Macrophages serve as vital defenders, protecting the body by exhibiting remarkable cellular adaptability in response to invading pathogens and various stimuli. These cells express nicotinic acetylcholine receptors, with the α7-nAChR being extensively studied due to its involvement in activating the cholinergic anti-inflammatory pathway. Activation of this pathway plays a crucial role in suppressing macrophages' production of proinflammatory cytokines, thus mitigating excessive inflammation and maintaining host homeostasis. Macrophage polarization, which occurs in response to specific pathogens or insults, is a process that has received limited attention concerning the activation of the cholinergic anti-inflammatory pathway and the contributions of the α7-nAChR in this context. This review aims to present evidence highlighting how the cholinergic machinery in macrophages, led by the α7-nAChR, facilitates the polarization of macrophages towards anti-inflammatory phenotypes. Additionally, we explore the influence of viral infections on macrophage inflammatory phenotypes, taking into account cholinergic mechanisms. We also review the current understanding of macrophage polarization in response to these infections. Finally, we provide insights into the relatively unexplored partial duplication of the α7-nAChR, known as dup α7, which is emerging as a significant factor in macrophage polarization and inflammation scenarios.

The characteristics of gap plasmon formed by nanoparticle-on-mirror (NPOM) structure composed of metal nanoparticles (MNP) and metal thin films have aroused the interest of various optoelectronic devices. The resonant spectrum obtained by the internal coupling effect of gap can be flexibly controlled by the polarization of incident light and the thickness of the dielectric layer between MNP and metal thin films. We have theoretically studied the resonance spectra of polarization-dependent gold ellipsoidal nanoparticles (GENP) and gold thin films in the gap region of NPOM structures. GENP and gold thin films are separated by a dielectric layer with a refractive index of 1.36. We observe that the intensity of the local electric field resonance peak in the gap region is inversely proportional to the polarization angle. Similarly, the intensity of the local electric field resonance peak in the gap region is inversely proportional to the thickness of the dielectric layer. We have obtained more than 2200 V/m local electric field intensity (dielectric layer thickness 0.3nm). Finally, the resonant peak wavelength of the electric field in the gap region of the NPOM structure is also controlled by the polarization angle of the incident light and the thickness of the dielectric layer.

Previous evidence in support of a slowly acting (scale of 100s of seconds) and volume-transmitted component of cholinergic signaling was based largely on studies using measures of extracellular brain acetylcholine (ACh) levels which required several minutes to generate a single data point and typically employed AChEsterase inhibitors (AChEIs) to foster the measurement of ACh. Moreover, collecting such data points in correlation with relatively stable behavioral states has supported the view that extracellular ACh levels vary at a relatively slow rate. Here we argue that forebrain cholinergic signaling is exclusively phasic (milliseconds to perhaps seconds), unlikely to be volume-transmitted, and that previous neurochemical evidence and associated behavioral correlates may be re-interpreted in terms of integrated phasic cholinergic activity and specific behavioral and cognitive operations. The highly potent catalytic enzyme for ACh, AChE, limits the presence of an ambient extracellular ACh level and thus renders it unlikely that ACh influences target regions via relatively slow changes in extracellular ACh concentrations. Real-time amperometric recordings of cholinergic signaling have suggested a specific function of rapid, phasic or transient cholinergic signaling in attentional contexts. Optogenetic studies support a causal relationship between these transients on behavior. Combined electrochemical and neurophysiological recordings revealed that the powerful behavioral control by cholinergic transients involves the generation of high-frequency oscillations. Such oscillations are thought to recruit efferent circuitry to (re)activate dormant task sets. Evidence showing the impact of genetic variations of the capacity of cholinergic synapses likewise can be interpreted in terms of their impact on the ability to sustain generation of repeated phasic cholinergic signals, as opposed to effects on ambient ACh levels. Further, while notions of slowly-changing, sleep stage-associated variations in extracellular ACh levels and their functions are widely accepted, the evidence is in fact limited. An alternative hypothesis offers a role for high-frequency cholinergic transient signaling during REM sleep. By employing a theoretical framework that focuses on the phasic and causative characteristics and functions of cholinergic signaling, results from human cognitive neuroscience studies of cholinergic function may be substantially clarified and simplified. Compared to the current treatment of cholinergic deficits using AChEIs, the conceptualization of forebrain cholinergic signaling as wired, phasic, and causative predicts that drugs that either rescue transient presynaptic signaling or amplify or rescue the postsynaptic impact of phasic signals will be more efficacious in treating age- and dementia-related cognitive and cognitive-motor disorders.

Despite the relative scarcity of studies focusing on pharmacotherapy in aphasia, there is evidence in the literature indicating that remediation of language disorders via pharmaceutical agents could be a promising aphasia treatment option. Among the various agents used to treat chronic aphasic deficits, cholinergic drugs have provided interesting results. In the current review, we focused on published reports investigating the impact of acetylcholine on language and further cognitive disturbances. It has been suggested that acetylcholine plays an important role in neuroplasticity and is related to several aspects of cognition, such as memory and attention. Moreover, cholinergic input is diffused to a wide network of cortical areas, which have been associated with language sub-processes. This could be a possible explanation for the positive reported outcomes of cholinergic drugs in aphasia recovery, and specifically in distinct language processes, such as naming and comprehension, as well as overall communication competence. However, evidence with regard to functional alterations in specific brain areas after pharmacotherapy is rather limited. Finally, despite the positive results derived from the relevant studies, cholinergic pharmacotherapy treatment in post-stroke aphasia has not been widely implemented. The present review aims to provide an overview of the existing literature in cholinergic pharmacotherapy interventions in post-stroke aphasia, following an integrated approach by converging evidence from neuroanatomy, neurophysiology, and neuropsychology.

Theoretical studies on the generation of nondiffracting and nondispersive light pulses and their experimental implementation are one of the renowned problems within electromagnetics. Current technologies enable creation of short-duration pulses of a few cycles with high power and fluency. An application of these techniques to the field of nondiffracting and nondispersive pulses requires a proper mathematical description of highly focused vector pulses. In this work, we study vector optical bullets in a dielectric medium with different polarization structures: linear, azimuthal, and radial. We report the differences caused by the vector model compared to the scalar model. We analyze effects caused by superluminal, subluminal, or even negative group velocity on properties of vector optical bullets inside a dielectric material.

Relativistic shocks are one of the most plausible sites of the emission of strongly variable, polarized multi-wavelength emission from relativistic jet sources such as blazars, via diffusive shock acceleration (DSA) of relativistic particles. This paper summarizes recent results on a self-consistent coupling of diffusive shock acceleration and radiation transfer in blazar jets. We demonstrate that the observed spectral energy distributions (SEDs) of blazars strongly constrain the nature of hydromagnetic turbulence responsible for pitch-angle scattering by requiring a strongly energy-dependent pitch-angle mean free path. The prominent soft X-ray excess (``Big Blue Bump'') in the SED of the BL Lac object AO 0235+164 can be modelled as the signature of bulk Compton scattering of external radiation fields by the thermal electron population, which places additional constraints on the level of hydromagnetic turbulence. It has further been demonstrated that internal shocks propagating in a jet pervaded by a helical magnetic field naturally produce polarization-angle swings by 180$^o$, in tandem with multi-wavelength flaring activity, without requiring any helical motion paths or other asymmetric jet structures. The specific application of this model to 3C279 presents the first consistent, simultaneous modeling of snap-shot SEDs, multi-wavelength light curves and time-dependent polarization signatures of a blazar during a polarization-angle (PA) rotation. This model has recently been generalized to a lepto-hadronic model, in which the high-energy emission is dominated by proton synchrotron radiation. It is shown that in this case, the high-energy (X-ray and $\gamma$-ray) polarization signatures are expected to be significantly more stable (not showing PA rotations) than the low-energy (electron-synchrotron) signatures.

Aiming at the limitations of single-functionality, limited applicability, and complex designs prevalent in current metasurfaces, we propose a terahertz multifunctional and multiband tunable metasurface utilizing a VO2-metal hybrid structure. This metasurface structure comprises a top VO2-metal resonance layer, a middle polyimide dielectric layer, and a gold film reflective layer at the bottom. This metasurface exhibits multifunctionality, operating independently of polarization and incident angle. The varying conductivity states of the VO2 layers, enable the metasurface to achieve various terahertz functionalities, including single-band absorption, broadband THz absorption, and multiband perfect polarization conversion for linear (LP) and circularly polarized (CP) incident waves. Finally, we believe that the functional adaptability of the proposed metasurface expands the repertoire of options available for future terahertz device designs.

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.

A simple design of an ultrathin six-band polarization-insensitive terahertz perfect metamaterial absorber (PMMA) composed of a metal cross-cave-patch resonator (CCPR) placed over a ground plane was proposed and investigated numerically. The numerical simulation results demonstrate that the average absorption peaks are up to 95% at six resonance frequencies with high quality-factors (>65). In addition, the absorption properties can be kept stability for both normal incident transverse magnetic (TM) and transverse electric (TE) waves. The physical mechanism behind the observed high level absorption is illustrated by the electric and power loss density distributions. The different absorption mainly originates from the higher order multipolar and multipolar plasmon resonance of the structure, which are sharp different to the most previous studies of the PMMAs. Furthermore, the resonance absorption of the PMMA can be tunable by varying the geometric parameters of the unit cell.

A simple design of an ultrathin six-band polarization-insensitive terahertz perfect metamaterial absorber (PMMA) composed of a metal cross-cave-patch resonator (CCPR) placed over a ground plane was proposed and investigated numerically. The numerical simulation results demonstrate that the average absorption peaks are up to 95% at six resonance frequencies with high quality-factors (>65). In addition, the absorption properties can be kept stability for both normal incident transverse magnetic (TM) and transverse electric (TE) waves. The physical mechanism behind the observed high level absorption is illustrated by the electric and power loss density distributions. The different absorption mainly originates from the higher order multipolar and multipolar plasmon resonance of the structure, which are sharp different to the most previous studies of the PMMAs. Furthermore, the resonance absorption of the PMMA can be tunable by varying the geometric parameters of the unit cell.

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.

Duchenne muscular dystrophy (DMD) is caused by genetic mutations in the cytoskeletal-sarcolemmal anchor protein dystrophin. Repeated cycles of sarcolemmal tearing and repair lead to a variety of secondary cellular and physiological stressors that are thought to contribute to weakness, atrophy, and fibrosis. Collectively, these stressors can contribute to a pro-inflammatory milieu in locomotor, cardiac, and respiratory muscles. Given the many unwanted side effects that accompany current anti-inflammatory steroid-based approaches for treating DMD (e.g., glucocorticoids), there is a need to develop new therapies that address inflammation and other cellular dysfunctions. Adiponectin receptor (AdipoR) agonists, which stimulate AdipoR1 and R2 isoforms on various cell types, have emerged as therapeutic candidates for DMD due to their anti-inflammatory, anti-fibrotic, and pro-myogenic properties in pre-clinical human and rodent DMD models. Although these molecules represent a new direction for therapeutic intervention, the mechanisms through which they elicit their beneficial effects are not yet fully understood, and DMD-specific data is limited. The overarching goal of this review is to investigate how adiponectin signaling may ameliorate pathology associated with dystrophin deficiency through inflammatory-dependent and -independent mechanisms, and to determine if current data supports their future progression to clinical trials.

Stimulation of the alpha 7 nicotinic acetylcholine receptor (α7nAChR) has shown beneficial effects in several acute inflammatory disease models. This study aims to examine whether treatment with the selective α7nAChR agonist PHA 568487 can dampen inflammation and thereby improve cardiac function after myocardial infarction in mice. The possible anti-inflammatory properties of α7nAChR agonist PHA 568487 were tested in vivo using the air pouch model and in a permanent occlusion model of acute myocardial infarction in mice. Hematology parameters and cytokine levels were determined. Infarct size and cardiac function were assessed via echocardiography 24 h and one week after the infarction. Treatment with α7nAChR agonist PHA 568487 decreased 12 (CCL27, CXCL5, IL6, CXCL10, CXCL11, CXCL1, CCL2, MIP1a, MIP2, CXCL16, CXCL12 and CCL25) out of 33 cytokines in the air pouch model of acute inflammation. However, α7nAChR agonist PHA 568487 did not alter infarct size, ejection fraction, cardiac output or stroke volume at 24 h nor at 7 days after the myocardial infarction compared with control mice. In conclusion, despite promising immunomodulatory effects in the acute inflammatory air pouch model, α7nAChR agonist PHA 568487 did not affect infarct size or cardiac function after a permanent occlusion model of acute myocardial infarction in mice. Consequently, this study does not strengthen the hypothesis that stimulation of the α7nAChR is a future treatment strategy for acute myocardial infarction when reperfusion is lacking. However, whether other agonists of the α7nAChR can have different effects remains to be investigated.

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.

Background: In this investigation, we explored the effects of pharmacological cholinergic stimulation on cardiac function and renal inflammation following acute myocardial infarction (AMI) in spontaneously hypertensive rats (SHRs). Methods: Adult male SHRs were randomized into three experimental groups: sham-operated; AMI+Veh (infarcted, treated with vehicle); and AMI+PY (infarcted, treated with the cholinesterase inhibitor pyridostigmine bromide (PY) - 40 mg/kg, once daily for seven days). Rats were euthanized 7 or 30 days post-surgery. Clinical parameters were assessed on the day before euthanasia. Subsequent to euthanasia, blood samples were collected and renal tissues were harvested for histological and gene expression analyses aimed to evaluate inflammation and injury. Results: Seven days post-surgery, the AMI+PY group demonstrated improvements in left ventricular diastolic function and autonomic regulation, and a reduction in renal macrophage infiltration compared to the AMI+Veh group. Furthermore, there was a notable downregulation of pro-inflammatory gene expression and an upregulation of anti-inflammatory gene expression. Analysis 30 days post-surgery showed that PY treatment had a sustained positive effect on renal gene expression, correlated with a decrease in biomarkers indicative of subclinical kidney injury. Conclusion: Short-term cholinergic stimulation with PY provides both cardiac and renal protection by mitigating the inflammatory response after AMI.

Tumor necrosis factor receptor 2 or TNFR2 is considered as an appealing target protein due its limited frequency to Tregs which are highly immunosuppressive and its presence on human malignancies. Numerous studies have revealed that TNFR2 is primarily found on MDSCs (myeloid derived suppressor cells) and CD⁺Foxp3⁺ regulatory T cell (Tregs). It has a great importance in the proliferation and functional activity of Tregs and MDSCs. To treat malignancies and diseases like autoimmune disorder, the suppressor activity of TNFR2 must be eliminated by downregulation or upregulation. Therefore, at the molecular level, advances in comprehension of TNFR2's complex structure and its binding to TNF have opened the door to structure-guided drug development. Two key obstacles of cancer treatment are the dearth of Treg-specific inhibitors and the lack of widely applicable ways to directly target tumors via frequently expressed surface oncogenes. Many researchers have discovered potential antagonist and agonist of TNFR2 which were successful in the inhibition of Tregs proliferation, reduction of soluble TNFR2 secretion from normal cells and in the expansion of T effector cells. The representation of the data in the following review article elucidates the clinically administrated TNFR2 antagonist and agonist in the treatment of cancers.

The agonist-antagonist myoneural interface (AMI), a surgical method to reinnervate physiologically-relevant proprioceptive feedback for control of limb prostheses, has demonstrated the ability to provide natural afferent sensations for limb amputees when actuating their prostheses. Following an AMI surgery, one potential challenge is atrophy of the disused muscles, which would weaken the reinnervation efficacy of AMI. It is well known that electrical muscle stimulus (EMS) can reduce the muscle atrophy. In this study, we conducted an animal investigation to explore whether the EMS can significantly improve the electrophysiological performance of AMI. The AMI surgery was performed in 14 rats, in which the distal tendons of bilateral solei donors were connected and positioned on the surface of the left biceps femoris. Subsequently, the left tibial nerve and the common peroneus nerve were sutured onto the ends of the connected donor solei. Two stimulation electrodes were affixed onto the ends of the donor solei for EMS delivery. The AMI rats were randomly divided into two groups. One group regularly received the EMS treatment (designated as EMS_on) for eight weeks and another was no EMS (designated as EMS_off). Two physiological parameters, nerve conduction velocity (NCV) and motor unit number, were derived from the electrically evoked compound action potential (CAP) signals to assess the electrophysiological performance of AMI. Our experimental results demonstrated that the reinnervated muscles of the EMS_on group generated higher CAP signals in comparison to the EMS_off group. Both NCV and motor unit number were significantly elevated in the EMS_on group. Moreover, the EMS_on group displayed statistically higher CAP signals on the indirectly activated proprioceptive afferents than the EMS_off group. These findings may suggested that the EMS treatment would be promise in enhancing the electrophysiological performance and facilitating the reinnervation process of AMI.

The G-protein-coupled estrogen receptor (GPER; G protein-coupled estrogen receptor 30, also known as GPR30) is a novel estrogen receptor and has emerged as a promising target for ovarian cancer. GPER, a seven-transmembrane receptor, suppresses cellular viability and migration in studied ovarian cancer cells. However, its impact on the fallopian tube, which is the potential origin of high-grade serous (HGSC) ovarian cancer, has not been addressed. This study was conducted to evaluate the relationship of GPER, ovarian cancer subtypes, i.e., high-grade serous cell lines (OV90 and OVCAR420), as well as potential HGSC ovarian cancer origin (i.e., the fallopian tube cell line FT190). The selective ligand assessed here is the agonist G-1, which was utilized in an in vitro study to characterize its effects on cellular viability and migration. As a result, this study has addressed the effect of a specific GPER antagonist in combination with an agonist on cell viability, providing a better understanding of the effects of these compounds on our diverse group of studied cell lines. Strikingly, attenuated cell proliferation and migration behaviors were observed in the presence of G-1. Thus, our in vitro study reveals the impact of the origin of HGSC ovarian cancers and highlights the GPER agonist G-1 as a potential therapy for ovarian cancer.

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.

Macrophages are essential innate immune cells characterized by a high diversity and plasticity. In vitro, their full dynamic range of activation profiles include the classical pro-inflammatory (M1) and the alternative anti-inflammatory (M2) program. Bistability usually arises in biological systems that contain a positive-feedback loop or a mutually inhibitory, double-negative-feedback loop, which are common regulatory motifs reported for macrophage transitions from one activation state to the other one. This switch-like behavior of macrophage is observed at four different levels. First, a decision-making module in signal transduction includes mutual inhibitory interactions between M1 (STAT1 and NF-KB/p50-p65) and M2 (STAT3 and NF-KB/p50-p50) signaling pathways. Second, a switch-like behavior at the gene expression level includes complex network motifs of transcription factors and miRNAs. Third, those changes impact metabolic gene expression leading to several switches in energy production, NADPH and ROS production, TCA cycle functionality, biosynthesis and nitrogen metabolism. Fourth, metabolic changes are monitored by specialized metabolic sensors coupled to AMPK and mTOR activity to provide stability by maintaining the signals to promote either M1 or M2 activation. The targeting of robust molecular switches has the potential to treat a broad range of widespread diseases such as sepsis, cancer or chronic inflammatory diseases.

In this article various heuristic approaches are discussed to solve the dark matter phenomenon by the concept of vacuum polarization. They are compared with a more fundamental approach, based upon an entropy model of the visible universe. They all make use of some kind of gravitational dipole. These dipoles seem to violate Einstein’s equivalence principle between inertial mass and gravitational mass. It is shown how the paradox can be solved by a quantum mechanical principle.

Based on some experiments, the paper describes with the help of polarization the physic-chemical processes that take place in the contact area of friction pairs, during the selective transfer as a result of the change in the input speed of the lubricant (glycerin), as well as how it influences their wear. Through polarization, the quantitative and qualitative transformations of glycerin are studied during frictional stress with selective transfer, the determination of the properties of the selective solution, and the damage to the metals and alloys of the friction pairs, but also after frictional stress.

This research presents the design and characteristics of new wideband polarizer based on the square waveguide with irises. Matching and polarization characteristics of the polarizer have been simulated and optimized. Frequency dependences of the characteristics are presented. Developed polarizer can be applied in satellite information systems.

In this letter, we propose a pattern-diversity antenna with different radiation patterns at two different frequency bands (f1 and f2) (f1: broadside radiation pattern, f2: conical radiation pattern). The proposed structure consists of a central circular antenna and two annular ring antennas; each of the three antennas has individual ports. Two of the ports exhibit orthogonal broadside radiation patterns; the other two ports exhibit orthogonal conical radiation patterns. Thus, they have polarization diversity characteristics. To improve isolation between ports, the inner part of the annular ring antennas is shorted via array, and the outermost port is positioned orthogonal to the other ports. Using this configuration, the isolation between ports was measured as -26.7 dB and -30.1 dB at the two frequency bands, respectively. Experimental results based on the fabricated prototype show that the proposed antenna achieves -10 dB bandwidths of 240 MHz (5.71~5.95 GHz) and 210 MHz (7.69~7.9 GHz) at f1 and f2, respectively.

We report on the role of synergistic polarization of Ba0.9Sr0.1TiO3 (BST) nanoparticles in sulfur cathodes to enhance the redox kinetics of polysulfides for high-capacity Li-S batteries. Ferroelectric nanoparticles are known to significantly improve the electrochemical performance of Li-S batteries due to their inherent self-polarization and high adsorption capacity towards polysulfides. X-ray diffraction spectra confirmed the tetragonal symmetry (c/a=1.0073), while Raman spectroscopic analysis validated the presence of tetragonal orientation Raman modes in BST-modified composites. Scanning electron microscope (SEM) images showed a homogeneous distribution of BST in the sulfur cathode system, with grain sizes ranging from 1 to 1.5 μm. Notably, the BST-coupled S50BST30CB10PVDF10 composite cathode achieved a capacity of approximately 820 mAh/g at 100 mA/g, maintaining stability over 100 cycles, demonstrating improved electrochemical performance. Two distinct plateaus between 2.3 V to 2.0 V and 2.0 V to 1.5 V further underscore the superior performance of BST ferroelectric nanoparticles in enhancing the redox kinetics of Li-S batteries. By leveraging the favourable affinity of polar substances towards polysulfides, we aimed to create a more stable reactive environment within the cathodic site, effectively trapping polysulfide intermediates through the synergistic polarization of BST nanoparticles. The synergistic polarization induced by the asymmetric crystal structure of ferroelectrics is anticipated to generate internal electric fields, enhancing chemisorption with heteropolar reactive. The observed high cyclic stability further validates the efficacy of these composite cathodes in mitigating the polysulfide shuttle effect, offering promising prospects for advancing Li-S battery technology.

Fixed-time artificial insemination is an important technique in swine production that can improve reproductive efficiency and meat production quality by making better use of the genetic potential of breeding males and reducing the costs associated with double or multiple inseminations. Our goal was to evaluate the vaginal application of the GnRH agonist triptorelin acetate to synchronize post-weaning sows and facilitate implantation of a single fixed-time insemination. In a first experiment, the efficacy of treatment with the triptorelin in animals with or without signs of estrus was analyzed using a single insemination at a fixed time compared to the control following the standard insemination strategy. Farrowing rate was comparable between triptorelin and control groups (100 vs. 87.50%), but triptorelin without estrus had a lower rate (50%). Litter size did not differ between groups. Estradiol and progesterone levels at 96- and 120-hours post-weaning were similar in the control and triptorelin groups (P>0.05). These results suggest that Triptorelin has the potential to synchronize ovulation in pigs without affecting post-weaning hormonal profiles. In a second experiment, the objective was to evaluate the productive and economic impact of implementing a treatment with triptorelin acetate 96 hours after weaning compared to the standard insemination protocol. Sows were grouped according to treatment (control vs. triptorelin) and estrus onset (≤5 days and >5 days after weaning considered as late estrus). Farrowing rate was lower in the control late estrus group than in the control and triptorelin groups and similar to the triptorelin late estrus group. No differences were found for litter size, live or dead piglets born (P>0.05). We developed an estimation model to assess the cost/benefit of intravaginal triptorelin administration at 96 h post-weaning. The overall result is that the use of triptorelin increases the benefit per inseminated sow in the range of €15-20. This improvement is mainly related to an increase in the reproductive performance of the treated sows compared to the control sows and the reduction in the number of inseminations per sow. These results highlight the potential of triptorelin to optimize reproductive management in pigs, improving efficiency and economic viability.

Despite numerous studies on cancer treatment, cancer remains a challenging disease to cure, even after decades of research. In recent years, cancer vaccine has emerged as a promising approach for cancer treatment, offering few unexpected side effects compared to existing therapies. How-ever, cancer vaccine faces obstacles to commercialization due to its low efficacy. Particularly, the Toll-like receptor (TLR) adjuvant system, specifically the TLR 7/8 agonist, has shown potential for activating Th1 immunity, which stimulates both innate and adaptive immune responses through T cells. In this study, we developed ProLNG-S, a cholesterol-conjugated form of resiquimod (R848), to enhance immune efficacy by stimulating the immune system and reducing toxicity. ProLNG-S was formulated as ProLNG-001, a positively charged liposome, and co-administered with oval-bumin (OVA) protein in the B16-OVA model. ProLNG-001 effectively targeted secondary lym-phoid organs, resulting in a robust systemic anti-tumor immune response and tumor-specific T cell activation. Consequently, ProLNG-001 demonstrated potential for preventing tumor progression and improving survival compared to AS01 by enhancing anti-tumor immunity.

The challenge of achieving ultrafast switching of electric polarization in ferroelectric materials remains unsolved, as there is no experimental evidence of such switching to date. In this study, we have developed an enhanced model that describes switching within a two-dimensional space of generalized coordinates. Our findings indicate that stable switching in barium titanate cannot be achieved through a single linearly polarized pulse. When the intensity of the linearly polarized pulse reaches a certain threshold, the sample experiences depolarization, but not stable switching. Our study also reveals that phonon friction plays a minor role in the switching dynamics and provides an estimate of the optimal parameters of the perturbing pulse with the lowest intensity that results in depolarization of an initially depolarized sample.

Leishmaniasis is a complex infectious parasitic disease caused by protozoa of the genus Leishmania, belonging to a group of neglected tropical diseases. It poses significant global health challenges, particularly in socio-economically disadvantaged regions. Macrophages, as innate immune cells, play a crucial role in initiating the inflammatory response against the pathogens responsible for this disease. Macrophage polarization, the process of differentiating macrophages into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes, is essential for the immune response in leishmaniasis. The M1 phenotype is associated with resistance to Leishmania infection, while the M2 phenotype is predominant in susceptible environments. Notably, various immune cells, including T cells, play a significant role in modulating macrophage polarization by releasing cytokines that influence macrophage maturation and function. Furthermore, other immune cells can also impact macrophage polarization in a T-cell-dependent manner. Therefore, this review comprehensively examines macrophage polarization's role in leishmaniasis and other immune cells' potential involvement in this intricate process.

Chloracne is the major skin symptom caused by dioxin intoxication. Dioxin activates the aryl hydrocarbon receptor (AHR)–cytochrome p450 1A1 (CYP1A1) system, generates oxidative stress, and induces hyperkeratinization of keratinocytes and sebocytes leading to chloracne. Nuclear factor-erythroid 2-related factor-2 (NRF2) is a master switch inducing expression of various antioxidative enzymes such as heme oxygenase-1. Cinnamaldehyde is an antioxidant phytochemical that inhibits AHR–CYP1A1 signaling and activates the NRF2–antioxidative axis. The cinnamaldehyde-containing Kampo herbal medicine Keishibukuryogan is capable of improving chloracne in Yusho patients who are highly contaminated with dioxin. Agents with dual functions in promoting AHR–CYP1A1 inhibition and NRF2 activation may be useful in managing dioxin-related health hazards.

Antibiotic beads were used to treat surgical infections. In this study, polylactide–polyglycolide (PLGA) was mixed with vancomycin, osteogenic enhancer lithium chloride (LiCl), and hot com-pressing to form PLGA-vancomycin-LiCl delivery beads to treat bone infection. An elution method was employed to characterize the in vitro release characteristics of the vancomycin and the Li over a 42-day period. The released profiles lasted for more than 42 days for vancomycin and 28 days for Li. The concentration of vancomycin in each sample was well above the breakpoint sensitivity. Lithium co-treatment enhanced the bactericidal effect of vancomycin. Released Li and vancomycin increased mRNA or protein expressions of osteogenic markers of mesenchymal stem cells (MSCs). In vivo, the PLGA delivery systems were implanted into the rabbit distal femoral cavities and the cavity fluid content was aspirated and analyzed at each time point. The released Li and vancomycin lasted more than 6 weeks, and vancomycin concentrations were much above the breakpoint sensitivity. Four rabbits in each group were killed at 8 weeks for histologic observation. More mature bone tissue was shown in the Li treatment group. This study provides a PLGA drug delivery system to meet the requirements of patients with bone infections.

Reductive amination is a powerful tool in sustainable organic synthesis that allows chemists to access a wide range of valuable amine products using renewable feedstocks, mild reaction con-ditions, and with minimal waste generation. Practical applications can be found in various fields, including pharmaceuticals, contributing to greener and more sustainable chemical processes. In this work we present a heterogeneous (Rh and Pt) catalysed protocol for the fast and efficient synthesis of ractopamine hydrochloride (-adrenergic drug) under MW-assisted reductive ami-nation protocol starting from raspberry ketone and octapamine. Microwave (MW) successfully accelerated the hydrogenation reaction and reduced the reaction time from 13 hours to only 3 hours under mild conditions (50°C at 10 bar). The best catalysts were Pt/C and Rh/C, which led to high conversion and selectivity towards ractopamine:HCl. The solvent has a significant effect on the reaction outcome. The replacement of methanol with other solvents had a negative impact on the reaction yield. We also replaced the raspberry ketone with other ketone substrates, especially cyclohexanone. These preliminary experiments may be useful for further process improvements in the synthesis of β-adrenergic agonists and related structures.

In order to properly cover different scenarios, radiation patterns of antennas should be accordingly adjusted before fabrication. However, most antennas are unable to provide both broadside beam and designable conical beam which are usually-used radiation patterns for radio coverage. In this paper, a planar Circular Polarized (CP) annular Leaky-Wave Antenna (LWA) with conical beam is proposed, which is realized on annular Substrate-Integrated Waveguide (SIW). Broadside beam or conical beam could be easily obtained by fabricating the LWA with modified structural parameters. The central operating band is 5.8 GHz. The LWA allows only the -1th spatial harmonic to radiate, while the fundamental wave and other spatial harmonics are suppressed in slow wave mode. In order to validate the design effectiveness, two examples for broadside beam and conical beam radiation are fabricated and measured. The measurement results show good agreement with the simulation results. The proposed LWA presents a promising radiation performance and is a good candidate for wireless communication applications.

Polarization in online social networks has gathered a significant amount of attention in the research community and in the public sphere due to stark disagreements with millions of participants in topics surrounding politics, climate, the economy and other areas where an agreement is required. There are multiple approaches to investigating the scenarios in which polarization occurs and given that polarization is not a new phenomenon but that its virality may be supported by the low cost and latency messaging offered by online social media platforms; an investigation into the intrinsic dynamics of online opinion evolution is presented for complete networks. Extending a model which utilizes the Binary Voter Model (BVM) to examine the effect of the degree of freedom for selecting contacts based upon homophily, simulations show that different opinions are reinforced for a period of time when users have a greater range of choice for association. The facility of discussion threads and groups formed upon common views further delays the rate in which a consensus can form between all members of the network. This can temporarily incubate members from interacting with those who can present an alternative opinion where a voter model would then proceed to produce a homogeneous opinion based upon pairwise interactions.

We considered a vacuum polarization around a massive object in the eikonal approximation and found two types of vacuum polarization. The first type has the equation of state similar to radiation and can produce a halo that increases the rotation velocity of a test particle with a radial distance. The second type of vacuum polarization has a more complicated equation of state. As a static physical effect, it produces renormalization of the gravitational constant. Besides, we demonstrate that a nonstationary polarization of the second type caused by a swift increase of the galactic nuclei mass results in a gravitational potential looking like a dark matter halo.

A temperature-modulated pyroelectricity measurement system for a small single crystal is developed and applied to standard sample measurements performed on a thin single crystal of lithium niobate. The modulation measurement is based on the AC technique, in which the temperature of the sample is periodically oscillated, and the synchronized pyroelectric signal is extracted using a lock-in amplifier. Temperature modulation is applied by irradiating periodic light on the sample placed in the heat exchange gas. To apply this technique to the transparent reference sample, a commercially available black resin is coated on the sample’s surface to absorb the light energy and transmits it to the specimen. The experimental results are analyzed using a two-layer heat transfer model to verify the effect of the light-absorbing layer as well as the non-contact temperature modulation system.

Smoking is a risk factor for respiratory infections and there is reasonable concern that it may affect COVID-19 susceptibility and severity. Recent studies have focused on the interaction between smoking (and nicotine) and ACE2 expression, suggesting that ACE2 up-regulation could contribute to enhanced viral cell entry. However, case series have shown that there is an unexpectedly low prevalence of smoking among hospitalized COVID-19 cases. Since early April, we were the first to hypothesize that dysfunction of the nicotinic cholinergic system (NCS) may be implicated in the pathophysiology of severe COVID-19. We recently reported that many of the clinical manifestations of severe COVID-19 could be explained by dysregulation of the NCS. In this study, we present an amino acid sequence in the receptor binding domain of the SARS-CoV-2 Spike glycoprotein which is homologous to a sequence of a snake venom toxin. We present the 3D structural location of this “toxin-like” sequence on the Spike Glycoprotein. These findings suggest that SARS-CoV-2 could potentially interact with acetylcholine receptors causing dysregulation of the NCS and the cholinergic anti-inflammatory pathway.

Refractive index measurements have been an important task for a long time because that index plays an essential role in describing the optical properties of a material. Many methods have been developed to perform that task. Some of them use interferometry to achieve high precision, however these configurations are complicated. Some measure the critical angle using simple structures, but the accuracy is not satisfactory because it is difficult to judge the exact critical angle with intensity variations. Here we propose several new schemes based on measuring the polarization change in the total internal reflection. The proposed method has the merits of simple structure and easy incident angle determination that gives the maximum phase change. Additionally, it is possible to find the material dispersion by measuring the wavelength dependence of the polarization ellipticity. Some useful formulas relating the refractive index with the maximum phase change are obtained. This work can provide valuable alternatives for index measurement.

Background. Azithromycin (AZM) is widely used in cystic fibrosis (CF) treatment following clinical trials demonstrating improved lung function and fewer pulmonary exacerbations. While the precise mechanisms remain elusive, immunomodulatory actions are thought to be involved. We previously reported impaired phagocytosis and defective anti-inflammatory M2 macrophage polarization in CF macrophages. This study systematically analyzed the effect of AZM on the functions of unpolarized and M1/M2 polarized macrophages in CF. Methods: Monocytes, isolated from the venous blood of patients with CF (pwCF) and healthy controls (HCs) were differentiated into monocyte-derived macrophages (MDMs) and infected with P. aeruginosa. P. aeruginosa uptake and killing by MDMs in the presence or absence of AZM was studied. M1 and M2 macrophage polarizations were induced and their functions and cytokine release were analyzed. Results: Following AZM treatment, both HC and CF MDMs exhibited a significant increase in P. aeruginosa uptake and killing, however, lysosomal acidification remained unchanged. AZM treatment led to higher activation of ERK1/2 in both HC and CF MDMs. Pharmacological inhibition of ERK1/2 using U0126 significantly reduced P. aeruginosa uptake in HC MDMs. M1 macrophage polarization remained unaffected, however, AZM treatment led to increased IL-6 and IL-10 release in both HC and CF M1 macrophages. AZM also significantly increased the phagocytic index for both pHrodo E. coli and S. aureus in CF M1 macrophages. In CF, AZM treatment promoted anti-inflammatory M2 macrophage polarization, with an increased percentage of CD209+ M2 macrophages, induction of the M2 gene CCL18, along with its secretion in the culture supernatant. However, AZM did not restore endocytosis in CF, another essential feature of M2 macrophages. Conclusions: This study highlights the cellular functions and molecular targets of AZM which may involve improved uptake of both gram-positive and gram-negative bacteria, restored anti-inflammatory macrophage polarization in CF. This may in turn shape the reduced lung inflammation observed in clinical trials. In addition, we confirmed the role of ERK1/2 activation for bacterial uptake.

We have investigated the canine of olive flounder in terms of the nonlinear optical signals of two-photon excitation autofluorescence (2PEF) and second harmonic generation (SHG), whereby two kinds of nonlinear microscope images of the canine were obtained using ~140 femtosecond pulses. For increasing excitation power of laser pulses, a photobleaching effect was found to be significant in the red and green ranges of autofluorescence, where a double-exponential decay of the intensity occurs within hundreds of second due to collagen fluorophores in the canine. In the blue range of autofluorescence, the photobleaching is suppressed due to an energy conversion of the incident laser pulse to SHG signal. As a result, the signal in blue range remains constant for long term exposure to laser. We have also found that the SHG intensity depends on the orienta-tion of linearly polarized excitation, and the optical anisotropy of SHG can be attributed to the collagen alignment of canines.

Activating the cytosolic innate immune sensor cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway via natural and synthetic agonists holds great potential for priming robust antitumor immunity. However, the effectiveness of STING agonists is often impeded by the insufficient tumor accumulation, poor cellular entry, and rapid clearance, thus leading to difficulty of their clinic translation. Herein, we apply the human serum albumin as the single-molecule nanoreactor to encapsulate SR-717 (SH-NPs) for enhanced targeting delivery efficiency and biological potency. SH-NPs with rational size distribution exhibited superior serum stability, considerable cellular uptake and abundant tumor accumulation, thus increasing the STING signaling including phosphorylation of STING-associated proteins (TBK1, IRF3), and cytokines secretion inside tumor region. Subsequently, SH-NPs remarkably reshape the immunosuppressive tumor microenvironment into an immunogenic one that boosts antitumor T-cell immunity and improves the therapeutic efficacy of checkpoint blockade against murine tumors. We also validate SH-NPs in freshly isolated human renal tumor tissues to highlight their clinic translation capability. These findings pave the way towards targeted STING agonist delivery for reinvigorated immunotherapy of intractable cancers.

Background: The standard surgical approach to amputation has failed to evolve significantly over the past century. Consequently, standard amputations often fall short with regards to improving the quality-of-life (QoL) for patients. A modified amputation has been designed at both the transtibial (TTA) and transfemoral (TFA) level that incorporates agonist-antagonist myoneural interface (AMI) constructs to provide patients with a novel alternative to standard amputation. Here, we present the patient reported outcome measures (PROMs) amongst our lower extremity AMI amputees and demonstrate an overall significant improvement in their physical and mental wellbeing. Methods: Four PROMs surveys, 1) EQ-5D-3L, 2) Lower Extremity Functional Scale (LEFS), 3) PROMIS-57, 4) Short Form-36 (SF-36), and 5) Sickness Impact Profile (SIP), were administered to lower extremity AMI amputees pre-operatively (baseline) and at 6 weeks, 3 months, 6 months, 9 months, 12 months, 24 months, 36 months, and 48 months post-operatively between June 24th, 2018, and December 15th, 2022. The surveys were either administered during a clinic visit or emailed at the encounter timepoint. Study data was collected and managed using REDCap (Research Electronic Data Capture) electronic data capture tools hosted at Brigham and Women’s Hospital. Analyses of collated data were performed by fitting a linear mixed model using SAS version 9.4 (SAS Institute, Cary, NC). Results: The cohort’s baseline and 12-month post-operative responses were compared to determine score improvement. The cohort demonstrated a significantly improved EQ-5D-3L index value (p<0.0001) and EQ VAS (p<0.0001) at 12-months post-operatively (n=22) when compared to baseline (n=28). The LEFS score significantly improved at 12-months post-operatively compared to baseline (p<0.0001) with a mean of 59.04 ± 3.14 (SE) at 12-months and a mean of 31.96 ± 2.84 (SE) at baseline. AMI patients demonstrated significantly improved scores across PROMIS-57 domains at 12-months compared to baseline scores; the p-value was <0.0001 for all domains except for the Depression domain where p=0.0181. The health domain scores significantly improved from baseline to 12-months post-operation for all SF-36 domains. Lastly, the SIP indicated a significant decrease in overall dysfunction from baseline to 12-months post-operation (p<0.0001). Conclusions: Modified lower extremity amputation with AMI construction has the potential to provide amputees with increased quality-of-life when compared to the pre-operative state. However, further investigation is necessary to determine whether the patient reported outcome measures of the AMI amputee cohort are superior to those who receive a standard amputation.

Light detection and ranging (LIDAR) sensors using a polarization-diverse receiver are able to capture polarimetric information about the target under measurement. This information can be used in a classifier to make an instantaneous assessment of the type of material present, enabling a shot-by-shot prediction of the material type and distance to the target.

Germanium (Ge) nanostrip is embedded in polymer and studied as a waveguide. Measurement reveals that this new type of semiconductor/polymer heterogeneous waveguide exhibits strong absorption for the TE mode from 1500 nm to 2004 nm, while the propagation loss for the TM mode declines from 20.56 dB/cm at 1500 nm to 4.89 dB/cm at 2004 nm. The transmission characteristics serves as an essential tool to verify the optical parameters (n-κ) of the thin strips, addressing to the ambiguity raised by spectroscopic ellipsometry regarding highly absorbing materials. Furthermore, the observed strong absorption for the TE mode at 2004 nm is well beyond the cut-off wavelength of the crystalline bulk Ge (~1850 nm at room temperature). This redshift is modeled to manifest the narrowing of the Tauc-fitted bandgap due to the grain order effect in the amorphous Ge layer. The accurate measurement of the nanometer-scale light-absorbing strips in a waveguide form is a crucial step toward the accurate design of integrated photonic devices that utilize such components.

Schistosomiasis, a crippling ailment that afflicts over 220 million people worldwide. Yet or up till now, there is no vaccine for schistosomiasis, and chemotherapy relies heavily on a single drug, the praziquantel. The present study was undertaken to investigate the therapeutic effect of Monophosphoryl Lipid A (MPLA) as an adjuvant in soluble egg antigen (SEA) vaccinated mice against the deleterious pathological impacts induced in hepatic tissues of mice by Schistosoma mansoni infection. In addition, to study the associated parasitological, immunological and biochemical parameters. Parasitological parameters showed that intraperitoneal injection of MPLA into SEA-vaccinated and S. mansoni-infected mice was effective to a significant degree in reducing the worm and egg burden, granuloma count and diameter as well as the total area of infection in their livers versus SEA-untreated but infected ones. In addition, MPLA showed ameliorative action on the elevated liver oxidative stress marker, including malondialdehyde (MDA) and decrease in the level of the antioxidant enzymes, reduced glutathione (GSH) and catalase (CAT) which may have a role in the liver damage and fibrosis due to S. mansoni infection. In conclusion, treatment with MPLA has multi-functions in attenuating the deleterious impacts of S. mansoni infection in mice livers. Its effects are mediated through a reduction of ova count, worm burden, granuloma diameter and amelioration of antioxidant defense systems, and liver function biomarkers.

Recent evidences support a role of menthol, a TRPM8 agonist, in enhanced energy expenditure, thermogenesis and BAT-like activity in classical WAT depots in TRPM8 dependent and independent manner. The present study was designed to analyze whether oral and topical administration of menthol is bioavailable at subcutaneous adipose tissue and is sufficient to induce desired energy expenditure effects directly. GC-FID was performed to study menthol bioavailability in serum and subcutaneous white adipose tissue following oral and topical administration. Further, 3T3L1 adipocytes were treated with bioavailable menthol doses and different parameters (lipid accumulation, “browning/brite” and energy expenditure gene expression, metal analysis, mitochondrial complex’s gene expression) were studied. No difference was observed in serum levels but significant difference was seen in the menthol concentration on subcutaneous adipose tissues after oral and topical application. Menthol administration at bioavailable doses significantly increased “browning/brite” and energy expenditure phenotype, enhanced mitochondrial activity related gene expression, increased metal concentration but didn’t alter the lipid accumulation. Further, we used pharmacological antagonism based approach to study the TRPM8 involvement in menthol effect. In conclusion, the present study provides an evidence that bioavailable menthol after single oral and topical administration is sufficient to induce “brite” phenotype in subcutaneous adipose tissue.

An event of increasing interest during host-pathogen interactions is the differentiation of patrolling monocytes (MOs) and the polarization of naive MOs into macrophage subsets (MФs). Therapeutic strategies aimed at modulating this event are under investigation. This review focuses on the mechanisms of induction, development, and profile of MФs polarized toward classically proinflammatory (M1) or alternatively anti-inflammatory (M2) phenotypes in response to bac-teria, fungi, parasites, and viruses. It highlights nuclear (PPARγ), cytoplasmic, and cell surface receptors (pattern recognition receptors/PPRs), microenvironmental mediators, and immune signaling. MФs polarize into phenotypes: M1 MФs, activated by IFN-γ, pathogen-associated mo-lecular patterns (PAMPs, e.g. LPS)/DAMPs and membrane-bound PPRs ligands (TLRs/CLRs lig-ands); or M2 MФs (a, b, c and d), induced by IL-4, -10 and -13, antigen-antibody complexes, and helminth PAMPs. The kinetics of M1 and M2 polarization evolve in a pathogen-specific manner, with or without canonicity, and can vary widely. Ultimately, this can result in varying degrees of host protection or more severe disease outcome. While the host is driving an effective MФs po-larization, pathogens are attempting to shift it to increase pathogenicity. The latter results from a bias toward an ineffective M1 or M2 response due to microbial virulence factors, culminating in pathogen evasion of host defenses. Plasticity of M1/M2 phenotypes is also ensured by cellu-lar/genomic reprogramming. Because modulation of this event can occur at multiple points, providing a therapeutic/vaccine design target to boost microbicidal (M1) or tissue repair (M2) response during the inflammation-to-resolution transition; new insights and emerging perspec-tives may have clinical implications.

Macrophages are the key effector cells of innate immunity which show two polarized states: M1, classically activated and M2, alternatively activated. Tumor-associated macrophages (TAMs) which usually show M2 polarization, are immunosuppressive cells that enhance tumor metastasis and invasion. Also, enrichment of TAMs is known to be closely associated with poor prognosis of cancer patients. Therefore, TAMs are considered to be promising targets for immunotherapy. Importantly, tumor-derived exosomes emerged as a crucial player in immune regulation which can remodel the tumor microenvironment towards immunosuppressive state. Of note, few studies have shown that exosomes could induce polarization of macrophages towards M2 type in tumor condition, while others showed activation of M1 or mixed phenotype. Considering the role of TAMs in cancer, there is an urgent need to decipher the exosome-mediated cross-talk between tumor cells and macrophages.For this, we used murine model of Dalton’s lymphoma (DL), wherein, firstly, we evaluated increased exosome burden by assessing exosome level in serum as well as in various tissues of tumor-bearing host. Next, proteomic profiling of lymphoma-derived exosomes was done which revealed the presence of immunomodulatory proteins. Of note, these proteins were known to alter the macrophage polarization. In order to assess the effect of these exosomes on macrophages, we performed in vitro study using RAW264.7 cells. In vitro study revealed that frequent uptake of exosomes mediated a morphological change in macrophages which reduced their phagocytic activity. In parallel, exosomes increased reactive oxygen species (ROS) level and inhibited LPS-induced nitric oxide (NO) level in macrophages. Also, exosomes upregulated the expression of arginase-1 (an M2 marker) in macrophages but decreased the LPS-induced nitric oxide synthase 2 (NOS2) (an M1 marker) expression. Moreover, we observed a pro-tumoral cytokine profile in macrophages incubated with exosomes. Our study suggests that exosome load increases in lymphoma-bearing hosts systemically. Importantly, lymphoma-derived exosomes mediate the activation of macrophages towards pro-tumoral M2 type. Our results give an insight into the exosome-mediated tumor and immune cell cross-talk which could serve as an important prospect for targeting in cancer immunotherapy.

The study of neurodegenerative diseases using pluripotent stem cells requires new methods to assess neurodevelopment and neurodegeneration of specific neuronal subtypes. The cholinergic system, characterized by its use of the neurotransmitter acetylcholine, is one of the first to degenerate in Alzheimer’s disease and is also affected in frontotemporal dementia. We developed a differentiation protocol to generate basal forebrain cholinergic neurons (BFCNs) from induced pluripotent stem cells (iPSCs) aided by the use of small molecule inhibitors and growth factors. Ten iPSC lines were successfully differentiated into BFCNs using this protocol. The neuronal cultures were characterised through RNA and protein expression, and functional analysis of neurons was confirmed by whole-cell patch clamp. We have developed a reliable protocol using only small molecule inhibitors and growth factors, while avoiding transfection or cell sorting methods, to achieve a BFCN culture that expresses the characteristic markers of cholinergic neurons.

Alpha-fetoprotein (AFP) is a major embryo- and tumor-associated protein capable of binding and transporting variety of hydrophobic ligands including estrogens. AFP has been shown to inhibit estrogen receptor (ER)-positive tumor growth and this can be attributed to its estrogen-binding ability. Despite AFP has long been investigated, its three-dimensional (3D) structure has not been experimentally resolved and molecular mechanisms underlying AFP-ligand interaction remain obscure. In our study we constructed homology-based 3D model of human AFP (HAFP) with the purpose to perform docking of ERα ligands, three agonists (17β-estradiol, estrone and diethylstilbestrol) and three antagonists (tamoxifen, afimoxifene and endoxifen) into the obtained structure. Based on ligand docked scoring function, we identified three putative estrogen- and antiestrogen-binding sites with different ligand binding affinities. Two high-affinity sites were located in (i) a tunnel formed within HAFP subdomains IB and IIA and (ii) opposite side of the molecule in a groove originating from cavity formed between domains I and III, while (iii) the third low-affinity site was found at the bottom of the cavity. 100 ns MD simulation allowed studying their geometries and showed that HAFP-estrogen interactions occur due to van der Waals forces, while both hydrophobic and electrostatic interactions were almost equally involved in HAFP-antiestrogen binding. MM/GBSA rescoring method estimated binding free energies (ΔG_bind) and showed that antiestrogens have higher affinities to HAFP as compared to estrogens. We performed in silico point substitutions of amino acid residues to confirm their roles in HAFP-ligand interactions and showed that Thr132, Leu138, His170, Phe172, Ser217, Gln221, His266, His316, Lys453, and Asp478 residues along two disulfide bonds, Cys224-Cys270 and Cys269-Cys277 have key roles in both HAFP-estrogen and HAFP-antiestrogen binding. Data obtained in our study contribute to understanding mechanisms underlying protein-ligand interactions and anti-cancer therapy strategies based on ER-binding ligands.

Grating (moiré) interferometry is one of the well-known methods for full-field in-plane displacement and strain measurement. There are many design solutions for grating interferometers, including systems with a microinterferometric waveguide head. This article proposes a modification to the conventional waveguide interferometer head, enabling the implementation of a polarization fringe phase shift for automatic fringe pattern analysis. The article presents both the theoretical consideration of the proposed solution and its experimental verification, along with the concept of the in-plane displacement/strain sensor using the described head.

The issue of polarization, as opposed to inequality, has been little explored for European countries. in this paper, using harmonized data produced by Luxembourg Income Study Database, observes income trends for 12 European countries, showing an increase in polarization in many of the countries considered. the drivers that led to this concentration of income are also analyzed, noting heterogeneous factors within countries.

The magnetic polarization tensor has a promising capability of determining the geometry and material properties of metallic samples. In this paper, a novel computation method is proposed to estimate the magnetic polarization tensors for the metallic samples using the boundary element method. In this method, the metallic sample is placed in a uniformly distributed magnetic field. Based on assumptions that the excitation frequency and/or the conductivity of the sample is very high, the metallic sample is regarded as a perfect electrical conductor (PEC). Therefore, the scattered field at a certain distance can be simulated. By utilising the boundary element method, the magnetic polarization tensor can be derived from the simulated scattered field. The theoretical calculation is presented and simulations and experiments have been carried out to validate the proposed method. The results from the simulation are matched with the analytical solution for the case of sphere samples. Moreover, there is a good agreement between the simulation results and the experimental results for the copper cylindrical samples.

(1) Background: Type-2 Diabetes (T2DM) is a long-term medical disorder characterized by Insulin deficiency and high blood glucose levels. Among other medication to cure T2DM, the review of the literature found that various Pyrimidine derivative act as an agonist for G-protein-coupled receptor 119 (GPR119) was proposed to control blood glucose levels by enhancing the function of pancreatic beta-cells and its mechanism of action with fewer adverse effects.; (2) Methods: In the present research work, in-silico investigations were carried out to investigate the potential of Pyrimidine analogue as an agonists to the protein target GPR119 receptor. We performed exhaustive molecular modelling and protein modelling methodologies such as homology mod-elling, molecular docking along with various drug designing tools such as 3D-QSAR and pharmacophore mapping to ascertain the design of better GPR119 agonists.; (3) Results: On the basis of in-depth computa-tional studies, we designed new pyrimidine moiety and analyzed them for GPR-119 receptor agonist and fur-ther explored the ADME properties. Designed compounds found to exhibit better predicted activities as com-pared to reference compound; (4) Conclusions: The current research on pyrimidine derivatives, using molec-ular docking, 3D-QSAR and Pharmacophore mapping demonstrated that the obtained computational model has significant properties and the designed molecules and Dataset from this model, produced antidiabetic compound against the target GPR119 i.e., compound 1S, 1Z and 1D with the docking score of −11.696, -9.314 and -8.721 respectively. The pharmacokinetics and drug-likeness studies revealed that these compounds may be the future candidate for the treatment of diabetes acting via GPR119 agonist mechanism.

In a software-defined radar (SDR) system, most of the signal processing usually implemented in hardware is implemented by software, thus allowing for higher flexibility and modularity compared to conventional radar systems. However, the majority of SDR demonstrators and proofs-of-concept reported in the open literature so far have been based on simple antenna systems. As a result, the full potentialities of an SDR approach have not been completely exploited yet. In this work, we propose a flexilbe antenna module to be integrated into an active electronically scanning array (AESA) with controlled sidelobe level over a wide angular range, exhibiting polarization reconfigurability with low cross-polarization level and high isolation. For this purpose, analytical and numerically efficient techniques for the synthesis of the aperture distribution and the correct evaluation of the radiating features (e.g., beamwidth, pointing angle, sidelobe levels, etc.) are presented in order to grant a real-time control of the digital beamforming network. A sub-array module demonstrator is fabricated and measured to corroborate the concept.

Recent experiments devoted to characterizing the behavior of sessile ferroelectric liquid droplets on ferroelectric solid substrates, showed the existence of a droplet electromechanical Rayleigh-like instability. The instability is induced by the bulk polarization of the ferroelectric fluid which couples to the polarization of the underlying substrate through its fringing field and solid-fluid interface coupling. With the aim of characterizing this phenomenon, namely the coupling between the polarizations of a fluid and a solid material, we studied the behavior of ferroelectric liquid droplets confined between two solid substrates, arranged in different configurations realized so to generate fringing fields with different profiles. Results show that the features of the droplets instability are indeed affected by the specific fringing field shape in a way dominated by the minimization of the electrostatic energy associated to the bulk polarization of the ferroelectric fluid.

The article presents an analysis of monthly precipitation totals based on the GPCC database, and monthly mean temperatures (NOAA data) for 377 catchments distributed across the globe. The analysis included 110-year data sequences from 1901 to 2010 calculated from grid data with a spatial resolution of 0.5°x 0.5° longitude and latitude. Long-term sequences of precipitation and temperature were used to assess the polarization of climatic phenomena. The noticeable impact of polarization in the area of extreme changes in temperature and precipitation is related to anthropogenic factors such as greenhouse gas emissions, deforestation and pollution, which affect ecosystem functioning, biodiversity, water resources and economies. The paper demonstrates the existence of trends related to the polarization of temperature and precipitation phenomena. The measures of polarization used in science are discussed. A simple measure of polarization was proposed and applied to both long-term sequences of monthly precipitation totals and monthly mean temperature. Due to the nature of the proposed polarization measure, other characteristics of the precipitation and temperature sequences are also presented as background for the discussion of the polarization index. The paper presents, for a selection of several hundred catchments from around the world, analyses of the assessment of precipitation and temperature trends using non-parametric tests. The trend analyses use Mann -Kendall tests at the 5% significance level. A Pettitt test was used to determine the trend change point for precipitation and temperature data. The whole is supported by rich graphical analyses and the results are presented tabularly.

We provide an extensive and systematic investigation of exciton dynamics in droplet epitaxial quantum dots comparing the cases of (311)A, (001) and (111)A surfaces. In spite of a similar s-shell exciton structure common to the three cases, the absence of a wetting layer for (311)A and (111)A samples leads to a larger carrier confinement with respect to (001), where a wetting layer is present. Moreover, this leads to a more pronounced dependence of the binding energies of s-shell excitons on the quantum dot size and to a strong anti-binding character of the positive charged exciton for smaller quantum dots. In-plane geometrical anisotropies of (311)A and (001) quantum dots lead to a large electron-hole fine interaction (fine structure splitting, FSS ~ 100 ueV) whereas for the three-fold symmetric (111)A counterpart this figure of merit is reduced of about one order of magnitude. In all these cases we do not observe any size dependence of the fine interactions. Heavy-hole/light-hole mixing is present in all the studied cases leading to a broad spread of linear polarization anisotropy (from 0 up to about 50%) irrespective of surface orientation (symmetry of the confinement), fine interactions and nanostructure size. These results are important for the further development of ideal single and entangled photon sources based on semiconductor quantum dots.

Liraglutide, a glucagon-like peptide 1 analog used to treat type 2 diabetes and obesity, is a po-tential new treatment modality for bile acid (BA) diarrhea. Here, we show that administration of liraglutide significantly decreased total BAs, especially the primary BAs, including cholic acid, chenodeoxycholic acid, taurocholic acid, taurochenodeoxycholic acid, glycocholic acid, and β-muricholic acid, in the liver and feces. In addition, liraglutide significantly decreased trypto-phan metabolites, including L-tryptophan, serotonin, 5-hydroxy indole-3-acetic acid, L-kynurenine, and xanthurenic acid, in the colon, whereas it significantly increased in-dole-3-propionic acid. Moreover, the administration of liraglutide remarkably decreased the ex-pression of apical sodium-dependent bile acid transporter, which mediates BA uptake across the apical brush border member in the ileum, ileal BA binding protein, and fibroblast growth factor 15 in association with decreased expression of the BA-activated nuclear receptor farnesoid X receptor and the heteromeric organic solute transporter Ostα/β, which induces BA excretion, in the ileum. Liraglutide acutely decreased body weight and blood glucose levels in association with decreases in plasma insulin and serotonin levels in food-deprived mice. These findings suggest the potential of liraglutide as a novel inhibitor of primary BAs and serotonin in the colon, which may be in-volved in the improvement of BA diarrhea.

The accuracy of star position simulation is the key factor affecting the accuracy of ground calibration test of spacecraft attitude measurement system. To solve the impact of nonimaging polarized stray light on the simulation accuracy of star position in the optical engine of the system, the generation mechanism of non-imaging polarized stray light has been investigated, and an optimization method for polarization balance of the optical engine is proposed. The mathematical model of the incident light aperture angle and the ideal polarization parameter of the optical engine thin film is established, and the optimization evaluation function of polarization balance of the optical engine is constructed. An optical engine polarization balance film with the corresponding full-band binomial attenuation is <0.001 and the phase delay is <1°. Experimental results show that the simulation accuracy of the weak starlight simulation system is improved by 1.64 times using polarization balanced optical engine.

We report a dual-polarization radio frequency (RF) channelizer based on microcombs. With the tailored mismatch between the FSRs of the active and passive MRRs, wideband RF spectra can be channelized into multiple segments featuring digital-compatible bandwidths via the Vernier effect. Due to the use of dual-polarization states, the number of channelized spectral segments, and thus the RF instantaneous bandwidth (with a certain spectral resolution), can be doubled. In our experiments, we used 20 microcomb lines with ~ 49 GHz FSR to achieve 20 channels for each polarization, with high RF spectra slicing resolutions at 144 MHz (TE) and 163 MHz (TM), respectively; achieving an instantaneous RF operation bandwidth of 3.1 GHz (TE) and 2.2 GHz (TM). Our approach paves the path towards monolithically integrated photonic RF receivers (the key components—active and passive MRRs are all fabricated on the same platform) with reduced complexity, size, and unprecedented performance, which is important for wide RF applications with digital-compatible signal detection.

In recent years, drones have been used in a wide range of fields such as agriculture, transportation of goods, and security. Drones equipped with communication facilities are expected to play an active role as base stations in areas where ground base stations are unavailable, such as disaster areas. In addition, asynchronous operation is being considered for local 5G in order to support all kinds of use cases. In asynchronous operation, cross-link interference between base stations is an issue. This paper attempts to reduce the interference caused by the drone network by introducing circularly polarized antennas. Numerical analyses are conducted to validate the effectiveness of the proposed system, where SIRs (Signal-to-Interference Ratio) are shown to be improved significantly as the numerical evaluation results.

Herein, we offer a numerical study on the devising of a unique 2D-heterostructure Photonic crystal (PC) that can split two orthogonally polarized light waves. The analysis is performed via a two-dimensional finite element method (2D-FEM) by utilizing COMSOL Multiphysics software. The device consists of two discrete designs of PC formation. The first PC formation is optimized so that it permits both TE and TM-polarization of light to transmit through it. Whereas the second PC formation possesses a Photonic Bandgap (PBG) only for TE-polarized light. These two formations are combined at an angle of 45 degrees, resulting in a reflection of self-collimated TE-polarized light at an angle of 90 degrees owing to the PBG present in the second PC formation. While permitting the self-collimated TM-polarized light wave to travel uninterrupted. The proposed device has a small footprint of ~10.5 μm2 offering low transmission loss and high polarization extinction ratio which makes it an ideal candidate to be employed as an on-chip polarization division multiplexing system.

Recent studies indicate that the Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) aboard the Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) satellite provides valuable information about ocean phytoplankton distributions. CALIOP’s attenuated backscatter coefficients, measured at 532 nm in receiver channels oriented parallel and perpendicular to the laser’s linear polarization plane, are significantly improved in the Version 4 data product. However, due to non-ideal instrument effects, a small fraction of the backscattered optical power polarized parallel to the receiver polarization reference plane is misdirected into the perpendicular channel, and vice versa. This effect, known as polarization crosstalk, typically causes the measured perpendicular signal to be higher than its true value and the measured parallel signal to be lower than its true value. Therefore, the ocean optical properties derived directly from CALIOP’s measured signals will be biased if the polarization crosstalk effect is not taken into account. This paper presents methods that can be used to estimate the CALIOP crosstalk effects from on-orbit measurements. The global ocean depolarization ratios calculated both before and after removing the crosstalk effects are compared. Using CALIOP crosstalk-corrected signals is highly recommended for all ocean subsurface studies.

Optical coherence tomography (OCT) is one of the most promising, innovative and rapidly emerging intraoperative imaging modalities for neurosurgical guidance in brain tissue imaging, "optical biopsy", brain cerebral vascular detection, nerve fibers and white matter tracts detection. In this article, we provide a short survey of cross-polarization OCT and different types of OCT probes that can be used in routine neurosurgical practice. Through different types of probes there are multiple applications where OCT can play a highly complementary role in offering the real-time microscopic assessment and imaging of normal and pathological brain tissues. The biopsy-needle based probe for CP OCT was shown to be an effective instrument for brain tissue mapping and express estimation of tissue status as well as for detecting large blood vessels to prevent causing bleeding during biopsy sampling. The folded CP OCT probe for intraoperative use for brain tissue examination was shown as a potentially efficient sensor head for CP OCT. The probe demonstrated high lateral resolution in diffractive limited probing beam quality. The length of dismountable probe tip allows using the probe under operating microscope. Due to the designed family of specialized probes CP OCT fills in the niche of devices for express brain tissue examination in situ.

Electrodynamics is usually written using polarization fields to describe changes in distribution of charge as electric fields change. This approach does not specify polarization fields uniquely from electrical measurements. Many polarization fields will produce the same electrodynamic forces and flows because only divergence of polarization enters Maxwell’s first equation, relating charge and electric field. The curl of any function can be added to a polarization field without changing the electric field at all. The divergence of the curl is always zero. To be unique, models must describe the charge distribution and how it varies. I propose a different paradigm to describe field dependent charge, i.e., the phenomenon of polarization. This operational definition of polarization has worked well in biophysics for fifty years, where a field dependent, time dependent polarization provides gating current that makes neurons respond sensitively to voltage. Theoretical estimates of polarization computed with this definition fit experimental data. I propose that operational definition be used to define polarization charge in general. Charge movement needs to be computed from a combination of electrodynamics and mechanics because ‘everything interacts with everything else’. The classical polarization field need not enter into that treatment at all. When nothing is known about polarization, it is necessary to use an approximate representation with a dielectric constant that is a single real positive number. This approximation allows important results in some cases, e.g., design of integrated circuits in silicon semiconductors, but can be seriously misleading in other cases, e.g., ionic solutions.

Microglia are resident immune cells of the central nervous system such as brain-specific macrophages and also known to regulate the innate immune functions of astrocytes through secretory molecules. This conversation plays an important role in brain functions and homeostasis as well as in neuropathologic disease. In this study, we aimed to elucidate whether astrocytes and microglia can cross-talk to induce microglial polarization and proliferation, which can be further regulated under the brain stroke-mimic microenvironment. Microglia in mixed glial culture increased their survival and proliferation and altered to the M2 microglia, whose role was provided by CD11b-GFAP+ astrocytes by showing approximately tenfold increase in microglia cell proliferation after the astrocyte reconstitution. Furthermore, GM-CSF stimulated microglial proliferation approximately tenfold and induced to CCR7+ M1 microglia, whose phenotype could be suppressed by anti-inflammatory cytokines such as IL-4, IL-10, and Substance-P. Also, astrocyte in the microglia co-culture revealed A2 phenotype, which could be activated to A1 astrocyte by TNFα and IFNγ under the stroke-mimic condition. Altogether, astrocyte in the mixed glial culture stimulated the microglia proliferation and M2 polarization possibly through its acquisition of A2 phenotype, both of which could be converted to M1 microglia and A1 astrocytes under the inflammatory stroke-mimic environment. This study demonstrated that microglia and astrocyte can be polarized to M2 microglia and A2 astrocytes respectively through the cross-talk in vitro and provided a system to explore how microglia and astrocyte may behave in the inflammatory disease milieu after in vivo transplantation.

Drug-target binding is a crucial parameter in drug discovery and design, ensuring drug efficacy and specificity. Semaglutide, a potent GLP-1 receptor agonist, is widely used to treat type 2 diabetes mellitus by regulating blood glucose levels and promoting weight loss. This study introduces a novel approach utilizing the concept of a general intermolecular binding affinity calculator (GIBAC) for designing semaglutide analogues with enhanced binding affinity to GLP-1R. For the first time, a Val27-Arg28 exchange was manually introduced to strengthen the semaglutide-GLP-1R binding affinity. A comprehensive structural and biophysical analysis was conducted to explore the semaglutide-GLP-1R sequence space, leading to the identification of promising analogues. Among these, one semaglutide analogue demonstrated a binding affinity to GLP-1R that is more than two orders of magnitude (113.3 times) higher than native semaglutide, achieving a Kd of 3.0 x 10^-8 M compared to the Kd of 3.4 x 10^-6 M for native semaglutide. This article proposes a promising structural biophysical approach for developing GLP-1 receptor agonists with improved efficacy. The prototype GIBAC, termed semaGIBAC, represents a paradigm shift in precise drug discovery and design, advocating for the construction of a full-scale GIBAC to be prioritized within the drug discovery and design community.

In obesity, white adipose tissue expresses inflammatory cytokines leading to insulin resistance. Non-physiological meta-tyrosine and ortho-tyrosine (meta-Tyr and ortho-Tyr), produced from phenylalanine by free radicals, may contribute to the development of insulin resistance. The resulting insulin resistance may have a significant impact on macrophage function. In this study we aim to investigate microscopically the effect of meta- and ortho-Tyr on insulin sensitivity and M1/M2 polarization of macrophages using Akt phosphorylation and the arginase 1/iNOS ratio. Macrophage cell lines were cultured in media containing para-, meta- or ortho-Tyr, 5 mmol/L or 25 mmol/L glucose (para25-Tyr group) and treated with insulin. Para25, meta- and ortho-Tyr increased pAkt levels and decreased the arginase 1/iNOS ratio in macrophages in the absence of insulin. In the case of physiological para-tyrosine treatment, insulin increased the amount of pAkt and decreased the arginase 1/iNOS ratio. Both meta- and ortho-Tyr treatment were able to abolish or reverse the insulin’s increasing effect on pAkt and the decreasing effect on arginase 1/iNOS ratio. Our results suggest that non-physiological tyrosine isomers may affect the insulin signaling of macrophages and influence their M1/M2 polarization.

This paper investigates the polarization and heat generation characteristics of batteries under different ambient temperatures and discharge rates by means of using a coupled electric-thermal model. The study found that the largest percentage of polarization is ohmic polarization, followed by concentration polarization and electrochemical polarization. The values of the three types of polarization are generally small and stable under normal-temperature environments and low-discharge rates. However, they increase significantly in low-temperature environments and high-discharge rates and continue to rise during the discharge process. Additionally, ohmic heat generation and polarization generation also increase significantly under these conditions. Reversible entropy heat is less sensitive to ambient temperature but increases significantly with the increase of the discharge rate. Ohmic heat generation and polarization heat generation contribute to the total heat generation of the battery at any ambient temperature, while reversible entropy heat only contributes to the total heat generation of the battery at the end of discharge.

The valley pseudospin properties of electrons in two–dimensional hexagonal materials result in lots of fascinating physical phenomena, which opens up the new field of valleytronics. The valley-contrasting physics aims at distinguishing the valley degree of freedom based on valley–dependent effects. Here, we theoretically demonstrate that both of the valley–selective high harmonic generation and valley–selective electronic excitation can be achieved by using an orthogonal two–color (OTC) laser field in gapped graphene. It is shown that the asymmetry degrees of harmonic yields in the plateaus, cutoff energies of generated harmonics and electron populations from two different valleys can be precisely controlled by the relative phase of the OTC laser field. Thus the selectivity of the dominant valley for the harmonic radiation and electronic polarization can be switched by adjusting the relative phase of the OTC laser field. Our work offers an all–optical route to produce the valley–resolved high harmonic emissions and manipulate the ultrafast valley polarization on a femtosecond timescale in condensed matter.

Eicheon properties are discussed. It is shown that the eicheon surface allows setting a boundary condition for the vacuum polarization and obtaining a solution describing the dark matter tail in the Milky Way. That is, the dark matter in the Milky Way is explained as the F-type of vacuum polarization, which could be treated as dark radiation. The model presented is spherically symmetric, but a surface density of a baryonic galaxy disk is taken into account approximately by smearing the disk over a sphere. This allows the reproduction of the large distance shape of the Milky Way rotational curve. Andromeda's rotational curves are also discussed.

Co-delivery of antigens and adjuvants to the same antigen presenting cells (APCs) can significantly improve the efficacy and safety profiles of vaccines. Here, we report amine-grafted silica nanoparticles (A-SNPs) as a tunable vaccine co-delivery platform for TLR7/8 agonists along with the recombinant influenza antigen hemagglutinin H7 (H7) to APCs. A-SNPs of two different sizes (50 and 200 nm) were prepared and coated with INI-4001 at different coating densities, followed by co-adsorption of H7. Both INI-4001 and H7 showed &gt; 90% adsorption to the tested A-SNP formulations. TNF-α and IFN-α cytokine release by human peripheral blood mononuclear cells as well as TNF-α, IL-6, and IL-12 release by mouse bone marrow-derived dendritic cells revealed that the potency of the INI-4001-adsorbed A-SNPs (INI-4001/A-SNP) formulations can be improved relative to aqueous formulation control. This improved potency was dependent on particle size and ligand coating density. In addition, slow-release profiles of INI-4001 were measured from INI-4001/A-SNP formulations in plasma with 30-50% INI-4001 released after 7 days. In vivo murine immunization studies demonstrated significantly improved H7-specific humoral and Th1/Th17-polarized T cell immune responses with no observed adverse reactions. Low-density 50 nm INI-4001/A-SNP elicited significantly higher IFN-γ and IL-17 induction over that of the H7 antigen only group and INI-4001 aqueous formulation controls. In summary, this work introduces an effective and biocompatible SNP-based co-delivery platform that enhances the immunogenicity of TLR7/8 agonist-adjuvanted subunit influenza vaccines.

Naive CD4+ T cells engage cognate peptide MHC-II complexes (pMHC-IIs) to differentiate and acquire one of several T helper (Th) fates whose specific trajectories are guided by a dynamic cytokine milieu that develops in response to antigenic entity. This physiological process is often erroneously conflated with a pathological one termed Th polarization. Using the SPIRAL model, we argue here that unlike Th fate choice, innate signaling alone is insufficient to initiate Th polarization in naive CD4+ T cells, that it instead develops from pre-existing memory CD4+ T cells that express cross-reactive TCRs, and that it inevitably leads to immunopathology.

Sentinel-1 (S1) extra-wide (EW) swath data in cross-polarization (horizontal-vertical, HV or vertical-horizontal, VH) are strongly affected by the scalloping effect and thermal noise, particularly over areas with weak backscattered signals, such as sea surfaces. Although noise vectors in both the azimuth and range directions are provided in the standard S1 EW data for subtraction, the residual thermal noise still significantly affects sea ice detection by the EW data. In this paper, we improve the denoising method developed in previous studies to remove the additive noise for the S1 EW data in cross-polarization. Furthermore, we propose a new method for eliminating the residual noise (i.e. multiplicative noise) at the sub-swath boundaries of the EW data, which cannot be well processed by simply subtracting the reconstructed 2-D noise field. The proposed method of removing both the additive and multiplicative noise was applied to EW HV-polarized images processed using different Instrument Processing Facility (IPF) versions. The results suggest that the proposed algorithm significantly improves the quality of EW HV-polarized images under various sea ice conditions and sea states in marginal ice zone (MIZ) of the Arctic. This is of great support for the utilization of cross-polarization SAR images in wide swaths for intensive sea ice monitoring in polar regions.

The modern era of polarimetric radar begins with radiowave propagation research starting in the early 1970s with applications to measurement and modeling of wave attenuation in rain and depolarization due to ice particles along satellite-earth links. While there is a rich history of radar in meteorology after World War II, the impetus provided by radiowave propagation requirements lead to high quality antennas and feeds. Our journey starts by describing the key institutions and personnel responsible for development of weather radar polarimetry. The early period was dominated by circularly polarized radars for propagation research and at S-band for hail detection. By the mid-to late 70s, a paradigm shift occurred which led to the dominance of linear polarizations with applications to slant path attenuation prediction as well as estimation of rain rates and inferences of precipitation physics. The period from early 1980s to 1995 can be considered as the “golden” period of rapid research that brought in meteorologists, cloud physicists and hydrologists. This article describes the evolution of this technology from the vantage point of the authors. Their personal reflections and “behind the scenes” descriptions offer a glimpse into the inner workings at several key institutions which cannot be found elsewhere.

Maternal infections during pregnancy may increase the risk of psychiatric disorders in offspring. We recently demonstrated that activation of peroxisome proliferator-activate receptor‐α (PPARα), with the clinically available agonist fenofibrate, attenuates the neurodevelopmental disturbances induced by maternal immune activation (MIA) in rat offspring. We hypothesized that fenofibrate might reduce MIA-induced cytokine imbalance using a MIA model based on the viral mimetic polyriboinosinic-polyribocytidilic acid [poly (I:C)]. By using the Bio-Plex Multiplex-Immunoassay-System, we measured cytokine/chemokine levels in maternal serum and in the fetal brain of rats treated with fenofibrate, at 6 and 24 hours after poly (I:C). We found that MIA induced time-dependent changes in the levels of several cytokines/chemokines/colony-stimulating factors (CSFs). Specifically, the maternal serum of the poly (I:C)/CTRL group showed increased levels of (i) proinflammatory chemokine macrophage inflammatory protein 1-alpha (MIP-1α), (ii) tumor necrosis factor-alpha (TNF-), the monocyte chemoattractant protein-1 (MCP-1), the macrophage (M-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Conversely, in the fetal brain of the poly (I:C)/CTRL group, interleukin 12p70 and MIP-1 levels were lower than in veh/CTRL group. Notably, MIP-1, TNF-, GRO/KC, GM-CSF, and M-CSF levels were lower in the poly (I:C)/FEN than in poly (I:C)/CTRL rats, indicating the protective role of the PPARα agonist. PPARα might represent a therapeutic target to attenuate the consequences of MIA.

This study explores religious diversity in Romania and how the trends of indices of religious fractionalization and polarization manifest at the county level in the post-communist period. The county is selected as the relevant level for analysis due to its spatial confessional dynamics being more clearly visible. Recent studies have revealed that erosion of diversity represents an important aspect for any country and needs to be considered as an important aspect of democracy. This paper highlights that religious polarization and fractionalization in Romania has been generally maintained, although the regions of Transylvania, Banat, Dobrogea and Western Moldova remain areas where there are different confessions. Besides the general aspect of religion diversity depending the ethnic trends, there is a rise of Pentecostals and Baptists at the county level. This aspect can inform policymakers to create new institutions for dialogue between majority Orthodox communities and Protestants so that potential conflicts do not appear between the Orthodox and emerging religious communities, but also to ensure objective, cultural, religious coherence.

The microglia, displaying diverse phenotypes, play a significant regulatory role in the development, progression, and prognosis of Parkinson's disease. Research has established that glycolytic reprogramming serves as a critical regulator of inflammation initiation in pro-inflammatory macrophages. Furthermore, the modulation of glycolytic reprogramming has the potential to reverse the polarized state of these macrophages. Previous studies have shown that levetistilide A (LA), a phthalide component derived from Angelica sinensis, possesses a range of pharmacological effects, including anti-inflammatory, antioxidant, and neuroprotective properties. In our study, we have examined the impact of LA on inflammatory cytokines and glucose metabolism in microglia induced by lipopolysaccharide (LPS). Furthermore, we explored the effects of LA on the AMPK/mTOR pathway and assessed its neuroprotective potential both in vitro and in vivo. The findings revealed that LA notably diminished the expression of M1 pro-inflammatory factors induced by LPS in microglia, while leaving M2 anti-inflammatory factor expression unaltered. Additionally, it reduced ROS production and suppressed IκB-α phosphorylation levels as well as NF-κB p65 nuclear translocation. Notably, LA exhibited the ability to reverse microglial glucose metabolism reprogramming and modulate the phosphorylation levels of AMPK/mTOR. In vivo experiments further corroborated these findings, demonstrating that LA mitigated the death of TH-positive dopaminergic neurons and reduced microglia activation in the ventral SNpc brain region of the midbrain and the striatum. In summary, LA exhibited neuroprotective benefits by modulating the polarization state of microglia and altering glucose metabolism, highlighting its therapeutic potential.

In this work, a method for measuring tow angles in carbon fiber components, based on the use of a polarized camera, is analyzed from a metrological point of view. Carbon fibers alter the direction of the reflected light electrical field, so that in each point of the surface of a composite piece the angle of polarization of reflected light matches the fiber orientation. A statistical analysis of the angle of linear polarization (AoLP) in each pixel of each examined area allows to evaluate the average winding angle. An evaluation of the measurement uncertainty of the method on a cylinder obtained by a filament winding process is carried out, and the result appears adequate for the study of the distribution of angles along the surface of the piece, in order to optimize the process.

In this paper we demonstrate first ever dual-period diffraction gratings that do not require electrical tuning to obtain the effect of period change. Our method allows for multiplication of the base period by proper modification of the subsequent slits of the grating. The proposed elements are fabricated by selective photopolymerization of a composite based on nematic liquid crystal. The gratings are formed by polymer stabilization of liquid crystal in different orientations of the molecules in selected grating slits to allow for period manipulation. The operating principle is based on changing the phase delay introduced by the slits depending on polarization direction of incident light with respect to the director in each type of slit, which allows to change the grating’s period. The proposed technique was successfully utilized to obtain diffraction gratings with either doubling or tripling of the period.

Social media platforms are not serving only as tools of communication rather they are acting like intricate systems managing our interactions. A major setback to our interactions occur when the flow of information in these networks gets distorted through polarization. It resembles a society where every debate turns into divide. Our research focuses exclusively on quantifying polarization as well as solving this issue head-on. In order to accurately gauge polarization, we’ve developed a new method that takes into consideration majority of its influencing factors. This helps us in correctly quantifying the polarization value of a given network and then by proposing it as an optimization problem we are attempting to maximally decrease polarization while staying within the set budget. We test our method on synthetic and real-world data sets, and find out that polarization is declining, and diversity is increasing. This proves that our recommendation engine has a penchant for finding the ideal connections between the nodes to start a dialogue. Our research presents a successful tactic to quantifying and reducing polarization in social media networks. The results indicate that our novel metric and intervention technique are effective in dismantling echo chambers, thereby promoting diversity in these networks.

Directional modulation (DM), as an emerging promising physical layer security (PLS) technique at the transmitter side with the help of an antenna array, has developed rapidly over decades. In this study, a DM technique using a polarization sensitive array (PSA) to produce the modulation with different polarization states (PSs) at different directions is investigated. A PSA, as a vector sensor, can be employed for more effective DM for an additional degree of freedom (DOF) provided in the polarization domain. The polarization information can be exploited to transmit different data streams simultaneously at the same directions, same frequency, but with different PSs in the desired directions to increase the channel capacity, and with random PSs off the desired directions to enhance PLS. The proposed method has the capability of concurrently projecting independent signals into different specified spatial directions while simultaneously distorting signal constellation in all other directions. The symbol error rate (SER), secrecy rate, and the robustness of the proposed DM scheme are analyzed. Design examples for single- and multi-beam DM systems are also presented. Simulations corroborate that 1) the proposed method is more effective for PLS; 2) the proposed DM scheme is more power-efficient than the traditional artificial noise aided DM schemes; and 3) the channel capacity is significantly improved compared with conventional scalar antenna arrays.

Dibutyl phthalate (DBP) is widely used as a plasticizer in the production of polymeric materials to give them flexibility, strength and extensibility. However, due to its negative impact on human health, in particular, reproductive function and fetal development, the content of DBP must be controlled in food and environmental objects. The present study aims to develop a sensitive, fast and simple polarization fluorescent immunoassay (FPIA) using monoclonal antibodies derived against DBP (MAb-DBP) for its detection in open waters. New conjugates of DBP with various fluorescein derivatives were obtained and characterized: 5-aminomethylfluorescein (AMF) and dichlorotriazinylaminofluorescein (DTAF). The advantages of using the DBP-AMF conjugate in the FPIA method are shown, the kinetics of binding of this drug with antibodies is studied, the analysis is optimized, and the concentration of monoclonal antibodies is selected for sensitive analysis - 16 nM. The calibration dependence of the fluorescence polarization signal for the detection of DBP was obtained. The observed IC50 (40 ng/mL) and LOD (10 ng/mL) values were improved by a factor of 35 for the previously described FPIA using polyclonal antibodies. This technique was tested by the added/found method, the percentage of DBP discovery in water ranged from 85 to 110%. Using the developed method, real water samples from Lake Onega were tested, and a good correlation was shown between the results of the determination of DBP by the FPIA method and GC-MS/MS. Thus, the FPIA method developed in this work can be used to determine DBP in open water reservoirs.

Zika Virus (ZIKV) is a pathogenic member of the flavivirus family, with several unique charac-teristics. Unlike any other arbovirus, ZIKV can be transmitted sexually and maternally, and thus produce congenital syndromes (CZS) due to its neurotropism. This challenges the search for safe active molecules that can protect pregnant women and their fetuses. In this context, and in the ab-sence of any existing treatment, it seemed worthwhile to test whether the known cytoprotective properties of adiponectin and its pharmacological analog, AdipoRon, could influence the outcome of ZIKV infection. We showed that both AdipoRon and adiponectin could significantly reduce in vitro infection of A549 epithelial cells, a well-known cell model for flaviviruses infection studies. This effect was particularly observed when a pre-treatment was carried out. Conversely, ZIKV revealed an ability to down-regulate adiponectin receptor expression and thereby limit adi-ponectin signaling.

Polygonum sibiricum is a traditional Chinese food and medicine homologues with multiple active ingredients and extensive bioactive effects. Polygonum sibiricum polysaccharides (PSP) are one of the main active ingredients with the antidepressant activity, meanwhile the specific mechanisms of its action are still unclear. Recently, it is recognized by researchers that microglia play a double-edged role in neuroinflammation and the transformation of M1/M2 microglial phenotypes appears to be a potential therapeutic strategy in depression. Therefore, the present study evaluated the effects of PSP on microglial M1/M2 polarization and the molecular mechanisms were studied based on the lipopolysaccharide (LPS)-induced BV2 cell activation model. The results show that PSP significantly inhibited NO and LDH release and reduced ROS levels in LPS-induced BV2 cells. PSP could significantly reduce the protein expression level of Iba-1, decreased the mRNA levels of TNF-, IL-1 and IL-6, increased the mRNA level of IL-10. PSP also significantly reduced the protein expression level of CD16/32 and increased it of CD206, reduced the mRNA level and fluorescence intensity of iNOS and increased them of Arg-1. However, PSP pretreatment reversed the alterations of BDNF/TrkB/CREB and Notch/Hes1 pathways in LPS-induced BV2 cells. These results suggested that PSP exerted the anti-inflammatory effects by inhibiting M1 phenotype polarization and promoting microglia polarization toward M2 phenotype, and its regulation of microglia M1/M2 polarization may be associated with modulating the BDNF/TrkB/CREB and Notch/Hes1 pathways.

Macrophages are cells involved in the primary response to debris derived from wear of implanted CoCr alloys. The biocompatibility of wear particles from a high carbon CoCr alloy produced under polarization in physiological hyaluronic acid (HA) solution was evaluated in J774A.1 mouse macrophages cultures. Polarization was applied to mimic the electrical interactions observed in living tissues. Wear tests were performed in a pin-on-disk tribometer integrating an electrochemical cell in phosphate buffer solution (PBS) and in PBS supplemented with 0.3% HA, physiological synovial fluid concentration, used as lubricant solution. Wear particles produced in 0.3% HA solution showed a higher biocompatibility in J774A.1 macrophages in comparison to those elicited by PBS. A considerable improvement in macrophages biocompatibility in the presence of 0.3 % of HA was further observed by the application of polarization at potentials having current densities typical of injured tissues suggesting that polarization produces an effect on the surface of the metallic material that leads to the production of wear particles that are macrophages biocompatible and less cytotoxic. The results showed the convenience to consider electric interactions together with other particles parameters, as are size and composition, to get a better understanding of the biological effects of the wear products.

We study the influence of high-order twisting phases on polarization states and optical angular momentum of a vector light field with locally linear polarization and a hybrid state of polarization (SoP). The initial SoP of a twisted vector optical field (TVOF) modulated by the high-order twisting phase possesses various symmetric distributions. The propagating properties of a high-order TVOF with locally linear polarization and hybrid SoP are explored, including the intensity compression, expansion, and conversion between the linear and circular polarization components. In particular, orbital angular momentum (OAM) appears in a high-order TVOF during propagation where no OAM exists in the initial field. The variation of OAM distribution in cross-section becomes more frequent with the increase of the twisting phase order. In addition, a non-symmetric OAM distribution appears in an anisotropic TVOF, leading to the rotation of the beam around the propagation axis during propagation. These results provide a new approach for optical field manipulation in a high-order TVOF.

Objectives: The current study aimed to compare the adaptation of the restored class-I cavities with two self-etch adhesives bonded to two resin composite using cross-polarization optical coherence tomography (CP-OCT). Materials and Methods: Cylindrical class-I cavities were prepared on twenty, extracted human premolars. Two self-etch adhesives; Clearfil SE bond 2 (SE; Kuraray Noritake Dental, Japan) and Bond Force (Palfique Bond) adhesive (PL; Tokuyama Dental, Japan) were used in this study that were bonded to either resin composites materials; Herculite XRV microhybrid dental composite (HRV; Kerr, Italy) or Estelite Alpha composite (ESA; Tokuyama Dental, Japan). The specimens were divided into four groups (n=5); SE-HRV, SE-ESA, PL-HRV and PL-ESA. All specimens were varnished and stored in distilled water for 24h. Then, they were submerged in a contrasting medium. After that, all groups were optically imaged under CP-OCT at every 250 µm interval distance. Later, image binarization and gap quantification were carried out using Image analysis software. Result: There was a significant difference between all the groups except between SE-ESA and PL-ESA (p = 0.51). The highest median gap % was seen in PL-HRV group followed by SE-ESA, PL-ESA and SE-HRV. Conclusion: Other than composite filler loading and adhesive formula, the interactions of the adhesive and composite copolymers have great influence on composite adaptation.

: Background: The polysaccharides are one of the main active ingredients of Polygonum sibiricum (PSP), which is a traditional food and medicine homologues in China. The antidepressant-like effects of PSP and its underlying mechanisms remain to be studied in depth, especially the regulation of microglial polarization. Methods: The chemical composition and structural characteristics of PSP was determined firstly. The CUMS procedure was carried out to the zebrafish for 5 weeks and PSP were immersed administration for 9 days (1 h/d). The body weight of zebrafish was monitored and the behavioral tests, including the novel tank test and light and dark tank test, were performed to evaluate the antidepressant-like effects of PSP. Then the function of HPI axis, the levels of peripheral inflammation, neuronal and blood-brain barrier damage in mesencephalon and telencephalon and the mRNA expression of M1/M2 phenotype genes in brain were examined. Results: PSP samples had the typical structure characteristics of polysaccharide, consisting of glucose, mannose and galactose with the average Mw 20.48 kDa, which owned a porous and agglomerated morphology. Compared with untreated zebrafish, the depression-like behaviors of CUMS-induced zebrafish were significantly attenuated. PSP significantly decreased the levels of cortisol and the pro-inflammatory cytokines and increased the levels of the anti-inflammatory cytokines in the body of CUMS-induced depressive zebrafish. Furthermore, neuronal and blood-brain barrier damage in mesencephalon and telencephalon and the mRNA expression of M1/M2 phenotype genes in brain were remarkably reversed by PSP. Conclusion: These findings indicated that the antidepressant-like effects of PSP were related to alter the HPI axis hyperactivation, suppress peripheral inflammation, inhibit neuroinflammation induced by microglia hyperactivation, and modulate microglial M1/M2 polarization. The current study provides foundation to the future exploitation of PSP in the functional foods of emotional regulation.

The bionic polarization imaging navigation sensor (BPINS) is a navigation sensor that provides absolute heading, and it is of practical engineering significance to model the measurement error of BPINS. The existing BPINSs are still modeled using photodiode-based measurements rather than imaging measurements and are not modeled systematically enough. This paper proposes a measurement model of BPINS that takes into account the geometric and polarization errors of the optical system. Firstly, the key error factors affecting the measurement accuracy of BPINS are systematically investigated and the Stokes vector-based measurement error model of BPINS is established. Secondly, based on its measurement error model, the effect of the error source on the measurement performance of BPINS is quantitatively analyzed by using Rayleigh scattering to generate scattered sunlight as a known incident light source. The experimental results show that the coordinate deviation of the principal point has a greater impact, followed by grayscale response inconsistency of CMOS and integration angle error of micro-polarization array, and finally lens attenuation. This finding can guide the subsequent calibration of BPINS, and the quantitative results provide an important reference for its optimal design.

The Tumor Microenviroment (TME) is a complex milieu that is increasingly recognized as a key factor in multiple stages of disease progression and responses to therapy as well as escape from immune surveillance. However, the precise contribution of specific immune effector and immune suppressor components of the TME in Burkitt lymphoma (BL) remains poorly understood. In this paper, we applied the computational algorithm CIBERSORT to Gene Expression Profile (GEP) datasets of 40 BL samples to draw a map of immune and stromal components of TME. Furthermore, by VECTRA multispectral immunofluorescence (IF) and multiple immunohistochemistry (IHC), we investigated the TME of an additional series of 40 BL cases and evaluated the possible role of the PD-1/PD-L1 immune checkpoint axis. Our results indicated that M2 polarized macrophages are the most prominent TME component in BL. In addition, we investigated the correlation between PD-L1 and latent membrane protein-2A (LMP2A) expression on tumour cells, highlighting a subgroup of BL cases characterized by a non- canonical latency program of EBV with an activated PD-L1 pathway. In conclusion, our study analysed the TME in BL and identified a tolerogenic immune signature highlighting new potential therapeutic targets.

The farnesoid X receptor (FXR)/βKlotho/fibroblast growth factors (FGFs) pathway is crucial for maintaining the intestinal barrier and preventing colorectal cancer (CRC). We used an FXR ago-nist, GW4064, and FXR knockout (KO) mice to investigate the role of FXR/Klothos/FGFs pathways in lipopolysaccharide (LPS)-induced intestinal barrier dysfunction and colon carcinogenesis. The results showed that upregulation of FXR in enterocytes effectively ameliorated intestinal tight junction markers (claudin1, Zonula occludens-1), inflammation, and bile acid levels, thereby protecting mice from intestinal barrier dysfunction and colon carcinogenesis. GW4064 treatment increased FXR, αKlotho, βKlotho, FGF19, FGF21, and FGF23 in wild-type mice exposed to LPS, while FXR KO mice had decreased levels. FXR KO mice exhibited elevated colon cancer markers (β-catenin, LGR5, CD44, CD34, Cyclin D1) under LPS, underscoring the pivotal role of FXR in inhibiting the development of colon tumorigenesis. The varying gut microbiota responses in FXR KO mice versus wild-type mice post-LPS exposure emphasize the pivotal role of FXR in pre-serving intestinal microbial health, involving Bacteroides thetaiotaomicron, Bacteroides acidifaciens, and Helicobacter hepaticus. Our study validates the effectiveness of GW4064 in alleviating LPS-induced disruptions to the intestinal barrier and colon carcinogenesis, emphasizing the importance of the FXR/αKlotho/βKlotho/FGFs pathway and the interplay between bile acids and gut microbiota.

Microglia-related retinal inflammation is associated with a variety of retinal diseases. Lycium barbarum Glycopeptide (LBGP) is the main active component of Lycium barbarum polysaccharide (LBP) isolated from Lycium barbarum, which possesses antioxidation, neuroprotection, and immunoregulation. However, whether LBGP has beneficial effects on LPS/IFN-γ (L/I) induced retinal microglial activation and its underlying mechanism remains to be elucidated. In this study, we observed the anti-inflammatory properties of LBGP in microglia activated by LPS and IFN-γ (L/I), examining both primary retinal microglia and BV2 microglial cells. Cells were pretreated with LBGP for 2h before stimulated with LPS/IFN-γ (L/I) for 24h. The dosages of LBGP for cells were evaluated by using the CCK-8 assay. The morphological changes were observed using an optical microscope. The changes in expression of cytokines and inflammatory mediators were measured with Griess assay, ELISA, qPCR, and immunofluorescence. Western blotting was used to assess MAPK, NF-κB signal transducer. LBGP pre-treatment significantly reversed L/I-induced microglia morphological alterations in area, perimeter, Feret's diameter, and roundness. LBGP significantly alleviated the L/I-induced microglial activation in primary and BV2 microglial cells. LBGP switched the M1 pro-inflammatory phenotype to the M2 anti-inflammatory phenotype by downregulating the expression of M1 markers (iNOS, IL-1β, IL-6, COX2, CD16, and CD86) and upregulating the expression of M2 markers (arginase 1 and CD206). Furthermore, LBGP attenuated the activation of NF-κB and MAPK pathways in L/I-activated BV2 cells. In summary, it is suggested that LBGP pretreatment significantly alleviated L/I-induced retinal inflammation by regulating microglial(M1/M2) polarization via NF-κB and MAPK signaling pathways.

Songorine (SON) is a diterpenoid alkaloid from Aconitum plants. Preparations of Aconitum roots have been employed in traditional oriental herbal medicine, however, their mechanisms of action are still unclear. Since GABA-receptors are possible brain targets of SON, we investigated which subtypes of GABA-receptors contribute to the effects of SON, and how SON affects anxiety-like trait behavior and psychomotor cognitive performance of rats. First, we investigated the effects of microiontophoretically applied SON alone and combined with GABA-receptor agents picrotoxin and saclofen on neuronal firing activity in various brain areas. Next, putative anxiolytic effects of SON (1.0-3.0 mg/kg) were tested against the GABA-receptor positive allosteric modulator refer-ence compound diazepam (1.0-5.0 mg/kg) in the elevated zero maze (EOM). Furthermore, basic cognitive effects were assessed in a rodent version of the psychomotor vigilance task (PVT). Local application of SON predominantly inhibited the firing activity of neurons. This inhibitory effect of SON was successfully blocked by GABA(A)-receptor antagonist picrotoxin but not by GABA(B)-receptor antagonist saclofen. Similar to GABA(A)-receptor positive allosteric modulator diazepam, SON increased the time spent by animals in the open quadrants of the EOM without any signs of adverse psychomotor and cognitive effects observed in the PVT. We showed that, under in vivo conditions SON acts as a potent GABA(A)-receptor agonist and effectively decreases anxiety without observable side effects. The present findings facilitate the deeper understanding of the mechanism of action and the widespread pharmacological use of diterpene alkaloids in various CNS indications.

[Objective] To investigate the expression of ALDH2 in hepatocellular carcinoma and its correlation with macrophage infiltration and with the activation of specific subtypes of macrophages. [Methods] Transcriptome and clinical data from patients with hepatocellular carcinoma were downloaded from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) databases and analyzed and collated using R and Perl software. In the TCGA hepatocellular carcinoma dataset, the Wilcoxon test was used to identify macrophage activation-related gene sets that show differential expression between hepatocellular carcinoma and normal tissues. Single-cell sequencing combined with bulk data was used to analyze macrophage infiltration of hepatocellular carcinoma immune cells and the activation and recruitment of different subtypes of macrophages. Single-factor Cox regression and minimum absolute convergence and selection operator (Lasso) were used to identify survival-related genes and construct prognostic models of HCC. The patients were divided into two groups based on their model scores. The Wilcoxon test was used to identify differentially expressed genes (DEGs) between the two groups, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses of the DEGs were performed. Single-sample gene set enrichment analysis (ssGSEA) was performed to explore the possible mechanism underlying the differences in prognosis. The reliability of the model was verified using the ICGC hepatocellular carcinoma dataset. A Kaplan‒Meier curve was constructed and used to analyze the influence of macrophage activation-related gene expression on survival and prognosis in patients with hepatocellular carcinoma. The log-rank test and the independent t test were used to analyze survival time data and to compare immune cell infiltration in the two groups. [Results] In a comparison of hepatocellular carcinoma and paracancerous tissues, the expression of six of 137 macrophage activation-related genes (ALDH2, CCNB2, CYP2C9, CYP3A4, F9 and KLKB1) was found to be significantly correlated with overall survival time (OS) in patients with hepatocellular carcinoma. Based on this finding, a prognosis assessment model for hepatocellular carcinoma was constructed. The OS of the patients in the high-scoring group was significantly shorter than the OS of the patients in the low-scoring group (P<0.05), and the model predicted the prognosis of patients with hepatocellular carcinoma independently of sex, age, tumor grade and stage. The area under the receiver operating characteristic (ROC) curve of the model used to predict 1-, 2-, and 3-year survival was greater than 0.7 in both the test set and the validation set. GO enrichment of DEGs between the high- and low-scoring groups of the model suggested that the DEGs are mainly related to immune function. GSEA suggested that the tumor-infiltrating immune cells in the high-scoring group were macrophages, Th2 cells and Treg cells and showed that the number of tumor-infiltrating immune cells, including NK cells, was lower in the high-scoring group than in the low-scoring group. With respect to immune function, the immune checkpoint of the high-scoring group was higher than that of the low-scoring group. Single-cell sequencing data indicated the recruitment of B cells, M0 cells, M1 cells and M2 cells to the hepatocellular carcinoma microenvironment and suggested that ALDH2 regulates related signaling pathways in a way that promotes the differentiation of macrophages into M2-type macrophages. [Conclusion] M2-type macrophages are the dominant type of macrophages associated with immune infiltration in hepatocellular carcinoma. The macrophage-associated activation gene ALDH2 activates the macrophage polarization signaling pathway and negatively regulates the differentiation of macrophages into M2-type macrophages.

In this paper we address one of the most important topics in the field of Social Networks Analysis: the community detection problem with additional information. That additional information is modeled by a fuzzy measure that represents the possibility of polarization. Particularly, we are interested in dealing with the problem of taking into account the Polarization of nodes in the community detection problem. Adding this type of information to the community detection problem makes it more realistic, as a community is more probably to be defined if the corresponding elements are willing to maintain a peaceful dialogue. The polarization capacity is modeled by a fuzzy measure based on the JDJpol measure of polarization related to two poles. We also present an efficient algorithm for finding groups whose elements are no polarized. Hereafter, we work in a real case. It is a network obtained from Twitter, concerning the political position against the Spanish government taken by several influential users. We analyze how the partitions obtained change when some additional information related to how polarized that society is, is added to the problem.

Here, we propose a novel scheme based on advanced techniques of digital modulation in optical communications to achieve a single-channel transmission rate above 100 Gb/s. We utilize a hybrid scheme amplitude/phase/frequency/dual polarization, combined with multidimensional dual lattice and a low-density parity-check-coded modulation. The Stokes parameters are applied to the proposed scheme to map the four-dimensional classical polarization \({I_X},{Q_X},{I_Y},{Q_Y}\) in a three-dimensional space. In addition, in the proposed system, the packing theory is applied to the bit interleaver process, three wavelengths are packaged before being transmitted over a wavelength-division multiplexing optical channel. This modulation process is carried out using symmetrical geometric shapes, such as a hypercube or a polyhedron, based on the molecular links theory using a grouping of 12 and 13/15 bits for the cubic and spherical lattices, respectively. The proposed technique is evaluated in the context of long distance communications over distances up to 100 km. The bit error rate results showed that the optical signal-to-noise ratio was approximately 4 dB over a distance of 50 km. In addition, the power spectral efficiency was found to be 3 lambda, which is considered good performance considering the effects of distance and the non-linear effects influencing the number of lambdas. Also, we use an optical time division multiplexing scheme (OTDM) in order to achieve a transmission rate beyond 1Tbit/s, where the speed effect is evaluated, taking into consideration that the power spectral efficiency is degraded. Furthermore, the average noise floor is -60dBm for all transmission distances. These findings are expected to contribute to the future implementation of robust long-distance optical communication infrastructure.

The decline in assisted reproductive technology (ART) success among older women, attributed to decreased oocyte quantity and quality, poses a significant challenge. Currently, no consensus ex-ists on the optimal ovarian stimulation protocol for older women undergoing IVF. This retrospec-tive registered cohort study aimed to compare cumulative live birth rates (CLBR), time to live birth (TTLB), and cost-effectiveness in women over 35 years using gonadotropin-releasing hor-mone agonist (GnRHa) or clomiphene-primed ovarian stimulation (CPOS). We performed pro-pensity score matching (PSM) on 2,871 IVF cycles in women over 35 who received either GnRHa or CPOS protocols, resulting in 375 cycles in each group to compare treatment outcomes. Addition-ally, a decision tree model was utilized to assess the cost-effectiveness of the two protocols. Fol-lowing PSM, both groups showed similar baseline characteristics. The CPOS protocol exhibited a higher cycle cancellation rate (13.07% vs 8.00%, p=0.032), yet maintained comparable fertilization and embryo quality. While CLBRs per initial cycle (41.07% vs. 45.33%, p=0.269) and delivery out-comes were similar between the groups after a 24-month follow-up, TTLB was longer in the CPOS group. Notably, the average cost per live birth in the CPOS group was 21.27% less than that in the GnRHa group (￥32,301.42 vs ￥39,174.22). In conclusion, for women over 35 undergoing IVF, the CPOS protocol demonstrated similar CLBR to GnRHa but with lower costs, suggesting its potential as a viable and cost-efficient ovarian stimulation option.

X-band dual-polarization phased array radar (XPAR-D) possesses high temporal-spatial resolutions and plays a significant role in detecting meso- and micro-scale convective systems. However, the precipitation attenuation it endures necessitates an effective correction method. This study selected radar data from XPAR-D at the peak of Maofeng Mountain in Guangzhou during May 16-17, 2020 from three precipitation stages after quality control. Attenuation coefficients are calculated for different precipitation types through scattering simulations of raindrop size distribution (RSD) data. Drawing upon this, an attenuation correction algorithm (MZH-KDP method) is proposed for radar reflectivity factor (ZH) according to different raindrop types, and is compared to the ZH-KDP method currently in use. The results indicate that the attenuation amount of XPAR-D echoes depends on the attenuation path and echo intensity. When the attenuation path is shorter and the echo intensity is weaker, the amount of attenuation and correction is smaller. Difficulties arise when there are noticeable deviations in such a situation, which are challenging to solve via attenuation correction methods. Longer attenuation paths and stronger echoes highlight the advantages of the MZH-KDP method, while the ZH-KDP method tends to overcorrect the bias. The MZH-KDP method outperforms the ZH-KDP method for different precipitation types. The superior correction capability of the MZH-KDP method provides a significant advantage in improving the performance of XPAR-D for the detection of extreme weather.