Peripheral blood interferon responses to toll-like receptor 1/2 signaling associate with longer survival in men with metastatic prostate cancer treated with Sipleucel-T.

Mounting evidence links systemic innate immunity with cancer immune surveillance. In advanced metastatic castration resistant prostate cancer (mCRPC), Black patients have been found to have increased inflammatory markers and longer survival after sipuleucel-T (sip-T) therapy, an FDA-approved, autologous cell therapy. We hypothesized these differences may be explained by previously reported ancestral differences in pattern recognition receptor (PRR) signaling, which broadly governs innate inflammation to control adaptive immune cell activation, chemotaxis, and functionality. We discovered that PBMC interferon (IFN)-ß responses to TLR1/2, a sensor of bacterial and gut microbiome constituents, associated with significantly longer survival after sip-T therapy in two separate cohorts of men with mCRPC (discovery cohort: n=106, HR=0.12, p=0.019; validation cohort: n=28, HR<0.01, p=0.047). Higher IFN-ß induction after TLR1/2 stimulation was associated with lower hazard ratios compared to biomarkers of vaccine potency and other prognostic factors in mCRPC. TLR1/2 dependent cytokine induction was stronger in Black individuals (1.2-fold higher for IFN-ß; p=0.04) but was associated with survival independently of race or numbers of vaccine-induced tumor antigen-specific T cells. IFN-ß responses to TLR1/2 signaling correlated with increased numbers of IFN-ß producing T cells after broad, tumor antigen independent stimulation. Thus, peripheral innate immunity differs by race, may predict survival after sip-T, and associates with peripheral T cell functionality in men with mCRPC.

Experimental and Computational Anticorrosion Behaviors of Pyrazole s-Triazine/anilino-morpholino Derivatives for Steel in Acidic Solutions.

The corrosion inhibition of C-steel by two s-triazine/morpholino-anilino-pyrazole derivatives, namely, 4-(3,5-dimethyl-1H-pyrazol-1-yl)-6-morpholino-N-phenyl-1,3,5-triazin-2-amine (1) and N-(4-bromophenyl)-4-(3,5-dimethyl-1H-pyrazol-1-yl)-6-morpholino-1,3,5-triazin-2-amine (2) was investigated by impedimetric and potentiometric studies. It was found that (1) and (2) acted as cathodic-type corrosion inhibitors that retard the hydrogen evolution reaction. The percent corrosion inhibition, 98.5% for compound (2) (with bromo substituent) at 80 ppm, was slightly higher than 97.8% for (1) at 100 ppm. Thus, the replacement of a -H with -Br substituent increased the corrosion inhibition properties. Compound (2) exhibited Temkin isotherm adsorption, whereas compound (1) exhibited Langmuir adsorption. Scanning electron microscopy (SEM) analysis of the steel surface indicated that the inhibitors caused protection of the surface. The weight loss experiment also proved the decrease in the corrosion rate when inhibitors were added. The difference in inhibitory efficiency between compounds (1) and (2) was investigated by density functional theory (DFT) to study neutral and protonated species in gaseous and aqueous phases. The theoretical analysis demonstrated that compound (2) exhibited higher inhibitory activity on a metal surface compared to compound (1), aligning with the experimental results. The energy associated with the metal/adsorbate arrangement, represented by dE ads/dNi , was higher for (2) (-380.91 kcal mol-1) compared to (1) (-371.64 kcal mol-1). This indicated better adsorption of (2) over (1).

Platelet-Rich Plasma (PRP) Mitigates Kidney Dysfunction in Alloxan-Induced Diabetic Mice via Modulation of Renal Iron Regulatory Genes.

Kidney dysfunction is a prevalent complication of diabetes mellitus, contributing significantly to diabetes-related morbidity and mortality. We aim to explore whether platelet-rich plasma administration can modulate iron regulation mechanism within the kidney, thereby mitigating renal dysfunction associated with diabetes. Albino mice with an average body weight of 20 ± 5 g were randomly divided into five groups (N = 50; n = 10): Control Group, PRP Group, diabetic group (DG), treated group A (TA), and treated group B (TB). A single intraperitoneal dose of alloxan (160 mg/kg of body weight) was administered to mice in the DG and in both treated groups. Upon confirmation of diabetes, the DG was left untreated, while PRP treatment (0.5 ml/kg of body weight) was administered to the TA and TB groups for two and four weeks, respectively. Histological examinations of kidney tissues revealed notable signs of damage in DG, which were subsequently improved upon PRP treatment. Likewise, PRP treatment restored the changes in liver enzymes, oxidative stress biomarkers and serum electrolytes in both treated groups. Furthermore, there was an observed upregulation of iron regulatory genes, such as Renin, Epo, Hepc, Kim1, and Hfe, in the DG, accompanied by a downregulation of Tfr1 and Fpn; however, Dmt1 and Dcytb1 expression remained unaltered. Treatment with PRP restored the expression of iron regulatory genes in both treated groups. This study concluded that PRP treatment effectively restored the renal histochemistry and the expression of renal iron regulatory genes in an alloxan-induced diabetic mice model.

Bis(dimethylpyrazolyl)-aniline-s-triazine derivatives as efficient corrosion inhibitors for C-steel and computational studies.

4,6-Bis(3,5-dimethyl-1H-pyrazol-1-yl)-N-phenyl-1,3,5-triazin-2-amine (PTA-1), N-(4-bromophenyl)-4,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)-1,3,5-triazin-2-amine (PTA-2) and 4,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)-N-(4-methoxyphenyl)-1,3,5-triazin-2-amine (PTA-3) were synthesized and characterized. Their corrosion inhibition of carbon C-steel in 0.25 M H2SO4 was studied by electrochemical impedance. The inhibition efficiency (IE%) of triazine was superior due to the cumulative inhibition of triazine core structure and pyrazole motif. Potentiodynamic polarizations suggested that s-triazine derivatives behave as mixed type inhibitors. The IE% values were 96.5% and 93.4% at 120 ppm for inhibitor PTA-2 and PTA-3 bearing -Br and -OCH3 groups on aniline, respectively. While PTA-1 without an electron donating group showed only 79.0% inhibition at 175 ppm. The adsorption of triazine derivatives followed Langmuir and Frumkin models. The values of adsorption equilibrium constant K°ads and free energy change ΔG°ads revealed that adsorption of inhibitor onto steel surface was favoured. A corrosion inhibition mechanism was proposed suggesting the presence of physical and chemical interactions. Density functional theory computational investigation corroborated nicely with the experimental results. Monte Carlo simulation revealed that the energy associated with the metal/adsorbate arrangement dE ads/dN i, for both forms of PTA-2 and PTA-3 with electron donating groups (-439.73 and -436.62 kcal mol-1) is higher than that of PTA-1 molecule (-428.73 kcal mol-1). This aligned with experimental inhibition efficiency results.

High-Dimensional Analyses Reveal IL15 Enhances Activation of Sipuleucel-T Lymphocyte Subsets and Reverses Immunoresistance.

Sipuleucel-T (sip-T) is the only FDA-approved autologous cellular immunotherapy for metastatic castration-resistant prostate cancer (mCRPC). To elucidate parameters of the response profile to this therapy, we report high-dimensional analyses of sip-T using cytometry by time of flight (CyTOF) and show a lymphoid predominance, with CD3+ T cells constituting the highest proportion (median ∼60%) of sip-T, followed by B cells, and natural killer (NK) and NKT cells. We hypothesized that treatment of sip-T with homeostatic cytokines known to activate/expand effector lymphocytes could augment efficacy against prostate tumors. Of the cytokines tested, IL15 was the most effective at enhancing activation and proliferation of effector lymphocytes, as well as augmenting tumor cytotoxicity in vitro. Co-culture of sip-T with IL15 and control or prostate-relevant antigens showed substantial activation and expansion of CD8+ T cells and NKT cells in an antigen-specific manner. Adoptive transfer of IL15-treated sip-T into NSG mice resulted in more potent prostate tumor growth inhibition compared with control sip-T. Evaluation of tumor-infiltrating lymphocytes revealed a 2- to 14-fold higher influx of sip-T and a significant increase in IFNγ producing CD8+ T cells and NKT cells within the tumor microenvironment in the IL15 group. In conclusion, we put forward evidence that IL15 treatment can enhance the functional antitumor immunity of sip-T, providing rationale for combining IL15 or IL15 agonists with sip-T to treat patients with mCRPC.

Exploring the Sensing Potential of g-C3N4 versus Li/g-C3N4 Nanoflakes toward Hazardous Organic Volatiles: A DFT Simulation Study.

Ab initio calculations were performed to determine the sensing behavior of g-C3N4 and Li metal-doped g-C3N4 (Li/g-C3N4) quantum dots toward toxic compounds acetamide (AA), benzamide (BA), and their thio-analogues, namely, thioacetamide (TAA) and thiobenzamide (TAA). For optimization and interaction energies, the ωB97XD/6-31G(d,p) level of theory was used. Interaction energies (Eint) illustrate the high thermodynamic stabilities of the designed complexes due to the presence of the noncovalent interactions. The presence of electrostatic forces in some complexes is also observed. The observed trend of Eint in g-C3N4 complexes was BA > TAA > AA > TBA, while in Li/g-C3N4, the trend was BA > AA > TBA > TAA. The electronic properties were studied by frontier molecular orbital (FMO) and natural bond orbital analyses. According to FMO, lithium metal doping greatly enhanced the conductivity of the complexes by generating new HOMOs near the Fermi level. A significant amount of charge transfer was also observed in complexes, reflecting the increase in charge conductivity. NCI and QTAIM analyses evidenced the presence of significant noncovalent dispersion and electrostatic forces in Li/g-C3N4 and respective complexes. Charge decomposition analysis gave an idea of the transfer of charge density between quantum dots and analytes. Finally, TD-DFT explained the optical behavior of the reported complexes. The findings of this study suggested that both bare g-C3N4 and Li/g-C3N4 can effectively be used as atmospheric sensors having excellent adsorbing properties toward toxic analytes.

Emerging role of lipophagy in liver disorders.

Lipophagy is a selective degradation of lipids by a lysosomal-mediated pathway, and dysregulation of lipophagy is linked with the pathological hallmark of many liver diseases. Downregulation of lipophagy in liver cells results in abnormal accumulation of LDs (Lipid droplets) in hepatocytes which is a characteristic feature of several liver pathologies such as nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Contrarily, upregulation of lipophagy in activated hepatic stellate cells (HSCs) is associated with hepatic fibrosis and cirrhosis. Lipid metabolism reprogramming in violent cancer cells contributes to the progression of liver cancer. In this review, we have summarized the recent studies focusing on various components of the lipophagic machinery that can be modulated for their potential role as therapeutic agents against a wide range of liver diseases.

Theoretical Study of Dodecafluorophenylene-Based Superalkalides with Significantly High NLO Response.

Scientists are continuously trying to discover new approaches to develop materials with exceptional nonlinear optical responses. Compared with the single-ring Janus face compound (F6C6H6), the three-ring Janus face compound (C13H10F12) has a larger surface, where superalkali metals can be doped quite easily. Herein, the nonlinear optical response of Janus molecule dodecafluorophenylene (DDFP)-based superalkalides has been explored. The stability of the newly designed complexes is evident in the negative interaction energy values (ranging from -42.17 to -60.91 kcal/mol). The superalkalide nature of the complexes is corroborated through natural bond orbital (NBO) analysis, which shows negative charges on M3. This feature is further confirmed through frontier molecular orbital (FMO) analyses showing the highest occupied molecular orbital (HOMO) density over superalkalis (M3). The analysis also reveals that the H-L gap is reduced from 9.57 eV (for bare DDFP) to 2.11 eV for doped systems by adsorption of dopants on the DDFP surface. Moreover, the NLO response of the studied complexes is evaluated via static hyperpolarizabilities. The maximum value of first hyperpolarizability (ßo) among all of the designed compounds is for K3-DDFP-K3 (7.80 × 104 au) at M06-2X/6-31+G(d,p) level of theory. The ßo is also rationalized through a two-level model. Furthermore, for ßvec, the projection of hyperpolarizability on the dipole moment is calculated. The comparable results of ßvec and ßo indicate that the charge transfer in the complexes is parallel to the molecular dipole moments. These compounds, besides providing a new entry into excess-electron compounds, will also pave the way for the design and synthesis of further novel NLO materials.

Diagnostic and therapeutic value of EVs in lungs diseases and inflammation.

Extracellular vesicles (EVs) are membrane-derived messengers which have been playing an important role in the inflammation and pathogenesis of lung diseases. EVs contain varieties of DNA, RNA, and membrane receptors through which they work as a delivery system for bioactive molecules as well as intracellular communicators. EV signaling mediates tumor progression and metastasis. EVs are linked with many diseases and perform a diagnostic role in lung injury and inflammation so are used to diagnose the severity of diseases. EVs containing a variety of biomolecules communicate with the recipient cells during pathophysiological mechanisms thereby acquiring the attention of clinicians toward the diagnostic and therapeutic potential of EVs in different lung diseases. In this review, we summarize the role of EVs in inflammation with an emphasis on their potential as a novel candidate in the diagnostics and therapeutics of chronic obstructive pulmonary disease, asthma, and sarcoidosis.

Maisotsenko Cycle for Heat Recovery in Gas Turbines: A Fundamental Thermodynamic Assessment.

This paper reports the Maisotsenko's cycle-based waste heat recovery system with enhanced humidification to exploit the maximum waste heat recovery potential of the gas turbine. This research uses an integrated methodology coupling thermodynamic balances with heat transfer model of air saturator. The performance of the system is deduced which are assisted with sensitivity analysis indicating the optimal mass flow rate ratio (0.7-0.8) and pressure ratio (4.5-5.0) between the topping and bottoming cycles, and the air saturator split (extraction) ratio (0.5). The net-work output, energy, and exergy efficiencies of the system are found to be ≈58.39 MW, ≈55.85%, and ≈52.79%, respectively. The maximum exergy destruction ratios are found as 68.2% for the combustion chamber, 16.0% for the topping turbine, 5.7% for topping compressor, 4.9% air saturator. The integration of Maisotsenko's cycle-based waste heat recovery system with a comprehensive thermodynamic model, as demonstrated in this research, offers valuable insights into enhancing the efficiency, cost-effectiveness, and environmental impact of gas turbines. By presenting fundamental equations related to thermodynamic balances, this work serves as an invaluable educational resource, equipping future researchers and students with the knowledge and skills needed to advance the study of thermodynamics and sustainable energy solutions.

Metallofullerenes as Robust Single-Atom Catalysts for Adsorption and Dissociation of Hydrogen Molecules: A Density Functional Study.

Hydrogen is currently considered as the best alternative for traditional fuels due to its sustainable and ecofriendly nature. Additionally, hydrogen dissociation is a critical step in almost all hydrogenation reactions, which is crucial in industrial chemical production. A cost-effective and efficient catalyst with favorable activity for this step is highly desirable. Herein, transition-metal-doped fullerene (TM@C60) complexes are designed and investigated as single-atom catalysts for the hydrogen splitting process. Interaction energy analysis (Eint) is also carried out to demonstrate the stability of designed TM@C60 metallofullerenes, which reveals that all the designed complexes have higher thermodynamic stability. Furthermore, among all the studied metallofullerenes, the best catalytic efficiency for hydrogen dissociation is seen for the Sc@C60 catalyst Ea = 0.13 eV followed by the V@C60 catalyst Ea = 0.19 eV. The hydrogen activation and dissociation processes over TM@C60 metallofullerenes is further elaborated by analyzing charge transfer via the natural bond orbital and electron density difference analyses. Additionally, quantum theory of atoms in molecule analysis is carried out to investigate the nature of interatomic interactions between hydrogen molecules and TMs@C60 metallofullerenes. Overall, results of the current study declare that the Sc@C60 catalyst can act as a low cost, highly efficient, and noble metal-free single-atom catalyst to efficiently catalyze hydrogen dissociation reaction.

Decorating Mg12O12 Nanocage with Late First-Row Transition Metals To Act as Single-Atom Catalysts for the Hydrogen Evolution Reaction.

In the pursuit of sustainable clean energy sources, the hydrogen evolution reaction (HER) has attained significant interest from the scientific community. Single-atom catalysts (SACs) are among the most promising candidates for future electrocatalysis because they possess high thermal stability, effective electrical conductivity, and excellent percentage atom utilization. In the present study, the applicability of late first-row transition metals (Fe-Zn) decorated on the magnesium oxide nanocage (TM@Mg12O12) as SACs for the HER has been studied, via density functional theory. The late first-row transition metals have been chosen as they have high abundance and are relatively low-cost. Among the studied systems, results show that the Fe@Mg12O12 SAC is the best candidate for catalyzing the HER reaction as it exhibits the lowest activation barrier for HER. Moreover, Fe@Mg12O12 shows high stability (Eint = -1.64 eV), which is essential in designing SACs to prevent aggregation of the metal. Furthermore, the results of the electronic properties' analysis showed that the HOMO-LUMO gap of the nanocage is decreased significantly upon doping of Fe (from 4.81 to 2.28 eV), indicating an increase in the conductivity of the system. This study highlights the potential application of the TM@nanocage SAC systems as effective HER catalysts.

A computational investigation towards substitution effects on 8π electrocyclisation of conjugated 1,3,5,7-octatetraenes.

A computational investigation using M06-2X/6-31+G(d) method is reported for the substitution effects on 8π electrocyclisation of conjugated octatetraene. This systematic study describes the mono- and di-substitution effect across the 1,3,5,7-octatetraene skeleton. A general preference of the outward substitution over the inward, at C1 position of the monosubstituted system is observed. However, mesomerically electron donating group (-NH2 and -OH) display an opposite effect with respect to secondary orbital interaction (SOI) between the lone pair on the substituent and the orbital. A comparative evaluation on the computed activation energies for the 1-, 2-, 3-, and 4-monosubstituted system showed an insignificant impact on the rate of the reaction, in contrast to the electrocyclic ring closure of the unsubstituted compound. Computations of disubstituted system are more pronounced, where a remarkable acceleration is observed for 2-NO2-7-NO2 substituted octatetraene at 4.9 kcal mol-1, and a noticeable deceleration for 4-CH3-5-CH3 substituted octatetraene at 25.4 kcal mol-1 from the parent molecule, 17.0 kcal mol-1. A visible accelerated effects are commonly exhibited by the substitution on the terminal double bonds (C1, C2, C7, and C8), that are 1,2-, 1,7-, 1,8-, and 2,7-patterns, in regard to the greater orbital interaction for the new σ-bond formation. Despite the unfavourable steric clashes of the substituents in the 1,8-system, an apparent reduction in the energy barrier up to 7.4 kcal mol-1 is computed for 1-NH2-8-NO2 system from 17.0 kcal mol-1. This is due to the synergistic effect of the electron donor and electron acceptor, enhancing the stability of the transition structure. The electrocyclic ring closure involving vicinal substitution patterns, such as 1,2-, 2,3-, 3,4-, and 4,5-systems are critically dominated by steric crowding between the adjacent functional groups. In certain cases of the 1,2-substituted system, a noticeable accelerated effects are found for 1-NH2-2-NH2-substituted compound (9.7 kcal mol-1) due to an increased in electronic density on the substituted terminal double bond (C1-C2), hence favouring the formation of the new σ-bond.

Enhanced nonlinear optical response of alkalides based on stacked Janus all-cis-1,2,3,4,5,6-hexafluorocyclohexane.

Significant efforts are continuously exerted by the scientific community to explore new strategies to design materials with high nonlinear optical responses. An effective approach is to design alkalides based on Janus molecules. Herein, we present a new approach to remarkably boost the NLO response of alkalides by stacking the Janus molecules. Alkalides based on stacked Janus molecule, M-n-M' (where n = 2 & 3 while M and M' are Li/Na/K) are studied for structural, energetic, electrical, and nonlinear optical properties. The thermodynamic stability of the designed complexes is confirmed by the energetic stabilities, which range between -14.07 and -28.77 kcal/mol. The alkalide character of alkali metals-doped complexes is confirmed by the NBO charge transfer and HOMO(s) densities. The HOMO densities are located on the doped alkali metal atoms, indicating their alkalide character. The absorptions in UV-Vis and near IR region confirm the deep ultraviolet transparency of the designed complexes. The maximum first static and dynamic hyperpolarizabilities of 5.13 × 107 and 6.6 × 106 au (at 1339 nm) confirm their high NLO response, especially for K-2-M' complexes. The NLO response of alkalides based on stacked Janus molecules is 1-2 orders of magnitude higher than the alkalide based on Janus monomer. The high values of dc-Kerr and electric field-induced response e.g., max ∼107 and 108 au, respectively have been obtained. These findings suggest that our designed complexes envision a new insight into the rational design of stable high NLO performance materials.

Role of Delocalization, Asymmetric Distribution of π-Electrons and Elongated Conjugation System for Enhancement of NLO Response of Open Form of Spiropyran-Based Thermochromes.

Switchable nonlinear optical (NLO) materials have widespread applications in electronics and optoelectronics. Thermo-switches generate many times higher NLO responses as compared to photo-switches. Herein, we have investigated the geometric, electronic, and nonlinear optical properties of spiropyranes thermochromes via DFT methods. The stabilities of close and open isomers of selected spiropyranes are investigated through relative energies. Electronic properties are studied through frontier molecular orbitals (FMOs) analysis. The lower HOMO-LUMO energy gap and lower excitation energy are observed for open isomers of spiropyranes, which imparts the large first hyperpolarizability value. The delocalization of π-electrons, asymmetric distribution and elongated conjugation system are dominant factors for high hyperpolarizability values of open isomers. For deep understanding, we also analyzed the frequency-dependent hyperpolarizability and refractive index of considered thermochromes. The NLO response increased significantly with increasing frequency. Among all those compounds, the highest refractive index value is observed for the open isomer of the spiropyran 1 (1.99 × 10-17 cm2/W). Molecular absorption analysis confirmed the electronic excitation in the open isomers compared to closed isomers. The results show that reversible thermochromic compounds act as excellent NLO molecular switches and can be used to design advanced electronics.

Breaking down barriers: The potential of smarter CAR-engineered NK cells against solid tumors.

Natural killer (NK) cells are considered to be the foremost fighters of our innate immune system against foreign invaders and thus tend to promptly latch onto the virus-infected and tumor/cancerous cells, killing them through phagocytosis. At present, the application of genetically engineered Chimeric antigen receptor (CAR) receptors ensures a guaranteed optimistic response with NK cells and would not allow the affected cells to dodge or escape unchecked. Hence the specificity and uniqueness of CAR-NK cells over CAR-T therapy make them a better immunotherapeutic choice to reduce the load of trafficking of numerous tumor cells near the healthy cell populations in a more intact way than offered by CAR-T immunotherapy. Our review mainly focuses on the preclinical, clinical, and recent advances in clinical research trials and further strategies to achieve an augmented and efficient cure against solid tumors.

Giant NLO response and deep ultraviolet transparency of dual (alkali/alkaline earth) metals doped C6O6Li6 electrides.

The designing of new materials having outstanding nonlinear optical (NLO) response is much needed for use in latest optics. Herein, the geometric, electronic and NLO properties of alkali and alkaline earth metals doped C6O6Li6 (alk-C6O6Li6-alkearth, alkearth = Ca, Mg, Be and alk = K, Na, Li) electrides is studied via quantum chemical approach. The interaction energies (Eint) are examined to illustrate their thermodynamic stability. The strong interaction energy of -39.99 kcal mol-1 is observed for Ca-C6O6Li6-Li electride in comparison to others. Frontier molecular orbitals (FMOs) energy gap of considered complexes is changed due to the electronic density shifting between metals and C6O6Li6 surface, which notifies the semi conducting properties of these electrides. The FMOs isodensities and natural bond orbital (NBO) charge analysis are performed to justify charge transfer between dopants and complexant. UV-Visible study also confirmed the application of these electrides as deep ultra-violet laser devices. NLO response is studied through calculation of first hyperpolarizability (ßo). The highest ßo value of 1.68 × 105 au is calculated for Mg-C6O6Li6-K electride. NLO response is further rationalized by three- and two-level models approach.

Effect of heterologous platelet-rich plasma on liver and modulation of glucose metabolism and Wnt signalling pathways in diabetic mice.

BACKGROUND: The current study was designed to highlight the effects of heterologous platelet-rich plasma (PRP) on deteriorated hepatic tissues and impaired glucose metabolism of alloxan-induced diabetic mice. METHODS: 30 male mice were divided into a control (CG), PRP (PG), diabetic (DG), and two treated groups (T1G and T2G). PG was given PRP treatment (0.5 ml/kg body weight) twice a week for four weeks. DG, T1G and T2G were given alloxan (150 mg/kg) to induce diabetes. After confirmation, PRP treatment was given to T1G and T2G for two and four weeks respectively while DG was left untreated. Upon completion of the said experimental period, liver samples were taken for histological and gene expression analyses. RESULTS: The study found that the liver tissue of the DG group showed signs of damage, including hepatocyte ballooning, sinusoid dilatation, and collagen deposition. However, these changes were significantly reduced in both T1G and T2G groups. The expression of several genes related to liver function was also affected, with upregulation of Fbp1 and Pklr, and downregulation of Pck1 in the DG group. PRP treatment restored Fbp1 expression and also increased the expression of glycolytic pathway genes Hk1 and Gck, as well as Wnt signalling pathway genes Wnt2, Wnt4, and Wnt9a in both treated groups. CONCLUSION: Current study revealed that heterologous PRP may partly alleviate high glucose levels in diabetics possibly by mediating glucose metabolism via inhibition of Wnt signalling pathway.

A three orders of magnitude increase in nonlinear optical response by external electric field on Cryptand[2.2.2] (C222) based alkaline earthides.

A new series of alkaline earthides based on Cryptand [2.2.2] (C222) containing nine complexes is designed by carefully placing alkali metals and alkaline earth metals inside and outside the C222 complexant, respectively i.e., M1(C222)M2 (M1 = Li, Na, K; M2 = Be, Mg, Ca). The designed complexes are reasonably stable both electronically and thermodynamically, as revealed through their vertical ionization potentials (VIPs) and interaction energies, respectively. Moreover, the true alkaline earthide nature of the complexes is confirmed through NBO and FMO analyses showing the negative charges and HOMOs over the alkaline earth metals, respectively. The further validity of true earthide characteristic is represented graphically by the spectra of partial density of states (PDOS). HOMO-LUMO gaps of the compounds are also very small (from 2.23 to 2.83 eV) when compared with pure cage's (C222) H-L gap i.e., 5.63 eV. All these features award these complexes with very small values of transition energies (ΔE) ranging from 0.68 to 2.06 eV ultimately resulting in remarkably high hyperpolarizability values up to 2.7 × 105 au (for Na+(C222)Mg-). Furthermore, applying external electric field (EEF) on the complexes enhances hyperpolarizability further. A remarkable increase of 1000 folds has been seen when hyperpolarizability of K+(C222)Ca- is calculated after EEF application i.e., from 8.79 × 104 au to 2.48 × 107 au; when subjected to 0.001 au external electric field.

Nonlinear Optical Properties and Phototunable Absorption of a Substituted Dihydroazulene-Vinylheptafulvene Pair of Photochromes.

Quantum calculations were used to study UV-vis absorption properties and nonlinear optical characteristics of a variety of substituted dihydroazulene (DHA)/vinylheptafulvene (VHF) photoswitches. The absorption properties are substantially based on the position and nature of the substituent. In general, electron-donating groups cause red shifts compared to the parent compound. Any electron-withdrawing group, on the other hand, would generate a blue shift. Furthermore, the steric effect at some positions is accountable for the loss of planarity and, as a response, a decrease in electronic conjugation within the molecule, which in most cases result in blue shifts in maximum absorption. The purpose of this research is to investigate the influence of substitution at the seven-membered ring of the DHA/VHF system on the absorption spectra and nonlinear optical characteristics of dihydroazulene photoswitches. UV-vis spectra and hyperpolarizability are determined since a prospective photoswitch should have a minimum overlap of absorption spectra from both isomers. Furthermore, the differential in hyperpolarizability between DHA and VHF is critical for practical applications.