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FA-HA-Amygdalin@Fe2O3 and/or γ-Rays Affecting SIRT1 Regulation of YAP/TAZ-p53 Signaling and Modulates Tumorigenicity of MDA-MB231 or MCF-7 Cancer Cells.

Breast cancer (BC) has a complex and heterogeneous etiology, and the emergence of resistance to conventional chemo-and radiotherapy results in unsatisfactory outcomes during BC treatment. Targeted nanomedicines have tremendous therapeutic potential in BC treatment over their free drug counterparts. Hence, this study aimed to evaluate the newly fabricated pH-sensitive multifunctional FAHA- Amygdalin@Fe2O3 nano-core-shell composite (AF nanocomposite) and/or γ-radiation for effective localized BC therapy. The physicochemical properties of nanoparticles were examined, including stability, selectivity, responsive release to pH, cellular uptake, and anticancer efficacy. MCF-7 and MDA-MB-231 cells were treated with AF at the determined IC50 doses and/or exposed to γ-irradiation (RT) or were kept untreated as controls. The antitumor efficacy of AF was proposed via assessing anti-proliferative effects, cell cycle distribution, apoptosis, and determination of the oncogenic effectors. In a bio-relevant medium, AF nanoparticles demonstrated extended-release characteristics that were amenable to acidic pH and showed apparent selectivity towards BC cells. The bioassays revealed that the HA and FA-functionalized AF markedly hindered cancer cell growth and enhanced radiotherapy (RT) through inducing cell cycle arrest (pre-G1 and G2/M) and increasing apoptosis, as well as reducing the tumorigenicity of BCs by inhibiting Silent information regulation factor 1 (SIRT1) and restoring p53 expression, deactivating the Yes-associated protein (YAP)/ Transcriptional coactivator with PDZ-binding motif (TAZ) signaling axis, and interfering with the tumor growth factor- β(TGF- β)/SMAD3 and HIF-1α/VEGF signaling hub while up-regulating SMAD7 protein expression. Collectively, the novel AF alone or prior RT abrogated BC tumorigenicity.

Direct Yeast Surface Codisplay of Sequential Enzymes with Complementary Anchor Motifs: Enabling Enhanced Glycosylation of Natural Products.

Yeast surface display is an appealing technique for constructing multienzyme cascades. This technique is commonly achieved using a scaffold for the ordered arrangement of various enzymes. However, this method is typically complicated because scaffold use may engender extra metabolic burden on the cell host. Here, we established a direct yeast surface codisplay strategy by employing two complementary anchor motifs, Agα1 and Pir1. These motifs allow for the codisplay of sequential uridine diphosphate-glycosyltransferase (UGT) and sucrose synthase (SUS) on the surface of Pichia pastoris (syn. Komagataella phaffii) for the glycosylation of natural products. We manipulated the displayed stoichiometry, amount, and assembly order of UGT and SUS by coupling them with anchor motifs. Furthermore, their effect on enzyme activity was thoroughly investigated. The surface-codisplayed strain UGT-Pir-SUS-Agα exhibited greater thermostability than the single-displayed strains and their free counterparts. Moreover, the strain UGT-Pir-SUS-Agα was successfully applied to glycyrrhetinic acid (GA) glycosylation to produce GA-3-O-Glc, with sucrose being the sugar donor in this process. This generated 7.5- to 20- and 5.3-fold higher GA-3-O-Glc concentration compared with the free counterparts (enzyme mass loading of 20-fold in excess) and mixed single-displayed strains of UGT-Agα and SUS-Pir, respectively. This increase was due to the improved biochemical properties and substrate channeling effect of strain UGT-Pir-SUS-Agα. This controllable direct surface codisplay strategy, based on complementary anchor motifs, is readily extendable to other enzyme cascades.

Sustainable production of formic acid from CO2 by a novel immobilized mutant formate dehydrogenase

Formate dehydrogenase (NAD+-dependent FDH) is an enzyme that catalyzes the reversible oxidation of formate to CO2 while reducing NAD+ to NADH. The enzyme has been used in industrial and chemical applications for NADH regeneration for a long time. However, discovering the unique ability of FDHs, which is to reduce CO2 and produce formic acid, leads studies focusing on discovering or redesigning FDHs. Despite using various protein engineering techniques, these studies mostly target the same catalytic site amino acids of FDHs. Here, for the first time, the effect of an Asp188 mutation on a potential allosteric site in NAD+-dependent CtFDH around its subunit-subunit interface was studied by molecular modelling and simulation in the presence of bicarbonate and formate. Biochemical and kinetic characterization of this Asp188Arg mutant and wild type CtFDH enzymes were performed in detail. Both enzymes were also immobilized on newly synthesized MWCNT-Ni-O-Si/Ald and MWCNT-Ni-O-Si/Glu supports designed to overcome well-known CtFDH stability problems including thermostability and reuse resistance. Integrating mutation and immobilization provided about a 25-fold increase in catalytic efficiency for carbonate activity. The one-way ANOVA analysis also ensured significant effect of the mutation and immobilization on kinetic constants. After characterizing the immobilization of highly purified wild type and mutant enzyme with instrumental analysis techniques, the thermal stability of MWCNT-Ni-Si@wt-CtFDH and MWCNT-Ni-Si@mt-CtFDH was found to increase about 11- and 18-fold, respectively, compared to their free counterparts at 50 °C. The mutant CtFDH and its immobilized counterpart produced around 2-fold more formic acid than those of wild type CtFDH and its immobilized counterpart under the same conditions. MWCNT-Ni-Si@wt-CtFDH and MWCNT-Ni-Si@mt-CtFDH remained around 82 % and 86 % of their initial activities respectively after lots of recycling. Integration of subunit interface amino acid position of NAD+ dependent FDHs engineering and immobilization provides a new insight can be scientifically and rationally employed for this current application FDHs as a solution to produce formic acids from renewable sources.

The Anionic Chemistry in Regulating the Reductive Stability of Electrolytes for Lithium Metal Batteries.

Advanced electrolyte design is essential for building high-energy-density lithium (Li) batteries, and introducing anions into the Li+ solvation sheaths has been widely demonstrated as a promising strategy. However, a fundamental understanding of the critical role of anions in such electrolytes is very lacking. Herein, the anionic chemistry in regulating the electrolyte structure and stability is probed by combining computational and experimental approaches. Based on a comprehensive analysis of the lowest unoccupied molecular orbitals, the solvents and anions in Li+ solvation sheaths exhibit enhanced and decreased reductive stability compared with free counterparts, respectively, which agrees with both calculated and experimental results of reduction potentials. Accordingly, new strategies are proposed to build stable electrolytes based on the established anionic chemistry. This work unveils the mysterious anionic chemistry in regulating the structure-function relationship of electrolytes and contributes to a rational design of advanced electrolytes for practical Li metal batteries.

The Anionic Chemistry in Regulating the Reductive Stability of Electrolytes for Lithium Metal Batteries

AbstractAdvanced electrolyte design is essential for building high‐energy‐density lithium (Li) batteries, and introducing anions into the Li+ solvation sheaths has been widely demonstrated as a promising strategy. However, a fundamental understanding of the critical role of anions in such electrolytes is very lacking. Herein, the anionic chemistry in regulating the electrolyte structure and stability is probed by combining computational and experimental approaches. Based on a comprehensive analysis of the lowest unoccupied molecular orbitals, the solvents and anions in Li+ solvation sheaths exhibit enhanced and decreased reductive stability compared with free counterparts, respectively, which agrees with both calculated and experimental results of reduction potentials. Accordingly, new strategies are proposed to build stable electrolytes based on the established anionic chemistry. This work unveils the mysterious anionic chemistry in regulating the structure–function relationship of electrolytes and contributes to a rational design of advanced electrolytes for practical Li metal batteries.

Efficient removal of dextran in sugar juice by immobilized α-dextranase from Chaetomium gracile

Abstract Dextran problem restricts the development of the sugar industry. Although the enzymatic treatment based on α-dextranase from Chaetomium gracile (α-dextranase (CG)) has been effective in solving this issue, the lack of immobilization products hinder its industrial applications. This research described a novel and suitable method to immobilize α-dextranase (CG). The purified α-dextranase (CG) was immobilized via cross-linking using modified chitosan as carriers. In addition, this study used a deep eutectic solvent that greatly improved the enzymatic properties of immobilized α-dextranase (CG). α-dextranase (CG) was immobilized by adding deep eutectic solvent (DES-IM-α-dextranase (CG)) showed better temperature tolerance and storage properties than free and ordinary immobilized counterparts. It can eliminate dextran by 59.71% in mixed sugarcane juice and 38.71% in clarified sugarcane juice. The achieved results were considerably better than those obtained using free and other immobilized enzymes. Altogether, these findings confirmed that DES-IM-α-dextranase (CG) displayed great potential in solving the dextran problem.

P-066 ABDOMINAL WALL RECONSTRUCTION FOLLOWING FULL THICKNESS BILATERAL RUPTURE OF THE RECTUS ABDOMINIS

Abstract Introduction Rupture of the rectus abdominis is rare injury with no consensus on management. Previous reported cases have been due to exercise-related injuries and blunt abdominal trauma. We report the case of a 20-year-old male trainee paratrooper who presented with severe lower abdominal pain that occurred during military training. MRI revealed full-thickness bilateral rupture of the rectus abdominis. Abdominal wall reconstruction involved bilateral rectus muscle repair and placement of a biosynthetic mesh in the retrorectus plane. Postoperatively, our patient could walk pain-free at 3 weeks, jog pain-free at 10 weeks, and run up to 2 miles at 25 weeks. Methods Pubmed, Medline and Embase were searched to identify relevant studies using the MeSH terms, “rectus abdominis” and “rupture”, as well as their free text counterparts and synonyms. Texts were restricted to publications in English and publications after the year 2000. The search resulted in 391 articles. Manual cross-referencing was performed, limiting the included articles to 8 for review. Results 6 out of the 8 selected articles discussed management using conservative means, while only 2 cases were managed surgically. Interestingly, no other exercise-related cases in the literature were managed surgically. Instead, all exercise related cases were managed conservatively, while only cases of traumatic aetiology were managed surgically. Among both surgically and conservatively treated patients, none suffered any treatment related complications, and all patients returned to normal levels of activity. Conclusion Full-thickness, bilateral rupture of the rectus abdominis can occur during exercise. Surgical and conservative treatment yield similar results.

Acidic Devinylation of Nickel Chlorophyll Derivatives

Abstract A nickel(II) complex of methyl pyropheophorbide-a bearing a vinyl group at the 3-position was treated with methanesulfonic acid in refluxing benzene to give smoothly the corresponding 3-devinylated product. The 7- and 8-vinyl groups in the related chlorophyll-a/b derivatives were readily removed under the same conditions, while the 12-vinyl group neighboring the electron-withdrawing 13-keto carbonyl moiety was hardly defunctionalized. The devinylations blue-shifted all the visible absorption bands in dichloromethane. The deethylation at the 3-position bathochromically moved the redmost Qy maximum, and the dealkylations at the 7-, 8-, and 12-positions hypsochromically moved the Qy(0,0) maxima, which were reproduced by time-dependent density functional theory calculation. Since no vinyl periphery in the free base counterparts was removed under the mild conditions, nickel 3-unsubstituted deoxophylloerythroporphyrin in geological samples would be produced via the nickel metalation of chlorophylls-a/b/c from ancient phototrophs or their derivatives followed by the acidic 3-devinylation.

The strategy of cell extract based metal organic frameworks (CE-MOF) for improved enzyme characteristics

A convenient cell extract based metal organic frameworks (CE-MOF) strategy was used to produce self-assembled hybrid microparticles of enzymes with improved characteristics. It was shown that many metal ions and enzymes could be used to construct catalytically active CE-MOF microparticles. As a proof-of-principle study, the β-xylosidase BH3683 was used to prepare FeSO4-CE-MOF-BH3683 microparticles to explore the factors influencing preparation of the microparticles. As a result, DNA, RNA, polysaccharides and proteins were found to play important roles in the formation of the microparticles and affected enzyme activities through interaction with enzyme molecules. Compared with the free BH3683, the optimum temperature of FeSO4-CE-MOF-BH3683 increased 5 °C, and the relative activity at 70 °C increased two times. Moreover, FeSO4-CE-MOF-BH3683 have stronger tolerance to different concentrations of various organic solvents and high-concentration xylose than the free BH3683, and the CE-MOF microparticles prepared by BH3683 and xylanase XynII could catalyze high-concentration xylan more efficiently than their free counterparts. In addition, FeSO4-CE-MOF-BH3683 exhibited about 40 % of its initial activity after reused for 10 times, showing satisfactory reusability. To sum up, this strategy might have wide application potential in the fields of biocatalysis, biofuel production, fertilizer industry, etc.

Enhanced antimicrobial, antibiofilm and ecotoxic activities of nanoencapsulated carvacrol and thymol as compared to their free counterparts

Essential oils active components emerged as captivating antimicrobials to control biofilms developed on food contact surfaces. Free and nanoencapsulated carvacrol (CAR) and thymol (THY) were assessed as antimicrobials against Salmonella Enteritidis biofilms adhered to stainless steel. The developed spherical nanocapsules using the spray-drying technique showed an average size ranged between 159.25 and 234.76 nm and zeta potential values ranged between 23.60 and 24.66 mV. The minimal inhibitory concentrations (MIC) of free THY and CAR were both 1.25 mg L−1. Nanoencapsulation reduced MIC values to 0.62 mg L−1 (THY) and 0.31 mg L−1 (CAR). Furthermore, the exposure to free and nanoencapsulated CAR and THY induced a destabilization of bacterial membranes with obvisous morphological deformations and a pronounced leakage of potassium ions and green fluorescent proteins. Eradication of S. Enteritidis biofilms developed on stainless steel was achieved following a 15 min treatment with nanoencapsulated CAR and THY at 2 MIC. Free antimicrobial exposures induced up to 4.27 log CFU cm−2 reductions. Additionally, the ecotoxicity tests against Daphnia magna crustaceans reported a non-toxicity of both free and nanoencapsulated CAR and THY after 48 h exposure. Thereby, both CAR and THY antimicrobials proved to be promising natural surface disinfectants that require further exploration and incorporation in food industries.

Corroborative insights into genetically related kerogen, asphaltenes and hydrocarbons using free and bound biomarkers

Unlike the free biomarkers, which can be routinely recovered via solvent extraction, the bound biomarkers are covalently linked to the kerogen or asphaltene macrostructures and are more resistant to secondary alteration processes. Although similarities have been identified between these two types of biomarkers using different techniques, it remains unclear how the kerogen- and asphaltene-bound biomarkers are complicatedly corelated with their free counterparts, thus limiting the applications of bound biomarkers in geoscience research. In this study, the characteristics of free biomarkers recovered from shale samples, from 10 sedimentary basin around the world, and petroleum samples, from the North Sea, have been systematically compared with their kerogen- and asphaltene-bound biomarkers, which were released by the newly developed Microscale Sealed Vessel Catalytic Hydrogenation (MSSV-Hy) method. Although the kerogen-bound biomarkers are characterized by the absence of rearranged biomarkers (e.g., Ts and diasteranes) and elevated C29/C30 hopane ratios, many key source-related parameters show strong positive correlations between free and bound fractions, including the steranes/hopane, C27/C29 sterane, C30/C29 sterane, C29/C30 hopane (αβ + βα), C35/C34 homohopanes and C24 tetracyclic terpane/C26 tricyclic terpane ratios. These results suggest that bound biomarkers can reveal critical information about deposits and organic matter precursors of source rocks. Thermal maturity indicators, such as C29 sterane ββ/(αα + ββ), C29 sterane S/(S + R), C31 hopane S/R, and Tβ/Tm ratios, also display excellent correlations between the free and bound counterparts in the source rocks. Although the correlations are not 1:1, empirical formulae, which are based on the correlations between free and bound biomarkers, can be used to calibrate bound biomarkers into values that can be directly compared to routine free biomarkers. Importantly, asphaltene-bound biomarkers of North Sea samples exhibit similar characteristics to kerogen-bound biomarkers, and the conversion between free and bound biomarkers of the source rock and reservoir samples is the same. In summary, the bound biomarkers are found highly effective in determining the organic facies, lithology, and thermal maturity of the parent kerogen and/or asphaltene, and, thus, have a great potential to be widely used in geoscience research when information from free biomarkers is hampered by oil mixing, contamination or biodegradation.

The Hilbert space of large N Chern-Simons matter theories

We demonstrate that the known expressions for the thermal partition function of large N Chern-Simons matter theories admit a simple Hilbert space interpretation as the partition function of an associated ungauged large N matter theory with one additional condition: the Fock space of this associated theory is projected down to the subspace of its quantum singlets i.e. singlets under the Gauss law for Chern-Simons gauge theory. Via the Chern-Simons / WZW correspondence, the space of quantum singlets are equivalent to the space of WZW conformal blocks. One step in our demonstration involves recasting the Verlinde formula for the dimension of the space of conformal blocks in SU(N)k and U(N)k,k′ WZW theories into a simple and physically transparent form, which we also rederive by evaluating the partition function and superconformal index of pure Chern-Simons theory in the presence of Wilson lines. A particular consequence of the projection of the Fock space of Chern-Simons matter theories to quantum (or WZW) singlets is the ‘Bosonic Exclusion Principle’: the number of bosons occupying any single particle state is bounded above by the Chern-Simons level. The quantum singlet condition (unlike its Yang-Mills Gauss Law counterpart) has a nontrivial impact on thermodynamics even in the infinite volume limit. In this limit the projected Fock space partition function reduces to a product of partition functions, one for each single particle state. These single particle state partition functions are q-deformations of their free boson and free fermion counterparts and interpolate between these two special cases. We also propose a formula for the large N partition function that is valid for arbitrary finite volume of the spatial S2 and not only at large volume.

Functionalized Mesoporous Silica Nanoparticles for Drug-Delivery to Multidrug-Resistant Cancer Cells

BackgroundMultidrug resistance is a common reason behind the failure of chemotherapy. Even if the therapy is effective, serious adverse effects might develop due to the low specificity and selectivity of antineoplastic agents. Mesoporous silica nanoparticles (MSNs) are promising materials for tumor-targeting and drug-delivery due to their small size, relatively inert nature, and extremely large specific surfaces that can be functionalized by therapeutic and targeting entities. We aimed to create a fluorescently labeled MSN-based drug-delivery system and investigate their internalization and drug-releasing capability in drug-sensitive MCF-7 and P-glycoprotein-overexpressing multidrug-resistant MCF-7 KCR cancer cells.Methods and ResultsTo track the uptake and subcellular distribution of MSNs, particles with covalently coupled red fluorescent Rhodamine B (RhoB) were produced (RhoB@MSNs). Both MCF-7 and MCF-7 KCR cells accumulated a significant amount of RhoB@MSNs. The intracellular RhoB@MSN concentrations did not differ between sensitive and multidrug-resistant cells and were kept at the same level even after cessation of RhoB@MSN exposure. Although most RhoB@MSNs resided in the cytoplasm, significantly more RhoB@MSNs co-localized with lysosomes in multidrug-resistant cells compared to sensitive counterparts. To examine the drug-delivery capability of these particles, RhoB@Rho123@MSNs were established, where RhoB-functionalized nanoparticles carried green fluorescent Rhodamine 123 (Rho123) - a P-glycoprotein substrate – as cargo within mesopores. Significantly higher Rho123 fluorescence intensity was detected in RhoB@Rho123@MSN-treated multidrug-resistant cells than in free Rho123-exposed counterparts. The exceptional drug-delivery potential of MSNs was further verified using Mitomycin C (MMC)-loaded RhoB@MSNs (RhoB@MMC@MSNs). Exposures to RhoB@MMC@MSNs significantly decreased the viability not only of drug-sensitive but of multidrug-resistant cells and the elimination of MDR cells was significantly more robust than upon free MMC treatments.ConclusionThe efficient delivery of Rho123 and MMC to multidrug-resistant cells via MSNs, the amplified and presumably prolonged intracellular drug concentration, and the consequently enhanced cytotoxic effects envision the enormous potential of MSNs to defeat multidrug-resistant cancer.

Multipole oscillator strength and polarizability for confined hydrogen-like atoms under high pressure

Multipole oscillator strength (f (k)) acts as a foundation in estimating multipole polarizability in a quantum system. Moreover, a knowledge of f (k) as well as under extreme pressure may be treated as the benchmark in high pressure spectroscopy. Further, an investigation of rate of change of these quantities and transition moment integral as a function of confinement radius (R) may offer many hitherto unexplained features. Here, we derive several such relations for confined H-like atom as a test case. In this regard, a virial theorem is utilized. The versatility of these derived relations in the context of atom is also discussed. Apart from that, we report numerically calculated results of α (k), f (k) for a confined H-like atom trapped inside a spherical cavity of radius R. A detailed and systematic analysis of these are undertaken in case of k ranging from 1–4, with special emphasis on 1s, 2s, 2p, 3d states. Their behavior is found to be significantly different from their respective free counterparts.

Decolorization of azo dyes by a novel aerobic bacterial strain Bacillus cereus strain ROC.

Synthetic dyes are widely used as colorant compounds in various industries for different purposes. Among all the dyestuffs, azo dyes constitute the largest and the most used class of dyes. These dyes and their intermediate products are common contaminants of ground water and soil in developing countries. Biological methods have been found to be promising for the treatment and degradation of these compounds. In the present study, we focused on the biological removal of azo dyes (Reactive orange 16 and Reactive black 5) under aerobic conditions using an indigenous bacterial strain isolated from contaminated industrial areas. The bacterial isolate was identified as Bacillus cereus strain ROC. Degradation experiments under agitation with both free and immobilized cells indicates that this strain degrades both azo- dyes in 5 days. The immobilized cells were more proficient than their free cell counterparts. The toxicity of the biotransformation products formed after decolorization were assessed by conducting bacteriotoxic and phytotoxic assays. All the toxicity assays indicate that the dyes' degraded products were non-toxic in nature, as compared to the dyes themselves. The kinetics of the azo dyes' degradation was also studied at various initial concentration ranges from 50 mg/L to 250 mg/L by growth independent kinetic models. Zero-order kinetics were fit to the experimental data, producing values of least squares regression (R2) greater than 0.98, which indicates that the bacterial strain degrades both dyes by co-metabolism rather than utilizing them as sole energy source. These results indicate that the Bacillus cereus ROC strain has great potential to degrade dye-contaminated water and soil.

Tuning quantum–classical correspondence for atomic and molecular systems in a cavity

We show that the correspondence between quantum and classical mechanics can be tuned by varying the coupling strength between an atom or a molecule and the modes of a cavity. In the acceleration gauge (AG) representation, the cavity–matter system is described by an effective Hamiltonian, with a non-trivial coupling appearing in the potential, and with renormalized masses. Importantly, and counterintuitively, the AG coupling changes non-monotonically with the strength of the cavity–matter interaction. As a result, one obtains an effective (approximately decoupled) cavity–matter dynamics both for the case of weak and strong interactions. In the weak coupling regime, the effective mass parameters essentially coincide with their standard interaction free counterparts. In contrast, the renormalized atomic/molecular mass increases as the cavity–matter interaction is increased. This results in AG dynamics of matter governed by a conventionally looking atomic/molecular Hamiltonian, whose effective Planck constant is reduced when the cavity–matter interaction is increased.

The Emerging Potential of Parthenolide Nanoformulations in Tumor Therapy.

Plant-derived sesquiterpene lactones are promising natural sources for the discovery of anti-cancer drugs. As an extensively studied sesquiterpene lactone, the tumor suppression effect of parthenolide (PTL) has been clarified by targeting a number of prominent signaling pathways and key protein regulators in carcinogenesis. Notably, PTL was also the first small molecule reported to eradicate cancer stem cells. Nevertheless, the clinical application of PTL as an antitumor agent remains limited, owing to some disadvantages such as low water solubility and poor bioavailability. Thus, nanomedicine has attracted much interest because of its great potential for transporting poorly soluble drugs to desired body sites. In view of the significant advantages over their free small-molecule counterparts, nanoparticle delivery systems appear to be a potential solution for addressing the delivery of hydrophobic drugs, including PTL. In this review, we summarized the key anticancer mechanisms underlined by PTL as well as engineered PTL nanoparticles synthesized to date. Therefore, PTL nanoformulations could be an alternative strategy to maximize the therapeutic value of PTL.

Pre-Clinical Evidence for the Anti-Obesity Potential of Quercetin and Curcumin Loaded Chitosan/PEG Blended PLGA Nanoparticles

This research aimed to formulate quercetin (Qu) and curcumin (CUR)-loaded PLGA NPs coated with chitosan (CS) & PEG and to explore their therapeutic effect against obesity in rats. Qu and CUR nanostructures were prepared and characterized by Zetasizer and TEM. Then, the formulated nanoparticles and their free couterparts were employed for mitigation of obesity in female rats. The size of NPs was in nanometer range with an average size distribution 307.9 nm for Qu NPs and 322.5 nm for CUR NPs. The Qu NPs and CUR NPs were appeared in the TEM image containing core in which the Qu or CUR was localized and surrounded by the coat of PLGA-CS-PEG. The Qu NPs exhibited negative zeta potential at -8.5 mV, while, CUR NPs exhibited positive zeta potential at +0.916 mV. Treatment with orlistat, free Qu, Qu NPs, free CURor CUR NPs elicited significant decline in body weight, BMI and Lee index. Orlistat and CUR NPs significantly diminished liver, heart and visceral adipose tissue weights. Furthermore, the suggested treatments significantly reduced the gonadal and subcutaneous adipose tissue weights. Orlistat significantly lessened kidney and adrenal weights. All treatments significantly minimized serum Chol., TG, LDL, glucose, INS, HOMA-IR, LH, MDA, TLR4 and NF-κB levels and elevated serum HDL, E2 and TAC levels. Orlistat significantly enhanced serum IL-10 level. Conclusively, Qu and CUR nanoformulations offer anti-obesity potency through their hypolipidemic, hypoglycemic,antioxidative and anti-inflammatory effects. Both Qu and CUR NPs manifested superior effect than their free counterparts, may be because of solubility elevation as well as bioavailability of the nanoencapsulation.

Stealth doxorubicin conjugated bimetallic selenium/silver nanoparticles for targeted cervical cancer therapy

Bimetallic nanosized delivery systems are attracting a lot of research interest as alternatives to monometallic delivery systems. This study evaluated the ability of bimetallic selenium silver chitosan pegylated folic acid targeted nanoparticles (SeAgChPEGFA NPs) to deliver doxorubicin (DOX) in cervical cancer cells. Comparison studies using monometallic selenium chitosan pegylated folic acid (SeChPEGFA NPs) targeted NPs and free DOX were also conducted. The prepared NPs and their drug nanocomplexes were characterised morphologically and physico-chemically. Drug binding and releasing studies were conducted under a simulated environment in vitro. The cytotoxicity and apoptosis studies were studied using the 3-[(4, 5-dimethylthiazol-2-yl)−2, 5-diphenyl tetrazolium bromide] (MTT) assay and the dual dye staining. The findings revealed that the bimetallic SeAgChPEGFA NPs displayed better colloidal stability, superior physico-chemical qualities, and higher binding abilities in comparison with monometallic SeChPEGFA NPs. In addition, the SeAgChPEGFA NPs showed the pH-triggered controlled drug release and cell-specific cytotoxicity. These findings suggest that the bimetallic NPs are superior delivery systems when compared to their monometallic NPs and free drug counterparts, thus, setting a platform for further in vivo examination.

Electronegativity under Confinement.

The electronegativity concept was first formulated by Pauling in the first half of the 20th century to explain quantitatively the properties of chemical bonds between different types of atoms. Today, it is widely known that, in high-pressure regimes, the reactivity properties of atoms can change, and, thus, the bond patterns in molecules and solids are affected. In this work, we studied the effects of high pressure modeled by a confining potential on different definitions of electronegativity and, additionally, tested the accuracy of first-order perturbation theory in the context of density functional theory for confined atoms of the second row at the Hartree–Fock level. As expected, the electronegativity of atoms at high confinement is very different than that of their free counterparts since it depends on the electronic configuration of the atom, and, thus, its periodicity is modified at higher pressures.