this new procedure may be more suitable in order to get larger amounts of EMICORON for further preclinical studies.

The literature offers limited information on the effect of obesity on the rate of force development, a critical parameter for mobility in older adults. The objectives of this study were; to explore the influence of obesity on RFD in older adults and to examine the association between this neuromuscular parameter and walking speed. 42 older adults were classified into two groups: the control group (CG, n=22; age=81.13±4.02 years; Body mass index (BMI)=25.13±3.35 kg/m²), and the obese group (OG, n=20; age=77.71±2.95 years; BMI=34.46±3.25 kg/m²). Walking speed (m/s) was measured using the 10-meter walking test. Neuromuscular parameters of the plantar flexors were evaluated during a maximal voluntary contraction test using a dynamometer. The RFD was calculated from the linear slop of the force – time curve in two phases: from the onset of the contraction to 50 ms (RFD50-100) and from 100 to 200 ms (RFD100-200). The gait speed was lower in the OG compared to the CG (p

This paper is the third application-oriented paper based on the "unified theory of forces" and also addresses the shortcomings of previous research in fully explaining the origin and nature of the weak force. The main conclusions of this paper are as follows: (1) It is argued that neutrinos are generated by the gravitational field, and their generation mechanism is similar to the radiation of photons from electron orbital transitions. Particles undergoing orbital transitions in a gravitational field will emit neutrinos. (2) We rigorously derive the energy formula for neutrinos and demonstrate that the energy formula for neutrinos does not comply with the Planck energy formula. Neutrinos with higher energy have longer wavelengths and are more easily observed in experiments.

Objectives The aim of this study was to measure the magnitude of forces in the joints of the lower limb whilst running barefoot and compare them to the forces generated whilst wearing running shoes with a thick midsole.MethodsTwenty-three volunteers who utilised running as their main sport or a training aid ran as training aid were included in this study. Each volunteer would run down a fourteen-meter-long corridor both barefoot and with running shoes. Forces for joints of the lower limb were collected using a Vicon motion analysis system and force plates. The joint forces for the ankles, knees and hips were taken as the largest joint force experienced during the stance phase and then averaged over five running trials.ResultsThere was significant reduction in the joint forces for the ankles, knees, and hips when barefoot running compared to the shod condition.ConclusionBarefoot running could be utilised to prevent both acute and degenerative injuries of the lower limb.

The model of T4 phage, Lambda phage and Escherichia coli is often used in research on virus-host interactions. This paper reports for the first time the thermodynamic driving force of biosynthesis, catabolism and metabolism for the three organisms, on the M9 medium. Moreover, the influence of activities of nutrients and metabolic products is analyzed. All three organisms were found to have very similar Gibbs energies of metabolism. Moreover, since they share the same catabolism, their Gibbs energies of catabolism are identical. However, Gibbs energies of biosynthesis differ. The calculated thermodynamic properties have been used to explain the coexistence of both bacteria and phages in a dynamic equilibrium in natural ecosystems.

The electric field is enormously more powerful than the gravitational field. However, in our normal experience there is no electric field, the electric force is missing. How is it that when you get to larger and larger scales the gravitational field is extremely important whereas the electric field becomes less and less important [1]? This paper proposes a model to explain why gravitation dominates at a larger scale.

Purposely slow velocity resistance exercise (i.e., 10 s concentric and eccentric phases) is a popular training method, but limits the loads that can be lifted (e.g., <50% 1 RM). This study compared the biomechanical properties of purposely slow velocity (SLOW) and traditional resistance exercise (TRAD) that uses maximal lifting velocities. Healthy resistance-trained men (n=5) performed two testing sessions (barbell squat and bench press) in random-order; a SLOW session (1 set x 10 repetitions at 28% 1 RM, 10 s concentric & eccentric), and a TRAD session (3 x 10 at 70% 1 RM, controlled eccentric and maximal concentric). A force plate and linear position transducer were used to collect kinetic and kinematic data for every repetition of both protocols (α = 0.05). For both exercises, both concentric and eccentric mean force (N) and power (W) for each repetition was greater for TRAD. When the entire training session (squat + bench press) was examined, SLOW exhibited greater time under tension, while TRAD produced greater work (J) and impulse (N·s). Contrary to suggestions in both the lay and scientific literature, purposely slow resistance exercise produced less force, power, and work than traditional velocity resistance exercise.

This paper first explains the theory of the origin of force from a new perspective, explaining that the origin of all forces is caused by the "missing of energy in the time dimension" (non-conservation in a certain period of time), and constructs a unified theory of force on this basis. Then, through the unified theory of force, the following phenomena are reinterpreted: (1) The common origin of the inverse square law of gravitation and electromagnetic force; (2) The origin of the repulsive force of electrons and protons at small distances; (3) The mystery of the rotation curve of galaxies and the new explanation of "dark matter"; (4) explain the origin of the magnetic field; (5) Predict that moving magnets have the same radiation effect as charged particles (electron magnetic moments also have radiation effects); (6) Reinterpret Maxwell's displacement current; (7) Reinterpret synchrotron radiation and bremsstrahlung; (8) Explain that the strong and weak forces are short-range forces; (9) Predict the true structure of black holes and the origin of gravitational waves;(10) Possible explanation for the origin of the speed of light.

A separate group consists of compounds that are able to simultaneously interact with both orthosteric and allosteric sites, which are classified as bitopic GPCR ligands [74, 76-81]. They have two pharmacophores, one of which binds with high affinity to the orthosteric site, while the other, with lower affinity, binds to the allosteric site. If these sites are spatially separated in the receptor, then the pharmacophores in the bitopic ligand must be connected with a flexible linker, the length of which exactly corresponds to the distance between the orthosteric and allosteric sites. At the same time, it is important that the linker does not significantly affect the conformational rearrangements in the receptor caused by its activation by orthosteric and (or) allosteric agonists [74, 79].

Mechanical ventilation (MV), used in patients with acute lung injury (ALI), induces diaphragmatic myofiber atrophy and contractile inactivity, termed ventilator-induced diaphragm dysfunction. Phosphoinositide 3-kinase- (PI3K-) is crucial in modulating fibrogenesis during the reparative phase of ALI; however, the mechanisms regulating the interactions among MV, myofiber fibrosis, and PI3K- remain unclear. We hypothesized MV with or without bleomycin treatment would increase diaphragm muscle fibrosis through the PI3K- pathway. Five days after receiving a single bolus of 0.075 units bleomycin intratracheally, C57BL/6 mice were exposed to 6 or 10 mL/kg MV for 8 h after receiving 5 mg/kg of AS605240 intraperitoneally. In wild-type mice, bleomycin exposure followed by MV 10 mL/kg prompted significant increases in disruptions of diaphragmatic myofibrillar organization, transforming growth factor-1, oxidative loads, Masson’s trichrome staining, extracellular collagen levels, positive staining of -smooth muscle actin, PI3K- expression, and myonuclear apoptosis (P &lt; 0.05). Decreased diaphragm contractility and peroxisome proliferator activated receptor- coactivator-1 levels were also observed (P &lt; 0.05). MV-augmented bleomycin-induced diaphragm fibrosis and myonuclear apoptosis were attenuated in PI3K-γ-deficient mice and through AS605240-induced inhibition of PI3K- activity (P &lt; 0.05). MV-augmented diaphragm fibrosis after bleomycin-induced ALI is partially mediated through PI3K-γ. Therapy targeting PI3K-γ may ameliorate MV-associated diaphragm fibrosis.

Introduction: The trophoblast derived angiogenic factors are considered to play an important role in the pathophysiology of various complications of pregnancy. The aim of this study was to establish relationship between concentrations of soluble Human Leukocyte Antigen-G (sHLA-G) in maternal serum and amniotic fluid at 16-22 weeks of gestation and the sonographic measurements of the fetal and placental growth. Materials and methods: sHLA-G in serum and amniotic fluid, as well as fetal biometric data and placental volume and perfusion indices were determined in 41 uncomplicated singleton pregnancies. Results: The sHLA-G levels were unchanged both in amniotic fluid and in serum during mid-pregnancy. The sHLA-G level in serum correlated positively with amniotic sHLA-G level (β=0.63, p<0.01). Significant correlation was found between serum sHLA-G level and abdominal measurement (β=0.41, p<0.05) and estimated fetal weight (β=0.41, p<0.05). The amniotic sHLA-G level and placental perfusion (VI: β = -0.34, p<0.01 and VFI: β = -0.44, p<0.01, respectively) were negatively interrelated. A low amniotic sHLA-G level was significantly associated with nuchal translucency (r = -0.102, p<0.05). Conclusions: sHLA-G assayed in amniotic fluid might be a potential indicator for placental function, whereas the sHLA-G level in serum can be a prognostic modality for feto-placental insufficiency.

Abstract Background: Numerous studies have demonstrated that the amalgamation of populations belonging to the same breed or closely related breeds leads to enhanced accuracies in genomic predictions (GP). Extensive experimentation with diverse Bayesian and Genome-enabled best linear unbiased prediction (GBLUP) models has been conducted to explore multi-breed genomic selection (GS) in livestock, ultimately establishing they as successful approaches for predicting genomic estimated breeding value (GEBV). This study aimed to examine the efficacy of BayesR and GBLUP model with different weighted genomic relationship matrices (GRM) in making genomic predictions for three distinct beef cattle breeds. Subsequently, we conducted a comparative analysis of the predictive accuracy pertaining to various marker densities and genetic correlations across three distinct beef cattle breeds. This investigation aimed to identify the optimal approach for enhancing the predictive accuracy of multi-breed genomic selection in beef cattle. Results：Genetic relationship matrices revealed moderate similarities between YL and the other breeds, with a striking genetic similarity of 0.87 between WG and HX. In HX cattle, BayesR demonstrated an enhancement in prediction accuracy, achieving 0.52 with HD and 0.46 with WGS, a marked improvement over 0.41 with HD and 0.42 with WGS in GBLUP. In WG and YL breeds, both methods showed comparable accuracies with HD, but BayesR slightly outperformed GBLUP with WGS. Further, multi-breed GS analysis indicated that BayesR consistently surpassed GBLUP in prediction accuracy, particularly with WGS data. For instance, in a combined HX and WG reference population, BayesR achieved a superior accuracy of 0.53 with WGS in HX cattle, a significant enhancement over GBLUP models. The study also underscores the advantage of incorporating multiple breeds in the reference population, which improved prediction accuracy, underscoring the value of broad-based genomic selection strategies. Conclusion: The results show that accuracy of multi-breed genomic predictions was higher with BayesR than with GBLUP, especially for the distantly genetic relationship between reference and validation breeds. Further improvements of multi-breed accuracy of genomic predictions could be achieved by increasing the density of the SNP marker. These findings underscore that BayesR providing a substantial improvement in genomic prediction and the importance of considering genetic relationships in the development of GS strategies for multi-breed cattle populations. Further research is warranted to optimize GRM construction and to explore alternative models for genomic prediction across breeds.

Methylation of cytosines at CpG sites in DNA, carried out by de novo by DNA methyltransferase Dnmt3a, is a basic epigenetic modification involved in gene regulation and genome stability. Aberrant CpG methylation in gene promoters leads to oncogenesis. In oncogene promoters, CpG sites often colocalize with guanine-rich sequences capable of folding into G-quadruplexes (G4s). Our in vitro study aimed to investigate how parallel G4s formed by a sequence derived from the c-MYC oncogene promoter region affect the activity of the Dnmt3a catalytic domain (Dnmt3a-CD). For this purpose, we designed synthetic oligonucleotide constructs: c-MYC G4-forming oligonucleotide and linear double-stranded DNA containing an embedded stable extrahelical c-MYC G4. The topology and thermal stability of G4 structures in these DNA models were analyzed by physicochemical techniques. We showed that Dnmt3a-CD specifically binds to an oligonucleotide containing c-MYC G4, resulting in inhibition of its methylation activity. c-MYC G4 formation in a double-stranded context significantly reduce Dnmt3a-CD-induced methylation of a CpG site located in close proximity to the quadruplex structure; this effect depends on the distance between the non-canonical structure and the specific CpG site. One would expect DNA hypomethylation near the G4 structure, while regions distant from this non-canonical form would maintain a regular pattern of high methylation levels. We hypothesize that the G4 structure sequesters the Dnmt3a-CD and impedes its proper binding to B-DNA, resulting in hypomethylation and activation of c-MYC transcription.

The size of seeds is particularly important for agricultural development, as it is a key trait that determines yield. It is controlled by the coordinated development of the integument, endosperm, and embryo. Large seeds are one of the important ways to improve the ultimate “sink strength” of crops, providing more nutrients for early plant growth and showing certain tolerance to abiotic stresses. There are several pathways for regulating plant seed size, including the HAIKU (IKU) pathway, ubiquitin-proteasome pathway, G (Guanosine triphosphate) protein regulatory pathway, mitogen-activated protein kinase (MAPK) pathway, transcriptional regulators pathway, phytohormone regulatory pathways including auxin, brassinosteroid (BR), gibberellin (GA), jasmonic acid (JA), cytokinin (CK), Abscisic acid (ABA), and MicroRNAs (miRNAs) regulatory pathway. This article summarized the seed size regulatory network and prospected ways to improve yield. We expect to provide valuable reference to researcher in the related field.

G protein-coupled receptors (GPCRs) are expressed essentially on all cells, facilitating cellular responses to external stimuli, and are involved in nearly every biological process. Several members of this family play significant roles in the regulation of adipogenesis and adipose me-tabolism. However, the expression and functional significance of a vast number of GPCRs in adipose tissue are unknown. We used a high-throughput RT-PCR panel to determine the expres-sion of the entire repertoire of non-sensory GPCRs in mouse white, and brown adipose tissue and assess changes in their expression during adipogenic differentiation of murine adipocyte cell line, 3T3-L1. In addition, the expression of GPCRs in subcutaneous adipose tissues from lean, obese, and diabetic human subjects was evaluated by re-analyzing RNA-sequencing data. We detected a total of 292 and 271 GPCRs in mouse white and brown adipose tissue, respectively. There is a significant overlap in the expression of GPCRs between the two adipose tissue depots but several GPCRs are specifically expressed in one of the two tissue types. Adipogenic differ-entiation of 3T3-L1 cells had a profound impact on the expression of several GPCRs. RNA se-quencing of subcutaneous adipose from healthy human subjects detected 255 GPCRs and obesity significantly changed the expression of several GPCRs in adipose tissue. Finally, we report sev-eral highly expressed GPCRs with no known role in adipose biology whose expression was sig-nificantly altered during adipogenic differentiation and/or in the diseased human subjects. These GPCRs could play an important role in adipose metabolism and serve as a valuable translational resource for obesity and metabolic research.

Abstract: It is assumed that upon SARS-CoV-2 infection granulocytes can undergo potentially destructive oxidative burst. Therefore, the aim of this study was to evaluate some parameters of redox and inflammatory signaling in granulocytes of recovered and of deceased COVID-19 pa-tients. Granulocytes were isolated from the blood of 32 COVID-19 patients on admission to the hospital (16 survived and 16 died within a week). The levels of proteins (immunoassay), eico-sanoids (UPLC-MS) and antioxidants activity (spectrophotometry) were examined. Enhanced activation of Nrf2 and NFκB and the levels of heme oxygenase and proinflammatory cytokines where found in granulocytes of all COVID-19 patients, while Cu,Zn-SOD and Mn-SOD activities were decreased, especially in deceased patients. Moreover, in patients who died increased levels of pro-inflammatory eicosanoids (PGE2 and TXB2) and decreased of anti-inflammatory (15d-PGJ2 and 5-HETE) were observed. However TXB2 was decreased, and IL-2 and IL-10 levels were in-creased in survivors, if compared both to healthy subjects and deceased patients, who did not change their cytokine generation. Therefore, it seems that by triggering transcription factors granulocytes activate redox signaling, leading to the production of pro-inflammatory eicosanoids, while reducing cellular antioxidant capacity via SOD, they express altered response to COVID-19, which might result in the onset of the vicious cycle of systemic oxidative stress in deceased patients.

G protein-coupled receptors (GPCRs) serve prominent roles in melanocyte lineage physiology, with an impact at all stages of development, as well as on mature melanocyte functions. GPCR ligands are present in the skin and regulate melanocyte homeostasis, including pigmentation. The role of GPCRs in the regulation of pigmentation and, consequently, protection against external aggression, such as ultraviolet radiation, has long been established. However, evidence of new functions of GPCRs directly in melanomagenesis has been highlighted in recent years. GPCRs are coupled, through their intracellular domains, to heterotrimeric G proteins, which induce cellular signaling through various pathways. Such signaling modulates essential cellular processes of melanomagenesis, such as proliferation and migration. GPCR-associated signaling in melanoma can be activated by the binding of paracrine factors to their receptors or directly by activating mutations. In this review, we present melanoma-associated alterations of GPCRs and their downstream signaling and discuss the various preclinical models used to evaluate new therapeutic approaches against GPCR activity in melanoma. Recent striking advances in our understanding of the structure, function, and regulation of GPCRs will undoubtedly broaden treatment options in melanoma in the future.

Immunoglobulin G (IgG), a type of antibody, represents approximately 75% of serum antibodies in humans, and is the most common type of antibody found in blood circulation Consequently, the development of simple, fast and reliable systems for IgG detection are of considerable interest which can be achieved using electrochemical sandwich-type immunosensors. In this study we have developed an immunosensor sub-strate using an inexpensive and very simple fabrication method based on ZnO nanorods obtained through the electrodeposition of ZnO. The ZnO nanorods were treated by electrodepositing a layer of reduced gra-phene oxide to ensure an easy immobilization of the antibodies. On this substrate, the sandwich configura-tion of the immunosensor was built through different incubation steps, that were all optimized. The im-munosensor is electrochemically active thanks to the presence of gold nanoparticles tagging the secondary antibody, therefore it has been used to measure the current density of the hydrogen development reaction which is indirectly linked to the concentration of H-IgG antigens. In this way the calibration curve was constructed obtaining a linear range of 1-100 ng / ml with a detection limit of few ng / mL and good sensi-tivity.

Background: The rate of force development (RFD) plays a pivotal role not only in preventing falls but also in ensuring successful completion of many functional tasks that demand swift muscle power rather than prolonged strength. Despite its importance, there is limited compre-hensive research on the relationship between RFD and walking speed, especially in older adults with Sarcopenic Obesity (SO). Objective: to investigate the influence of obesity on neuromuscular markers in older adults with SO and to assess the relationship between neuromuscular markers and gait speed in older adults with SO. Methods: a cohort of 42 participants was categorized based on their BMI into two groups: the sarcopenic non-obese group (CG, n=22; age=81.13±4.02; BMI=25.13±3.35) and the sarcopenic obese group (SOG, n=20; age=77.71±2.95; BMI=34.46±3.25). Gait speed was measured using a 10-meter test. Additionally, the isometric strength of the plantar flexor muscles was assessed during maximal voluntary contractions. Absolute Peak force (aPeak, N) were documented at intervals of 50 ms (a50, N), 100 ms (a100, N), and 200 ms (a200, N), subsequently normalized to body mass (r50, r100, r200, N). The RFD was derived in two phases: from the start of the contraction to 50 ms (RFD50-100) and from 100 to 200 ms (RFD100-200) and calculated from the linear slop of the force – time curve (Δ force/Δ time). Conclusion: Obesity negatively impacts neuromuscular markers in older adults. Notably, RFD emerges as the dominant factor influencing gait speed, accounting for an impressive 51% of its variability, far surpassing the impact of relative peak force. This underscores the imperative of evaluating neuromuscular health in older adults with SO to provide insights into mobility out-comes.

Cancer cells exhibit aberrant extracellular matrix mechanosensing due to altered expression of mechanosensory cytoskeletal proteins. Aberrant mechanosensing of the tumor microenvironment (TME) by cancer cells has been shown to be associated with cancer development and progression. Recent studies show that altered mechanosensing changes the mechanobiological properties of cells, and, in turn, cells become susceptible to mechanical perturbations. Due to an increasing understanding of cell biomechanics and cellular machinery, several approaches have emerged to target the mechanobiological properties of cancer cells and cancer-associated cells to inhibit cancer growth and progression. In this review, we summarize the progress that happened in the development of mechano-based approaches to target cancer by interfering with the cellular mechanosensing machinery and overall TME.

Impact force and maximum velocity are important indicators of kick efficiency in fighting activities. Therefore, this systematic review compared the front kick (FK) and roundhouse kick (RK), including maximal and impact force, maximum velocity, maximum angular velocity, and execution time, at different target types and experience levels. The Web of Science, SportDiscus, and PubMed were systematically searched from January 1982 to May 2022, according to PRISMA guidelines. The normalized kicking values were compared using one-way ANOVA. Eighteen articles, including FK with a pooled sample of 113 elite men, 109 sub-elite men, and 46 novices, and 25 articles, including RK with a sample of 238 elite men, 143 sub-elite men, and 27 novice men, fulfilled the inclusion criteria. The primary findings were that the impact forces of FK were higher than RK for the novice, sub-elite, and elite groups by 47% (p<0.01), 92% (p<0.01), and 120% (p<0.01), respectively. Moreover, the maximum foot velocity of RK was faster than FK for the sub-elite and elite groups by 44% (p<0.01) and 48% (p<0.01), respectively. The Elite group had 65% (p<0.01) higher knee extension angular velocity within RK than FK, and 138% (p<0.01) higher hip extension angular velocity within FK than RK.

Tolman VII solution \citep{ref-journal 2} is an exact analytic solution to the Einstein field equations describing the space-time of a static spherically symmetric distribution of matter. The solution has been shown to be capable of describing the interior of compact objects like neutron stars. Generalized \cite{ref-journal 13} and modified \cite{ref-journal 10} versions of the solution are also available in the literature, which have been subsequently developed to accommodate more realistic descriptions of neutron stars. The stability of the modified Tolman VII solution has recently been analyzed by Posada {\em et al} \cite{ref-journal 9 }, who evaluated a critical value of the adiabatic index above which the stellar configuration becomes unstable against radial oscillations. In this paper, making use of the generalized version of the Tolman VII solution, we prescribe an upper bound on the compactness ($M/R$) beyond which the star becomes unstable. Our investigation is based on the stability analysis of a star against radial oscillations developed by Chandrasekhar \cite{ref-journal 1}. The analysis brings out to attention the role of a particular model parameter in the generalized Tolman VII solution which can be linked to the inhomogeneity of the matter distribution vis-a-vis equation of state (EOS).

The detection and enrichment of circulating melanoma cells is a challenge as the cells are very heterogeneous in terms of their biomechanical properties and surface markers. In addition, there is a lack of valid and reliable biomarkers that predict progress and therapeutic response. We here analyzed the elasticity of A375 melanoma cells applying force spectroscopy and a microfluidic method. To identify and eventually separate circulating tumor cells, it is crucial to precisely know their physical properties. First, we used standard AFM force spectroscopy, where the elasticity of the cells is calculated from indentation with a pyramidal tip. To extend the limits of measurement with a tip, we then used cantilevers without a tip to press on the cells over a large area. The resulting Young’s moduli are slightly lower and vary less without tip presumably because of the inhomogeneity of the cells. Finally, we implemented our microfluidic method. We measured single cell elasticity by analyzing its deformation in high-speed micrographs while passing a stenosis. Combining the force field and the change in shape provides the basis for a stress strain diagram. The results from microfluidic deformation analysis were in accordance with the results from force spectroscopy. The microfluidic method provides advantages over conventional methods, since it is less invasive and less likely to harm the cell during the measurement, and the whole cell is measured as one entity without contact to a stiff substrate, while force spectroscopy is limited to the contact area of the tip, and in some cases dependent of the cell substrate interaction. Consequently, microfluidic deformation analysis allows to predict the overall elastic behavior of the whole inhomogeneous cell in three-dimensional force fields. This method may contribute to improve the detection of circulation melanoma cells in the clinical practice.

Classical laws of friction suggest that friction force is proportional to the normal load and independent of the nominal contact area. As a great improvement in this subject, it is now widely accepted that friction force is proportional to the real area in contact, and much work has been conducted based on this hypothesis. In present study, this hypothesis will be carefully revisited by measuring the friction force and real contact area in-site and real-time at both normal loading and unloading stages. Our experiments reveal that the linear relation always holds between friction force and normal load. However, for the relation between friction force and real contact area, the linearity holds only at the loading stage while fails at the unloading stage. This study may improve our understanding of the origin of friction.

As the coproduct of steelmaking, steelmaking slag, volumetrically expansive-prone without treatment, has been satisfactorily used as an aggregate base course material in highway construction. Although numerous technical reports and papers have revealed that steel slag aggreged using in rigid matrixes, the end product, paving block, non-structural concrete, for example, possesses superb strength and durability properties, the application of steel slag aggregate as a concrete aggregate is currently prohibited in highway construction. Naturally, researchers explore the practicality of use of steel slag, how to connect the laboratory experiment results to the end-product behavior, and further convert the research results into real construction? For all nontraditional or secondary materials utilization, the procedure of laboratory material examination, lab and field trial test are critical. To generalize the utilization, usability criteria establishment is necessary. This paper tries to use step-by-step method and plain language to explain how the volumetrically expansion can be simulated in lab testing apparatus, and based on the model, the mathematical deduction can result in a numerical usability criterion for steel slag use as a coarse aggregate in concrete (a rigid material). Therefore the paper is composed four main parts, laboratory test methods to examine the expansion force resulted from steel slag; converting the measured expansion force in a given volume of mass aggregate to the expansion (body) force of a single particle; modeling of slag and end material disruption; and a usability criterion from numerical deduction for the use of expansive-prone coarse slag in concrete or other rigid matrices. The paper provides the solutions to answer the above questions. Through the mathematical and mechanical modeling, provides the potential criteria that could result in specifications and guidance establishment for broad volumetric expansive-prone slags.

To quantify damage to reinforced concrete (RC) column members after an earthquake, an engineer needs to know the maximum applied force that was generated by the earthquake. Therefore, in this work, piezoceramic transducers are used to detect the applied force on an RC column member under dynamic loading. To investigate the use of post-embedded piezoceramic sensors in detecting the force that is applied to RC columns, eight full-size RC column specimens with various failure modes are tested under specific earthquake loadings. Post-embedded piezoceramic sensors are installed at a range of depths (70-80 mm) beneath the surface of a column specimen to examine the relationship between the signals that are obtained from them and the force applied by the dynamic actuator. The signals that are generated by the post-embedded piezoceramic sensors, which correlate with the applied force, are presented. These results indicate that the post-embedded piezoceramic sensors have great potential as tools for measuring the maximum applied force on an RC column in an earthquake. Restated, signals that are obtained from post-embedded piezoceramic sensors on an RC column in an earthquake can be used to determine the applied force and corresponding damage or residual seismic capacity.

Abstract: Objective: The aim of this study is to evaluate the effectiveness of an affective-sexual education programme among 14-15 year-old adolescents and its impact on their perception of their health. Design: This is a quantitative, descriptive and prospective quasi-experimental study, employing various cross-sections throughout the school year. It constitutes an educational promotion intervention where a health blog serves as a supplementary component to the "Health and School" programme. This phase is assessed using specific tools designed to evaluate scales. The study aims to assess the programme's effectiveness in the areas of knowledge and attitudes related to sexuality, sexually transmitted diseases, and affectivity. Additionally, it aims to evaluate the intervention's impact on 292 secondary school students, divided into a control group (N=144) and an intervention group (N=148). Both groups belong to the same population and have undergone affective-sexual education interventions focusing on gender and sexual diversity perspectives. The assessment considers perceptions and behaviours related to knowledge about HIV and other STDs/STIs, attitudes towards HIV, health anxiety, and AIDS phobia. Cross-sectional comparisons between the control and intervention groups are conducted at three points during the school year: longitudinal study, baseline, at month 4, and at month 9 post-intervention. Methods: Median and interquartile range, Wilcoxon test for numerical variables and Fisher's test for categorical variables were calculated according to intervention group. Results: 53% of the students reported a very good perception of health, compared to 45% with a good perception. Boys reported a good perception of health (85%) and had perceptions of their physical appearance and health (p=0.023) and (p<0.001) in the intervention group. Differences were found between perceptions of physical appearance in the control group, which was close to normal (p=0.429). In terms of level of knowledge about HIV and other STDs/STIs, the most significant difference was found in knowledge about HIV transmission, which varied between groups. Conclusions: Early affective-sex education sessions have an impact on health perception and behaviours related to knowledge about HIV and other STDs/STIs, leading to reduced anxiety in adolescents. School nurses should focus on health promotion, prevention of sex-related diseases, healthy attitudes from a gender perspective and integrated affective relationships in all their dimensions.

Piceatannol (PIC), a natural analog of resveratrol, has various biological functions. We previously reported that PIC had an anti-obesity effect only in ovariectomized mice. While ovariectomized mice have low phosphorylation levels of hormone-sensitive lipase (pHSL) at Ser563, we found that PIC increased those levels. Here, we investigated the effect of PIC using 3T3-L1 adipocytes to clarify the mechanism by which PIC activates HSL. First, PIC was confirmed to induce HSL phosphorylation at Ser563 in 3T3-L1 cells as in vivo experiments showed. pHSL (Ser563) is believed to be activated through the β-adrenergic receptor (β-AR) and protein kinase A (PKA) pathway; however, the addition of a selective inhibitor of β-AR did not inhibit the effect of PIC. The addition of PKA inhibitor with PIC blocked pHSL (Ser563), suggesting that PIC’s effects are mediated by PKA from a different pathway than β-AR. The addition of G15, a selective inhibitor of the G protein-coupled estrogen receptor (GPER), lowered HSL activation by PIC. Furthermore, PIC inhibited insulin signaling and did not induce pHSL (Ser565), which represents its inactive form. This study is the first to suggest that the GPER pathway might regulate HSL activation in adipocytes.

Introduction: An increasing body of evidence shows the significant role of the angiogenic factor levels in screening of pregnancy outcome. Purpose: To examine the potential relationship between concentrations of placental protein 13 (PP13) and soluble Human Leukocyte Antigen-G (sHLA-G) in maternal serum and amniotic fluid at 16-23 weeks of gestation and the sonographic features of pregnancy as well as pregnancy outcome. Materials and methods: PP13 and sHLA-G in serum and amniotic fluid, and fetal biometrical data and placental volume and perfusion indices were determined in 71 euploid, singleton pregnancies. Results: The serum sHLA-G level correlated negatively with serum PP13 level (r = -0.186, p&lt;0.001) and positively with sHLA-G level in the amniotic fluid (r = 0.662, p&lt;0.001). Significant correlation was found between serum sHLA-G level and placental volume (r = 0.142, p&lt;0.05) and between amniotic sHLA-G level and placental perfusion (r = -0.450, p&lt;0.001). A low amniotic PP13 level significantly predicted the birth weight (r = -0.102, p&lt;0.05), the duration of pregnancy (r = -0.155, p&lt;0.05), and the fetal abdominal circumference (r=-0.098, p&lt;0.05). Conclusions: PP13 assayed in amniotic fluid might be a potential marker of fetal growth and sHLA-G can be an adjunct modality reflecting placental sonographic parameters.

The intricacies of translational strategies make this stage of the implementation of genetic information one of the most difficult to understand and, at the same time, perhaps the most interesting. It also becomes clear that all this variety of strategies is not just a consequence of a long evolutionary history but is of paramount importance for fine-tuning gene expression and metabolic modulation. This is especially true for those organisms that demonstrate predominantly biochemical and physiological reactions with a lack of behavioural ones. Plants are just such a group of organisms. Overcoming unfavourable environmental conditions occupies a key place in plant physiology. This is especially true with the changing conditions of global warming and the irretrievable loss or depletion of natural ecosystems. Conceptually, the response of plants to abiotic stress is a set of complex and intricate strategies. This is dictated both by a variety of abiotic factors that provoke stressful conditions and by a variety of molecular genetic mechanisms that make it possible to fine-tune the metabolic pathways through which the plant organism overcomes non-standard and non-optimal conditions. In the presented review, we tried to focus on the state-of-the-art in the field of translational regulation in plants under abiotic stress conditions. Various regulatory elements and patterns are considered in relative chronological order. We also considered it necessary to pay attention to key high-performance methods for studying the dynamics of genetic information at the stage of translation.

Mature B cells notably diversify immunoglobulin (Ig) production through class switch recombination (CSR), allowing the junction of distant “switch” (S) regions. CSR is initiated by activation-induced deaminase (AID) which targets cytosines adequately exposed within single-stranded DNA of transcribed targeted S regions, with a specific affinity for WRCY motifs. In mammals, G-rich sequences are additionally present in S regions, forming canonical G-quadruplexes (G4s) DNA structures which favor CSR. Small molecules interacting with G4-DNA (G4 ligands), proved able to regulate CSR in B lymphocytes, either positively (such as for nucleoside diphosphate kinase isoforms) or negatively (such as for RHPS4). G4-DNA is also implicated in the control of transcription, and due to their impact on both CSR and transcriptional regulation, G4-rich sequences likely play a role in the natural history of B cell malignancies. Since G4-DNA stands at multiple locations in the genome, and notably within oncogene promoters, it remains to be clarified how it can more specifically promote legitimate CSR in physiology, rather than pathogenic translocation. The specific regulatory role of G4 structures in transcribed DNA and/or in corresponding transcripts and recombination hereby appears as a major issue for understanding immune responses and lymphomagenesis.

Fatty acids (FFAs) are important biological molecules that serve as a major energy source and are key components of biological membranes. Besides, FFAs play important roles in metabolic regulation and contribute to the development and progression of metabolic disorders like diabetes. Recent studies have shown that FFAs can act as important ligands of G-protein coupled receptors (GPCRs) on the surface of cells and impact key physiological processes. Free fatty acid activated receptors include FFAR1 (GPR40), FFAR2 (GPR43), FFAR3 (GPR41) and FFAR4 (GPR120). FFAR2 and FFAR3are activated by short chain fatty acids like acetate, propionate and butyrate whereas FFAR1 and FFAR4 are activated by medium and long chain fatty acids like palmitate, oleate, linoleate and others. FFARs have generated considerable attention over the last few years and have become attractive pharmacological targets in the treatment of type 2 diabetes and metabolic syndrome. Several lines of evidence point to their importance in the regulation of whole-body metabolic homeostasis including adipose metabolism. Here we summarize our current understanding of the physiological functions of FFAR isoforms in adipose biology and explore the prospect of FFAR based therapies to treat patients with obesity and Type 2 Diabetes.

G-quadruplexes are noncanonical nucleic acid structures formed from stacked guanine tetrads. They are frequently used as building blocks and functional elements in fields such as synthetic biology and also thought to play widespread biological roles. G-quadruplexes are often studied as monomers but can also form a variety of higher-order structures. This increases the structural and functional diversity of G-quadruplexes, and recent evidence suggests that it could also be biologically important. In this review we describe the types of multimeric topologies adopted by G-quadruplexes and highlight what is known about their sequence requirements. We also summarize the limited information available about potential biological roles of multimeric G-quadruplexes and suggest new approaches that could facilitate future studies of these structures.

Glycerol represents a useful functional component of heat-transfer fluids. Glycerol is known to be triboelectrically active. We report how the flow of glycerol, stopped in a cylindrical coiled pipe, influences horseradish peroxidase (HRP) enzyme. Namely, glycerol flow was pumped through the coil and then stopped. After that, we incubated the 0.1 µM solution of HRP near the side of the coil, and then adsorbed HRP onto mica. This operation markedly increased the HRP aggregation on mica in comparison with the control sample. We explain this phenomenon by the influence of triboelectrically induced electromagnetic fields. Our results can be useful in the development of flow-based systems for biosensors and bioreactors.

Based on the panel data from 31 provinces in China from 2012 to 2020, this paper uses the TOPSIS method to measure the development level of the digital economy and environmental quality. Then, a coupled coordination degree model is used to analyse the relationship between the digital economy and environmental quality. Kernel density estimation and the Dagum Gini coefficient method were used to reveal the dynamic evolution trend of the coupled coordination level between the digital economy and environmental quality and the regional trends of coupled indicators. Finally, the dynamics of the above relations were explored with an econometric model. The results show that the coupled coordination degree of the digital economy and environmental quality displays obvious regional heterogeneity, and the national coordination level exhibits dynamic convergence characteristics. The heterogeneity of the coupled coordination degree of the two systems in the eastern region has decreased year by year, except in the western region, the central region and the northeast region, where an upwards trend is observed. Overall, the Gini coefficient of the coupled coordination degree between the digital economy and environmental quality displays a certain downwards trend. The level of economic development, technological innovation level, industrial structure, degree of opening to the outside world, degree of environmental regulation, marketization index and financial development level have a positive influence on the coupled coordination of the digital economy and environmental quality. Environmental regulation is the core driver of the coupling of the two systems, and the economic development level, technological innovation level, industrial structure and degree of openness are the other major drivers. Therefore, in the processes of digital economy transformation and environmental governance, all regions should focus on balanced development between regions to optimize the overall efficiency of the two systems, consider external influence, enhance internal capabilities, and promote the coordination and co-development of the two systems.

We studied the magnetostriction coefficients, λs, Curie temperature, Tc, and their dependence on annealing conditions in Fe47Ni27Si11B13C2 and Co67Fe3,9Ni1,5B11,5Si14,5Mo1,6 amorphous glass-coated microwires with rather different character of hysteresis loops. A positive λs≈20x10-6is observed in as-prepared Fe47Ni27Si11B13C2, while low and negative λs ≈-0.3x10-6 is ob-tained for Co67Fe3,9Ni1,5B11,5Si14,5Mo1,6 microwire. Annealing affects the magnetostriction coeffi-cients and Curie temperatures, Tc, of both Fe47Ni27Si11B13C2 and Co67Fe3,9Ni1,5B11,5Si14,5Mo1,6 glass-coated microwires in a similar way. Observed dependencies of hysteresis loops, λs and Tc on annealing conditions are discussed in terms of superposition of internal stresses relaxation and structural relaxation of studied microwires. We observed linear λs dependence on applied stress, σ, in both studied microwires. A decrease with applied stress is observed for Co-rich mi-crowires with negative magnetostriction coefficient. In contrast, a linear increase of the magne-tostriction coefficient with applied stress is observed for Fe-Ni- rich microwires with positive magnetostriction coefficient. Observed results are discussed in terms of influence of internal stresses and short range atomic rearrangements induced by annealing on hysteresis loops, magnetostriction coefficients and Curie temperatures of studied microwires.

When a suspension passes through a high-frequency standing sound wave, the particles it contains are manipulated by acoustic forces. In a one-dimensional sound field, these forces lead to a planar arrangement of the particles and the formation of agglomerates. It is known that the combination of these forces and depth filtration can be utilized to significantly increase the filter efficiency of coarse-pored media. So far, this concept has only been used in microfluidics. In this paper, we present the results of a scaled-up filtration channel to test the viability of the industrial application of acoustically assisted filtration systems for the removal of microparticles. The influences of acoustic power input, flow rate, and the porosity of the filter media are investigated. In addition to verifying the scalability, a significant decrease in the large particle fraction in the outflow of the channel was observed when a high-power sound field is applied. Furthermore, the formed agglomerates tend to rise to the fluid surface. The floating particles mostly consist of a large particle fraction.

The need for miniaturized shear force sensors is expanding, particularly for biomedical applications. Examples include measuring interfacial shear stresses between a human and an external device (e.g., footwear or a prosthesis). However, there are considerable challenges in designing a shear sensor for these applications due to the need for a small package, low power requirements, and resistance to interference from motion artifact and electromagnetic fields. This paper presents the design, fabrication, and characterization sensor that measures two-axis shear force by detecting displacement between a color panel and a red, green, and blue light-sensing photodiode. The sensor response to applied displacements and forces was characterized under benchtop testing conditions. We also present the design of a prototype wireless version of the sensor for integration into footwear. The sensor exhibited strong agreement with gold standard measurements for two axis shear displacements (R2>0.99, RMSE≤5.0 µm) and forces (R2>0.99, RMSE≤0.94 N). This performance, along with the sensor’s scalability, miniaturized form, and low power requirements make it well-suited a variety of biomedical applications.

Unpaid family caregivers must consider the economic trade-off between caregiving and paid employment. Prior literature has suggested labour force participation (LFP) to decline with caregiving intensity, but no study has evaluated this relationship by accounting for the presence of both kinks and discontinuities. Here we used respondents of the China Health and Retirement Longitudinal Study baseline survey who were non-farming, of working-age (aged 45-60) and had a young grandchild and/or a parent/parent-in-law. For women and men separately, a caregiving threshold-adjusted probit model was used to assess the association between LFP and weekly unpaid caregiving hours. Instrumental variables were used to rule out the endogeneity of caregiving hours. Of the 3,718 respondents in the analysis, for men, LFP was significantly and inversely associated with caregiving that involved neither discontinuities nor kinks. For women, a kink was identified at the caregiving threshold of 8 hours per week such that before 8 hours, each caregiving hour was associated with an increase of 0.0257 in the marginal probability of LFP, but each hour thereafter was associated with a reduction of 0.0014 in the marginal probability of LFP. These results have implications for interventions that simultaneously advance policies of health, social care and labour force.

The entropic gravity conception proposes that what has been traditionally interpreted as unobserved dark matter might be merely the product of quantum effects. These effects would produce a novel sort of positive energy that translates into dark matter via $E=mc^2$. In the case of axions, this perspective as been shown to yield quite sensible, encouraging results [DOI:10.13140/RG.2.2.17894.88641] . There, a simple Schrodinger mechanism was utilized, in which his celebrated equation is solved with a potential function based on the microscopic Verlinde's entropic force advanced in [Physica A {\bf 511} (2018) 139]. In this effort we revisit such technique with regards to fermions' behavior (specifically, baryons).

Domain walls were studied for permalloy wires with different depth trenches (500 nm wide, 30 nm thick, 7.5 µm long, the depth of the trench was 0, 4, 5, 8, 10, 12 and 15nm). Permalloy (Ni80Fe20) wires were fabricated by electron beam lithography and Ar ion milling. When the depth of trench is smaller than 12 nm, the switching field (Hs) is increasing with the deeper trench. However, the depth of trench is bigger than half depth of thickness, the Hs is decreasing with the deeper trench. We believed that Hs increased as the trench depth increased was because the magnetic diploes force increased between the magnetic poles on two sides of the trench. The domains of the wires were divided by the trenches and the domain walls were pinned on the trenches these were confirmed by magnetic force microscopy images.

In the manufacturing industry, cutting tool failure is a probable fault which causes damage to the cutting tools, workpiece quality and unscheduled downtime. It is very important to develop a reliable and inexpensive intelligent tool wear monitoring system for use in cutting processes. A successful monitoring system can effectively maintain machine tools, cutting tool and workpiece. In the present study, the tool condition monitoring system has been developed for Die steel (H13) milling process. Effective design of experiment and robust data acquisition system ensured the machining forces impact in the milling operation. Also, ANFIS based model has been developed based on cutting force-tool wear relationship in this research which has been implemented in the tool wear monitoring system. Prediction model shows that the developed system is accurate enough to perform an online tool wear monitoring system in the milling process.

This study introduces a low-cost solution provided by a specialized source measure unit (SMU), offering an alternative to conventional source meter units. Through precise IV curve measurements for graphene-channel FETs, the SMU demonstrates its capability in accurately characterizing these devices with minimal noise and high accuracy. This cost-effective solution presents a promising avenue for researchers and developers seeking reliable tools for sensor development and characterization, providing valuable insights into the behavior of graphene-channel FETs and the effect of surface illumination without the need for expensive equipment. Additionally, the SMU was validated with known passive and active components, along with probe station integration for microscale connection, ensuring its effectiveness in capturing accurate measurements. The SMU’s focus on collecting IV curves, coupled with its ability to identify device defects, such as Schottky junctions, contributes to its utility in quality testing for semiconductor devices. Its low-cost nature makes it accessible for various research endeavors, enabling efficient data collection and analysis for graphene-based sensor applications.

In this work, the use of graphite-like carbon nitride (g-C3N4) with improved texture characteristics for the synthesis of supported palladium catalysts of dehydrogenation of nitrogen-containing heterocycles was studied. This process is key to the creation of liquid organic carrier technology (LOHC) using N-heterocycles as reversibly hydrogenated/dehydrogenated substrates. For the preparation of g-C3N4-mca supports with advanced textural characteristics, well-established technology of the melamine cyanurate complex carbonization and standard techniques of adsorption precipitation together with wet impregnation were used for the synthesis of Pd-containing systems. The activity of the synthesized catalysts was studied in decahydroquinoline dehydrogenation. The high weight content of extractable hydrogen (7.2 wt %) and the high extraction rate, respectively, make it possible to consider these substances as the most promising N-heterocyclic compounds for this technology. It was shown that an increase in the specific surface area of g-C3N4 allows for achieving a slightly lower, but comparable fineness of palladium particles for the 1 wt% Pd/MCA-500 sample, compared to the standard 1 wt% Pd/C. In this case, the catalytic activity of 1 wt% Pd/MCA-500 in dehydrogenation of both substrates exceeded the analogous parameter for catalysts supported by nitrogen free supports. This regularity is presumably associated with the electron-donor effect of surface nitrogen, which favorably affects the dehydrogenation rate as well as the stability of catalytic systems.

In a bid to resolve lingering problems in cosmology, more focus is being tilted towards cosmological models in which physical constants of nature are not necessarily real constants, but varying with cosmic time. In this paper we have study cosmology in nonlinear electrodynamics with the Newton's gravitational constant $G$ not a constant but vary in form of power-law of the scale factor of the universe. The evolution of the scale factor $a (t)$ is studied in this model which depends on nonlinear electrodynamics fine tuning term of $\alpha$. Then we check the stability of the model using the speed of sound.

Background: Metastatic cancer is associated with an invariably fatal outcome. However, DeltaRex-G, a tumor- targeted retrovector encoding a CCNG1 inhibitor gene, has induced long term (>10 years) survival of patients with chemo-resistant metastatic pancreatic adenocarcinoma, MPNST, osteosarcoma, B-cell lymphoma, and breast carcinoma. Objective: To evaluate the level of CCNG1 expression in tumors as a potential biomarker for CCNG1 inhibitor therapy. Methods: CCNG1 RNA expression levels were measured in tumors (TCGA, N=9161), adjacent “tissues” (TCGA, N=678) and GTEx normal tissues (N=7187) across 22 organ sites. Differential expression of CCNG1 and Ki-67 in primary (N= 9161) vs metastatic (N= 393) tumors were also compared and particularly in primary (N=103) vs. metastatic (N=367) skin cancer (i.e., melanoma). Results: Enhanced CCNG1 RNA and protein expression were noted in tumors compared to normal analogous counterparts, and CCNG1 expression correlated significantly with that of Ki-67. Further, CCNG1 expression tended to be higher than that of Ki-67 in metastatic vs primary tumors, particularly in skin cancer (melanoma). Conclusions: Taken together, these data indicate that (1) CCNG1 expression is frequently enhanced in tumors when compared to their normal analogous counterparts, (2) CCNG1 and Ki-67 expressions are higher in metastatic vs primary tumors, (3) CCNG1 expression is significantly correlated with that of Ki-67, and (4) CCNG1 may be a stronger marker of metastasis than Ki-67. Phase 2 studies are planned to identify patients who are likely to respond favorably to CCNG1 inhibitor therapy by correlating treatment outcome parameters with CCNG1 expression levels in various cancer types.

Acyclic olygoheteroaryl-based compounds represent a valuable class of ligands for nucleic acid recognition. In this regard, acyclic pyridyl polyoxazoles and polyoxadiazoles were recently identified as selective G-quadruplex stabilizing compounds with high cytotoxicity and promising anticancer activity. Herein, we describe the synthesis of a new family of polyheteroaryl oxadiazole/pyridine-ligands targeting DNA G-quadruplexes. In order to perform a structure-activity analysis identifying determinants of activity and selectivity, we followed a convergent synthetic pathway to modulate the nature and number of the heterocycles (1,3-oxazole vs 1,2,4-oxadiazole and pyridine vs benzene). Each ligand was evaluated towards secondary nucleic acid structures, which have been chosen as a prototype to mimic cancer-associated G-quadruplex structures (e.g., the human telomeric sequence, c-myc and c-kit promoters). Interesting, heptapyridyl-oxadiazole compounds showed preferential binding towards the telomeric sequence (22AG) in competitive conditions vs duplex DNA. In addition, G4-FID assays suggest a different binding mode from the classical stacking on the external G-quartet. Additionally, CD titrations in the presence of the two most promising compounds for affinity, TOxAzaPy and TOxAzaPhen, display a structural transition of 22AG in K-rich buffer. This investigation suggests that the pyridyl-oxadiazole motif is a promising recognition element for G-quadruplexes, combining seven heteroaryls in a single binding unit.

A critical quality attribute of therapeutic monoclonal antibodies (mAbs) is the terminal sugar molecules of the N-linked glycan attached to the fragment crystalizable (Fc) region. There exists naturally-occurring heterogeneity in the N-linked glycan structure of mAbs, and such heterogeneity has a significant influence on the clinical safety and efficacy of mAb drugs. We previously proposed a constraint-based modeling method called glycosylation flux analysis (GFA) to characterize the rates (fluxes) of intracellular glycosylation reactions and applied the method to examine the N-linked glycosylation of immunoglobulin G (IgG) in fed-batch Chinese hamster ovary (CHO) fed-batch cultivations. In this work, we significantly improved the computational efficiency of the GFA, and employed the method to analyze the glycosylation of IgG in continuous perfusion CHO cultivations. Perfusion cell cultures have several advantages over the traditional (fed-)batch operation, including higher productivity per unit volume of reactor and more consistent product quality. The GFA showed that as in the fed-batch cultivation, the dynamical changes of IgG glycan heterogeneity in the perfusion culture are mainly attributed to alterations in the galactosylation flux activity. Furthermore, a regression analysis of the galactosylation flux activity using random forest regression linked the dynamics of galactosylation activity with the cell-specific productivity of IgG and the extracellular ammonia concentration.

Mungbean [Vigna radiata (L.) Wilczek] in Australia has been transformed from a niche opportunistic crop into a major summer cropping option for dryland growers in the summer-dominant rainfall regions of Queensland and New South Wales. This transformation followed stepwise genetic improvements in both grain yields and disease resistance. For example, more recent cultivars such as ‘Crystal’, ‘Satin II’ and ‘Jade-AU‘ have provided up to a 20% yield advantage over initial introductions. Improved agronomic management to enable mechanised management and cultivation in narrow (<50 cm) rows has further promised to increase yields. Nevertheless, average yields achieved by growers for their mungbean crops remain less than 1 t/ha, and are much more variable than other broad acre crops. Further increases in yield and crop resilience in mungbean are vital. In this review, opportunities to improve mungbean have been analysed at four key levels including phenology, leaf area development, dry matter accumulation and its partitioning into grain yield. Improving the prediction of phenology in mungbean may provide further scope for genetic improvements that better match crop duration to the characteristics of target environments. There is also scope to improve grain yields by increasing dry matter production through the development of more efficient leaf canopies. This may introduce additional production risks as dry matter production depends on the amount of available water, which varies considerably within and across growing regions in Australia. Improving crop yields by exploiting photo-thermal sensitivities to increase dry matter is likely a less risky strategy for these variable environments. Improved characterisation of growing environments using modelling approaches could also better define and identify the risks of major abiotic constraints. This would assist in optimising breeding and management strategies to increase grain yield and crop resilience in mungbean for the benefit of growers and industry.

Diabetic foot is a serious complication that poses significant risks for diabetic people. The resulting reduction in protective sensitivity in the plantar region requires early detection to prevent the imminent ulceration and amputation. The primary method employed for evaluating this sensitivity loss is the 10 g f Semmes-Weinstein monofilament test, commonly used as a first-line procedure. However, the lack of calibration in existing devices often introduces decision errors due to unreliable feedback. In this paper, a new equipment designed to address these limitations and enhance the assessment of the sensitivity loss using the 10 g f monofilament is introduced. The proposed system automates metrological verification and evaluation processes, ensuring accurate and reliable results. Furthermore, it simulates the practitioner’s procedure, serving both as a valuable training tool and a means to provide force-feedback information. An analytical model of the monofilament buckling and deflection is also presented. The obtained results showed that the tested monofilaments had a very high error compared to the 10 g f declared by the manufacturers. It is aimed, by introducing this advanced equipment, to improve the precision and reliability of assessing the sensitivity loss. The integration of automated verification, simulation capabilities, and precise measurements shows great promise for diabetic patients, reducing the likelihood of adverse outcomes such as ulceration and amputation.

The complex dynamics of the neocortex, the outermost layer of the brain, have been a subject of intense research in neuroscience. Recent studies have suggested that magnetic fields generated by neuronal activity may play a significant role in neocortical dynamics. This paper presents a simplified mathematical model that explores the hypothesized interactions between magnetic dynamos, nondissipative systems, Hamiltonian equations, and the Lorenz force in the context of neocortical dynamics. The proposed model is based on a set of coupled Hamiltonian equations inspired by the Lorenz system, a well-known chaotic dynamical system. The generalized coordinates in the model represent the magnetic field components, while the generalized momenta are related to the electric field components or other relevant quantities. The Hamiltonian equations describe the conservative dynamics of the system, and the coupling terms in the equations are interpreted as representing the interactions between the magnetic and electric field components, analogous to the Lorenz force in electromagnetism. The model is implemented using Python, and the Hamiltonian equations are numerically solved using the odeint function from the scipy.integrate module. The resulting dynamics of the magnetic field components are visualized using matplotlib. While the model is highly simplified and does not capture the full complexity of neocortical dynamics, it serves as a starting point for investigating the potential role of magnetic dynamos and Lorenz force interactions in the brain. The paper discusses the limitations of the current model and highlights the need for further refinements, such as incorporating more realistic biological constraints, considering energy dissipation and compensation mechanisms, and validating the model against experimental data. Future work should focus on developing a more comprehensive and biologically plausible model that integrates the latest findings from neuroscience, physics, and computational modeling. By presenting this simplified Hamiltonian model, the paper aims to stimulate further research and discussion on the potential significance of magnetic dynamos and Lorenz force interactions in neocortical dynamics. The model provides a framework for exploring these hypothesized mechanisms and may guide future experimental and theoretical investigations in this emerging field of neuroscience

The ageing global population and changing labor force participation are having a profound impact on state pension programs worldwide, including Malaysia. However, the effects of an ageing workforce and declining fertility rates are having a significant impact on future trends in labor force participation and the duration of retirement. This paper presents an innovative examination of labor force participation rate (LFPR) forecasting within the context of an aging workforce, utilizing the Lee-Carter and Cairns-Blake Dowd stochastic models, traditionally applied to mortality data. By adapting these models to LFPR data, the study offers a novel perspective on predicting workforce participation trends and understanding the dynamics of retirement planning from year 2001 to 2047. Additionally, by incorporating the mortality forecasts from the United Nations, the research navigates through the complexities of applying actuarial methods to labor economics, revealing differentiated pathways for male and female participation in the labor market and the anticipated length of retirement. This study offers a unique comparison between the Lee-Carter and the Cairns-Blake-Dowd (CBD) LFPR models. It focuses on fitting and forecasting the LFPR of senior employees aged 50 to 64. The results highlighted discrepancies among models that demonstrated evidence of model risk for extended retirement duration.