Terpenoids as potential phytoconstituent in the treatment of diabetes: From preclinical to clinical advancement.

BACKGROUND: Diabetes mellitus, a hyperglycemic condition associated with multitudinous organ dysfunction, is a hallmark of the metabolic disorder. This life-threatening condition affects millions of individuals globally, harming them financially, physically and psychologically in the course of therapy. PURPOSES: The course therapy for illnesses has undergone ground-breaking transformations due to recent technical advances and insights. Alternatively, the administration of hyperglycemia-reducing agents results in several complications, including severe cardiovascular disease, kidney failure, hepatic problems, and several dermatological conditions. Consideration of alternate diabetic therapy having minimal side effects or no adverse reactions has been driven by such problems. STUDY DESIGN: An extensive literature study was conducted in authoritative scientific databases such as PubMed, Scopus, and Web of Science to identify the studies elucidating the bioactivities of terpenoids in diabetic conditions. METHODS: Keywords including 'terpenoids', 'monoterpenes', 'diterpenes', 'sesquiterpenes', 'diabetes', 'diabetes mellitus', 'clinical trials', 'preclinical studies', and 'increased blood glucose' were used to identify the relevant research articles. The exclusion criteria, such as English language, duplication, open access, abstract only, and studies not involving preclinical and clinical research, were set. Based on these criteria, 937 relevant articles were selected for further evaluation. RESULTS: Triterpenes can serve as therapeutic agents for diabetic retinopathy, peripheral neuropathy, and kidney dysfunction by inhibiting several pathways linked to hyperglycemia and its complications. Therefore, it is essential to draw special attention to these compounds' therapeutic effectiveness and provide scientific professionals with novel data. CONCLUSION: This study addressed recent progress in research focussing on mechanisms of terpenoid, its by-products, physiological actions, and therapeutic applications, particularly in diabetic and associated disorders.

Examining the effectiveness of municipal street sweeping in removing road-deposited particles and metal(loid)s of respiratory health concern.

Road dust is a demonstrated source of urban air pollution. Given this, the implementation of street sweeping strategies that effectively limit road dust accumulation and resuspension should be a public health priority. Research examining the effectiveness of street sweeping for road dust removal in support of good air quality has been limited to date. To address this, the study aimed to assess the use of a regenerative-air street sweeper to efficiently remove road dust particles and metal(loid)s in size fractions relevant for respiratory exposure in Toronto, Canada. As part of this, the mass amounts, particle size distribution and elemental concentrations of bulk road dust before and after sweeping at five arterial sites were characterized. Sweeping reduced the total mass amount of thoracic-sized (<10 µm) road dust particles by 76 % on average. A shift in the size distribution of remaining particles toward finer fractions was observed in post-sweeping samples, together with an enrichment in many metal(loid)s such as Co, Ti and S. Overall, the mass amounts of metal(loid)s of respiratory health concern like Cu and Zn were greatly reduced with sweeping. Traffic volume and road surface quality were predictors of dust loadings and elemental concentrations. Road surface quality was also found to impact street sweeping efficiencies, with larger mass amounts per unit area collected post-sweeping where street surfaces were distressed. This study demonstrates that street sweeping using advanced technology can be highly effective for road dust removal, highlighting its potential to support air quality improvement efforts. The importance of tailoring sweeping service levels and technologies locally as per the quality of road surface and traffic patterns is emphasized. Continued efforts to mitigate non-exhaust emissions that pose a respiratory health risk at their source is essential.

Structural basis of human NOX5 activation.

NADPH oxidase 5 (NOX5) catalyzes the production of superoxide free radicals and regulates physiological processes from sperm motility to cardiac rhythm. Overexpression of NOX5 leads to cancers, diabetes, and cardiovascular diseases. NOX5 is activated by intracellular calcium signaling, but the underlying molecular mechanism of which - in particular, how calcium triggers electron transfer from NADPH to FAD - is still unclear. Here we capture motions of full-length human NOX5 upon calcium binding using single-particle cryogenic electron microscopy (cryo-EM). By combining biochemistry, mutagenesis analyses, and molecular dynamics (MD) simulations, we decode the molecular basis of NOX5 activation and electron transfer. We find that calcium binding to the EF-hand domain increases NADPH dynamics, permitting electron transfer between NADPH and FAD and superoxide production. Our structural findings also uncover a zinc-binding motif that is important for NOX5 stability and enzymatic activity, revealing modulation mechanisms of reactive oxygen species (ROS) production.

Nano-inducer of ferroptosis for targeted chemotherapy of human triple negative breast carcinoma.

Triple negative breast carcinoma (TNBC) accounts for 15-20 % of all incident breast cancers (BC) and is known to be highly invasive, has fewer treatment options, and tends to have a worse prognosis. However, due to its biological heterogeneity and diverse clinical and epidemiological behaviors, TNBC lacks a tumor-specific targeted therapy. In the present work we have developed a TNBC-specific targeted nano-delivery agent comprising of a cRGD labeled magneto-liposome (T-LMD) co-encapsulated with oleic acid coated iron oxide nanoparticles (MN-OA) and doxorubicin (Dox) in the liposome bilayer and core, respectively. T-LMD was found to show enhanced uptake and induction of ferroptotic cell death in MDA-MB-231, a TNBC model cell line. Additionally, T-LMD induced ferroptosis was found to be accompanied by release of HMGB1, an immunogenic cell death marker, suggesting its immunogenicity for augmenting the activation of anti-tumor immunity in TNBC. The strategic placement of IONPs in the liposome bilayer of T-LMD facilitates the sensitization of MDA-MB-231 cells to undergo ferroptosis; predominantly via the activation of the iron/lipid metabolism pathway, as validated by use of small molecule ferroptosis inhibitor (ferrostatin-1) and iron chelator (deferoxamine). Activation of ferroptotic cell death was also corroborated by ferroptosis specific-ultrastructural alterations in the shape/size of cellular mitochondria and cell ballooning as observed by transmission electron microscopy and bright field imaging, respectively. Thus, our ferroptosis nano-inducer (T-LMD) can efficiently kill TNBC cells via enhanced LPO and ROS generation leading to membrane damage and consequent release of LDH and HMGB1, induce mitochondrial alterations and enhanced DNA double strand breaks. Altogether, our results suggest significant implications of T-LMD for treatment of TNBC.

Effect of diamagnetic Zn(II) ions on the SMM properties of a series of trinuclear ZnDy2 and tetranuclear Zn2Dy2 (LnIII = Dy, Tb, Gd) complexes: combined experimental and theoretical studies.

To study the effect of diamagnetic ions on magnetic interactions, utilizing a compartmental ligand (Z)-2-(hydroxymethyl)-4-methyl-6-((quinolin-8-ylimino)methyl)phenol (LH2), two different series of ZnII-LnIII complexes, namely the trinuclear series of [DyZn2(L)2(µ2-OAc)2(CH3OH)2]·NO3·MeOH (1), [TbZn2(L)2(µ2-OAc)2(CH3OH)2]·NO3·5MeOH·H2O (2), and [GdZn2(L)2(µ2-OAc)2(CH3OH)2]·NO3·MeOH·CHCl3 (3) and the tetranuclear series of [Dy2Zn2(LH)4(NO3)4(µ2OAc)]·NO3·MeOH·H2O (4), [Tb2Zn2(LH)4(NO3)4(µ2-OAc)]·NO3·MeOH·2H2O (5), and [Gd2Zn2(LH)4(NO3)4(µ2-OAc)]·NO3·MeOH·2H2O (6), were synthesized. Trinuclear ZnII-LnIII complexes 1-3 consist of one LnIII ion sandwiched between two peripheral ZnII ions forming a bent type ZnII-DyIII-ZnII array with an angle of 110.64°. Tetranuclear ZnII-LnIII complexes 4-6 are basically a combination of two dinuclear moieties of [LnZn(LH)2(NO3)2]+ connected by one bidentate bridging acetate ion in µ2-OAc coordination mode. The detailed magnetic analysis reveals that complexes 1 and 4 are single molecule magnets having energy barriers of 34.98 K and 46.71 K with relaxation times (τ0) of 5.05 × 10-4 s and 5.24 × 10-4 s, respectively. Ab initio calculations were employed to analyze the magnetic anisotropy and magnetic exchange interaction between the ZnII and LnIII centers with the aim of gaining better insights into the magnetic dynamics of complexes 1-6.

Isolation and characterization of bioactive alkaloids and GC-MS based identification of volatile oil metabolites from fruits of Glycosmis pentaphylla and evaluation of their cytotoxic activity.

Glycosmis pentaphylla, a member of the Rutaceae family, has been extensively studied for its pharmacological activities, focusing mainly on the cytotoxic properties of its roots and stems. Conversely, limited researched has been done in terms of the phytochemical composition of the fruits. The objective of this study is to isolate and identify the bioactive compounds found in the fruits of G. pentaphylla and then evaluate their potential for anti-cancer activity in oral cancer CAL 27 cell lines. The extraction of bioactive compounds from fruits was done by maceration, and the isolation of alkaloids and volatile oil fractions (F1-F5) was performed by column chromatography. The alkaloids, such as 3-O-methoxyglycocitrine II, noracronycine, 1-hydroxy-3-methoxy-10-methyl-9-acridone and kokusaginine, were first isolated from the fruits of G. pentaphylla. Additionally, GC-MS analysis identified 78 metabolites. The isolated compounds and identified volatile oil fractions were explored for their anti-cancer activity by cell viability assay. Results demonstrated that isolated compounds were found inactive, while the volatile fraction F1 was found active in CAL 27 cell line. Fraction F1 impeded wound healing in CAL 27 cells by scratch assay, and significantly inhibited colony formation in colony formation assay. In cell cycle analysis, treatment with fraction F1 redistributed cells to the S and G2 phases of the cell cycle. α-elemol (2) is the major metabolite identified from the F1 fraction by GC-MS, which could be responsible for the anti-cancer activity. There is potential for future work to further isolate volatile oil metabolites and evaluate their anti-cancer activity through in-vivo techniques.

Tetranuclear CoII4O4 Cubane Complex: Effective Catalyst Toward Electrochemical Water Oxidation.

The reaction of Co(OAc)2·6H2O with 2,2'-[{(1E,1'E)-pyridine-2,6-diyl-bis(methaneylylidene)bis(azaneylylidene)}diphenol](LH2) a multisite coordination ligand and Et3N in a 1:2:3 stoichiometric ratio forms a tetranuclear complex Co4(L)2(µ-η1:η1-OAc)2(η2-OAc)2]· 1.5 CH3OH· 1.5 CHCl3 (1). Based on X-ray diffraction investigations, complex 1 comprises a distorted Co4O4 cubane core consisting of two completely deprotonated ligands [L]2- and four acetate ligands. Two distinct types of CoII centers exist in the complex, where the Co(2) center has a distorted octahedral geometry; alternatively, Co(1) has a distorted pentagonal-bipyramidal geometry. Analysis of magnetic data in 1 shows predominant antiferromagnetic coupling (J = -2.1 cm-1), while the magnetic anisotropy is the easy-plane type (D1 = 8.8, D2 = 0.76 cm-1). Furthermore, complex 1 demonstrates an electrochemical oxygen evolution reaction (OER) with an overpotential of 325 mV and Tafel slope of 85 mV dec-1, required to attain a current density of 10 mA cm-2 and moderate stability under alkaline conditions (pH = 14). Electrochemical impedance spectroscopy studies reveal that compound 1 has a charge transfer resistance (Rct) of 2.927 Ω, which is comparatively lower than standard Co3O4 (5.242 Ω), indicating rapid charge transfer kinetics between electrode and electrolyte solution that enhances higher catalytic activity toward OER kinetics.

Exploration of the impact of graphene oxide, acetylenic gemini, and CTAT on the photophysical and aggregation properties of dipolar coumarin 153.

Advanced spectroscopic techniques have been utilized to study the interaction between the laser dye coumarin 153 (C153) and graphene oxide (GO) nanoparticles. GO was synthesized using a modified Hummers' method and characterized by UV-vis spectroscopy, Raman laser spectroscopy, FTIR-ATR spectroscopy, FESEM, HR-TEM, and XRD techniques. The GO@C153 composite was formed by mixing two aqueous solutions of GO and C153 due to their strong interaction through stacking and hydrophobic interactions. In this case, GO acts as an effective fluorescence quencher for C153 molecules, which undergo H-type aggregation in the presence of GO. The Stern-Volmer equation and time-dependent fluorescence studies were utilized to analyse the mechanism of fluorescence quenching. According to the findings, both static and dynamic quenching processes are responsible for the reduction in fluorescence intensity. The effect of surfactants (both cetyltrimethylammonium p-toluenesulfonate (CTAT) and synthesized N,N'-dihexadecyl-N,N,N',N'-tetramethyl-N,N'-but-2-ynediyl-di-ammonium chloride (16-4-16)) on the aggregation and photophysical properties of the dye was investigated using surface tensiometry, conductometry, UV-vis absorption spectroscopy, steady-state fluorescence measurements, DLS, and time-dependent fluorescence spectroscopy. Surfactants change the microenvironment of the C153 dye, leading to spectrum shifting and a higher quantum yield, which causes a rapid rise in fluorescence intensity in the micellar medium. It has been noted that in a micellar medium rather than in an aqueous one, the luminous intramolecular charge transfer (ICT) state of C153 stabilises. Lastly, we investigated the photophysical behavior of the GO-C153-micelle ternary system and discovered that, in the presence of a micellar medium, the quenched and blue-shifted (H-type aggregation) fluorescence peak of C153 (in the presence of GO) began to intensify once more. The main goal of this work is to create an effective and fairly cost powerful fluorescence sensor. Additionally, the ternary system (GO-C153-micelle) analytical idea can be employed to identify the onset of micelle formation. In wastewater treatment analysis, the GO-C153-surfactant ternary system concept can also be used to regenerate the adsorbent (in this case, GO) from dye molecules by allowing the dye molecules to exit the adsorbent and enter the micellar medium.

ROS mediated Cu[Fe(CN)5NO] nanoparticles for triple negative breast cancer: A detailed study in preclinical mouse model.

Triple negative breast cancer (TNBC) is an aggressive form of tumor, more prevalent in younger women resulting in poor survival rate (2nd in cancer deaths) because of its asymptomatic existence. The most popular and convenient approach for the treatment of TNBC is chemotherapy which is associated with several limitations. Considering the importance of nanotechnology in health care system, in the present manuscript, we have designed and developed a simple, efficient, cost effective, and ecofriendly method for the synthesis of copper nitroprusside analogue nanoparticles (Cu[Fe(CN)5NO] which is abbreviated as CuNPANP that may be the potential anti-cancer nanomedicine for the treatment of TNBC. Copper (present in CuNPANP) is used because of its affordability, nutritional value and various biomedical applications. The CuNPANP are thoroughly characterized using several analytical techniques. The in vitro cell viability (in normal cells) and the ex vivo hemolysis assay reveal the biocompatible nature of CuNPANP. The anti-cancer activity of the CuNPANP is established in TNBC cells (MDA-MB-231 and 4T1) through several in vitro assays along with plausible mechanisms. The intraperitoneal administration of CuNPANP in orthotopic breast tumor model by transplanting 4T1 cells into the mammary fat pad of BALB/c mouse significantly inhibits the growth of breast carcinoma as well as increases the survival time of tumor-bearing mice. These results altogether potentiate the anti-cancer efficacy of CuNPANP as a smart therapeutic nanomedicine for treating TNBC in near future after bio-safety evaluation in large animals.

Transient Metallo-Lipidoid Assemblies Amplify Covalent Catalysis of Aqueous and Non-Aqueous Reactions.

Dissipative supramolecular assemblies are hallmarks of living systems, contributing to their complex, dynamic structures and emerging functions. Living cells can spatiotemporally control diverse biochemical reactions in membrane compartments and condensates, regulating metabolite levels, signal transduction or remodeling of the cytoskeleton. Herein, we constructed membranous compartments using self-assembly of lipid-like amphiphiles (lipidoid) in aqueous medium. The new double-tailed lipidoid features Cu(II) coordinated with a tetravalent chelator that dictates the binding of two amphiphilic ligands in cis-orientation. Hydrophobic interactions between the lipidoids coupled with intermolecular hydrogen bonding led to a well-defined bilayer vesicle structure. Oil-soluble SNAr reaction is efficiently upregulated in the hydrophobic cavity, acting as a catalytic crucible. The modular system allows easy incorporation of exposed primary amine groups, which augments the catalysis of retro aldol and C-N bond formation reactions. Moreover, a higher-affinity chelator enables consumption of the Cu(II) template leveraging the differential thermodynamic stability, which allows a controllable lifetime of the vesicular assemblies. Concomitant temporal upregulation of the catalytic reactions could be tuned by the metal ion concentration. This work offers new possibilities for metal ion-mediated dynamic supramolecular systems, opening up a massive repertoire of functionally active dynamic "life-like" materials.

Enhancing Immunological Memory: Unveiling Booster Doses to Bolster Vaccine Efficacy Against Evolving SARS-CoV-2 Mutant Variants.

A growing number of re-infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in previously immunized individuals has sparked discussions about the potential need for a booster vaccine dosage to counteract declining antibody levels and new strains. The protective immunity produced by vaccinations, and past illnesses relies on immunological memory. CD4 + T cells, CD8 + T cells, B cells, and long-lasting antibody responses are all components of the adaptive immune system that can generate and maintain this immunological memory. Since novel mutant variants have emerged one after the other, the world has been hit by repeated waves. Various vaccine formulations against SARS-CoV-2 have been administered across the globe. Thus, estimating the efficacy of those vaccines against gradually developed mutant stains is the essential parameter regarding the fate of those vaccine formulations and the necessity of booster doses and their frequency. In this review, focus has also been given to how vaccination stacks up against moderate and severe acute infections in terms of the longevity of the immune cells, neutralizing antibody responses, etc. However, hybrid immunity shows a greater accuracy of re-infection of variants of concern (VOCs) of SARS-CoV-2 than infection and immunization. The review conveys knowledge of detailed information about several marketed vaccines and the status of their efficacy against specific mutant strains of SARS-CoV-2. Furthermore, this review discusses the status of immunological memory after infection, mixed infection, and vaccination.

Development of direct compression Acetazolamide tablet with improved bioavailability in healthy human volunteers enabled by cocrystallization with p-Aminobenzoic acid.

Pharmaceutical cocrystallization has been widely used to improve physicochemical properties of APIs. However, developing cocrystal formulation with proven clinical success remains scarce. Successful translation of a cocrystal to suitable dosage forms requires simultaneously improvement of several deficient physicochemical properties over the parent API, without deteriorating other properties critical for successful product development. In the present work, we report the successful development of a direct compression tablet product of acetazolamide (ACZ), using a 1:1 cocrystal of acetazolamide with p-aminobenzoic acid (ACZ-PABA). The ACZ-PABA tablet exhibits superior biopharmaceutical performance against the commercial tablet, DIAMOX® (250 mg), in healthy human volunteers, leading to more than 50 % reduction in the required dose.

Selective CK1α degraders exert antiproliferative activity against a broad range of human cancer cell lines.

Molecular-glue degraders are small molecules that induce a specific interaction between an E3 ligase and a target protein, resulting in the target proteolysis. The discovery of molecular glue degraders currently relies mostly on screening approaches. Here, we describe screening of a library of cereblon (CRBN) ligands against a panel of patient-derived cancer cell lines, leading to the discovery of SJ7095, a potent degrader of CK1α, IKZF1 and IKZF3 proteins. Through a structure-informed exploration of structure activity relationship (SAR) around this small molecule we develop SJ3149, a selective and potent degrader of CK1α protein in vitro and in vivo. The structure of SJ3149 co-crystalized in complex with CK1α + CRBN + DDB1 provides a rationale for the improved degradation properties of this compound. In a panel of 115 cancer cell lines SJ3149 displays a broad antiproliferative activity profile, which shows statistically significant correlation with MDM2 inhibitor Nutlin-3a. These findings suggest potential utility of selective CK1α degraders for treatment of hematological cancers and solid tumors.

Tunable Regioselective Allylic Alkylation/Iodination of Imidazoheterocycles in Water.

The switchable roles of allylic alcohol and molecular iodine as reagents and catalysts have been demonstrated in the regioselective allylic alkylation and iodination of imidazoheterocycles employing the mixture of allylic alcohol-I2. First, we have explored the catalytic activity of iodine for the allylation of imidazoheterocycles using allylic alcohol in an aqueous medium. The allylation of a library of imidazoheterocycles and other electron-rich heterocycles like indole, pyrazole, 4-hydroxy coumarin, and 6-amino uracil has been achieved by employing this methodology. The efficiency of the I2 catalyst for N-allylation of azoles has also been demonstrated. Next, we have shown that this mixture of allylic alcohol and I2 could be beneficial for the iodination of imidazoheterocycles under room temperature. Mechanistic studies indicate that the activation of allylic alcohol by molecular iodine took place probably through halogen bonding, and NMR studies show that the reaction did not proceed through allylic ether formation.

Fluorescent MOF and Its Gel Composite for the Fluorescence Recovery "Turn-On" Detection of Al3+ Ions and "Turn-Off" Detection of Oxo-Anions.

The exploration of smart sensors is of great significance for the selectivity, sensitivity, and ability to show the low detection limit for the target analyte. Here, we have used the linker H2L (5-((anthracen-9-ylmethyl)amino)isophthalic acid) for the construction of {[Cd(L)(DMF)(H2O)2]·H2O}n (1) which is in order with the chromophore anthracene moiety and the free -NH functionality as a guest interaction site. This framework showed the luminescence recovery "turn-on" detection of the Al3+ ion in an aqueous solution. An exhaustive mechanism study disclosed that the Lewis acid-base-type interaction between the Al3+ ion and the -NH functionality of the linker in the framework revealed that the absorbance caused an enhancement for the "turn-on" sensing event. Besides the "turn-on" sensing event, the "turn-off" sensing phenomenon of 1 is also noticed when it detects the hazardous oxo-anions (MnO4- and CrO42-) with limit of detection values of 17.08 and 19.91 ppb, respectively. The detection of these diverse analytes are very fast (10 s) and they can also be recognized through a colorimetric response. The sensing mechanisms for these analytes are established by photoinduced electron transfer, Forster resonance energy transfer, and inert filter effect along with theoretical investigation. Furthermore, to show the sensing application of 1 in a versatile podium, a MOF gel composite, 1@AA (AA = Agar-Agar), was developed from 1 with AA. Interestingly, 1@AA showed the colorimetric detection of these analytes under UV light. Therefore, sensor 1 behaves as a smart sensory material for the recognition of the above analytes through a simultaneous "turn-on" and "turn-off" effect.

Microplastics contamination in two species of gobies and their estuarine habitat of Indian Sundarbans.

Sundarbans, a Ramsar site of India is contaminated with heterogeneous microplastic wastes. Boddart's goggle eye mudskipper and Rubicundus eelgoby, were common gobies of Sundarbans estuary which accumulated microplastics during their normal biological activities. We estimated the abundance of microplastics in water, sediment; skin, gills, bucco-opercular cavity and gastrointestinal tract of these two goby fishes. Microplastic load estimated in gobies were 0.84 and 2.62 particles per fish species with a dominance of transparent, fibrous microplastics with 100-300 µm in length. ATR-FTIR and Raman spectroscopy revealed polyethylene as prevalent polymer. Surface degradations and adsorption of contaminants on microplastic surface were investigated by SEM-EDX analysis. Presence of hazardous polymers influenced high polymer hazard index and potential ecological risk index which indicated acute environmental threat to Sundarbans estuary and its resident organisms. Current study will provide a new information base on the abundance of microplastics and its ecological hazard in this biosphere reserve.

Respirable Metals, Bacteria, and Fungi during a Saharan-Sahelian Dust Event in Houston, Texas.

Although airborne bacteria and fungi can impact human, animal, plant, and ecosystem health, very few studies have investigated the possible impact of their long-range transport in the context of more commonly measured aerosol species, especially those present in an urban environment. We report first-of-kind simultaneous measurements of the elemental and microbial composition of North American respirable airborne particulate matter concurrent with a Saharan-Sahelian dust episode. Comprehensive taxonomic and phylogenetic profiles of microbial communities obtained by 16S/18S/ITS rDNA sequencing identified hundreds of bacteria and fungi, including several cataloged in the World Health Organization's lists of global priority human pathogens along with numerous other animal and plant pathogens and (poly)extremophiles. While elemental analysis sensitively tracked long-range transported Saharan dust and its mixing with locally emitted aerosols, microbial diversity, phylogeny, composition, and abundance did not well correlate with the apportioned African dust mass. Bacterial/fungal diversity, phylogenetic signal, and community turnover were strongly correlated to apportioned sources (especially vehicular emissions and construction activities) and elemental composition (especially calcium). Bacterial communities were substantially more dissimilar from each other across sampling days than were fungal communities. Generalized dissimilarity modeling revealed that daily compositional turnover in both communities was linked to calcium concentrations and aerosols from local vehicles and Saharan dust. Because African dust is known to impact large areas in northern South America, the Caribbean Basin, and the southern United States, the microbiological impacts of such long-range transport should be assessed in these regions.

Extraction of heavy metals from wastewater using amine-modified mesoporous silica.

Presence of heavy metals in wastewater is a critical environmental issue, and efficient extraction of the metals remains a challenging task. In this study, the adsorption behavior of Ce(III), Hg(II), and Cu(II) metal ions using MCM-48 material modified with acid and base functional groups was examined. The modified materials were characterized using various techniques, including XRD, BET, FT-IR, NMR, and SEM, which revealed that the materials' properties remained unchanged after modification. The adsorption capacity of the modified materials for metal ions was then evaluated and was found that the amine-modified MCM-48 material exhibited the highest adsorption efficiency. Precisely, the amine-modified material achieved an adsorption capacity of 97% for Ce(III), 98% for Hg(II), and 90% for Cu(II) after 180 min of adsorption. These results highlight the effectiveness of amine functionalization in enhancing the adsorption capacity of silica material for heavy metals.

Fragment-Based NMR Screening of the BPTF PHD Finger Methyl Lysine Reader Leads to the First Small-Molecule Inhibitors.

Methyl lysine readers, specifically PHD fingers, are emerging epigenetic targets in human diseases. For example, several PHD finger fusions are implicated in clinical cases of acute myeloid leukemia, highlighting the potential for PHD inhibitors in disease regulation. However, limited chemical matter targeting PHD fingers exists. Here we report the first fragment-based screen against the BPTF PHD to identify several of the first reported BPTF PHD-targeting small-molecule ligands. We used ligand-observed NMR to first screen a fragment library, followed by biophysical validation to prioritize two scaffolds, pyrrolidine- and pyridazine-containing fragments. Structural predictions show that these respective scaffolds may engage two distinct subpockets on the protein. The demonstrated ligandability of the BPTF PHD supports the future development of methyl lysine reader chemical probes to study their oncogenic functions.