Soil microbes: a natural solution for mitigating the impact of climate change.

Soil microbes are microscopic organisms that inhabit the soil and play a significant role in various ecological processes. They are essential for nutrient cycling, carbon sequestration, and maintaining soil health. Importantly, soil microbes have the potential to sequester carbon dioxide (CO2) from the atmosphere through processes like carbon fixation and storage in organic matter. Unlocking the potential of microbial-driven carbon storage holds the key to revolutionizing climate-smart agricultural practices, paving the way for sustainable productivity and environmental conservation. A fascinating tale of nature's unsung heroes is revealed by delving into the realm of soil microbes. The guardians of the Earth are these tiny creatures that live beneath our feet and discreetly work their magic to fend off the effects of climate change. These microbes are also essential for plant growth enhancement through their roles in nutrient uptake, nitrogen fixation, and synthesis of growth-promoting chemicals. By understanding and managing soil microbial communities, it is possible to improve soil health, soil water-holding capacity, and promote plant growth in agricultural and natural ecosystems. Added to it, these microbes play an important role in biodegradation, bioremediation of heavy metals, and phytoremediation, which in turn helps in treating the contaminated soils. Unfortunately, climate change events affect the diversity, composition, and metabolism of these microbes. Unlocking the microbial potential demands an interdisciplinary endeavor spanning microbiology, ecology, agronomy, and climate science. It is a call to arms for the scientific community to recognize soil microbes as invaluable partners in the fight against climate change. By implementing data-driven land management strategies and pioneering interventions, we possess the means to harness their capabilities, paving the way for climate mitigation, sustainable agriculture, and promote ecosystem resilience in the imminent future.

Molecular Detection of Streptococcus mutans and Streptococcus sobrinus in Dental Plaque Samples in Children Aged Six to Nine Years.

Context Dental caries is a widespread threat, usually in children, although it has been observed at other stages of life. Various pieces of literature have confirmed the prevalence of S treptococcus mutans and S treptococcus sobrinus in the progression of the disease. However, establishing procedures to detect these species remains a challenge, posing a barrier to treatment plans. Aim The aim of this study is to detect the species in dental plaque samples from children aged six to nine years by polymerase chain reaction (PCR) and correlate their prevalence in various dentitions. Material and Methods This is an observational analytical cross-sectional study conducted in a tertiary care dental hospital. After sample isolation, microbiological processing was performed, genomic DNA was isolated, and PCR run was performed using specific primers to detect the species. SPSS for Windows Version 17 (IBM Corp., Armonk, NY) and Microsoft Excel (Microsoft Corporation, Redmond, WA, USA) were used to perform statistical analysis. A p-value of <0.05 was considered statistically significant. Results The technique could identify S. Mutans and S. Sobrinus in a short turnaround time. The frequency of S. mutans and S. sobrinus infections was higher in individuals with dental caries. Conclusions Molecular detection via PCR is a reliable, economical, and less time-consuming method for detecting S. mutans and S. sobrinus in dental plaque samples.

Structure-Activity Relationship Explorations and Discovery of a Potent Antagonist for the Free Fatty Acid Receptor 2.

Free fatty acid receptor 2 (FFA2) is a sensor for short-chain fatty acids that has been identified as an interesting potential drug target for treatment of metabolic and inflammatory diseases. Although several ligand series are known for the receptor, there is still a need for improved compounds. One of the most potent and frequently used antagonists is the amide-substituted phenylbutanoic acid known as CATPB (1). We here report the structure-activity relationship exploration of this compound, leading to the identification of homologues with increased potency. The preferred compound 37 (TUG-1958) was found, besides improved potency, to have high solubility and favorable pharmacokinetic properties.

Cysteine Modification by Ebselen Reduces the Stability and Cellular Levels of 14-3-3 Proteins.

The 14-3-3 proteins constitute a family of adaptor proteins with many binding partners and biological functions, and they are considered promising drug targets in cancer and neuropsychiatry. By screening 1280 small-molecule drugs using differential scanning fluorimetry (DSF), we found 15 compounds that decreased the thermal stability of 14-3-3ζ Among these compounds, ebselen was identified as a covalent, destabilizing ligand of 14-3-3 isoforms ζ, ε, γ, and η Ebselen bonding decreased 14-3-3ζ binding to its partner Ser19-phosphorylated tyrosine hydroxylase. Characterization of site-directed mutants at cysteine residues in 14-3-3ζ (C25, C94, and C189) by DSF and mass spectroscopy revealed covalent modification by ebselen of all cysteines through a selenylsulfide bond. C25 appeared to be the preferential site of ebselen interaction in vitro, whereas modification of C94 was the main determinant for protein destabilization. At therapeutically relevant concentrations, ebselen and ebselen oxide caused decreased 14-3-3 levels in SH-SY5Y cells, accompanied with an increased degradation, most probably by the ubiquitin-dependent proteasome pathway. Moreover, ebselen-treated zebrafish displayed decreased brain 14-3-3 content, a freezing phenotype, and reduced mobility, resembling the effects of lithium, consistent with its proposed action as a safer lithium-mimetic drug. Ebselen has recently emerged as a promising drug candidate in several medical areas, such as cancer, neuropsychiatric disorders, and infectious diseases, including coronavirus disease 2019. Its pleiotropic actions are attributed to antioxidant effects and formation of selenosulfides with critical cysteine residues in proteins. Our work indicates that a destabilization of 14-3-3 may affect the protein interaction networks of this protein family, contributing to the therapeutic potential of ebselen. SIGNIFICANCE STATEMENT: There is currently great interest in the repurposing of established drugs for new indications and therapeutic targets. This study shows that ebselen, which is a promising drug candidate against cancer, bipolar disorder, and the viral infection coronavirus disease 2019, covalently bonds to cysteine residues in 14-3-3 adaptor proteins, triggering destabilization and increased degradation in cells and intact brain tissue when used in therapeutic concentrations, potentially explaining the behavioral, anti-inflammatory, and antineoplastic effects of this drug.

Introducing Tb4+ in (Ce0.09/Eu0.96)Tb0.92Mo1.1O6.93 Metal Oxide at Room Temperature and Its Use in Amyloid Defibrillation.

Tunable optical properties in nanomaterials enable a variety of applications in multidisciplinary areas. These properties are directly related to several different factors such as solvent conditions, synthesis methods, and most significantly, the oxidation states of metals participating in the absorption or emission properties. Lanthanide metals containing ABO3 perovskites are among such nanomaterials that can be tuned to a great extent by only modifying the charged states on the metals in the composition. We report a green synthesis method through sonication to synthesize ABO3 perovskites to incorporate Tb4+ into the perovskite composition at room temperature. The optical properties of the nanomaterial show emission in the entire ultraviolet-visible-near-infrared spectral regions through charge transfer between europium and terbium. The combination of cerium (C), molybdenum (M), europium (E), and terbium (T) results in a sheet-like CMET perovskite obeying hexagonal geometry. The nanomaterial is highly stable in an aqueous medium, showing finely suspended Tyndall effect due to particle size <300 nm. Owing to their wide range of emission behavior, surface charge, and aqueous stability, CMET perovskites were used to study the defibrillation of hen egg-white lysozyme (HEWL) as an amyloid model protein. The intrinsic property of the nanomaterial assists in the interaction of the fibrils with the perovskite and the emission range becomes the reporter of the defibrillation. Infrared spectroscopy shows the change in the material properties during the defibrillation. A preliminary test on the varying concentration of HEWL incubated with CMET perovskites shows linear behavior with R2 = 0.9841. The tunable emission characteristic and aqueous stability of the perovskite material make it suitable for future biological applications.

Druggable genome in attention deficit/hyperactivity disorder and its co-morbid conditions. New avenues for treatment.

Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder with only symptomatic care available. Genome-wide association (GWA) studies can provide a starting point in the search for novel drug targets and possibilities of drug repurposing. Here, we explored the druggable genome in ADHD by utilising GWA studies on ADHD and its co-morbid conditions. First, we explored whether the genes targeted by current ADHD drugs show association with the disorder and/or its co-morbidities. Second, we aimed to identify genes and pathways involved in the biological processes underlying ADHD that can be targeted by pharmacological agents. These ADHD-associated druggable genes and pathways were also examined in co-morbidities of ADHD, as commonalities in their aetiology and management may lead to novel pharmacological insights. Strikingly, none of the genes encoding targets of first-line pharmacotherapeutics for ADHD were significantly associated with the disorder, suggesting that FDA-approved ADHD drugs may act through different mechanisms than those underlying ADHD. In the examined druggable genome, three loci on chromosomes 1, 4 and 12 revealed significant association with ADHD and contained nine druggable genes, five of which encode established drug targets for malignancies, autoimmune and neurodevelopmental disorders. To conclude, we present a framework to assess the druggable genome in a disorder, exemplified by ADHD. We highlight signal transduction and cell adhesion as potential novel avenues for ADHD treatment. Our findings add to knowledge on known ADHD drugs and present the exploration of druggable genome associated with ADHD, which may offer interventions at the aetiological level of the disorder.

Total Synthesis of Phorbazole B.

Phorbazoles are polychlorinated heterocyclic secondary metabolites isolated from a marine sponge and several of these natural products have shown inhibitory activity against cancer cells. In this work, a synthesis of the trichlorinated phorbazole B using late stage electrophilic chlorination was developed. The synthesis relied on the use of an oxazole precursor, which was protected with an iodine in the reactive 4-position, followed by complete chlorination of all pyrrole positions. Attempts to prepare phorbazole A and C, which contain a 3,4-dichlorinated pyrrole, were unsuccessful as the desired chlorination pattern on the pyrrole could not be obtained. The identities of the dichlorinated intermediates and products were determined using NMR techniques including NOESY/ROESY, 1,1-ADEQUATE and high-resolution CLIP-HSQMBC.

Electrocatalytic synthesis of black tin oxide nanomaterial as photothermal agent for cancer therapy.

Photothermal therapy (PTT) is among the popular approach for treating solid tumours. The rapid killing of cancer cells under the influence of infrared radiation by a rapid increase in the temperature of the remote area now demands external agents with high photothermal transduction efficiency (PTE). Despite their improved PTE, black nanomaterials such as black phosphorus and titanium oxide are unable to meet the challenges in the physiological conditions. To address this major concern, we have developed black tin oxide (bSnO) with enhanced capabilities to respond in the physiological milieu. To make the synthesis cost-effective and eco-friendly, we have used electrochemical oxidation at 5 V and 100 mA to achieve ∼15 nm nanoparticle of bSnO. The as-synthesized bSnO exhibited high NIR absorption as well as high photothermal transduction efficiency. To circumvent the low aqueous solubility and photostability, bSnO was functionalized with polyethyleneimine (PEI). Upon exposure to 808 nm laser for ∼8-10 min, the temperature of the bSnO@PEI solution reached ∼58.5 °C. PTE of bSnO@PEI was calculated to be 51.2%. Owing to its high biological compatibility, tin offers relatively better stability when exposed to cancer cells in vitro and in vivo. In comparison to other black nanomaterials, bSnO@PEI was found to exhibit better response under NIR irradiance for non-invasive photothermal therapy of cancer.

Unequivocal structure confirmation of a breitfussin analog by anisotropic NMR measurements.

Structural features of proton-deficient heteroaromatic natural products, such as the breitfussins, can severely complicate their characterization by NMR spectroscopy. For the breitfussins in particular, the constitution of the five-membered oxazole central ring cannot be unequivocally established via conventional NMR methods when the 4'-position is halogenated. The level of difficulty is exacerbated by 4'-iodination, as the accuracy with which theoretical NMR parameters are determined relies extensively on computational treatment of the relativistic effects of the iodine atom. It is demonstrated in the present study, that the structure of a 4'-iodo breitfussin analog can be unequivocally established by anisotropic NMR methods, by adopting a reduced singular value decomposition (SVD) protocol that leverages the planar structures exhibited by its conformers.

Kinase Chemodiversity from the Arctic: The Breitfussins.

In this work, we demonstrate that the indole-oxazole-pyrrole framework of the breitfussin family of natural products is a promising scaffold for kinase inhibition. Six new halogenated natural products, breitfussin C-H (3 - 8) were isolated and characterized from the Arctic, marine hydrozoan Thuiaria breitfussi. The structures of two of the new natural products were also confirmed by total synthesis. Two of the breitfussins (3 and 4) were found to selectively inhibit the survival of several cancer cell lines, with the lowest IC50 value of 340 nM measured against the drug-resistant triple negative breast cancer cell line MDA-MB-468, while leaving the majority of the tested cell lines not or significantly less affected. When tested against panels of protein kinases, 3 gave IC50 and Kd values as low as 200 and 390 nM against the PIM1 and DRAK1 kinases, respectively. The activity was confirmed to be mediated through ATP competitive binding in the ATP binding pocket of the kinases. Furthermore, evaluation of potential off-target and toxicological effects, as well as relevant in vitro ADME parameters for 3 revealed that the breitfussin scaffold holds promise for the development of selective kinase inhibitors.

Synthesis of fluorescent molybdenum nanoclusters at ambient temperature and their application in biological imaging.

We introduce for first time a facile protocol for the rapid synthesis of a molybdenum nanoclusters (MoNCs) at room temperature using thiolated dithiothreitol (DTT) as capping agents. The initial fluorescence from the MoNCs is observed in 30 min and further intensified in 48 h. The mean diameter of nanoclusters was found to be 1.5 nm with -77 mV zeta potential. The nanoclusters have good stability in all tested pH ranges, especially between pH 7 and 10. This property makes the nanomaterial to be ideal for many types of possible biological/biomedicine applications such as drug delivery or biological imaging. The quantum yield of thiolated MoNCs was calculated to be 59% which is higher than the noble metal nanoclusters reported earlier. The mechanism of formation of MoNCs was investigated using the UV-Vis spectroscopy and cyclic voltammetry. Owing to these characteristics, MoNCs were used for imaging of HaCaT and A549 cancer cells. The current approach on novel synthesis of MoNCs is found to be a superior alternative to conventional/popular MoS2 based on the method of synthesis, particle size, and fluorescence quantum yield. The current approach on the MoNCs has created a new platform for future biomedicine applications.

Cysteine capped copper/molybdenum bimetallic nanoclusters for fluorometric determination of methotrexate via the inner filter effect.

A method is reported for the synthesis of highly luminescent copper/molybdenum bimetallic nanoclusters (Cu/Mo NCs) using cysteine as both a capping and reducing agent. The nanoclusters display bluish-green luminescence (excitation/emission peaks at 370/490 nm) and a relative quantum yield of 26%. The capped Cu/Mo NCs were used as a fluorescent probe for determination of the antineoplastic drug methotrexate (MTX) via an inner filter effect. Fluorescence intensity decreases linearly in the 50 nM to 100 µM MTX concentration range. The limit of detection is 13.7 nM. This approach has been successfully applied to the determination of MTX in spiked human urine with a typical recovery of 99%. Graphical abstract Schematic of a fluorometric method for the determination of methotrexate (MTX) which exerts a strong inner filter effect on the fluorescence of cysteine-capped copper/molybdenum nanoclusters (CuMo NCs) at the wavelength of excitation (370 nm).

Evaluation of Total Salivary Secretory Immunoglobulin A and Mi/fans-specific SIgA among Children having Dissimilar Caries Status.

INTRODUCTION: The occurrence of dental caries has become quite a common phenomenon nowadays. The varying levels of salivary secretory immunoglobulin A (SIgA) usually determine the progression of caries. The present study was aimed to determine the correlation between SIgA and mutans-specific antigen SIgA in children having different caries status. Scanning electron microscopic analysis was also completed to correlate the results. MATERIALS AND METHODS: This study comprised 60 subjects, who were divided into three groups depending on caries status. In all, saliva was collected to determine the level of SIgA and mutans-specific antigen SIgA using enzyme linked immunosorbent assay (ELISA). The World Health Organization (WHO) criteria and method were used to evaluate dental caries. Bradford reagent was used to evaluate the levels of protein in the antigen. Furthermore, 20 sections of enamel were randomly obtained to estimate the severity of caries development among groups. RESULTS: Categorical characteristics among all groups were compared by basic statistical analysis and Chi-squared test. Mean age (years) was found to be 9.214 ± 2.28, 9.5 ± 2.51, and 10.2 ± 2.35 in groups I, II, and III respectively. Mutans-specific IgA level (|jg/mL) was 34.63 ± 7.46, 28.24 ± 4.52, and 23.56 ± 1.62 in groups I, II, and III respectively. Total SIgA (jg/mL) was 142.53 ± 22.4, 186.10 ± 24.70, and 214.8 ± 27.56 in groups I, II, and III respectively. Caries index was 6.74 ± 2.16, 2.32 ± 0.86, and 0 ± 0 in groups I, II, and III respectively. CONCLUSION: Immunoglobulin A is dominantly present in saliva and it plays a significant role in prevention of dental caries. Hence, dental caries is more likely to develop in subjects with low level of salivary IgA (high caries index). CLINICAL SIGNIFICANCE: A low level of IgA may be associated with a high risk of developing dental caries. This association may possibly be useful in predicting the future caries status. Accordingly, suitable caries-preventive measures can be selected and employed.

Aggregation of cysteamine-capped gold nanoparticles in presence of ATP as an analytical tool for rapid detection of creatine kinase (CK-MM).

Creatine kinase, a key biomarker associated with many debilitating physiological conditions has seldom been detected in biological fluids using functionalized gold nanoparticles (GNPs). We have developed a method based on the aggregation of cysteamine (Cys) functionalized GNPs in presence of ATP for effective detection of creatine kinase (CK-MM). Positively charged Cys-GNPs (brick red color) aggregate in presence of negatively charged ATP (blue color) but the process is prevented when CK-MM is added to the solution. The analytical response to the concentration of CK-MM is linear (R2 = 0.9850). The proposed method is selective in sensing the CK-MM for a range of 5.617 × 103 ng/ml, 0.5617 ng/ml. The limit of detection was found to be 0.569 ng/ml in solution and 0.553 ng/ml in human serum with high selectivity.

Utility of Ischemia Modified Albumin as an Early Marker for Diagnosis of Acute Coronary Syndrome.

BACKGROUND: The diagnosis of acute coronary syndrome remains challenging, as cardiac troponins and creatine kinase-MB do not detect myocardial ischemia. Ischemia modified albumin is biomarker positive within 6-10 minutes following ischemic onset, where oxygen free radicals leads to reduction in binding capacity of human serum albumin to transitional metal-cobalt. The objective of this study was to compare ischemia modified albumin between acute coronary syndrome patients and healthy controls, and evaluate diagnostic performance of ischemia modified albumin compared to cardiac troponins, creatine kinase-MB and electrocardiogram in acute coronary syndrome patients. METHODS: Fifty ACS patients and 50 healthy controls were enrolled in this cross-sectional study. Ischemia modified albumin was measured after addition of known amount of cobalt to human serum albumin, followed by spectrophotometric determination of unbound cobalt fraction at 470 nm using dithiothreitol as coloring agent. Independent student t-test and One-way ANOVA to compare differences of mean between groups; diagnostic sensitivity and specificity of ischemia modified albumin was determined by receiver operating characteristic curve; McNemar-test was used to assess diagnostic performance of entire test parameters, when used alone and in combinations. RESULTS: Ischemia modified albumin was significantly higher in acute coronary syndrome patients compared to controls (0.823±0.191 vs 0.410±0.081)(p<0.001). Receiver operating characteristic curve derived optimal cut-off of 0.475 Absorbance unit had sensitivity and specificity of 92% and 82% respectively (area under curve- 0.96). However, no significant differences in mean ischemia modified albumin values between three categories of acute coronary syndrome were seen. Sensitivity of ischemia modified albumin assay (92%) was significantly higher compared to electrocardiogram (72%), cardiac troponin I (18%), and creatine kinase-MB(42%). CONCLUSIONS: Ischemia modified albumin is elevated in acute coronary syndrome patients with better diagnostic performance compared to electrocardiogram, cardiac troponin I, and creatine kinase-MB for early diagnosis, however, with limited ability to discriminate between ST-elevation myocardial infarction, non-ST-elevation myocardial infarction and unstable angina.

Comparative Photothermal Performance among Various Sub-Stoichiometric 2D Oxygen-Deficient Molybdenum Oxide Nanoflakes and In†Vivo Toxicity.

The present study deals with photothermal therapy of solid tumors using different forms of oxygen-deficient sub-stoichiometric two-dimensional (2D) molybdenum oxide nanoflakes (α-MoO3-x ). Upon exfoliation of molybdenum oxide power using fine gridding followed by ultrasonication, bluish green molybdenum oxide (BG α-MoO3 ) was obtained. Oxygen vacancies in BG were generated upon irradiation with an intense xenon lamp. Irradiating the BG for 3 and 5 h, deep blue (B) and olive green (G) oxygen-deficient nanoflakes were obtained respectively. All exhibited high NIR absorption, making these nanomaterials suitable for photothermal therapy. All three forms were functionalized with polypyrrole (PPy@BG, PPy@B, PPy@G) to boost the photothermal stability and transduction efficiency. After functionalization and irradiation with 808 nm laser, the enhancement of temperature for BG, B, G was 50, 65, 52 °C respectively and the corresponding photothermal transduction efficiencies (PTE) were 29.32, 44.42 and 42.00 %. Each of the nanoflakes were found to be highly biocompatible and photostable both in vitro and in vivo. There was substantial decrease in the size of tumors after seven days of treatment on tumor-bearing experimental mice models.

Two dimensional α-MoO3-x nanoflakes as bare eye probe for hydrogen peroxide in biological fluids.

We report a rapid and facile method for detection of hydrogen peroxide (H2O2) in biological fluids using sub-stoichiometric two-dimensional (2D) molybdenum trioxide (α-MoO3-x) nanoflakes. The two-dimensional nanoflakes, initially blue in color, is oxidized after interaction with hydrogen peroxide thereby changing its oxidation state to form α-MoO3. The change in oxidation state of nanoflakes transforms from blue to a visually distinct hazy blue color with change in absorption spectrum. The phenomenal property is explored here in sensing up to 34 nM as limit of detection. The efficacy of the detection system was analyzed by "zone of inhibition" based agar diffusion assay with different concentrations of H2O2. The current approach is highly accurate, effective and reproducible for quantification of physiological concentration of H2O2 in biological fluid such as human urine.

A New Regression Equation Proposed For Mixed Dentition Analysis in Chhattisgarh, Central India Population

Objective: To develop and propose a new regression for mixed dentition analysis in Chhattisgarh, Central India population. Material and Methods: The permanent dentition dental casts of 800 (400 males and 400 females) Chhattisgarh subjects were selected. Digital caliper was used to measure the mesiodistal crown widths of teeth. The linear regression equations and correlation between four mandibular incisors and the canine-premolars segments of maxillary and mandibular arches were developed (modified Tanaka-Johnston equation) and proposed for Chhattisgarh population. Results: New standardized regression equations were formulated to predict the mesiodistal widths of unerupted canines and premolars especially for Chhattisgarh, Central India population. The equation in males for maxillary arch was Y = 11.90 + 0.39 (X) and for mandibular arch was Y = 12.23 + 0.36 (X). Similarly, the equation in females for maxillary arch was Y = 14.40 + 0.26 (X) and for mandibular arch was Y= 10.26 + 0.43 (X). A significant sexual dimorphism in teeth sizes was seen with higher mesio distal dimension in males in Chhattisgarh population. Conclusion: Sum of the mesiodistal diameter of permanent mandibular incisors can be used reliably to predict/estimate the sum of mesiodistal diameters of unerupted canines and premolars with the new regression equations.

Graphene oxide@gold nanorods for chemo-photothermal treatment and controlled release of doxorubicin in mice Tumor.

Graphene oxide (GO) is a close derivative of graphene has unlocked many pivotal steps in drug delivery due to their inherent biocompatibility, excellent drug loading capacity, and shows antibacterial, antifungal properties etc. We used a novel plant material called Gum arabic (GA) to increase the solubility of GO as well as to chemically reduce it in the solution. GA functionalized GO (fGO) exhibited increased absorption in near infra-red region (NIR) which was exploited in photothermal therapy for cancer. In order to understand the shape and size effect of GO which may affect their rheological properties, we have conjugated them with gold nanorods (GNRs) using in situ synthesis of GO@GNRs via seed mediated method. To the above conjugate, Doxorubicin (DOX) was attached at ambient temperature (28±2°C). The release kinetics of DOX with the effect of NIR exposure was also carefully studied via in vitro photothermal killing of A549 cell lines. The enhancement in NIR induced drug release and photothermal property was observed which indicates that the fGO@GNRs-DOX method is an ideal choice for chemotherapy and photothermal therapy simultaneously.