Effect of Scaling and Root Planing in Conjunction with Antimicrobial Therapy on Glycated Hemoglobin Levels in Type 2 Diabetes Mellitus Patients.

Background: Scaling and root planing with systemic doxycycline had an effect on blood glucose levels in type 2 diabetes patients, according to the results of a glycosylated hemoglobin assay. The trial was conducted to determine whether periodontal therapy affected blood sugar regulation as a result of this finding. Methods: A total of 60 people with type 2 diabetes (diabetes mellitus not caused by insulin deficiency) were split into three groups. Group I (control group) consists of patients who are only taking an oral anti-diabetic medication. Patients on an oral anti-diabetic drug plus scaling and root planing make up group II. Patients on an oral anti-diabetic drug, scaling, root planing, and doxycycline constitute Group III. The patients were re-evaluated for glycated hemoglobin levels and periodontal status using the clinical parameters of gingival index by Loe and Silness and clinical attachment level at baseline, 30th, 60th, and 90th day. Results: Compared with group II, the findings showed a statistically significant decrease in glycated hemoglobin values (p =0.001) and improvements in clinical attachment level (p =0.022, 0.05) and gingival index (p = 0.009.,01) in group III. In the control group (group I), no such finding was made. The average gingival index, however, increased statistically significantly (p = 0.032, 0.05). Conclusion: Various studies have been showing the benefits of non-surgical periodontal therapy as a benefit for improving the overall glycemic status of the patient. Non-surgical mechanical periodontal therapy combined with systemic administration of antimicrobials such as doxycycline enhances the metabolic status of type 2 diabetes mellitus patients better than non-surgical mechanical periodontal therapy alone.

Correction: Secondary ligand-induced orthogonal self-assembly of silver nanoclusters into superstructures with enhanced NIR emission.

Correction for 'Secondary ligand-induced orthogonal self-assembly of silver nanoclusters into superstructures with enhanced NIR emission' by Korath Shivan Sugi, et al., Nanoscale, 2023, https://doi.org/10.1039/d3nr02561f.

Secondary ligand-induced orthogonal self-assembly of silver nanoclusters into superstructures with enhanced NIR emission.

Orthogonal self-assembly is one of the crucial strategies for forming complex and hierarchical structures in biological systems. However, creating such ordered complex structures using synthetic nanoparticles is a challenging task and requires a high degree of control over structure and multiple non-covalent interactions. In this context, nanoarchitectonics serves as an emerging tool to fabricate complex functional materials. Here, we present a secondary ligand-induced orthogonal self-assembly of atomically precise silver nanoclusters into complex superstructures. Specifically, we use Ag14NCs protected with naphthalene thiol and 1,6-bis(diphenylphosphino)hexane ligands. Controlled addition of 1,6-bis(diphenylphosphino)hexane, the secondary ligand resulted in a self-assembled supracolloidal structure including helical fibers, spheres, and nanosheets. The self-assembly process is tunable by controlling the molar ratio of the ligand. The resulting superstructures exhibit enhanced NIR emission due to restricted intramolecular motion. This demonstrates that by tuning supramolecular interactions, hierarchical nanostructures with desired properties similar to biomolecules can be obtained from atomically precise building blocks.

Negative Electrospray Supercharging Mechanisms of Nucleic Acid Structures.

When sprayed from physiological ionic strength, nucleic acids typically end up with low levels of charging and in compact conformations. Increasing the electrospray negative charging of nucleic acids while preserving the native noncovalent interactions can help distinguish solution folds by ion mobility mass spectrometry. To get fundamental insight into the supercharging mechanisms of nucleic acids in the negative mode, we studied model G-quadruplex structures and single-strand controls in 100 mM ammonium acetate. We found that adding 0.4% of propylene carbonate, 0.4% of sulfolane, or 0.1% of m-NBA induces native supercharging. However, although 0.4% of m-NBA shows the highest supercharging ability, it induces unwanted unfolding of solution-folded G-quadruplexes. The supercharging effect resembles the effect of lowering the ionic strength, and this could be explained by partial neutralization of the ampholytes when droplets become more concentrated in their nonaqueous components. The supercharging ability ranks PC < sulfolane < m-NBA. m-NBA adducts to G-quadruplexes with high-charge states confirm that the supercharging agent interacts directly with DNA. Surprisingly, in the presence of supercharging agents, the most negatively-charged states also bear more alkali metal ion adducts. Larger droplets are known to result in more counterion adduction, so our results are consistent with native supercharging conditions producing larger droplets evaporating to a charged residue. However, when negative charge carriers from the electrolyte become too rare, chain ejection accompanied by denaturation, and hence non-native supercharging, can become predominant.

Mass Spectrometry of Nucleic Acid Noncovalent Complexes.

Nucleic acids have been among the first targets for antitumor drugs and antibiotics. With the unveiling of new biological roles in regulation of gene expression, specific DNA and RNA structures have become very attractive targets, especially when the corresponding proteins are undruggable. Biophysical assays to assess target structure as well as ligand binding stoichiometry, affinity, specificity, and binding modes are part of the drug development process. Mass spectrometry offers unique advantages as a biophysical method owing to its ability to distinguish each stoichiometry present in a mixture. In addition, advanced mass spectrometry approaches (reactive probing, fragmentation techniques, ion mobility spectrometry, ion spectroscopy) provide more detailed information on the complexes. Here, we review the fundamentals of mass spectrometry and all its particularities when studying noncovalent nucleic acid structures, and then review what has been learned thanks to mass spectrometry on nucleic acid structures, self-assemblies (e.g., duplexes or G-quadruplexes), and their complexes with ligands.

Hierarchical Assembly of Atomically Precise Metal Clusters as a Luminescent Strain Sensor.

We demonstrate the formation of a versatile luminescent organo-inorganic layered hybrid material, composed of bovine serum albumin (BSA)-protected Au30 clusters and aminoclay sheets. X-ray diffraction revealed the intercalation of Au30@BSA in the layered superstructure of aminoclay sheets. Coulombic attraction of the clusters and the clay initiates the interaction, and the appropriate size of the clusters allowed them to intercalate within the lamellar aminoclay galleries. Electron microscopy measurements confirmed the hierarchical structure of the material and also showed the cluster-attached clay sheets. Zeta potential measurement and dynamic light scattering probed the gradual formation of the ordered aggregates in solution. The hybrid material could be stretched up to 300% without fracture. The emergence of a new peak in the luminescence spectrum was observed during the course of mechanical stretching. This peak increased in intensity gradually with the degree of elongation or strain of the material. A mechanochromic luminescence response was further demonstrated with a writing experiment on a luminescent mat of the material, made by electrospinning.

Preservative potential of biosynthesized silver nanoparticles: prevention of xylem occlusion and microbial proliferation at postharvest stage of preservation.

The purpose of the current study was to determine the appropriate genotype and concentration of biosynthesized silver nanoparticles effectual in preserving mulberry leaves at the postharvest stage. The preservative effect of silver nanoparticles was determined by their potentiality to prevent xylem blockage, chlorophyll content retention and inhibition of microbial proliferation within a preservative solution. For synthesizing silver nanoparticles, a blend of 10-3 M silver nitrate and S1 genotype of the mulberry leaf was found to be most effective. Silver nanoparticles at 6 ppm were observed to be the least effective concentration for preserving mulberry leaves for at least 7 days at the postharvest stage, as evident from physical texture and retention of chlorophyll content. Biosynthesized silver nanoparticles showed negative microbial count during the course of preservation as evident from no colony-forming unit (CFU) until the last day of preservation, while conventional preservative silver nitrate showed traces of CFU on a nutrient agar plate. Besides, these leaves preserved in nanosilver solution showed an almost negligible number of xylem blockage in the petiole, almost equivalent to the blockage nature of fresh leaves caused by the deposition of macromolecules like protein, lignin and suberin. Nanosilver- and silver nitrate-preserved leaves also displayed insignificant accumulation of reactive oxygen species (ROS) and greater retention of membrane integrity than leaves preserved in normal distilled water. Nanosilver solution showed greater durability of preserving mulberry leaves than conventional floral preservative silver nitrate, useful for feeding silkworm larvae during the rainy season.

Interparticle Reactions between Silver Nanoclusters Leading to Product Cocrystals by Selective Cocrystallization.

We present an example of an interparticle reaction between atomically precise nanoclusters (NCs) of the same metal, resulting in entirely different clusters. In detail, the clusters [Ag12(TBT)8(TFA)5(CH3CN)]+ (TBT = tert-butylthiolate, TFA = trifluoroacetate, CH3CN = acetonitrile) and [Ag18(TPP)10H16]2+ (TPP = triphenylphosphine) abbreviated as Ag12 and Ag18, respectively, react leading to [Ag16(TBT)8(TFA)7(CH3CN)3Cl]+ and [Ag17(TBT)8(TFA)7(CH3CN)3Cl]+, abbreviated as Ag16 and Ag17, respectively. The two product NCs crystallize together as both possess the same metal chalcogenolate shell, composed of Ag16S8, making them indistinguishable. The occupancies of Ag16 and Ag17 are 66.66 and 33.33%, respectively, in a single crystal. Electrospray ionization mass spectrometry (ESI MS) of the reaction product and a dissolved crystal show the population of Ag16 and Ag17 NCs to be in a 1:1 and 2:1 ratio, respectively. This suggests selective crystallization in the cocrystal. Time-dependent ESI MS was employed to understand the formation of product clusters by monitoring the reaction intermediates formed in the course of the reaction. We present an unprecedented growth mechanism for the formation of silver NCs mediated by silver thiolate intermediates.

Formation of an NIR-emitting Ag34S3SBB20(CF3COO)62+ cluster from a hydride-protected silver cluster.

Recent reports have shown that the intercluster reaction is a new synthetic strategy to prepare alloy clusters. In this work, we performed an intercluster reaction between silver clusters and produced highly ionizable Ag-S-type clusters; we examined their formation by mass spectrometry. [Ag18(TPP)10H16]2+ (Ag18), a highly reactive hydride and phosphine-protected silver cluster, was used as a sacrificial cluster in this synthesis. An intercluster reaction between Ag18 and smaller silver-chalcogenolate clusters (SCC) resulted in a new cluster, [Ag34S3SBB20(CF3COO)6]2+. The cluster showed an NIR emission at around 1100 nm. The cluster composition was confirmed by high-resolution electrospray ionization mass spectrometry (ESI-MS), thermogravimetry (TGA), and X-ray photoelectron spectroscopy (XPS).

Monolayer-Protected Noble-Metal Clusters as Potential Standards for Negative-Ion Mass Spectrometry.

A detailed mass-spectrometric study of atomically precise monolayer-protected clusters revealed the potential application of such materials as mass-spectrometric standards, mostly in negative-ion mode and in the high-mass range. To date, very few molecules are known that can be efficiently ionized and detected at lower concentrations as negative ions with high signal intensities beyond m/ z 3000. Noble-metal clusters are molecules with definite masses, sizes, and shapes, which makes them excellent candidates to choose as standards over conventional low-molecular-weight polymers or clusters of ionic salts. They may be used as calibrants in all possible modes, including tandem mass spectrometry and ion mobility. With the advancement in materials science, more and more molecules are being added to the list that are inherently negatively charged in solution and can be examined by mass spectrometry. In this report, we demonstrate the use of three such model cluster systems for their potential to calibrate mass spectrometers in negative-ion mode. This idea can be extended to many other clusters known so far to achieve calibration in extended mass ranges.

Exploiting the biomimetic and luminescence properties of multivalent dendrimer-semiconductor nanohybrid materials in the ultra-low level determination of folic acid.

In view of the enhanced generation of folate receptors in cancerous cells and diseases linked to the deficiency of folic acid, such as anemia, mental devolution, congenital malformation, etc., the development of a simple method for the ultra-sensitive determination of folic acid remains a long-standing issue for practical applications in medicine and biotechnology. Thus, the proposed luminescence based strategy involving multifunctional poly(amidoamine) (PAMAM) dendrimer encapsulated quantum dots (QDs) as a probe provides a simple, fast and efficient method for the selective determination of folic acid at the nano-molar level. Absorption and Fourier transform infra-red (FTIR) spectroscopy provide evidence of the binding of folic acid with dendrimer amine groups. The emission quenching of dendrimer encapsulated CdS QDs follows a linear Stern-Volmer plot with an exceedingly high value of the Stern-Volmer constant (KSV = 8.4 × 106 M-1) facilitating a higher detection efficiency. Similar quenching analysis with dendrimer-ZnS QDs showed a slightly lower Stern-Volmer constant (KSV = 2.29 × 106 M-1). The lower probing efficiency of the protein or amino acid capping of QDs has been explained through zeta potential measurements. The solvent polarity dependence suggests a charge transfer process responsible for the emission quenching of CdS QDs, which is static in nature as revealed by lifetime measurements. The determination of folic acid at this low level is not affected by possible interfering molecules, such as vitamin C, vitamin B12 and uric acid. Calorimetric measurements showed that the exothermic binding of folic acid with a dendrimer follows enthalpy-entropy compensation. The detailed mechanistic aspect of interactions of folic acid with the QD probe helps in a better understanding of the detection process, which in turn can assist in developing a dendrimer based material for image analysis and drug delivery in folate receptor rich cells.

[Ag59(2,5-DCBT)32]3-: a new cluster and a precursor for three well-known clusters.

We report the synthesis of a new silver cluster, [Ag59(2,5-DCBT)32]3- (I) (2,5-DCBT: 2,5-dichlorobenzenethiol), which acts as a precursor for the synthesis of three well-known silver clusters, [Ag44(2,4-DCBT/4-FTP)30]4- (II) (4-FTP: 4-fluorothiophenol and 2,4-DCBT: 2,4-dichlorobenzenethiol), [Ag25(2,4-DMBT)18]- (III) (2,4-DMBT: 2,4-dimethylbenzenethiol) and [Ag29(1,3-BDT)12(PPh3)4]3- (IV) (1,3-BDT: 1,3-benzenedithiol and PPh3: triphenylphosphine). This newly synthesized silver cluster, I, is characterized using UV-vis absorption studies, high resolution electrospray ionization mass spectrometry (ESI MS) and other analytical tools. The optical absorption spectrum shows distinct features which are completely different from the previously reported silver clusters. We perform the rapid transformations of I to other well-known clusters II, III and IV by reaction with different thiols. The time-dependent UV-vis and ESI MS measurements reveal that I dissociates into distinct thiolate entities in the presence of thiols and the thiolates recombine to produce different clusters. The conversion mechanism is found to be quite different from the previous reports where it occurs through the initial formation of ligand exchanged products. Here, we also show the synthesis of a different cluster core, [Ag44(2,4-DCBT)30]4- (IIa) using 2,4-DCBT, a structural isomer of 2,5-DCBT under the same synthetic conditions used for I. This observation demonstrates the effect of isomeric thiols on controlling the size of silver clusters. The conversion of one cluster to several other clusters under ambient conditions and the effect of ligand structure in silver cluster synthesis give new insights into the cluster chemistry.

Aqueous Synthesis of Protein-Encapsulated ZnSe Quantum Dots and Physical Significance of Semiconductor-Induced CuII Ion Sensing.

In view of their promising bio-applicability, we have synthesized water-soluble bovine serum albumin (BSA)-encapsulated ZnSe quantum dots (QDs) with visible emission with longer average luminescence lifetimes of approximately 125 ns at ambient conditions. BSA-ZnSe QDs are shown to be efficient selective copper ion probes in the presence of physiologically important metal ions through luminescence quenching with a high Stern-Volmer constant (3.3×105 m-1 ). The mechanism of sensing has been explained in terms of electron transfer processes and the apparent rate of electron transfer (Ket ) from ZnSe QDs to Cu2+ has been calculated to be 2.8×108  s-1 . It is demonstrated that the negative conduction band potential plays a major role in the feasibility of the electron transfer process, which is reflected in the higher efficacy of ZnSe QDs in sensing copper(II) ions over other group II-VI quantum dots, namely, CdSe, ZnS, or CdS. The results observed with cysteine-capped QDs are almost identical to those with BSA-encapsulated QDs and this presumably negates the possible reason of CuII ion induced quenching ascribed to its binding with surface groups or replacement of metal sites as proposed by several groups previously.

A comparative evaluation of the activity modulation of flavo and non-flavo enzymes induced by graphene oxide.

Graphene, and its water soluble derivative graphene oxide, has shown great promise in various biomedical applications, such as cancer therapeutics, drug delivery, etc. and in industrial applications such as enzyme immobilization, etc. Thus, modulation of the activities of different classes of enzymes by graphene materials is an important aspect in the formulation of different biological applications. We have demonstrated here how flavin adenine dinucleotide (FAD) moieties protect the binding site from conformational change in the presence of an inhibitor, graphene oxide, and also explore differences in the mode of interactions between flavo and non-flavo enzymes. It was shown that there was a much greater loss of activity with the non-flavo enzyme, l-lactate dehydrogenase (LDH), of ∼74% compared to that with the flavo-enzyme, glucose oxidase (GOX), of ∼45%, in the presence of equal concentrations of GO. Furthermore, GO acts as an enzyme inhibitor and the mode of inhibition is uncompetitive for GOX and competitive for LDH. Circular dichromism measurements showed a 21% decrease in the α helix of GOX and a 31% decrease in the α helix of LDH in the presence of a given concentration of GO (0.5 mg mL-1). There was a slight change in the average emission lifetime of tryptophan in GOX in the presence of GO from 3.2 to 2.6 ns. In contrast, there was no change in the average emission lifetime of tryptophan in LDH in the presence of GO. The extents of fluorescence quenching for GOX and LDH were 39% and 70% upon addition of a certain amount of GO. The present study provides insight into the development of sensors through the immobilization of enzymes and the possible formulation of a multifunctional protein and graphene composite system for various biomedical applications such as bio-sensing, gene and drug delivery, etc.

Unusual reactivity of dithiol protected clusters in comparison to monothiol protected clusters: studies using Ag51(BDT)19(TPP)3 and Ag29(BDT)12(TPP)4.

We report the synthesis and unique reactivity of a new green dithiol protected cluster (DTPC), Ag51(BDT)19(TPP)3 (BDT and TPP are 1,3-benzenedithiol and triphenylphosphine, respectively). The cluster composition was confirmed by electrospray ionization (ESI) and matrix-assisted laser desorption ionization (MALDI) mass spectrometric studies as well as by other supporting data. Surprisingly, the chemical reactivity between this DTPC and Au25(SR)18 involves only metal ion exchange in Au25(SR)18 without any ligand exchange, while reactions between monothiol protected clusters (MTPCs) show both metal and ligand exchange, an example being the reaction between Ag25DMBT18 and Au25PET18 (where DMBT and PET are 2,4-dimethylbenzenethiol and phenylethanethiol, respectively). The conclusions have been confirmed by the reaction of another DTPC, Ag29(BDT)12(TPP)4 with Au25BT18 (where BT corresponds to butanethiol) in which only metal exchange happens in Au25BT18. We also show the conversion of Ag51(BDT)19(TPP)3 to Ag29(BDT)12(TPP)4 in the presence of a second monothiol, DMBT which does not get integrated into the product cluster. This is completely different from the previous understanding wherein the reaction between MTPCs and a second thiol leads to either mixed thiol protected clusters with the same core composition or a completely new cluster core protected with the second thiol. The present study exposes a new avenue of research for monolayer protected clusters, which in turn will give additional impetus to explore the chemistry of DTPCs.

Dual Probe Sensors Using Atomically Precise Noble Metal Clusters.

This article adds a new direction to the functional capability of protein-protected atomically precise gold clusters as sensors. Counting on the extensively researched intense luminescence of these clusters and considering the electron donating nature of select amino acids, we introduce a dual probe sensor capable of sensing changes in luminescence and conductivity, utilizing bovine serum albumin-protected atomically precise gold clusters hosted on nanofibers. To this end, we have also developed a hybrid nanofiber with a conducting core with a porous dielectric shell. We show that clusters in combination with nanofibers offer a highly selective and sensitive platform for the detection of trace quantities of trinitrotoluene, both in solution and in the vapor phase. In the solution phase, trinitrotoluene (TNT) can be detected down to 1 ppt at room temperature, whereas in vapor phase, 4.8 × 109 molecules of TNT can be sensed using a 1 mm fiber. Although the development in electrospinning techniques for fabricating nanofibers as sensors is quite substantial, a hybrid fiber with the dual properties of conductivity and luminescence has not been reported yet.

SERS Enhancement on the Basis of Temperature-Dependent Chemisorption: Microcalorimetric Evidence.

The mechanism of surface-enhanced Raman spectroscopy (SERS) is not very clear in view of the magnitude of the contribution of electromagnetic factor as well as the chemical mechanism. This report presents the extent of adsorption at different temperatures in terms of signal enhancements in SERS employing silver nanoparticles (AgNPs) of various shapes as substrate and dye molecules, crystal violet or Rhodamine 6G, as model Raman probes. Initially, the SERS signal increases with increasing temperature until a maximum intensity is reached, before it gradually decreases with increasing temperature. This trend is independent of the shape of the Raman substrates and probes. However, the temperature at which maximum intensity is obtained may depend upon the nature of the Raman probe. The energetics involved in the chemisorption process between dye molecules and AgNPs were determined through isothermal titration calorimetry and their implications for the observed SERS signals were assessed. The maximum heat change occurred at the temperature at which the maximum signal enhancement in SERS was obtained and the enhanced interaction at optimum temperature was confirmed by absorption spectroscopy.

Synthesis and spectral measurements of sulphonated graphene: some anomalous observations.

The present report demonstrates how a sulphonation process, a key route for synthesizing water soluble graphene, can influence the optical behavior of precursor graphene oxide, intermediate reaction products and sulphonated graphene. We observed that there is constant emission maximum at 500 nm for graphene oxide in the excitation range of 320-450 nm. During sulphonation, sulphonated reduced graphene oxide (rGO-SO3H) is initially formed which has an emission at 358 nm. However, the reduction of oxygen containing groups in rGO-SO3H with hydrazine hydrate leading to the formation of SG caused a shift in the emission to 430 nm, which has been attributed to the extended delocalization of π-electrons involving the phenyl sulphonate group. In the present investigation, we have identified many existing anomalies in the important spectral features of these materials, such as violation of Kasha's rule on fluorescence and pH dependence emission. Furthermore, it has also been shown that proper care is necessary to be taken in monitoring the fluorescence of sulphonated graphene in view of possible interference from the components produced during sulphonation.

Reductant Control on Particle Size, Size Distribution and Morphology in the Process of Surface Enhanced Raman Spectroscopy Active Silver Colloid Synthesis.

The present study demonstrates how reducing agents play an important role in synthesis of silver nanoparticles (AgNPs) in colloidal phase. It is apparent from the observed results that borohydride, one of the most widely used reductants, induces reduction leading to the formation of spherical particles with narrowest size distribution. In contrast, ascorbic or citrate mediated reduction leads to formation of anisotropic silver nanoparticles, indicating the role of anionic carboxylate in template driving process. In view of recent green chemistry approach for synthesizing silver nanoparticles involving glucose as reductant and starch as capping groups, we have followed in detail the dependence of glucose-induced reduction process on different synthesis parameters, such as concentration, temperature and time of reactions. The phase of the synthesized particles was found to be face centred cubic (fcc), which was independent of the reductants employed. Further, we have endeavored to look into the Surface enhanced Raman spectroscopy (SERS) of crystal violet and rhodamine 6G in the presence of AgNPs substrate synthesized by using the reducing agents in question without involving any other structural modulating additive, such as ionic salt, etc. Here, the observed results provide a guideline on the selection of reducing agents and appropriate conditions for application specific synthesis of silver nanoparticles.

Evolution of biofunctional semiconductor nanocrystals: a calorimetric investigation.

Semiconductor nanomaterials have found numerous applications in optoelectronic device fabrication and in platforms for drug delivery and hyperthermia cancer treatment, and in various other biomedical fields because of their high photochemical stability and size-tunable photoluminescence (PL). However, little attention has been paid to exploring the energetics of formation of these semiconductor nanoparticles. We demonstrate that formation of nanocrystals with biofunctionalization supported by widely used groups, BSA and cysteine, is an exothermic spontaneous process driven by enthalpy. The whole energetics of the reaction shows that formation of smaller particles is favored with lower synthesis temperature. Further, it is shown that the thermodynamics of nanoparticle formation is strongly influenced by the conformation of the protein matrix. We also demonstrate that protein supported formation of nanocrystals is thermodynamically more favorable compared to that involving smaller organic thiol groups. The favorable enthalpy of formation compensates unfavorable entropy, resulting in favorable Gibbs free energy. Thus, this study can open up new avenues for establishing a thermodynamic basis for the design of nanosystems with new and tunable properties.