This paper presents Mathematical Formulation for Neutrino-Fission of a heavy nuclei in Neutrino-environments. It has been proposed that neutrino fission is a dynamic two-process reaction, where more than one neutrino can be captured by target nucleus. A quantity named Neutrino-Zeta with units of eV^-1 has been defined to represent Neutrino-environments. Neutrino-zeta with assumed excited energy states for heavy nuclei A∼230-270 is estimated to be 0.0212 MeV^-1, with the probability of fission Barrier energy state P(E_x,f)= 0.169064014 with E_x,f =6MeV. P(E_x,f)=0.222664 is highest at zeta=0.1MeV^-1 . It has been shown that probabilities of certain excitation energy states and their corresponding decay reactions at those excitation energies can be equal for two neutrino-zetas. Neutron induced fission for different neutrinos hypothesize that probability of symmetric fission channels is higher at low neutrino-zetas, which can be tested experimentally.

Chemotherapy treatment based on Cisplatin (CDDP) is established as the drug of choice for head and neck squamous cell carcinoma (HNSCC). Malignant tumors respond to microenvironment alteration through a dynamic balance of mitochondrial fission and fusion. HNSCC is known to have hypoxic conditions, yet the effects and underlying mechanisms of hypoxia on chemosensitivity and mitochondrial dynamics remain unclear. We found that hypoxia promoted mitochondrial fission and CDDP sensitivity in HNSCC cells. Importantly, Mff was shown to be correlated with chemosensitivity in clinical samples of HNSCC that underwent a hypoxic condition. Hypoxia-inducible factor 1 α-subunit (HIF-1α) dramatically increased Mff transcriptional expression and directly bound to Mff. Hypoxia enhanced the release of reactive oxygen species (ROS) and upregulated the expression of Mff via HIF-1α in HNSCC cells. ROS depletion in HNSCC cells attenuated HIF-1α, Mff expression, and mitochondrial fission. Moreover, a knockdown of Mff suppressed hypoxia-induced mitochondrial fission and decreased CDDP chemosensitivity in vivo and in vitro. Our findings revealed that the hypoxia-induced release of ROS promoted mitochondrial fission and CDDP chemosensitivity via the regulation of HIF-1α/Mff in HNSCC cells, indicating that Mff may serve as a new biomarker to predict neoadjuvant chemosensitivity in HNSCC patients

Background: The control of energy metabolism is fundamental for cell growth and function, and anomalies are implicated in complex diseases and ageing. It is important for cells to carefully tune metabolic pathways to optimize their function in response to different nutrient or physiological conditions. Metabolism in yeast cells can be easily manipulated by supplying different carbon sources: on glucose yeast rapidly proliferates by fermentation, analogous to tumour cells growing by aerobic glycolysis, whereas on non-fermentable carbon sources metabolism shifts towards respiration. Results: We screened deletion libraries of fission yeast to identify over 200 genes required for respiratory growth. The growth medium and auxotrophic mutants strongly influenced respiratory metabolism. Most genes uncovered in the mutant screens have not been implicated in respiration in budding yeast. We applied gene expression profiling approaches to compare steady-state fermentative and respiratory growth and to analyse the dynamic adaptation to respiratory growth. The transcript levels of most genes functioning in key energy metabolism pathways were coherently tuned, reflecting anticipated differences in metabolic flows between fermenting and respiring cells. We show that the acetyl-CoA synthase, rather than the citrate lyase, is essential for acetyl-CoA synthesis in fission yeast. We also investigated the transcriptional response to mitochondrial damage by genetic or chemical perturbations, defining a retrograde response that involves the concerted regulation of distinct groups of nuclear genes that may avert harm from mitochondrial malfunction. Conclusions: These systematic and targeted analyses provide a rich framework of the genetic and regulatory basis of fundamental metabolic states to guide future studies on energy metabolism in fission yeast and beyond. Our study pinpoints weaknesses of commonly used auxotroph mutants for investigating energy metabolism. As a model for cellular energy regulation, fission yeast provides an attractive and complementary system to budding yeast.

December 4, 2020 marks 90 years since the concept of neutrinos was proposed as a consequence of the observed discrepancies in several experiments on radioactive decays of various isotopes. There have been great many developments in our understanding of this elusive particle over the past nine decades, also leading to several Nobel Prizes awarded to work on neutrino physics. But there are many aspects of the neutrinos that are still not completely understood, including even its actual rest mass. The neutrino still remains an enigma and we have yet to learn a lot about its different properties. This article summarises the overall picture of the current understanding of the neutrino, right from its inception.

The ΛCDM model successfully models the expansion of matter in the universe with an expansion of the underlying metric. However, it does not address the physical origin of the big bang and dark energy. A model of cosmology is proposed, where the state of high energy density of the big bang is created by the collapse of an antineutrino star that has exceeded its Chandrasekhar limit. To allow the first neutrino stars and antineutrino stars to form naturally from an initial quantum vacuum state, it helps to assume that antimatter has negative gravitational mass. While it may prove incorrect, this assumption may also help identify dark energy. The degenerate remnant of an antineutrino star can today have an average mass density that is similar to the dark energy density of the ΛCDM model. When in hydrostatic equilibrium, this antineutrino star remnant can emit isothermal cosmic microwave background radiation and accelerate matter radially. This model and the ΛCDM model are in similar quantitative agreement with supernova distance measurements. Other observational tests of the above model are also discussed.

We herein described an investigation of a theory, which describes the energies of neutrinos and the source of neutrino oscillations. A series of experiments were conducted to show evidences of the existence a neutrino mass. We also applied theories to explain the reason for the extremely small energy of a neutrino, mainly by employing a vacuum-derived superconducting energy gap from the Bardeen–Cooper–Schrieffer ground state. Moreover, we succeeded in obtaining the transition probabilities of neutrinos’ flavors (i.e., in terms of neutrino oscillation). We focused on the fact that up- and down-quantized space pairs combine by the Lorentz forces, undertake Bose-Einstein condensation, and then create a superconducting energy gap at the energy level of the vacuum with quantum mechanics fluctuation. Eventually, the superconducting energy gap vanishes to form a real body of the neutrino. Furthermore, assuming that the speed of the neutrino is near the speed of light and exhibits Planck’s blackbody emissions, we derived many-body interactions of neutrinos and applied them in Fermi’s golden rule. As a result, the neutrino energy we calculated agreed well within the realms of the experimental results. The calculated transition probabilities of neutrino’s flavor also explain the experiment results very well.

This work argues the mass term in the neutrino wavefunction propagator is due to entanglement with its associated origins. The implication being that neutrino flavor is conserved in weak processes and shared among all particles emanating from the last interaction with a nucleon. In so doing, the neutrino mass propagator is real but not ascribed to the neutrino outside of entanglement. The proposed theory will be readily testable in that reactor and solar neutrinos will oscillate but both muon decay neutrinos and accelerator neutrinos created by pure lepton interactions will not oscillate..

The Jiangmen Underground Neutrino Observatory (JUNO) is a 20 kton liquid scintillator multi-purpose underground detector, under construction near the chinese city of Jiangmen, with data taking expected to start in 2021. The main goal of the experiment is the neutrino mass hierarchy determination, with more than three sigma significance, and the high precision neutrino oscillation parameters measurements, detecting electron anti-neutrinos, emitted from two near-by (baseline of about 53 km) nuclear power plants. Besides, the unprecedented liquid scintillator type detector performance in target mass, energy resolution, energy calibration precision and low-energy threshold, features a rich physics program for the detection of low-energy astrophysical neutrinos, such as galactic core-collapse supernova neutrinos, solar neutrinos and geo-neutrinos.

Mitochondria are involved in many cellular processes and their main role is cellular energy production. They constantly undergo fission and fusion, and these counteracting processes are under strict balance. The cytosolic dynamin-related protein 1, Drp1 or dynamin-1-like protein (DNM1L) mediates mitochondrial and peroxisomal division. Defects in the DNM1L gene results in a complex neurodevelopmental disorder with heterogeneous symptoms affecting multiple organ systems. Currently there is no curative treatment available for this condition. We have previously described a patient with a de novo heterozygous c.1084G>A (p.G362S) DNM1L mutation and studied the effects of a small molecule, Bezafibrate, on mitochondrial functions in this patient’s fibroblasts compared to controls. Bezafibrate normalized growth on glucose-free medium, ATP production, oxygen consumption and s improved mitochondrial morphology in patient’s fibroblasts, albeit concomitantly causing a mild increase ROS production. Further studies would be needed to show the consistency of the response to Bezafibrate, possibly using fibroblasts from patients with different mutations in DNM1L, and this treatment should be confirmed in clinical trials. However, taking into account the favorable effects in our study, we suggest that Bezafibrate could be a possible treatment option for patients with certain DNM1L mutations.

Recently, a new theory based on superluminal tunnelling has been proposed to explain the transition of highly energetic neutrinos propagating in matter to tachyonic states. In this work, we determine the possible mechanisms that lead neutrinos into a superluminal realm based on the assumption that ultrarelativistic particles travelling in matter lose part of their energy with the emission of Bremsstrahlung radiation. The obtained photons, in turn, can create neutrino-antineutrino pairs, one or both of which can be superluminal. We also prove that pair creation may occur with neutrino flavour oscillation provided that only one of them is a space-like particle. This suggests that mass oscillation and superluminal behaviour could be related phenomena. Finally, using the generalised Lorentz transformations, we formulate the Lagrangian of the kinematically allowed scattering processes. The structure of this Lagrangian is consistent with the formalism of the Standard Model. Based on this Lagrangian, at least one of the particles forming the pair must always be subluminal. The possibility that the pair creation process is mediated by a dark photon is also discussed.

Due to limitation of the binding energy of a self-gravitating matter, the radius of a body is at least twice larger than the Schwarzschild radius. The total energy is adsorbed at the body surface, giving rise of a size-dependent surface tension. Since the Hawking temperature appears to be the critical one, the black holes possess zero surface tension. Microscopic neutrino stars are also introduced.

Five fundamental problems—neutrino mass, baryogenesis, dark matter, inflation, strong CP problem—are solved at one stroke in a model, dubbed as “SM-A-S-H” (Standard Model-Axion-Seesaw-Higgs portal inflation) by Andreas Ringwald et. al. The Standard Model (SM) particle content is extended by three right-handed SM-singlet neutrinos $N_i$, a vector-like color triplet quark $Q$, a complex SM-singlet scalar field $\sigma$ that stabilises the Higgs potential, all of them being charged under Peccei-Quinn (PQ) $U(1)$ symmetry, the vacuum expectation value $v_\sigma\sim10^{11}$ GeV breaks the lepton number and the Peccei-Quinn symmetry simultaneously. We found that numerically SMASH model not only solves five fundamental problems but also the sixth problem “Vacuum Metastability” through the extended scalar sector and can predict approximately correct atmospheric neutrino mass splitting around 0.05 eV and the solar neutrino mass splitting around 0.009 eV.

A hybrid organic molecules as ligands and inorganic NCs in this research combines the chemical properties of organic semiconductors with the chemical stability of inor- ganic nanoparticles like PbS. It is possible to improve the ligand exchange and PbS-NCs' distribution by adding Amino phynel anchor group to TIPs-pentacene and Carboxylic anchor group to Tetraphenylporphyrin molecules. By adding anchor groups to one or two sides of these molecules, they would convert the molecules to ecient ligands to obtain superlattice coupled organic-inorganic nanostrcuture semicondcutor layers (COINs). Adding on side group would cap the PbS nanoparticles while adding two an- chor group would play a linker role between two PbS NCs. This morophology enhance- ment paves the way to manipulate the physical properties of the COINs and fabricate solar cells. Singlet ssion phenomena demonstrates pentacene molecule's advantage for high eciency in organic solar cells and its ability to overcome the Schockley-Queisser limit. Ultraviolet photo-emission spectroscopy (UPS) determines the highest occupied molecular orbital (HOMO) and the work function of COINs, while the lowest unoccu- pied molecular orbital (LUMO) of COINs were calculated subsequently by adding both the exciton binding energy and the optical band gap to the measured HOMO energy. The current versus voltage characteristics and impedance spectroscopy were studied for these molecules as well.

The coupled Dirac equations for solar e- and μ-neutrinos are solved in the presence of a small uniform interaction of the e-neutrinos with matter (the Sun). It is shown that the interaction leads to an increase of the amplitude of the neutrinos oscillations and a decrease of the lo- calization probability of the e-neutrinos. However, the strength of this interaction is insufficient to explain the magnitude of the discrepancy between the solar neutrino flux and the neutrino flux measured on the Earth. An alternative interpretation related to a possible superfluid neutrino state is advanced, which may throw some light on the solar neutrino problem.

Cells form a bipolar spindle during mitosis to ensure accurate chromosome segregation. Proper spindle architecture is established by a set of kinesin motors and microtubule-associated proteins. In most eukaryotes, kinesin-5 motors are essential for this process, and genetic or chemical inhibition of their activity leads to the emergence of monopolar spindles and cell death. However, these deficiencies can be rescued by simultaneous inactivation of kinesin-14 motors, as they counteract kinesin-5. We conducted detailed genetic analyses in fission yeast to understand the mechanisms driving spindle assembly in the absence of kinesin-5. Here we show that deletion of the nrp1 gene, which encodes a putative RNA-binding protein with unknown function, can rescue temperature sensitivity caused by cut7-22, a fission yeast kinesin-5 mutant. Interestingly, kinesin-14/Klp2 levels on the spindles in the cut7 mutants were significantly reduced by the nrp1 deletion, although the total levels of Klp2 and the stability of spindle microtubules remained unaffected. Moreover, RNA-binding motifs of Nrp1 are essential for its cytoplasmic localization and function. We have also found that a portion of Nrp1 is spatially and functionally sequestered by chaperone-based protein aggregates upon mild heat stress and limits cell division at high temperatures. We propose that Nrp1 might be involved in post-transcriptional regulation through its RNA-binding ability to promote the loading of Klp2 on the spindle microtubules.

We use Big Bang Nucleosynthesis (BBN) to probe Beyond Standard Model physics in the neutrino sector. Recently the abundances of primordially produced light elements D and He-4 were determined from observations with better accuracy. The good agreement between the theoretically predicted abundances of primordially produced and derived from observations light elements allows to update the BBN constraints on Beyond Standard Models (BSM) physics. We provide numerical analysis of several BSM models of BBN and obtain precise cosmological constraints and indications for new neutrino physics. Namely, we derive more stringent BBN constraints on electron neutrino-sterile neutrino oscillations corresponding to 1% uncertainty of the observational determination of the primordial He-4. The cosmological constraints are obtained both for the case of zero and non-zero initial population of the sterle neutrino state. Then in a degenerate BBN model with neutrino νe↔νs oscillations we analyze the change of the cosmological constraints in case lepton asymmetry L is big enough to suppress oscillations. We obtain constraints on the lepton asymmetry L . We discuss a possible solution to the dark radiation problem in degenerate BBN models with νe↔νs oscillations in case L is large enough to suppress neutrino oscillations during BBN epoch. Interestingly, the required value of L for solving DR problem is close to L indicated by EMPRESS experiment and close to the value of lepton asymmetry necessary to relax Hubble tension.

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.

Recently Palle has investigated the chiral vorticity and Cartan torsion in neutrino asymmetries. In his case he addressed this problem in Goedel s like anisotropic Einstein-Catan cosmology. In this paper we discusse how these ideas applied to sheared Bianchi types I Einstein-Cartan (EC) neutrino amisotropic cosmology, affect the handness of neutrinos in the universe. Actually here a novel concept of the chiral metric is introduced where metric functions also possess two distinct signs as in neutrino flipping or helicity. The axial anomaly equation for neutrinos in the presence of torsion and metric chirality is shown to produce left-handed neutrinos from right-handed torsion. Metric chirality is shown to be able to define how the metric would behave far away of neutrino density. Chiral flipping of the chiral neutrinos in the presence of torsion is also investigated. It is shown that when the chiral torsion is left-handed the chemical chiral potential vanishes as the universe expands.

The true ternary fission, the fission of a nucleus into three fragments of nearly equal mass, is an elusive and poorly known process influenced by shell effects. It has been envisaged an increase of the probability of this process with respect to the binary fission, very low in spontaneous and neutron-induced fission, by adopting heavy-ion induced reactions due to the possibility to increase the fissility parameter and the excitation energy of the compound nuclei. Nuclei with mass number around A=250, accessible in heavy-ion induced reactions, are favorable and should be investigated. It is still debated if the process takes place in a single step, direct ternary fission, or in two steps, sequential ternary fission. The purpose of this work is to define experimental conditions and observables that allow the disentangling of the products from the direct and sequential ternary fission as well as from the usual most probable binary fission. This step is essential to gain insight on the ternary fission dynamics and on the binary to ternary fission competition. The method proposed here is to simulate the kinematics of the ternary and binary fission processes to compute the energy distributions and angular correlations of direct and sequential ternary fission products, as well as those of binary fission. The reaction taken as benchmark is 40Ar+208Pb at 230 MeV supposed to form the 248Fm* compound nucleus. The simulation results have been filtered by considering the response function of a multi-coincidence detection system virtually constructed using the Geant4 simulation toolkit. The simulations support the possibility to separate the products of different multimodal fission decays with the proposed setup that consequently represents an effective tool to get insight on ternary fission from the observables selected.

Recently, a concept known as μTRISTAN, which involves the acceleration of μ+, has been proposed. This initiative has led to considerations of a new design for a neutrino factory. Additionally, leveraging the polarization of μ+, measurements of T violation in neutrino oscillations are also being explored. In this paper, we present analytical expressions for T violation in neutrino oscillations within the framework of standard three flavor neutrino oscillations, a scenario involving nonstandard interactions, and a case of unitarity violation. We point out that examining the energy spectrum of T violation may be useful for probing new physics effects.

In this article, we give a brief review of the origin of the neutrino mass in some interesting non-linear supersymmetric models with R-symmetry. These models are able to address and solve the most important problems of the particle physics and provide mechanisms for neutrino mass generation and their mixing parameters in agreement with the current experimental data. Their prediction could be experimentally tested in the near future by collider experiments.

The search for dark matter is one the hottest topics in Physics today. The fact that about 80% of the matter of the Universe is of unknown nature has triggered an intense experimental activity to detect such kind of matter and a no less intense effort on the theory side to explain it. Given the fact that we do not know well the properties of dark matter, searches from different fronts are mandatory. Neutrino telescopes are part of this experimental quest and offer specific advantages. Among the targets to look for dark matter, the Sun and the Galactic Center are the most promising ones. Neutrino telescopes have put the best limits on spin-dependent cross section of proton-WIMP scattering. Moreover, they are competitive in the constraints on the thermally averaged annihilation cross-section for high WIMP masses when looking at the Galactic Centre. Other results are also reviewed.

The crucial phenomenological and experimental predictions for new physics are outlined, where the number of problems of the Standard Model (neutrino masses and oscillations, dark matter, baryon asymmetry of the Universe, leptonic CP-violation) could find their solutions. The analogies between the cosmological neutrino mass scale from the early universe data and laboratory probes are discussed and the search for new physics and phenomena.

Cytokinesis, as the last stage of the cell division cycle, is a tightly controlled process amongst all eukaryotes, and defective division can lead to severe cellular consequences, and is implicated in serious human diseases and conditions such as cancer. Both mammalian cells and the fission yeast Schizosaccharomyces pombe use binary fission to divide into two equal sized daughter cells. In S. pombe such cytokinetic division is driven by the assembly of an actin-myosin contractile ring (ACR) at the cell equator between the two cell tips. The ACR is composed of a complex network of membrane scaffold proteins, actin filaments, myosin motors, and other cytokinesis regulators. Contraction of the ACR leads to the formation of a cleavage furrow which is severed leading to the final cell separation during the last stage of cytokinesis, abscission. This review describes recent findings defining the three phases to establish cytokinesis in S. pombe: ACR assembly, ACR constriction, and its coordination with septation. Collectively, we provide an overview of current understanding of the mechanisms regulating the ACR-mediated cytokinesis in S. pombe.

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.

According to observations leptons are always produced in pairs. Both particles can be electrically charged, or just one, in which case the charged particle is accompanied by a particle specific neutrino. The period doubling process in nonlinear dynamical systems creates stable pair structures from the Planck units. The electron-positron pair is one of the stable structures, and the rest mass, electric charge and magnetic moment can be accurately calculated by the period doubling process. That the pair structure is stable means, that e.g., an electron and a positron are always born together. In the muon decay one of the pair is charged, while the other remains chargeless because there is only one charge available. It is suggested in this article that neutrino is the chargeless part of the lepton pair.

The neutrino is perhaps the most elusive member of the particle zoo. The questions about its nature, namely: Dirac or Majorana, the value of its mass and the interactions with other particles, the number of its components including sterile species, are long standing ones and still re- main in large extent without conclusive answers. From the side of the nuclear structure and nuclear reactions, both theories and experiments, the need to elucidate these questions have, and still has, prompt crucial developments in the fields of double beta decay, double charge exchange and neutrino induced reactions. The measurements of neutrino flavor os- cillation parameters contribute largely to restrict models with massless neutrinos. From the particle physics side, the possibilities to extent the standard model of electroweak interactions to incorporate a right handed sector of the electroweak lagrangian are directly linked to the adopted neu- trino model. Here, I would like to address another aspect of the problem by asking the question of the neutrino mass mechanism in the cosmological context, and particularly about dark matter.

After a long a glorious history, marked by the first direct proofs of neutrino existence and of the mixing between the first and third neutrino generations, the reactor antineutrino experiments are still well alive and will continue to give important contributions to the development of elementary particle physics and astrophysics. In parallel to the SBL experiments, that will be dedicated mainly to the search for sterile neutrinos, a new kind of experiments will start playing an important role: the medium baseline reactor experiments, aiming to study the neutrino mass ordering. The first example of this kind, the liquid scintillator JUNO experiment, characterized by a very high mass and unprecedented energy resolution, will soon start data taking in China. Its main aspects are discussed here, together with its potentialities for what concerns the mass ordering investigation and also the other issues that can be studied with this detector, spanning from the accurate oscillation parameter determination, to the study of solar neutrinos, geoneutrinos, atmospheric neutrinos and neutrinos emitted by supernovas and to the search for signals of potential Lorentz invariance violation.

Recent theory of tachyon neutrinos, providing an explanation for Dark Matter, leads to two sets of experiments for testing that theory. One predicts an enhanced signal in detection of the Cosmic Neutrino Background. The other compares models of Dark Matter used to fit data on galaxy rotation curves and also gravitational lensing. In addition, an apparent contradiction within the new theory, related to Dark Energy, is identified and addressed.

In this study the tachyon-like Dirac equation, formulated by Chodos to describe superluminal neutrino, is solved. The analytical solutions are Gaussian wave packets obtained using the envelope method. It is shown that the superluminal neutrino behaves like a pseudo-tachyon, namely a particle with subluminal velocity and pure imaginary mass that fulfils the energy-momentum relation typical of classical tachyons. The obtained results are used to prove that the trembling motion of the particle position around the median, known as Zitterbewegung, also takes place for the superluminal neutrino, even if the oscillation velocity is always lower than the speed of light. Finally, the pseudo-tachyon wave packet is used to calculate the probability of oscillation between mass states, obtaining a formula analogous to the one obtained for the ordinary neutrino. This suggest that in the experiments concerning neutrino oscillation is not possible to distinguish tachyonic neutrinos from ordinary ones.

Quantitative analysis of human gait is critical for early discovery, progressive tracking, and rehabilitation of neurological and musculoskeletal disorders, such as Parkinson’s Disease, stroke, and Cerebral Palsy. Gait analysis typically involves estimating gait characteristics, such as spatio-temporal gait parameters and gait health indicators (e.g., step time, length, symmetry, and balance). Traditional methods of gait analysis involve the use of cameras, wearables, and force plates, but are limited in operational requirements when applied in daily life - such as direct line-of-sight, carrying devices, and dense deployment. This paper introduces a novel approach for gait analysis by passively sensing footstep-induced floor vibrations during walking using vibration sensors mounted on the floor surface. Our approach is non-intrusive, scalable, and perceived as more privacy-friendly, making it suitable for continuous gait health monitoring in daily life. We developed a floor vibration-based gait analysis framework to estimate various gait parameters that are used as standard metrics in medical practices, including temporal parameters (step, stride, stance, swing, double-support, single-support time) and spatial parameters (step length, width, angle, stride length), and extracts gait health indicators (cadence/walking speed, left-right symmetry, gait balance, initial contact types). The main challenge is that floor vibrations are distinct across different floor types. To address this challenge, our approach develops floor-adaptive algorithms to extract floor-specific features and is designed to be generalizable to various settings, including homes, hospitals, and eldercare facilities. We evaluate our approach through real-world walking experiments with 20 adults with 12,231 labeled gait cycles across concrete and wooden floors. Our results show 90.5% (RMSE 0.08s), 71.3% (RMSE 0.38m), and 92.3% (RMSPE 7.7%) accuracy in estimating temporal, spatial parameters, and gait health indicators, respectively.

Background: Amyloid beta peptides (Aβ) have been identified as the main pathogenic agents in Alzheimer’s disease (AD). Soluble Aβ oligomers, rather than monomer or insoluble amyloid fibrils, show membrane-binding capacity to red blood cells (RBCs) and trigger several morphological and functional alterations in RBCs that can result in impaired oxygen transport and delivery. Since bioactive lipids have been recently proposed as potent protective agents against Aβ toxicity, we investigated the role of sphingosine-1-phosphate (S1P) in signaling pathways involved in the mechanism underlying ATP release in Aβ-treated RBCs. Methods: In RBCs following different treatments, ATP, 2,3 DPG, cAMP levels, and caspase 3 activity were determined by spectrophotometric and immunoassay. Results: S1P rescued the inhibition of ATP release from RBCs triggered by Aβ through a mechanism involving caspase-3 and restoring 2,3 DPG and cAMP levels within the cell. Conclusions: These findings reveal the molecular basis of S1P protection against Aβ in RBCs and suggest new therapeutic avenues in AD.

Diabetes mellitus is one of the most common endocrinopathies, estimated to affect about 5.4% of the world's population around 2025. It is thought that nearly a third of diabetic patients have some type of skin condition. Frequently, the cutaneous effects of this heterogeneous syndrome are ac-curately detected late in the progressive form of the disease. The main objective of the present study was to identify the main cellular characteristics of the cutaneous microenvironment in exper- imentally induced diabetes mellitus. Skin fragments were harvested from adult white Wistar rats of both sexes, with the weight of 200 g, 12 weeks after streptozotocin diabetes was induced. In parallel with histopathological diagnosis by using hematoxylin and eosine staining, samples were processed by transmission electron microscopy technique and examined with a Philips CM100 microscope. In the apparently macroscopically unchanged tegument, photon microscopy revealed both progres ive thinning of the epidermis in the early stages of diabetes and a significant process of fibrosis and collagen hyalinization in the dermis. In addition, in the early stages, the electron microscopic study provided ultrastructural details characteristic of a senescent phenotype with reduced cell proliferation. The morphological changes in the skin may be the first signs of disruption of carbohydrate metabolism and in the case of established diabetes may reflect its progression and the efficacy of therapy.

The mechanism of ciprofloxacin action involves interference with transcription and replication of bacterial DNA, which results in elevated oxidative stress, and bacterial cell death. Vorinostat was shown to induce oxidative DNA damage. In the current work, the possibility for interactive effect of vorinotat on ciprofloxacin-induced cytotoxicity against a number of reference bacteria was investigated. Standard bacterial strains were Escherichia coli ATCC 35218, Staphylococcus aureus ATCC29213, Pseudomonas aeruginosa ATCC 9027, Staphylococcus epidermidis ATCC 12228, Acinetobacter baumannii ATCC 17978, Proteus mirabilis ATCC 12459, Klebsiella pneumoniae ATCC 13883, methicillin-resistant Staphylococcus aureus (MRSA) (ATCC 43300), and Streptococcus pneumoniae (ATCC 25923). The antibacterial activity of ciprofloxacin with or without pretreatment of bacterial cells by vorinostat was examined using disc diffusion procedure and determination of the minimum inhibitory concentration (MIC) and zones of inhibition of bacterial growth. All tested bacterial strains showed sensitivity to ciprofloxacin. When pretreated with vorinostat, significantly larger zones of inhibition and smaller MIC values were observed in all bacterial strains compared ciprofloxacin alone. As a conclusion, current results showed the possible agonistic properties for vorinostat when it is used together with ciprofloxacin. Future research will be focus on molecular mechanisms possible for such interactive effect.

Proper bipolar spindle assembly underlies accurate chromosome segregation. A cohort of microtubule-associated proteins orchestrates spindle microtubule formation in a spatiotemporally coordinated manner. Among them, the conserved XMAP215/TOG family of microtubule polymerase plays a central role in spindle assembly. In fission yeast, two XMAP215/TOG members, Alp14 and Dis1, share essential roles in cell viability; however how these two proteins functionally collaborate remains undetermined. Here we show the functional interplay and specification of Alp14 and Dis1. Creation of new mutant alleles of alp14, which display temperature sensitivity in the absence of Dis1, enabled us to conduct detailed analyses of a double mutant. We have found that simultaneous inactivation of Alp14 and Dis1 results in early mitotic arrest with very short, fragile spindles. Intriguingly, these cells often undergo spindle collapse, leading to a lethal “cut” phenotype. By implementing an artificial targetting system, we have shown that Alp14 and Dis1 are not functionally exchangeable and as such are not merely redundant paralogues. Intriguingly, while Alp14 promotes microtubule nucleation, Dis1 does not. Our results uncover that the intrinsic specification, not the spatial regulation, between Alp14 and Dis1 underlies the collaborative actions of these two XMAP215/TOG members in mitotic progression, spindle integrity and genome stability.

Facing global warming consequences is a major issue of present times. For what concerns climate, projections say that heavy rainfalls are going to increase with high probability together with temperature rise, thus also the hazard related to rainfall induced shallow landslides will likely increase in density over susceptible territories. Different modeling approaches exist and any of them is forced to make simplifications in order to reproduce landslide occurrences over space and time. Process based models can help in quantifying the consequences of heavy rainfall on the different involved processes. In this paper, a narrative review about physically-based deterministic distributed models (PBDDMs) is presented. Models were selected based on: the adoption of the infinite slope scheme (ISS), the use of a deterministic approach (i.e., input and output are treated as absolute values), the inclusion of new approaches in modeling slope stability through the ISS. Models are presented in chronological order with the aim of drawing a timeline of the evolution of PBDDMs and to give researchers and practitioners a basic knowledge on how much has been already done. Results indicate that including vegetation effects on slope stability has raised in importance over time but that there is still the need of finding an efficient way to include them, and that in the last years the literature production seems to be more focused on probabilistic approaches.

Drp1 is considered the master regulator of mitochondrial fission and affects the proper segregation during mitosis. Here, we identified two clusters on mitochondria, including Drp1-Ser-616/Mff/Mid51 and-Drp1-Ser637/Fis1/Mid49 for midzone fission (division) and peripheral fission signatures, respectively. This study revealed that phospho-Drp1-Ser637 is involved in mitigating mitochondrial oxidative stress, resolving a long-standing localization issue. Additionally, we demonstrated that Mid49 and Mid51 exhibit distinct functions in recruiting Drp1 for mitochondrial fission. It also confirmed the essential role of the Fis1 and Mid49 adaptors contributed into mitochondrial fission within the phospho-Drp1-Ser637/Fis1/Mid49 cluster during M-phase. Moreover, it suggested that there is mutual exclusivity between two clusters of phospho-Drp1 with four adaptors on mitochondria, as well as varied responses to specific anti-cancer drugs during mitotic arrest. Remarkably, the upregulation of the spindle assembly checkpoint (SAC) was also observed, ensuring the prolongation of M-phase with the formation of multipolar spindles. Collectively, the phospho-Drp1-637/Fis1/Mid49 cluster may not only function in peripheral fission (mitophagy) but also serve as a key SAC coordinator for the regulation of spindle assembly during mitotic arrest. These findings appear to be mutually exclusive of phospho-Drp1 with four adaptors on mitochondria and vary in response to specific anti-cancer drugs.

Cytokinesis, as the last stage of the cell division cycle, is a tightly controlled process amongst all eukaryotes, and defective division can lead to severe cellular consequences, and is implicated in serious human diseases and conditions such as cancer. Both mammalian cells and the fission yeast Schizosaccharomyces pombe use binary fission to divide into two equal sized daughter cells. Similar to mammalian cells, in S. pombe such cytokinetic division is driven by the assembly of an actin-myosin contractile ring (ACR) at the cell equator between the two cell tips. The ACR is composed of a complex network of membrane scaffold proteins, actin filaments, myosin motors, and other cytokinesis regulators. Contraction of the ACR leads to the formation of a cleavage furrow which is severed by the endosomal sorting complex required for transport (ESCRT) proteins leading to the final cell separation during the last stage of cytokinesis, abscission. This review describes recent findings defining the three phases to establish cytokinesis in S. pombe: ACR assembly, ACR constriction, and its coordination with septation. Collectively, we provide an overview of current understanding of the mechanisms regulating the ACR-mediated cytokinesis in S. pombe with a potential role of ESCRT proteins in this process.

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 < 0.05). Decreased diaphragm contractility and peroxisome proliferator activated receptor- coactivator-1 levels were also observed (P < 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 < 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.

Drought negatively affects the growth and development of barley. To explore the genetic variation in barley under drought stress, ten breeding genotypes were tested using polyethylene glycol-6000 to simulate drought conditions. We observed that drought stress adversely affected germination-related traits across all barley genotypes and this impact varied between genotypes, suggesting genotype-specific drought tolerance. The drought tolerance index was an ideal criterion for selecting drought-tolerant genotypes as it well characterized the gradient responses of barely genotypes to drought stress. Based on this indicator, genotype OB1878-ON-50 is recommended as a significant germplasm resource for breeding programs under lower precipitation conditions due to its superior tolerance to drought stress.

We constrain two dynamical dark energy models that are parametrized by the logarithm form of $w(z)=w_{0}+w_{1}\left(\frac{\ln (2+z)}{1+z}-\ln 2\right)$ and the oscillating form of $w(z)=w_{0}+w_{1}\left(\frac{\sin(1+z)}{1+z}-\sin(1)\right)$. Comparing with the Chevallier-Polarski-Linder (CPL) model, the two parametrizations for dark energy can explore the whole evolution history of the universe properly. Using the current mainstream observational data including the cosmic microwave background data and the baryon acoustic oscillation data as well as the type Ia supernovae data, we perform the $\chi^2$ statistic analysis to global fit these models, finding that the logarithm parametrization and the oscillating parametrization are almost as well as the CPL scenario in fitting these data. We make a comparison for the impacts of the dynamical dark energy on the cosmological constraints on the total mass of active neutrinos. We find that the dark energy properties could significantly change the fitting results of neutrino mass. Looser constraints on $\sum m_{\nu}$ are obtained in the logarithm and oscillating models than those derived in the CPL model. Consideration of the possible mass ordering of neutrinos reveals that the most stringent constraint on $\sum m_{\nu}$ appears in the degenerate hierarchy case.

In this paper, a novel microwave catalyst Ni@SiC/CNFs (NSC), C/Ni (NC), and C/SiC (SC) were successfully synthesized by electrostatic spinning method, and proved to degrade methylene blue with high efficiency under microwave irradiation. The results imply that the catalyst Ni@SiC/CNFs with double shell structure gave a 99.99 % removal rate in 90 s for the degradation of methylene blue under microwave irradiation, outperformed the C/Ni and C/SiC and most other reported catalysts in similar studies. On the one hand, the possible mechanism of the methylene blue degradation should be ascribed to that double shell structure increases the polarization source of the material, resulting in excellent microwave absorption properties; and on the other, the in-situ generation of active species OH• and O2 - under microwave radiation and the synergistic coupling effect of metal plasma greatly improved the degradation efficiency of methylene blue. The findings of this study could provide a valuable reference for the green degradation of industrial dye wastewater and its sustainable development process.

The BKL singularity inside a rotating black hole would be a neutrino star. Once its mass exceeds the limit that neutrino degeneracy pressure could support (larger than 3×10²² M_⊙), the neutrino star singularity would collapse, raising the temperature to the maximum and dropping the entropy to the minimum to initiate a Big Bang. From the cosmic microwave background, we find where the Big Bang occurred at about 0.66 times the radius of the surface of last scattering away from us and at Galactic coordinates (l, b) ≃ (286°,-43°). As it expands, the clockwise spinning universe has been veering towards the ellipsoidal. These findings are consistent with independent observations of cosmic inhomogeneities, spatial anisotropies, and time variations.

We study the possibility of determining the octant of the neutrino mixing angle 23, that is, whether 23 > 45 or 23 < 45, in long baseline neutrino experiments. Here we numerically derived the sensitivity limits within which these experiments can determine, by measuring the probability of the  ! e transitions, the octant of 23 with a 5 certainty. The interference of the CP violation angle  with these limits, as well as the effects of the baseline length and the run-time ratio of neutrino and antineutrino modes of the beam have been analyzed.

We hypothesis that large earthquakes generate Horndeski-like Gravitational Wave (GW). We find that such a Horndeski-like GW propagates with the speed of sound. The sound waves generated by an earthquake make a local and temporal change to the Earth’s diagravitational medium; therefore, they modify the GW speed in a standard, Alternative-Theory-of-Gravity (ATG) sense. The quantum of the Horndeski-like GW is a massless scalar quasiparticle and cannot exist outside of the propagation region of the P-field. The Horndeski-like GW may be detectable by future GW detectors with a sensitivity of 10−15 Hz^−1/2 in the region of 0.1–1 Hz.

: Background: Brain-derived neurotrophic factor (BDNF) is a crucial mediator of neuronal plasticity. Here, we investigated the effects of controlled normobaric hypoxia (NH) combined with physical inactivity on BDNF blood levels and executive functions. Methods: Twenty-five healthy adults (25.8±3.3 years, 15 female) were analyzed in a randomized, controlled cross-over study. Each intervention began with a 30 min resting phase under normoxia (NOR), followed by a 90 min continuation of NOR or NH (peripheral oxygen saturation [SpO₂] 85-80%). Serum and plasma samples were collected every 15 min. Heart rate and SpO₂ were continuously measured. Before and after each exposure, cognitive tests were performed and after 24 h another follow-up blood sample was taken. Results: NH decreased SpO₂ (p<.001, η_p²=.747) and increased heart rate (p=.006, η_p²=.116) significantly. The 30-min resting phase under NOR led to a significant BDNF reduction in serum (p <.001, η_p²=.581) and plasma (p <.001, η_p²=.362). Continuation of NOR further significantly reduced BDNF after another 45 min (p=.018) in serum and after 30 min (p=.040) and 90 min (p=.005) in plasma. There was no significant BDNF decline under NH. 24 h Follow-up examination showed a significant decline of serum BDNF, both after NH and NOR. Conclusion: Our results show that NH has the potential to counteract physical inactivity-induced BDNF decline. Therefore, our study emphasizes the need for a physically active lifestyle and its positive effects on BDNF. This study also demonstrates the need for a standardized protocol for future studies to determine BDNF in serum and plasma.

We propose and experimentally realize a scheme of the optical nonreciprocity (ONR) using degenerate two-level atoms embedded in an optical ring cavity. For the degenerate transition Fg=4→Fe=3, we first study the cavity-transmission property in different coupling field, and verify that within the strong-coupling regime, the single-dark-state peak formed by electromagnetically induced transparency (EIT) shows ONR. Qualitative theoretical analysis shows that the stable ground-state Zeeman coherence is necessary for intracavity EIT. However, due to the frequency degeneracy, the large Rabi frequency of counter-propagating coupling field can reduce the number of effective atoms and weaken the strong-coupling of the atom-cavity, which determines that ONR based on intracavity EIT occurs only at weaker probe intensity. Furthermore, the ONR transmission with high contrast, linewidth-narrowed and broadband is experimentally demonstrated.

The normal growth and development of skeletal muscle is essential for the health of the body. The regulation of skeletal muscle by intestinal microorganisms and their metabolites has been continuously revealed. Acetate is the predominant short-chain fatty acid synthesized by gut microbiota through the fermentation of dietary fiber, however, the underlying molecular mechanisms governing the interaction between acetate and skeletal muscle during rapid growth stage remain to be further elucidated; Here, specific pathogen-free (SPF) mice, germ-free (GF) mice, and germ-free mice supplemented with sodium acetate (GS) were used to evaluate the effects of acetate on skeletal muscle growth and development of young mice with gut microbiota deficiency; We found the concentration of serum acetate, body mass gain, succinate dehydrogenase activity and expression of myogenesis maker gene of skeletal muscle in the GS group was higher than GF group following sodium acetate supplement. Furthermore, the transcriptome analysis revealed that acetate activated biological processes regulating skeletal muscle growth and development in GF group that are inhibited due to gut microbiota deficiency. In vitro experiment, we proved that acetate up-regulated Gm16062 to promote skeletal muscle cell differentiation; Overall, our findings proved that acetate promote skeletal muscle growth and development in young mice via increase Gm16062 expression.

The Qiushuwan Cu-Mo deposit, located in the East Qinling molybdenum belt, which is a major mining site recognized for its enormous reserves of medium-sized molybdenum. In order to enhance our comprehension and ascertain supplementary mineral resources, it is critical to conduct an in-depth investigation of both the deep and peripheral regions. The primary goal of this study is to investigate the Qiushuwan Copper Molybdenum Mine, which is located in Zhenping County, Henan Province. The spread spectrum-induced polarization (SSIP) method is utilized as a means of conducting mining exploratory analysis. Significant findings have been obtained through the collection of SSIP data, geological analysis, and electrical parameter study of rock and ore samples along profile-80. By conducting a meticulous examination of the SSIP data at suitable frequencies, two prominent conductive ore bodies, specifically C2 and C4, have been successfully discovered. C2 exhibits a correlation with granite porphyry and molybdenum veins, while C4 is linked to a skarn deposit that contains a concentration of copper ore. The spatial differences in conductivity within the research area have been precisely characterized using resistivity models obtained from the SSIP data. The precision and dependability of our conclusions have been confirmed through the integration of borehole data and the matching of geological sections with inversion models. The recovered core samples show a diverse range of minerals, containing both valuable ores and minerals that have undergone alteration. Pyrite constantly appears with molybdenite in the majority of samples. The aforementioned results provide a strong foundation for future exploration initiatives and sustainable resource exploitation, enabling informed decision-making in the effective use and administration of natural resources. This study adds to the existing body of knowledge on the Qiushuwan Cu-Mo deposit and improves exploration methods in the region by utilizing the SSIP approach. The findings are a useful asset for geologists, mining experts, and stakeholders, offering essential knowledge for future exploration and sustainable utilization of resources.

The super-weak interaction includes three simple extensions of the standard model: gauge extension, fermionic extension, and scalar extension. All of these extensions are strongly influenced by their complex phenomenology. They can explain a number of unresolved questions in particle physics and cosmology, including the genesis of dark matter, cosmic inflation, asymmetry of matter and antimatter, neutrino masses, and vacuum stability, if combined into a single structure. This is an extension of the gauge group of the standard model $G_{\rm SM}$ by $G_{\rm SM}\otimes U(1)_Z$ without any anomalies. We investigate the implications of the development of a general Majorana mass renormalization group for neutrinos with masses in the range of 0.03 $eV$ and 0.1 $eV$, which fall within the recently published range as well as the range to be explored in future planned experiments.

Drug-induced liver injury (DILI) stands as a significant cause of drug attrition. To mitigate clinical DILI risks, assessing drugs using human liver models is crucial since animal studies may fall short due to species-specific liver pathway variations. Cell-based preclinical hepatotoxicity testing is often pertinent. In the present study, cells from a human liver cancer line (HepG2, HepaRG) were cultured in both formats of 2D and 3D spheroids to explore their responses to drugs. Liver-specific marker expressions across cell lines and culture formats were also examined to assess disparities in drug-induced liver injury marker expressions. In cytotoxicity assays, HepG2 cells exhibited heightened sensitivity to amiodarone HCl, while HepaRG cells showed greater sensitivity to acetaminophen. Generally, 2D cultures were more responsive to drugs than 3D cultures. Consistency was observed between cytotoxicity assays and liver injury markers AST and ALT. Variations were also noted in liver cell marker secretion, with albumin and urea concentrations declining post-drug treatment, particularly with higher baseline expression in HepaRG cells and 3D cultures. Additionally, mRNA expression levels of CYP enzymes involved in hepatocellular drug metabolism were compared following treatment with enzyme inducers. CYP1A2 and CYP2C9 were not expressed in HepG2 cells. On the other hand, CYP3A4 was expressed higher in 3D culture than in 2D culture. HepaRG cells exhibited significantly increased expression of all three enzymes post-treatment. Notably, enzyme expression was notably higher in 3D cultures than in 2D cultures. Collectively, these findings suggest that HepaRG cells and 3D cultures hold promise for evaluating DILI during early-stage drug development.

Background: In response to inflammation, the absorption of nutritional iron is restricted. Multiple inflammation-related signaling pathways can lead to ferroptosis, an iron-dependent mechanism of programmed cell death. Since the pathophysiological significance of the presence and uptake of iron in chronic inflammation is still unknown, we tested the effect of a low iron diet on the clinical course of arthritis in the mouse model of collagen-induced arthritis (CIA). Methods: Six- to eight-week-old male DBA/1 mice were fed either a normal or a low iron diet starting three weeks before arthritis induction. From day four after the collagen-booster made on day 25, the development of arthritis was regularly monitored until the end of the experiment (day 34), using a standard clinical arthritis score. The complete blood count was determined as well as Fe2+, Fe3+, oxidized and reduced glutathione (GSH and GSSG) and malondialdehyde (MDA) in whole paw tissue by ELISA. Quantitative PCR was performed from whole paw tissue for glutathione peroxidase 4 and other key regulator genes of iron metabolism and ferroptosis. We used nonparametric tests to com-pare markers of iron metabolism and ferroptosis as well as nonlinear regression models for longitu-dinal data for signs of arthritis. Results: Mice fed a low iron diet showed a significantly less severe course of arthritis compared to mice fed a normal iron diet (p

Chronic inflammatory diseases are considered the most significant cause of death worldwide. Current treatments for inflammatory diseases are limited due to the lack of understanding of the biological factors involved in early-stage disease progression. Nerve growth factor (NGF) is a neurotrophic factor directly associated with inflammatory and autoimmune diseases like osteoarthritis, multiple sclerosis, and rheumatoid arthritis. It has been shown that NGF levels are significantly upregulated at the site of inflammation and play a crucial role in developing a robust inflammatory response. However, little is known about NGF's temporal expression profile during the initial progressive phase of inflammation. This study aimed to determine the temporal expression pattern of NGF in rat skin during Adjuvant-Induced Arthritis (AIA). Sprague Dawley rats were randomly divided into control and Complete Freund's Adjuvant (CFA) treated groups. Levels of NGF were evaluated following unilateral AIA at different time points and it was found that peripheral inflammation due to AIA significantly upregulated the expression of NGF mRNA and Protein in a biphasic pattern. These results suggest that NGF signaling is crucial for initiating and maintaining peripheral neurogenic inflammation in rats during AIA.

In recent years, cerium dioxide (CeO2) has attracted considerable attention owing to its remarkable performance in various applications, including photocatalysis, fuel cells, and catalysis. This study explores the effect of nickel (Ni) doping on the structural, thermal, and chemical properties of CeO2 nanorods, particularly focusing on oxygen vacancy-related phenomena. Utilizing X-ray powder diffraction (XRD), alterations in crystal structure and peak shifts were observed, indicating successful Ni doping and the formation of Ni2O3 at higher doping levels, likely due to non-equilibrium reactions. Thermal gravimetric analysis (TGA) revealed changes in oxygen release mechanisms, with increasing Ni doping resulting in the release of lattice oxygen at lower temperatures. Raman spectroscopy corroborated these findings by identifying characteristic peaks associated with oxygen vacancies, facilitating the assessment of Ni doping levels. Overall, this study underscores the substantial impact of Ni doping on CeO2 nanorods, shedding light on tailored catalytic applications through modulation of oxygen vacancies while preserving the nanorod morphology.

Reducing the hardness of hard water is of great concern nowadays due to some adverse effects on water pipes, boilers and soap consumption. Using the method of biomineralization to precipitate calcium and magnesium ions to become carbonate minerals was one of the most important innovations for reducing the hardness of hard water. The present study sought to explore the physical and chemical conditions of carbonates bio-precipitation and the potential use of Bacillus licheniformis SRB2 strain (GenBank: KM884945.1) isolated from sludge sample of Moshui River (Shandong University of Science and Technology, Qingdao, China) in reducing the hardness of hard waters by the induction of carbonate minerals. In this study, B. licheniformis SRB2 strain was identified based on the morphological, biochemical and 16S rDNA gene sequence homology analysis. The carbonate minerals induced by B. licheniformis bacteria in the liquid culture medium with 3% NaCl and Mg/Ca molar ratio of 0, 6, 8, 10 and 12 were investigated. The culture medium was inoculated with the bacterial liquid seed was set as the experimental group and the other culture medium was inoculated with the same volume of distilled water was set as the control group. The mineral phases, micromorphologies, and crystal structures were analyzed using X-ray powder diffraction, scanning electron microscope, energy dispersive X-ray detector, high resolution transmission electron microscopy and selected area electron diffraction. The bacterial concentrations and pH values of the solution were measured by a spectrophotometer and a pH meter, respectively. The urease secreted by B. licheniformis SRB2 was found to greatly increase the pH values of the liquid medium, which favored the formation of calcium carbonate.As a result, Mg²⁺ and Ca²⁺ ion concentrations decreased greatly due to the biomineralization of calcium carbonate and nesquehonite minerals in the presence of B. licheniformis SRB2 bacterium. There were only few calcium carbonates and no nesquehonite minerals in the control groups. It was also found that the minerals of nesquehonite induced by B. licheniformis SRB2 had a phenomenon of preferred orientation. What was more, even though Mg²⁺ ions inhibited the precipitation of Ca²⁺ ions, but under the action of B. licheniformis SRB2 bacteria, the inhibition effect was significantly declined. The bio-precipitation of calcium carbonate and nesquehonite minerals may represent a new method of pretreatment for the hardness reduction of hard water. The accomplished study is of certain interest for interpretation of the carbonates biomineralization in natural environment, and maybe also has a certain application value in the former processing of hard water

Background: Previous neuroimaging studies have identified brain regions related to respiratory motor control and perception. However, little is known about the resting-state functional connectivity (FC) associated with respiratory impairment. We aimed to determine the FC involved in mild respiratory impairment without changing the saturation of percutaneous oxygen. Methods: We obtained resting-state functional magnetic resonance imaging data from 36 healthy volunteers during normal respiration and mild respiratory impairment induced by resistive load (effort breathing). ROI-to-ROI and seed-to-voxel analyses were performed using Statistical Parametric Mapping 12 and the CONN toolbox. Results: Compared to normal respiration, effort breathing activated FCs within and between the sensory perceptive area of respiration (the postcentral gyrus, anterior insular cortex (AInsula), and anterior cingulate cortex) and visual cortex (the visual occipital, occipital pole (OP), and occipital fusiform gyrus). Graph theoretical analysis showed strong centrality in the visual cortex. A significant positive correlation was observed between the dyspnoea score (modified Borg scale) and FC between the left AInsula and right OP. Conclusions: These results suggested that the FCs within the respiratory sensory area via the network hub may be neural mechanisms underlying effort breathing and modified Borg scale scores.

Raru’s plants bark has long been used as traditional medicine in Batak’s tribe. Raru’s bark is derived from several trees that are usually used in a mixture in Batak traditional beverages. This bark is generally used as antidiabetic remedies. This study aims to combine the rarus’s bark extract and mocaf activated-carbon (MAC) in order to study antidiabetics in rats. The combination of raru’s bark extract and MAC were tested on male rats as of Sprague Dawley strain for testing antidiabetic bioactivity. The result showed that antidiabetic activity of raru’s extract and MAC exposed the antidiabetic level declines in rat’s blood. The various treatments of different concentration ratios of raru’s extract and MAC useful in the experiments showed that the levels of blood level reduction were slightly different (14-21%). The raru’s extract pure was observed more effective in decreasing the blood glucose level in rat’s blood, in comparison the positive control. The mixture of raru’s extract and MAC with 75:25 ratio is better than 50:50 ratio. The involvement of MAC in the alleged antidiabetic agent did little in improving the blood glucose level decrease in rat’s blood. Raru’s extract and MAC indicate its potential utilization as an antidiabetic agent.

In this paper, a semi-empirical model of air waves induced by falling rock is described. The model is composed of a uniform motion phase (velocity close to 0 m·s^-1) and an acceleration movement phase. The uniform motion phase was determined based on experimentally and the acceleration movement phase was derived by theoretical analysis. A series of experiments were performed to verify the semi-empirical model and elucidated the law of the uniform motion phase. The acceleration movement phase accounted for a larger portion with a greater height of the falling rock. Experimental results of different falling heights of the goaf showed close agreement with theoretical analysis values. The semi-empirical model could accurately and conveniently estimate the velocity of air wave induced by falling rock. Thus, the semi-empirical model can provide a reference and basis for estimating the speed of air waves and designing protective measures in mines.

The mechanism underlying microbiologically induced carbonate precipitation have not been thoroughly characterized, although numerous scholars and experts have specifically investigated questions regarding minerals induced by bacteria. The study of the precipitation of carbonate minerals induced by halophilic bacteria has aroused wide concern. The present study aimed to investigate the characterization and process of biomineralization in high salt systems by a halophilic bacterium, Chromohalobacter israelensis strain LD532 (GenBank: KX766026), which was isolated from the Yinjiashan Saltern in China. Carbonate minerals induced by LD532 were investigated in several sets of comparative experiments that employed magnesium sulfate and magnesium chloride as Mg resources. Magnesium calcite and aragonite were induced by LD532 bacteria, whereas these minerals did not appear in the control group. The mineral phases, micromorphologies, and crystal structures were analysed using X-ray powder diffraction, scanning electron microscopy, and energy dispersive X-ray detection. The carbonic anhydrase and urease secreted by strain LD532 through metabolism increased the pH value of the liquid medium and promoted the process of carbonate precipitation. Further study using high resolution transmission electron microscopy, energy dispersive X-ray detection and analysis of ultrathin slices showed that the nucleation sites of carbonate minerals were located on extracellular polymeric substances and the membranes of intracellular vesicles of LD532 bacteria, which provided favourable conditions for the growth of carbonate mineral crystals. The morphologies and compositions of minerals formed in solutions of MgSO₄ and MgCl₂ display significant differences, indicating that different sources of Mg²⁺ may also affect the physiological and biochemical activities of microorganisms and thus mineral deposition. This study will be of some interest for the interpretation of carbonate biomineralization in natural salt environments and has some value as a reference in understanding sedimentary carbonates in ancient marine environments, such as tidal flats.

Maintaining the optimal microclimate in broiler houses is crucial for bird productivity, yet enabling efficient temperature control remains a significant challenge. This study developed and validated a computational fluid dynamics (CFD) model to predict temporal changes in indoor air temperature in response to variable ventilation operations in a commercial broiler house. The model accurately simulated air velocity and airflow distribution for different numbers of tunnel fans in operation, with air-velocity errors ranging from -0.22 to 0.32 m s-1. The predicted airflow rates through inlets and cooling pads showed good agreement with measured values with an accuracy of up to 108.1%. Additionally, the CFD model effectively predicted temperature dynamics, accounting for chicken heat production and ventilation effect. The model successfully predicted the longitudinal temperature gradients and their variations during ventilation cycles, validating its reliability through comparison with experimental data. The study also explored different variable inlet configurations to mitigate the temperature gradient. The variable inlet adjustment showed the potential to relieve the high temperatures but may reduce overall ventilation efficiency or intensify temperature gradients, which confirms the importance of optimising ventilation strategies. This CFD model provides a valuable tool for evaluating and improving ventilation systems and contributes to enhanced indoor microclimates and productivity in poultry houses.

In this paper the one-to-one correspondences and equivalences between ideals, primals, filters and grills are introduced. It is shown the local functions and the topological spaces induced by them are the same. From this point of view, the topological properties with respect to one topology can be derived from topological properties valid in the corresponding topology.

Obesity is a highly prevalent chronic disease characterized by excessive weight gain and fat accumulation. There is growing evidence that Lactiplantibacillus plantarum strains with bile salt hydrolase (BSH) activity are effective in preventing and alleviating obesity. However, few of them has confirmed the anti-obesity effect of BSH by gene deletion. In this study, 23 BSH-positive Lp. plantarum strains were screened by bile salt precipitation halo assay. Among these strains, Lp. plantarum Lp20 showed the highest BSH activity with a hydrolysis rate to glycodeoxycholic acid (GDCA) by 91.62%. Genomic sequencing and bioinformatics analysis indicated that gene bsh1 was associated with BSH activity of Lp. plantarum Lp20 and gene deletion of bsh1 confirmed the role of Bsh1 in GDCA hydrolysis. To investigate if the Bsh1 from Lp. plantarum Lp20 could alleviate obesity, the wild type and bsh1 deletion mutant strains were administered daily for 8 weeks to diet-induced obese mice, respectively. Compared with mutant strain, the wild type strain Lp20 significantly reduced body weight gain, inguinal white adipose tissue and mesenteric fat mass in obese mice. In addition, Lp20 also reduced serum total cholesterol levels and LDL-C by 20.8% and 33.3%, respectively. Furthermore, the recovered liver steatosis was only observed in Lp. plantarum Lp20 treated mice. Taken together, the bile salt hydrolase Bsh1 from Lp. plantarum Lp20 was a key functional factor on ameliorating HFD-induced obesity by reducing cholesterol levels and suppressing adipogenesis in mice.

Urinary tract diseases are common in cats, and often require surgical reconstruction. Here, to explore the possibility of urinary tract reconstruction in cats using in-vivo tissue architecture (iBTA), biosheets fabricated using iBTA technology were implanted into the feline bladder and the regeneration process was histologically evaluated. The biosheets were prepared by embedding molds into the dorsal subcutaneous pouches of six cats for 2 months. A section of the bladder wall was removed, and the biosheets were sutured to the excision site. After 1 and 3 months of implantation, the biosheets were harvested and evaluated histologically. Implantable biosheets were formed with a success rate of 67%. There were no major complications following implantation, including tissue rejection, severe inflammation, or infection. Urinary incontinence was also not observed. Histological evaluation revealed the bladder lumen was almost entirely covered by urothelium after 1 month, with myofibroblast infiltration into the biosheets. After 3 months, the urothelium became multilayered, and mature myocytes and nerve fibers were observed at the implantation site. In conclusion, this study showed that tissue reconstruction using iBTA can be applied to cats, and that biosheets have the potential to be useful in both the structural and functional regeneration of the feline urinary tract.

Elevated carbon dioxide (eCO₂) stimulates wheat grain yield, but simultaneously reduces protein (N) concentration. Also other essential nutrients are subject to change. This study is a comprehensive synthesis of wheat experiments with eCO₂, estimating effects on N, minerals (B, Ca, Cd, Fe, K, Mg, Mn, Na, P, S, Zn), and starch. Analysis was made by i) deriving response functions for the relative effect on element concentration in relation to CO₂ concentration, ii) meta-analysis to test the magnitude and significance of observed effects, and iii) relating CO₂ effects on minerals to effects on N and grain yield. Responses range from zero to strong negative effects of eCO₂ on mineral concentration, with largest reductions for the nutritionally important elements N, Fe, S, Zn and Mg. Together with the positive but small and non-significant effect on starch concentration, the large variation in effects suggests that CO₂-induced responses cannot be explained by a simple dilution model. To explain the observed pattern, uptake and transport mechanisms may have to be considered, along with the link of different elements to N uptake. Our study shows that eCO₂ has a significant effect on wheat grain stoichiometry, with implications for human nutrition in a world of rising CO₂.

Transition metal dichalcogenides (TMDs) monolayers exhibit unique valleytronics properties due to the dependency of the coupled valley and spin state at the hexagonal corner of the first Brillouin zone. Precisely controlling valley spin-polarization via manipulating the electron population enables its application in valley-based memory or quantum technologies. This study uncovered the uncompensated spins of the antiferromagnetic oxide (NiO) serving as the ferromagnetic (FM) order to induce valley spin-polarization in molybdenum disulfide (MoS₂) monolayers via the magnetic proximity effect (MPE). A spin-resolved photoluminescence spectroscopy (SR-PL) was employed to observe MoS₂, where the spin-polarized trions appear to be responsible for the MPE, leading to a valley magnetism. Results indicate that local FM order from the uncompensated surface of NiO could successfully induce significant valley spin-polarization in MoS₂ with the depolarization temperature approximately at 100 K, which is relatively high compared to related literature. This study reveals new perspectives and potential of AFM materials in the field of exchange-coupled van der Waals heterostructures.

Background: Peritoneal sclerosis (PS) and its most severe form, encapsulating PS (EPS), are rare entities that can occur in various procedures (liver transplantation, intraperitoneal chemotherapy), secondary to medications ( beta-blockers); however, PS or EPS typically occur in patients undergoing peritoneal dialysis as a form of renal function substitution. Medical or surgical treatments can be applied, but morbidity and mortality have high rates . This condition typically presents clinically as an intestinal obstruction caused by the inclusion of the intestinal loops in the peritoneal fibrous membrane. Methods: Herein we present data from a single tertiary surgery center that has dedicated teams for patients receiving dialysis. In 12 years we analyzed a group of 63 patients admitted for catheter replacement/removal or for acute surgical pathology. In 5 cases (7,9%) we diagnosed EPS . Two patients with EPS presented with atypical abdominal pathologies requiring emergency surgery: one case of hemoperitoneum caused by a ruptured ovarian cyst and one case of uterine fibroids and metrorrhagia. Results: The definitive diagnoses were established intraoperatively and by analyzing the morpho-pathological changes of the peritoneum. The possible intraoperative challenges included laborious dissection, difficulties in restoring the correct anatomical landmarks, increased duration of the surgical intervention and a high rate of incidents and accidents Conclusions: The aim of the present study was to emphasize the possibility of other surgical pathologies overlapping with EPS, increasing the complexity of the surgical intervention. Also, we sought to determine whether there is a correlation between the morpho-pathological results of these patients who underwent emergency surgery and the common EPS morpho-pathological changes.

Successful geophysical exploration works in Gucheng-Yaxi area located in Gaochun District, Jiangsu province, China, have been limited partly due to complex geological condition of the area and high artificial noise in data acquired using electrical and electromagnetic methods. In this work, we deployed the new anti-interference spread spectrum induced polarization method (SSIP) and audio magnetotellurics (AMT) method to detect a copper-polymetallic deposit in the area. Two-dimensional (2D) inversion results at Gucheng-Yaxi Area revealed a high chargeability anomalous zone on SSIP profile that coincided with a zone of moderate resistivity located between two resistor bodies on AMT profile. A follow up 1200 meters drill hole was established at this high chargeability-moderate resistivity zone which encountered polymetallic (copper, lead, zinc, gold and silver) mineralization at the depth ≥ 400 m. Drill hole data analysis showed that mineralization occurs interspaced in marble rock mass at varies depth. Furthermore, several low resistivity-weak chargeability sections were revealed and inferred attributed to Cretaceous sediments and faults. These faults are thought to have played critical role in the polymetallic mineralization genesis. In summary, this work demonstrated the successful of application of SSIP and AMT at detecting a metallic deposit in an area with high artificial noise. Hence the geophysical prospection potential of Gucheng-Yaxi area is great.

The chemotactic cytokine fractalkine (FKN, chemokine CX3CL1) has unique properties resulting from the combination of chemoattractants and adhesion molecules. The soluble form (sFKN) has chemotactic properties and potently attracts T cells and monocytes. The membrane-bound form (mFKN) facilitates diapedesis and is responsible for cell-to-cell adhesion, especially by promoting the strong adhesion of leukocytes (monocytes) to activated endothelial cells with the subsequent formation of an extracellular matrix and angiogenesis. FKN signaling occurs via CX3CR1, which is the only known member of the CX3C chemokine receptor subfamily. Signaling within the FKN-CX3CR1 axis plays an important role in many processes related to inflammation and the immune response, which often occur simultaneously and overlap. FKN is strongly upregulated by hypoxia and/or inflammation-induced inflammatory cytokine secretion, and it may act locally as a key angiogenic factor in the highly hypoxic tumor microenvironment. The importance of the FKN/CX3CR1 signaling pathway in tumorigenesis and cancer metastasis results from its influence on cell adhesion, apoptosis and cell migration. This review presents the role of the FKN signaling pathway in the context of angiogenesis in inflammation and cancer. The mechanisms determining the pro- or anti-tumor effects are presented, which are the cause of the seemingly contradictory results that create confusion regarding the therapeutic goals.

Bangladesh faces significant wheat grain deficiency compared to its demand due to the lengthy process (10-12 years) required to release a variety through a conventional breeding approach. Traditional breeding methods involve several years of various types of crosses between male and female parents and/or progenies, along with recurrent selection-crossing to obtain a homozygous line (F₁ to F₆ generations) with desired traits within almost 10 years. The double haploid (DH) method is also a time-saving, easier, and more reliable technique to achieve the desired traits in homozygous lines within 2-3 years. DH lines were produced by crossing two F₁ hybrids of spring wheat with maize. 0.1% solution of colchicine was applied to produce DH of F₂ progeny of wheat in the study. 80.8% (340) of the 421 pollinated florets from the two F₁ wheat hybrids were produced as green parthenocarpic caryopses (GPCs) (F₂). 35 of the 70 rescued embryos (or 20.6% of the GPCs) germinated. The germinated embryos regenerated 10 haploid green plants (14.3% of total embryos). After being applied colchicine, 8 of the regenerated haploid (H₁) plants made it. Out of the 8 plants that made it through, only one developed homozygous double haploid seed (DH₁ seed). These seeds were multiplied to produce DH₂, used in the preliminary yield in the next year. The results demonstrated the potential of this method to produce a homozygous line within a short period (2-3 years) by doubling the haploid line generated through pollination of spring bread wheat F₁ with maize.

Cancer cells can release EGF-like peptides, acquiring the capacity of autocrine stimulation via EGFR-mediated signaling. One of these peptides (HBEGF) was found to be released from a membrane-bound precursor protein, and is critically implicated in the proliferative potential of cancer cells. We observed that the increased lactate levels characterizing neoplastic tissues can induce the release of uPA, a prote-ase promoting HBEGF shedding. This effect led to EGFR activation and increased ERK1/2 phosphoryla-tion. Since EGFR-mediated signaling potentiates glycolytic metabolism, this phenomenon can induce a self-sustaining deleterious loop, favoring tumor growth. A well characterized HBEGF inhibitor is CRM197, a single-site variant of diphtheria toxin. We observed that when administered individually, CRM197 did not trigger evident antineoplastic effects. However, its association with a uPA inhibitor caused dampening of EGFR-mediated signaling and apoptosis induction. Overall, our study highlights that the increased glycolytic metabolism and lactate production can foster the activated state of EGFR receptor, and suggests that the inhibition of EGFR-mediated signaling can be attempted by means of CRM197 administered with an appropriate protease inhibitor. This attempt could help in overcoming the problem of the acquired resistance to the conventionally used EGFR inhibitors.

Bacillus amyloliquefaciens GL18 has been proven to have good resistance ability and can promote the growth of Avena sativa cultivar ‘Qingyan 1’. Herein, Illumina high-throughput transcriptome sequencing technology was used to analyze the differential expression of genes between the interaction group (LB) and the control group (LCK) when ‘Qingyan 1’ roots interacted with GL18 bacterial suspension or sterile water for 12 h under 4 °C low-temperature stress. The gene function annotation information was obtained using Gene Ontology (GO) functional classification and enrichment analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and annotation of differentially expressed genes was used to explore the related signal transduction pathway of ‘Qingyan 1’ response to cold stress induced by Bacillus GL18. The results showed that after ‘Qingyan 1’ seedlings interacted with GL18 bacterial suspension or sterile water for 12 h, comparing the LB with the LCK or CK (the control group at 26 °C), there were 12,061 and 25,489 differentially expressed genes, respectively. Their functions were mainly related to metabolic process, cellular process, catalytic activity, binding, and cellular parts, and they were significantly enriched in plant tissue growth and development, cell wall, organelle membrane synthesis, thiamine and its compounds, biosynthesis, polyamine decomposition, and other metabolic processes. Signal transduction was detected through KEGG pathway enrichment analysis, and corresponding genes, such as AUXI, PP2C, SNRK2, ABF, BRI1, and PIF4, were expressed. The expression of genes directly involved in plant growth was upregulated in the presence of GL18, as shown by real-time quantitative PCR analysis. It was speculated that the normal growth and development of ‘Qingyan 1’ under low-temperature stress promoted by GL18 is a result of the integration of multiple pathways in terms of regulating endogenous hormone metabolism, secondary metabolite synthesis, and photosynthesis.

Objective: This research was aimed to estimate the anti-fatigue effects of arecoline and elucidate its underlying mechanisms using a murine model of central fatigue precipitated by sleep deprivation (SD). Methods: Seventy-two male C57BL/6 mice were randomly allocated into six groups: a control group, a SD-induced fatigue model group, a group receiving Rhodiola Rosea capsules (2.5 mg/kg), and arecoline groups administered low, medium, and high doses (10, 20, and 40 mg/kg, respectively). Following 28 days of continuous administrations, the effects of arecoline on the mouse fatigue-related behaviors was assessed by the behavioral tests, including grip strength, rotarod performance, and weight-bearing swimming endurance. Enzyme-linked immunosorbent assays (ELISAs) were utilized to measure the levels of the relevant biochemical markers. Western blotting was employed to quantify the expression of nuclear factor erythroid 2-related factor (Nrf2), Kelch-like ECH-associated protein 1 (Keap1), heme oxygenase 1 (HO-1), sequestosome-1 (p62), and NADPH quinone oxidoreductase 1 (NQO1) in the gastrocnemius muscle. Results: Arecoline administration notably enhanced grip strength, delayed the onset of fatigue as evidenced by extended latencies in rotarod tests, and increased the duration of weight-bearing swimming in mice. In the elevated plus maze, arecoline significantly reduced both the number of entries and the total distance traveled in the open arms. Arecoline markedly decreased serum levels of creatine kinase, blood urea nitrogen, lactate dehydrogenase, triglycerides, and cholesterol, while elevated total testosterone, lactate dehydrogenase, and immunoglobulin G levels. Furthermore, it significantly increased superoxide dismutase(SOD), catalase(CAT), and glutathione peroxidase activity in the gastrocnemius muscle, reduced malondialdehyde levels, augmented hippocampal SOD and CAT activity, and elevated glycogen stores in both liver and muscle tissues. Neurotransmitter levels were significantly increased, cytokine levels were markedly reduced, and the expression of Nrf2, Keap1, NQO1, p62, and HO-1 in brain tissue was significantly upregulated. Conclusion: The current study for the first time demonstrated that arecoline has significant anti-fatigue activity, and its mechanism of action is related to elevate the levels of glucose and lipid metabolism, relieve oxidative stress damage, inhibit neuroinflammatory response, regulate neurotransmitter levels and Keap1/Nrf2/HO-1 signaling pathway. The current study provides a new insight into the potential of arecoline in prevention and improvement of fatigue.

Surface initiated atom transfer radical polymerization (SI-ATRP) is one of the most versatile technique to modify the surface properties of material. Recent developed metal free SI-ATRP makes such technique more widely applicable. Herein photo-induced metal-free SI-ATRP of methacrylates, such as methyl methacrylate, N-isopropanyl acrylamide, and N,N- dimethylaminoethyl methacrylate, on the surface of SBA-15 was reported to fabricate organic-inorganic hybrid materials. SBA-15 based polymeric composite with adjustable graft ratio was obtained. The structure evolution during the SI-ATRP modification of SBA-15 was monitored and verified by FT-IR, XPS, TGA, BET, and TEM. The obtained polymeric composite showed enhanced adsorption ability for the model compound toluene in aqueous. This procedure provides a low cost, ready availability, and facile modification way to synthesize the polymeric composites without the contamination of metal.

Aspalathin (ASP) can protect H9c2 cardiomyocytes against high glucose (HG)-induced shifts in myocardial substrate preference, oxidative stress and apoptosis. While the protective mechanism of aspalathin remains unknown, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) has emerged as a key factor for intracellular responses against oxidative stress. Therefore, we hypothesized that aspalathin protects the myocardium against hyperglycemia-induced oxidative damage by up-regulating Nrf2 expression in H9c2 cardiomyocytes and diabetic (db/db) mice. Using an oxidative stress RT2 Profiler PCR array, ASP at a dose of 1 µM was demonstrated to protect H9c2 cardiomyocytes against HG-induced oxidative stress, but silencing of Nrf2 abolished this protective response of ASP and exacerbated cardiomyocyte apoptosis. Db/db mice and their non-diabetic (db/+) littermate controls were subsequently treated daily for 6 weeks with either a low (13 mg/kg) or high (130 mg/kg) ASP dose. Compared to nondiabetic mice the db/db mice presented increased cardiac remodeling and enlarged left ventricular wall that occurred concomitant to enhanced oxidative stress. Daily treatment of mice with ASP at a dose of 130 mg/kg for 6 weeks was more effective at reversing complications than both a low dose ASP or metformin, eliciting enhanced expression of Nrf2 and its downstream antioxidant genes. These results indicate that ASP maintains cellular homeostasis and protects the myocardium against hyperglycemia-induced stress through activation of Nrf2 and its downstream target genes.

Titanium dioxide nanoparticles (TiO2NPs) are used in products that are applied to the human body, such as cosmetics and food, but their biocompatibility remains controversial. Pycnogenol (PYC), a natural extract of pine bark, exerts anti-inflammatory and antioxidant effects. In this study, we investigated whether PYC effectively alleviates pulmonary toxicity induced by airway exposure to TiO2NPs, and the beneficial effects of PYC were explained through the analysis of changes to the mechanism of cytotoxicity. TiO2NPs induced pulmonary inflammation and mucus production, increased the levels of malondialdehyde, and upregulated thioredoxin-interacting protein (TXNIP) and cleaved-caspase 3 (Cas3) in the lungs of mice. However, PYC treatment reduced the levels of all toxicity markers of TiO2NPs and restored glutathione levels. These antioxidant and anti-inflammatory effects of PYC were also demonstrated in TiO2NP-exposed human airway epithelial cells by increasing the mRNA levels of antioxidant enzymes and decreasing the expression of TXNIP, cleaved-Cas3, and inflammatory mediators. Taken together, our results showed that PYC attenuated TiO2NP-induced lung injury via TXNIP downregulation. Therefore, our results suggest the potential of PYC as an effective anti-inflammatory and antioxidant agent against TiO2NP-induced pulmonary toxicity.

Models of subsurface structures are important for successful deposit exploration but are challenged by the need to integrate data from different geophysical methods. In the present study, we evaluated a method of joint inversion in which audio-magnetotelluric (AMT) and dual frequency induced polarization (DFIP) data sets are inverted simultaneously to produce a consistent 2D resistivity model to show a clear image of subsurface structures. To achieve the objectives, we conducted AMT and DFIP surveys first on the same survey line within the Dongjun lead-zinc deposit in inner Mongolia by developing 31 AMT survey sites with an interstation separation of 40 m on a 1440 m survey track and operated in fifty-three frequencies in the range 1–10,400 Hz to record the resistivity distribution of subsurface to depths exceeding 800 m. The same survey setup up was applied to the DFIP method by utilizing the SQ-3C model with a pole-dipole array configuration and conducted measurements at frequencies of 4 Hz and 4/13 Hz. We first separately inverted AMT and DFIP measurements. The two-dimensional (2D) model obtained from AMT data revealed distinct low resistivity anomalies in the middle of the 2D inversion model. In contrast, the DFIP inversion model showed a high resistive body in the same region. In response to the discrepancies observed in the separate 2D inversion models, we implemented a joint inversion for both the AMT and DFIP datasets. The joint inversion resistivity model shows surficial conducting bodies and a high conductive body along the profile with relatively high Percent Frequency Effect (PEF) indicating high chargeability. The final joint inversion resistivity model clearly images the large silica alteration zone and the Pb-Zn mineralization. This study demonstrates the feasibility of a joint inversion methodology and highlights the value of integrating geophysical methods through joint inversion for enhanced characterization and exploration of lead-zinc ores.

Preeclampsia (PE) is a complex and multifaceted obstetric syndrome characterized by several distinct molecular subtypes. It complicates up to 5% of pregnancies and significantly contributes to maternal and newborn morbidity, thereby diminishing the long-term quality of life for affected women. Due to the widespread dissatisfaction with the effectiveness of existing approaches for assessing PE risk, there is a pressing need for ongoing research to identify newer, more accurate predictors. This study aimed to investigate early changes in the maternal serum proteome and associated signaling pathways. The levels of 125 maternal serum proteins at 11-13 weeks of gestation were quantified using liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MRM MS) with the BAK-125 kit. Ten serum proteins emerged as potential early markers for PE: Apolipoprotein M (APOM), Complement C1q subcomponent subunit B (C1QB), Lysozyme (LYZ), Prothrombin (F2), Albumin (ALB), Zinc-alpha-2-glycoprotein (AZGP1), Tenascin-X (TNXB), Alpha-1-antitrypsin (SERPINA1), Attractin (ATRN), and Apolipoprotein A-IV (APOA4). Notably, nine of these proteins have previously been associated with PE in prior research, underscoring the consistency and reliability of our findings. These proteins play key roles in critical molecular processes, including complement and coagulation cascades, platelet activation, and insulin-like growth factor pathways. To improve the early prediction of PE, a highly effective Support Vector Machine (SVM) model was developed, analyzing 19 maternal serum proteins from the first trimester. This model achieved an Area Under the Curve (AUC) of 0.91, with 87% sensitivity and 95% specificity, and a hazard ratio (HR) of 13.5 (4.6 - 40.8) with p&lt;0.001. These findings demonstrate that serum protein-based SVM models possess significantly higher predictive power compared to the routine first-trimester screening test, highlighting their superior utility in the early detection and risk stratification of PE.

Fast-scan cyclic voltammetry (FSCV) is an electrochemical sensing technique that can be used for neurochemical sensing with high spatiotemporal resolution. Carbon fiber microelectrodes (CFMEs) are traditionally used as FSCV sensors. However, CFMEs are prone to electrochemical fouling caused by oxidative byproducts of repeated serotonin (5-HT) exposure, which makes them less suitable as a chronic 5-HT sensor. Our team is developing a boron-doped diamond microelectrode (BDDME) that has previously been shown to be relatively resistant to fouling caused by protein adsorption (biofouling). We sought to determine if the BDDME exhibits resistance to electrochemical fouling, which we explored on electrodes fabricated with either femtosecond laser cutting or physical cleaving. We recorded the oxidation current response after 25 repeated injections of 5-HT in a flow-injection-cell and compared the current drop from the first to the last injection. The 5-HT responses were compared to dopamine (DA), a neurochemical that is known to produce minimal fouling oxidative byproducts and have a stable repeated response. Physical cleaving of the BDDME yielded a reduction in fouling due to 5-HT compared to the CFME and the femtosecond laser cut BDDME. However, the femtosecond laser cut BDDME exhibited a large increase in sensitivity over the cleaved BDDME. An extended stability analysis was conducted for all device types following 5-HT fouling tests. This analysis demonstrated an improvement in the long-term stability of boron doped diamond over CFMEs, as well as a diminishing sensitivity of the laser cut BDDME over time. This work reports the electrochemical fouling performance of the BDDME when it is repeatedly exposed to DA or 5-HT, which informs the development of a chronic, diamond-based electrochemical sensor for long-term neurotransmitter measurements in vivo.

Oxidative stress and chronic inflammation, both at the systemic and central level, are critical early events in atherosclerosis and Alzheimer’s disease (AD). Purpose. To investigate the oxidative stress, inflammatory, and Tau-phosphorylation lowering effects of pomegranate polyphenols (PP) (punicalagin, ellagic acid, peels, and arils extracts). Methods. We used flow cytometry to quantify protein expression of proinflammatory cytokines (IL-1β) and anti-inflammatory mediators (IL-10) in THP-1 macrophages, as well as M1/M2 cell-specific markers (CD86 and CD163) expression in human microglia HMC3 cells. IL-10 protein expression was also quantified in U373-MG human astrocytes. The effect of PP on human amyloid beta 1-42 (Aβ1-42)-induced oxidative stress was assessed in microglia by measuring ROS generation and lipid peroxidation, using respectively two ′,7′-dichlorofluorescein diacetate (DCFH-DA) and thiobarbituric acid reactive substances (TBARS) tests. Neuronal viability and cell apoptotic response to Aβ1-42 toxicity were assayed using the MTT (3-(4, 5-dimethyl thiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay and the annexinV-FITC apoptosis detection kit; respectively. Finally, flow cytometry analysis was also performed to evaluate the ability of PP to modulate Aβ1-42-induced Tau-181 phosphorylation (pTau-181). Results. Our data indicate that PP was significantly (p<0.05) effective in countering Aβ1-42-induced inflammation through increasing the anti-inflammatory cytokines (IL-10) (in U373-MG astrocytes and THP1 macrophages) and decreasing proinflammatory markers (IL-1β) expression in THP1 macrophages. PP was also significantly (p<0.05) effective in inducing the phenotypic transition of THP-1 macrophages and microglial cells from M1 to M2 by decreasing CD86 and increasing CD163 surface receptor expression. Moreover, our treatments have a significant (p<0.05) beneficial impact on oxidative stress, illustrated in the reduction of TBARS and ROS generation. Our treatments have significant (p<0.05) cell viability improvement capacities and anti-apoptotic effects on human H4 neurons. Furthermore, our results suggest that Aβ1-42 significantly (p<0.05) increases pTau-181. This effect was significantly (p<0.05) attenuated by arils, peels, and punicalagin and drastically reduced by ellagic acid treatments. Conclusion. Our results are attributed to PP's anti-inflammatory, antioxidant, anti-apoptotic, and anti-Tau pathology potential. Future studies should aim to extend our knowledge of the potential role of PP on A1-42-induced neurodegeneration, mainly its association with the tauopathy involved in AD.

Inflammation is implicated in the etiology of obesity-related diseases. Thromboxane-prostanoid receptor (TPR) is known to play a role in mediating an inflammatory response in a variety of cells. Gut-derived lipopolysaccharide (LPS), a TLR4 agonist, is elevated in obesity. Moreover, free fatty acids (FFAs) are important mediators of obesity-related inflammation. However, the role and mechanisms by which TPR regulates the inflammatory response in human immune cells remain unclear. We sought to determine the link between TPR and obesity and the role/mechanisms by which TPR alters LPS or stearic acid (SA)-induced inflammatory response in PBMCs. Cells were pre-treated with agents blocking TPR signaling, followed by treatment with LPS or stearic acid (SA). Our findings showed that TPR mRNA levels are higher in PBMCs from individuals with obesity. Blockade of TPR as well as ROCK which acts downstream of TPR, attenuated LPS and/or SA-induced pro-inflammatory response. On the other hand, TPR activation using its agonist enhanced the pro-inflammatory effects of LPS and/or SA. Of note, TPR agonist by itself elicits an inflammatory response which was attenuated by blocking TPR or ROCK. Our data suggest that TPR plays a key role in promoting an inflammatory response in human PBMCs and this effect is mediated via TLR4 and/or ROCK signaling.

Cisplatin is a widely used anticancer drug for treating solid tumors, but it is associated with severe side effects, including nephrotoxicity. Various studies have suggested that the nephrotoxicity of cisplatin could be overcome; nonetheless, an effective adjuvant drug has not yet been established. Oleanolic acid acetate (OAA), a triterpenoid isolated from Vigna angularis, is commonly used to treat inflammatory and allergic diseases. This study aimed to investigate the protective effects of OAA against cisplatin-induced apoptosis and necroptosis using TCMK-1 cells and a mouse model. In cisplatin-treated TCMK-1 cells, OAA treatment significantly reduced Bax and cleaved-caspase3 expression, whereas increased Bcl-2 expression. Moreover, in cisplatin-induced kidney injury mouse model, OAA treatment alleviated weight loss in the body and major organs and also relieved cisplatin-induced nephrotoxicity symptoms. RNA sequencing analysis of kidney tissues identified lipocalin-2 as the most upregulated gene by cisplatin. Additionally, necroptosis-related genes such as receptor interacting protein kinase (RIPK) and mixed lineage kinase domain like (MLKL) were identified. In vitro study, the phosphorylation of RIPKs and MLKL was reduced by OAA pretreatment in both cisplatin-treated cells and cells boosted by co-treatment with z-VAD-FMK. In conclusion, OAA could protect the kidney from cisplatin-induced nephrotoxicity and may serve as an anticancer adjuvant.

The liver diseases are posing serious threat to human health associated with abusive use of allopathy medicines, especially in developing economies like Pakistan. The strengthening of detoxification system using natural products might be a suitable option to minimize the liver problems. In this current research, Zingiber officinale and Azadirachta indica were evaluated for their hepatoprotective role. For the purpose, 20 Sprague Dawley rats were equally divided into four groups i.e., negative control, paracetamol positive control, 2.5% ginger and 2% neem powder, respectively. During 42 days study, the levels of bilirubin and liver enzymes significantly elevated due to liver damage. Although, the values dropped (20-25%) in treatment group. Serum glucose and serum lipid profile increased in positive control group, but reduced (5-10%) in both ginger and neem groups. The serum protein profile declined in liver damage group, however, improved (~5%) in treatment groups. The hematological parameters slightly declined in liver damage group, but increased in ginger and neem groups. Moreover, the white blood cells differential count and renal parameters showed abnormal values in liver damage group, but improved after treatment. This study is promising and highlighted the hepato-protective role of neem and ginger that may open several avenues of research.

: In this paper we present an optimization of the planar manufacturing scheme for stretch-free, shape induced metal interconnects to simplify the fabrication with the aim of maximizing the flexibility in the structure regarding to stress and strain. The Formation of trenches between silicon islands are actively used in the lithographic process to create arc shape structures by spin coating resist into the trenches. The resulting resist form is used as a template for the metal lines, which are structured on top. Because this arc shape is beneficial for the flexibility of these bridges. The trench depth as a key parameter for the stress distribution is investigated by applying numerical simulations. The simulated results show that the increase in penetration depth of the metal bridge into the trench increases the tensile load which is converted into a shear Force Q(x), that usually leads to increased strains the structure can generate. For the fabrication the filling of the trenches with resist is optimized by varying the spin speed. Compared to the theoretical resistance, the current-voltage measurements of the metal bridges show a similar behavior and almost every structural variation is capable of functioning as a flexible electrical interconnect in a complete island-bridge array.

Type-1 Diabetes Mellitus (T1D) onset and development is closely linked with imbalance of gut microbiome, while supplementation with probiotics may result in positive alterations in gut microbiome composition. In the present study, the effect of a dietary intervention including free or immobilized cells of the presumptive probiotic Pediococcus acidilactici ORE5 on Corinthian currants, a food with beneficial impact in the condition of diabetes, was investigated. Male Wistar rats were studied which were divided into 4 groups: healthy animals, which received the free (H_FP) or the immobilized cells (H_IPC), and diabetic animals, which received the free (D_FP) or the immobilized cells (D_IPC), for 4 weeks (109 cfu/day, in all groups). At the end of the dietary intervention, D_IPC group exerted lower concentration of the inflammatory cytokine IL-1b compared to D_FP. Consumption of immobilized on Corinthian currants P. acidilactici ORE5 cells by diabetic animals led to increased loads of fecal lactobacilli and lower levels of Enterobacteriaceae, coliforms, and E. coli, while Actinobacteria phylum, Akkermansia, and Bifidobacterium genera abundances were increased, and fecal lactic acid was elevated. Overall, the results of the present research demonstrated that functional ingredients can ameliorate gut dysbiosis present in T1D and could be used to design dietary patterns aiming at T1D management. However, well-designed clinical trials are necessary, in order to confirm the beneficial effects in humans.

Previously, we described a 19-base pair double-stranded RNA with 3'-trinucleotide overhangs, acting as immunostimulatory RNA (isRNA). This molecule demonstrated notable antiproliferative effects on cancer cells, inhibited tumor growth, and elicited immunostimulatory and antiviral responses by inducing cytokine and interferon production. Within this study, we compared the efficiency of lung fibrosis development, initiated in mice by BLM or LPS using different schemes of induction. Then we compared the effect of isRNA used in a preventive or therapeutic regimen on the development of fibrosis in selected BLM- and LPS-induced mouse models and showed that isRNA can be used in pathological conditions accompanied by the development of inflammation and the risk of fibrosis formation, without adverse side effects. Prophylactic regimen of isRNA application is beneficial for prevention of the development of pulmonary fibrosis.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising chemotherapeutic agent because of its selective apoptotic action on cancer cells. However, resistance to TRAIL-induced apoptosis remains a challenge in many cancers. The gintonin-enriched Panax ginseng extract fraction (GEF) has diverse pharmacological benefits. We explored the combined efficacy of GEF and TRAIL in inducing apoptosis in human renal cell carcinoma (RCC) cells. The effect of GEF treatment on viability, clonogenic potential, wound healing, and TRAIL-induced apoptotic signaling of RCC cells was studied in vitro. Our investigation revealed that GEF pre-treatment sensitized RCC cells to TRAIL-induced apoptosis, as evidenced by DNA fragmentation and cell proliferation, colony formation, and migration inhibition. This sensitization was linked to the upregulation of death receptors 4 and 5 and alterations in apoptotic protein expression; notably, decreased expression of Mu-2-related death-inducing gene, a novel anti-apoptotic protein. Our findings underscore the necessity of caspase activation for GEF/TRAIL-induced apoptosis using the pan-caspase inhibitor Z-VAD-FMK. It demonstrates that GEF sensitizes human RCC cells to TRAIL-induced apoptosis by upregulating DR4/5 and modulating apoptotic protein expression. These findings suggest a promising strategy for overcoming TRAIL resistance in cancer therapy and highlight the potential of GEF as a valuable adjunct to TRAIL-based treatments.

Curcumin, a hydrophobic polyphenol compound derived from the rhizome of the Curcuma genus, has a wide spectrum of biological and pharmacological applications. Previously, curcumin nanoparticles with different stabilizers had been produced successfully in order to enhance solubility and per oral absorption. In the present study, we tested the anti-inflammatory effect of D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS)-stabilized curcumin nanoparticles in vivo. Lambda-carrageenan (λ-carrageenan) was used to induce inflammation in rats; it was given by an intraplantar route and intrapelurally through surgery in the pleurisy test. In the λ-carrageenan-induced edema model, TPGS-stabilized curcumin nanoparticles were given orally one hour before induction and at 0.5, 4.5, and 8.5 h after induction with two different doses (1.8 and 0.9 mg/kg body weight (BW)). Sodium diclofenac with a dose of 4.5 mg/kg BW was used as a standard drug. A physical mixture of curcumin-TPGS was also used as a comparison with a higher dose of 60 mg/kg BW. The anti-inflammatory effect was assessed on the edema in the carrageenan-induced paw edema model and by the volume of exudate as well as the number of leukocytes reduced in the pleurisy test. TPGS-stabilized curcumin nanoparticles with lower doses showed better anti-inflammatory effects, indicating the greater absorption capability through the gastrointestinal tract.

Background and objective: Iliopsoas abscess (IPA) is a rare condition with varied symptomology and etiology. Less than one-third of patients with IPA present on the emergency department (ED) admission with the traditional triad of fever, back pain, and restricted hip motion (or limp), leading to delays in diagnosis and management. This case report aims to bring awareness among healthcare professionals regarding the atypical presentation and introduce a potential differential diagnosis when evaluating patients with fever and back pain. The intention is to provide insights into the signs and symptoms that may indicate the presence of an iliopsoas abscess and prompt additional investigations. Case report: Here, we describe a case of primary iliopsoas abscess associated with drug-induced acute liver failure in our ED. The patient complained of pain in the left lumbar region and fatigue that started two weeks before this presentation, claiming that, during the previous night, the pain suddenly worsened. She had a fever, pain at palpation in the right hypochondriac and left lumbar regions, accompanied by fever and vomiting, jaundiced skin, and sclera at the examination in ED. On abdominal ultrasonography, the diagnosis of acute cholangitis was suspected. The laboratory test shows leukocytosis with neutrophilia, thrombocytosis, hepatocytolysis syndrome, and hyperbilirubinemia with the predominance of indirect bilirubin. We performed then abdominal and pelvic computed tomography, which confirmed the diagnosis of cholelithiasis observed with the diameter of the bile duct within normal limits but also showed an abscess-like collection fused to the interfibrillar level of the left iliopsoas muscle; a diagnosis we most likely would have been missed. After that, the patient was hospitalized in the General Surgery Department, and surgery drainage of the abscess was performed. The patient's evolution was excellent; she was discharged after 11 days. Conclusions: The case presented here exemplifies how iliopsoas abscess, a rare cause of back pain, can quickly go unrecognized, especially in the emergency department. Our experiences will raise awareness among doctors in emergency departments about this uncommon but essential diagnosis. With advancements in diagnostic tools and techniques, we aspire that more cases of iliopsoas abscess will be accurately diagnosed.

The epidemic of obesity has increased worldwide and is associated with comorbidities as diabetes as cardiovascular disease. Strategies that modulate body weight and improves glycemic metabolism has increased, and the bariatric surgeries as Sleeve Gastrectomy (SG) has been highlighted in obesity treatment. However, the mechanism by which SG reduces body weight and improves glycemic control are unknow. C57BL mice were submitted to a 10 weeks high fat-diet protocol and submitted to SG. Food intake, fed/fasted glycemia and hypothalamic anorexigenic and orexigenic gene expression were evaluated. SG reduces body weight, fasting glycemia, insulinemia and leptinemia in obese mice. Moreover, SG reduces food and total calorie intake with no alterations in the expression of anorexigenic and orexigenic gene expression. These data indicates that SG improves obesity associated alterations, at least in part, by reduction on food intake. This effect is not associated with the classic food intake pathway in hypothalamus, indicating the involvement of supplementary pathways in this process.

Our hypothesis that controlled ozone applications interfere into the redox balance of the biological organism (first published in 1998 with a preclinical trial on protecting the liver from CCl4 intoxication), has been verified over the last 2 decades in reactive oxygen species (ROS)-induced mitochondrial pathologies, such as rheumatoid arthritis, osteoarthritis, aging processes, diabetes-2 and in prevention of intoxications. Low-dose ozone acts as a redox bioregulator: The restoration of the disturbed redox balance is comprehensible in a number of preclinical and clinical studies by a remarkable increase of the antioxidant repair markers, here mainly shown as glutathione increase and a reduction in oxidative stress markers, mainly malondialdehyde. The mechanism of action is shown, relevant data are displayed, evaluated and comprehensively discussed: The repair side of the equilibrium increases by 21% up to 140% compared to the non-ozone treated groups and depending on the indication; the stress markers are simultaneously reduced, the redox system regains its balance.

Whey protein was pretreated with multi-frequency ultrasound in mono, dual, and tri-frequency modes. The effect of multi-frequency ultrasound pretreatment on the hardness, chemical forces, and microstructure of acid-induced whey protein gel was investigated. Whey protein gels pretreated with dual and tri-frequency ultrasound showed higher hardness (p3.35 mm) in those samples were resisted to gastric digestion. Moreover, the tri-frequency ultrasound pretreatment of whey protein gel released the least free amino group during gastric digestion. In contrast, whey protein gel with the mono-frequency ultrasound pretreatment released the highest amount of free amino acid group during intestinal digestion. Findings from this study suggested that gel hardness and network density could modulate the digestion behaviors of protein gels.

The over use of pharmaceutical compounds, essentially antibiotics, led to an increase of their concentrations in aquatic ecosystems. In this study, the white-rot fungus Coriolopsis gallica (high-laccase-producing fungus) was investigated for the biodegradation of ampicillin (AMP) under different cultivation conditions. The biotransformation of the antibiotic was confirmed by means of high-performance liquid chromatography (HPLC), and the antibacterial activity was evaluated via the bacterial growth inhibition agar well diffusion method using Escherichia coli as an ampicillin-sensitive test strain. The results showed that AMP (50 mg L-1) was totally removed by C. gallica after 6 days of incubation in a liquid medium. The antibiotic removal rate was maximal with a fungal culture aged 9 days. Such a culture achieved the removal of a higher concentration of up to 500 mg L-1 of ampicillin in 3 days. This higher antibiotic removal rate was concomitant with the maximal laccase production in culture supernatant. In addition, four consecutive doses of 500 mg L-1 of ampicillin were transformed by the same fungal culture in 24 days. After that, the fungus was unable to remove the antibiotic. The measurement of ligninolytic enzyme activity showed that laccase of C. gallica might participate in the biotransformation of AMP.

Objective: Lower extremity ischemia-reperfusion injury (IRI) may occur with trauma-related vascular injury and various vascular diseases, during the use of a tourniquet, temporary clamping of the aorta in aortic surgery, and acute or bilateral acute femoral artery occlusion. Mitochondrial dysfunction and increased basal oxidative stress in diabetes may cause an increase in the effects of increased reactive oxygen species (ROS) and mitochondrial dysfunction due to IRI. It is of great importance to examine therapeutic approaches that can minimize the effects of IRI, especially for patient groups under chronic oxidative stress. Cerium oxide (CeO2) nanoparticles mimic the antioxidant enzymes and act as a catalyst that scavenges ROS. In this study, it was aimed to investigate whether CeO2 has protective effects on skeletal muscles in lower extremity IRI in mice with streptozocin-induced diabetes. Methods: A total of 38 Swiss albino mice were divided into six groups as follows: control group (group C, n=6), diabetes group (group D, n=8), diabetes-CeO2 (group DCO, n=8), diabetes-ischemia/reperfusion (group DIR, n=8), and diabetes-ischemia/reperfusion-CeO2 (group DIRCO, n=8). DCO and DIRCO groups were given doses of CeO2 0.5mg/kg intraperitoneally 30 minutes before the IR procedure. A 120-minute ischemia-120-minute reperfusion period with 100% O2 was performed. At the end of the reperfusion period, muscle tissues were removed for histopathological and biochemical examinations. Results: Total antioxidant status (TAS) levels were found to be significantly lower in group DIR compared with group D (p=0.047 and p=0.022, respectively). In group DIRCO and total oxidant status (TOS) levels were found to be significantly higher than in group DIR (p

Sinkhole formation caused by leaking pipes in karst soluble rocks is a significant concern, leading to infrastructure damage and safety risks. In this paper, an experiment was conducted to investigate sinkhole formation in dense sand induced by a leaking pipe. Fibre Bragg gratings (FBGs) sensors were used to record the strain. A balloon was gradually deflated within a bed of wet silica sand to create an underground cavity. Eighteen FBG sensors, with a wavelength range between 1550 nm and 1560 nm, were embedded horizontally and vertically in the physical model at different levels to monitor deformation at various locations. A leaking pipe was installed to induce the collapse of the formed arch above the cavity. The strain measurements suggest four phases in the sinkhole formation process: (1) cavity formation, (2) progressive weathering and erosion, (3) catastrophic collapse, and (4) subsequent equilibrium conditions. The results showed differences in strain signatures and distributions between horizontal and vertical measurements. During the critical phase of sinkhole collapse, horizontal measurements primarily showed tension, while vertical measurements indicated compression. This investigation demonstrates the effectiveness of FBGs as advanced monitoring tools for sinkhole precursor identification. The study also suggests using FBGs in geotechnical monitoring applications to improve understanding and mitigation of sinkholes and related geohazards.

Acute Respiratory Distress Syndrome (ARDS) is a severe lung condition with a high mortality rate for which there are no effective therapeutics. The failure of the alveolar-capillary barrier, composed of lung endothelial (EC) and alveolar epithelial (AEC) cells, is a critical factor leading to excessive inflammation and edema characteristics of acute lung injury (ALI). Phosphodiesterases (PDE) are enzymes well-recognized for their roles in regulating endothelial permeability and inflammation. Although PDE inhibitors are used as therapeutics for inflammatory diseases like COPD (chronic obstructive pulmonary disease), their efficacy in treating ARDS has not yet been established. In this study, we investigate the effects of ensifentrine, an FDA-approved novel dual PDE 3/4 inhibitor, on lung endothelial and epithelial dysfunction caused by methicillin-resistant S. aureus (MRSA), a pathogen involved in bacterial ARDS. Human primary lung endothelial cells and alveolar epithelial cell lines (A549 and immortalized AEC) were treated with heat-killed MRSA, and their responses were assessed in the presence or absence of ensifentrine. Ensifentrine given either pre- or post exposure attenuated MRSA-induced increased lung endothelial permeability. VE-cadherin junctions, which serve to stabilize the EC barrier, were disrupted by MRSA; however, ensifentrine effectively prevented this disruption. Pre-treatment with ensifentrine protected against MRSA-induced EC pro-inflammatory signaling by inhibiting the expression of VCAM-1, ICAM-1, and by reducing the IL-6 release. In AEC, MRSA caused upregulation of ICAM-1, activation of NF-kB and production of IL-8, all of which were inhibited by ensifentrine. These results indicate that dual inhibition of phosphodiesterases 3 and 4 by ensifentrine is barrier protective and attenuates MRSA-induced inflammation in both lung endothelial and epithelial cells. The PDE3/4 inhibitor ensifentrine may represent a promising novel strategy for the treatment of ALI.

(1) Background: Globally, about 600 million people are afflicted with diabetes, and one of its most prevalent complications is neuropathy, a debilitating condition. At present, the exploration of novel therapies for alleviating diabetic neuropathy-associated pain is genuinely captivating, considering that current therapeutic options are characterized by poor efficacy and significant risk of side effects. In the current research, we evaluated the antihyperalgesic effect of sildenafil (phosphodiesterase-5 inhibitor) – metformin (antihyperglycemic agent) combination and its impact on biochemical markers in alloxan-induced diabetic neuropathy in rats; (2) Methods: The study comprised a cohort of 70 diabetic rats and 10 non-diabetic rats which were submitted to hot, cold, and tactile stimulus tests. Morover, we investigated the influence of this combination on TNF-α, IL-6 nitrites and thiols levels in brain and liver tissues; (3) Results: The results demonstrated that all sildenafil-metformin combinations decreased the pain sensitivity in von Frey test, Hot-plate test and Cold-plate test. Furthermore, alterations in nitrites and thiols concentrations and pro-inflammatory cytokines (specifically TNF-α and IL-6) were noted following a 15-day regimen of various sildenafil-metformin combinations. (4) Conclusions: The combination of sildenafil and metformin has a synergistic effect in alleviating pain in alloxan-induced diabetic neuropathy rats. Additionally, the combination effectively decreased inflammation, inhibited the rise in NOS activity, and provided protection against glutathione depletion.

Background: beta blockers of three generations are first-line drugs in the treatment of chronic heart failure (CHF). However, to date there is no clear understanding of the effect of beta blockers on myocardial energy metabolism disorders in CHF. The aim of the study: to conduct a study of beta-blockers of different generations on myocardial energy metabolism in the experimental CHF. Methods: CHF was modeled in white outbred rats by administering doxorubicin. The study drugs were administered intragastrically – new drug Hypertril (1-(β-phenylethyl)-4-amino-1,2,4-triazolium bromide)-3.5 mg/kg, metoprolol - 15 mg/kg, Nebivolol -10 mg/kg, Carvedilol 50 mg/kg, Bisoprolol, 10 mg/kg. In the myocardium, the main indices of energy metabolism were determined - ATP, ADP, AMP, malate, lactate, pyruvate, succinate dehydrogenase (SDH) activity, NAD-dependent malate dehydrogenase (NAD-MDH) activity. Results: traditional second-generation beta-blockers (Metoprolol and Bisoprolol) did not affect the studied indices of energy metabolism, and third-generation beta-blockers with additional properties - Carvedilol and, especially, Nebivalol and Hypertril improved myocardial energy metabolism. Conclusions: obtained results will help to expand our understanding of the effect of beta-blockers of various generations used to treat cardiovascular diseases on energy metabolism, and are also an experimental justification for the practical choice of these drugs in the complex therapy of CHF.

Epigenetic mechanisms, including histone post-translational modifications (PTMs), play a critical role in regulating pain perception and the pathophysiology of burn injury. However, the epigenetic regulation and molecular mechanisms underlying burn injury-induced pain remain insufficiently explored. Spinal dynorphinergic (Pdyn) neurons contribute to heat hyperalgesia induced by severe scalding-type burn injury through p-S10H3-dependent signaling. Beyond p-S10H3, burn injury may impact various other histone H3 PTMs. Double immunofluorescent staining and histone H3 protein analyses demonstrated significant hypermethylation at H3K4me1 and H3K4me3 sites and hyperphosphorylation at S10H3 within the spinal cord. By analyzing Pdyn neurons in the spinal dorsal horn, we found evidence of chromatin activation with a significant elevation in p-S10H3 immunoreactivity. We used RNA-seq analysis to compare the effects of burn injury and forma-lin-induced inflammatory pain on spinal cord transcriptomic profiles. We identified 98 DEGs for burn injury and 86 DEGs for formalin-induced inflammatory pain. A limited number of shared differentially expressed genes (DEGs) suggest distinct central pain processing mechanisms between burn injury and formalin models. KEGG pathway analysis supported this divergence, with burn injury activating Wnt signaling. This study enhances our understanding of burn injury mechanisms and uncovers converging and diverging pathways in pain models with different origins.

Introduction: Substance-induced psychotic disorder (SIPD) is a mental health condition linked to the use of a psychotropic substance whose pathogenesis has not been totally clarified. The present retrospective observational study has the objective to identify differences in clinical features and peripheral biomarkers in SIPD patients according to the main substance of abuse.Methods: A total sample of 218 patients was divided in 3 groups according to the type of consumed substance: alcohol, cannabis and psychostimulants. The 3 groups were compared for continuous variables by one-way analyses of variance (ANOVAs) and for qualitative variables by χ² tests. After removing alcohol-induced psychotic disorder group, the same analyses were repeated. Statistically significant variables from these latter analyses were included in a binary logistic regression model to confirm their reliability as predictors for cannabis- or psychostimulants-induced psychotic disorders. Results: Psychotic cannabis abusers were younger (p<0.01) and had an earlier age at onset (p<0.01). On the contrary, alcohol consumers resulted to have a longer duration of illness (p<0.01), more previous hospitalizations (p=0.04), more frequent medical comorbidity (p<0.01), higher mean Modified Sad Person Scale scores (p<0.01). Finally, psychostimulant abusers had more frequently a lifetime history of poly-substance use disorders (p<0.01). Binary logistic regression revealed that higher mean Brief Psychiatric Rating Scale scores (p<0.01) higher sodium (p=0.012) and haemoglobin(p=0.040) plasma levels were predictors of cannabis misuse in SIPD patients.Conclusions: Different clinical factors and biochemical parameters con be associated to SIPD according to the main substance of abuse, thus requiring a specific management by clinicians.

The present study analyses the influence of scratches and fatigue on the mechanical characteristics of aluminium alloys commonly used in the aviation industry: 2024-T4, 6061-T4, 6061-T4 uncoated, 6061-T6 uncoated, 7075-T0, and 7076-T6. 120 specimens were used for the study. Out of these, 60 samples were scratched, and the other 60 samples were also scratched under the same circumstances and then subjected to low-cycle fatigue (LCF) before undergoing the tensile test. Based on the statistical examination of the measured data, mathematical prediction models have been established. Compared to their unscratched counterparts, the results indicate a significant decrease in the mechanical properties of both scratched and scratched-fatigued sample sets. The LCF pre-treatment contributes to the negative impacts of scratches, resulting in a reduced value for the ultimate tensile strength and elongation at break. The results conclude that surface integrity plays an essential role in preserving aircraft components' structural strength.