Emerging investigator series: preferential adsorption and coprecipitation of permafrost organic matter with poorly crystalline iron minerals.

Future permafrost thaw will likely lead to substantial release of greenhouse gases due to thawing of previously unavailable organic carbon (OC). Accurate predictions of this release are limited by poor knowledge of the bioavailability of mobilized OC during thaw. Organic carbon bioavailability decreases due to adsorption to, or coprecipitation with, poorly crystalline ferric iron (Fe(III)) (oxyhydr)oxide minerals but the maximum binding extent and binding selectivity of permafrost OC to these minerals is unknown. We therefore utilized water-extractable organic matter (WEOM) from soils across a permafrost thaw gradient to quantify adsorption and coprecipitation processes with poorly crystalline Fe(III) (oxyhydr)oxides. We found that the maximum adsorption capacity of WEOM from intact and partly thawed permafrost soils was similar (204 and 226 mg C g-1 ferrihydrite, respectively) but decreased to 81 mg C g-1 ferrihydrite for WEOM from the fully thawed site. In comparison, coprecipitation of WEOM from intact and partly thawed soils with Fe immobilized up to 925 and 1532 mg C g-1 Fe respectively due to formation of precipitated Fe(III)-OC phases. Analysis of the OC composition before and after adsorption/coprecipitation revealed that high molecular weight, oxygen-rich, carboxylic- and aromatic-rich OC was preferentially bound to Fe(III) minerals relative to low molecular weight, aliphatic-rich compounds which may be more bioavailable. This selective binding effect was stronger after adsorption than coprecipitation. Our results suggest that OC binding by Fe(III) (oxyhydr)oxides sharply decreases under fully thawed conditions and that small, aliphatic OC molecules that may be readily bioavailable are less protected across all thaw stages.

Interactions between iron and carbon in permafrost thaw ponds.

Thawing permafrost forms "thaw ponds" that accumulate and transport organic carbon (OC), redox-active iron (Fe), and other elements. Although Fe has been shown to act as a control on the microbial degradation of OC in permafrost soils, the role of iron in carbon cycling in thaw ponds remains poorly understood. Here, we investigated Fe-OC interactions in thaw ponds in partially and fully thawed soils ("bog" and "fen" thaw ponds, respectively) in a permafrost peatland complex in Abisko, Sweden, using size separation (large particulate fraction (LPF), small particulate fraction (SPF), and dissolved fraction (DF)), acid extractions, scanning electron microscopy (SEM), Fe K-edge X-ray absorption spectroscopy (XAS), and Fourier Transform Infrared (FTIR) spectroscopy. The bulk total Fe (total suspended Fe) in the bogs ranged from 135 mg/L (mean = 13 mg/L) whereas the fens exhibited higher total Fe (1.5 to 212 mg/L, mean = 30 mg/L). The concentration of bulk total OC (TOC) in the bog thaw ponds ranged from 50 to 352 mg/L (mean = 170 mg/L), higher than the TOC concentration in the fen thaw ponds (8.5 to 268 mg/L, mean = 17 mg/L). The concentration of 1 M HCl-extractable Fe in the bog ponds was slightly lower than that in the fens (93 ± 1.2 and 137 ± 3.5 mg/L Fe, respectively) with Fe predominantly (>75 %) in the DF in both thaw stages. Fe K-edge XAS analysis showed that while Fe(II) was the predominant species in LPF, Fe(III) was more abundant in the DF, indicating that the stage of thawing and particle size may control Fe redox state. Furthermore, Fe(II) and Fe(III) were partially complexed with natural organic matter (NOM, 8 to 80 %) in both thaw ponds. Results of our work suggest that Fe and OC released during permafrost thaw into thaw ponds (re-)associate, potentially protecting OC from microbial decomposition while also stabilizing the redox state of Fe.

Hypernatremia and Its Rate of Correction: The Evidence So Far.

Hypernatremia or high serum sodium levels can have many different causes, including insufficient free water intake, or excess free water losses. The management of hypernatremia focuses on resolving the underlying cause, replenishing free water deficit, and preventing further losses while closely monitoring serum sodium concentration. This systematic review was carried out using medical databases such as PubMed, PubMed Central, and Google Scholar for relevant medical literature. The identified articles were reviewed, eligibility criteria were applied, and seven research articles were identified. The effect of the rate of hypernatremia correction on both short- and long-term outcomes in volume-resuscitated patients was the focus of our search for randomized or observational studies. Based on our analysis of the clinical evidence, we concluded that the present recommendations for treating acute and chronic hypernatremia in resuscitated patients do not stem from high-quality research.

Amino acids and glycine derivatives differently affect refolding of mesophilic and thermophilic like α-amylases: implications in protein refolding and aggregation.

α-amylases are industrially important enzymes which are used in different starch-based industries. They are adapted to different environmental conditions like extremes of temperature, pH and salinity. Herein, α-amylases from Bacillus amyloliquifaciens (BAA) and Bacillus licheniformis (BLA), representing mesophilic and thermophilic-like proteins, respectively, have been used to investigate the effect of naturally occurring osmolytes like arginine, proline, glycine and its methyl derivatives, sarcosine and betaine on their refolding. In this study, we have shown that among amino acids and glycine derivatives, betaine is the most promising osmolyte, while arginine and glycine exhibit moderately positive effect at their lower concentrations on the refolding of BAA only. Except betaine, all other osmolytes above 0.25 M showed inhibitory effect on the native enzyme activity of BLA and BAA. However, aggregation kinetics monitored by static light scattering indicates suppression of aggregation by all of these osmolytes. Further investigation by tryptophan and ANS fluorescence spectroscopy indicates the formation of compact hydrophobic core in the presence of the osmolytes. The morphology of protein aggregates having different sizes was visualized by atomic force microscopy ,and it was observed that amorphous aggregates of variable heights were formed. Our study highlights the importance of differential effects of arginine, proline, glycine, sarcosine and betaine on the native state as well as on refolding of BLA and BAA which may be helpful in devising strategies for developing effective protein formulation and prevention of aggregation of industrially and therapeutically important proteins.Communicated by Ramaswamy H. Sarma.

Deciphering the Patterns of Dual Primary Cases Registered at the Hospital-Based Cancer Registry: First Experience from Rural Cancer Center in North India.

Objectives The objective is to present the patterns of dual primary malignancies diagnosed at the Pathology Laboratory of Cancer Hospital with the support from hospital-based cancer registry (HBCR), Sangrur, Punjab, India for the years 2018 and 2019. Methods HBCR abstracts data from electronic medical records. Trained cancer registry staff abstracts cases in standard pro forma. Dual primary was coded as per the International Agency for Research on Cancer rule and was rechecked by the pathologist. Statistical Analysis Data about multiple primary was entered and documented in an Excel sheet. Time interval was calculated by subtracting the date of diagnosis for second primary and first primary. Results A total of 6,933 cases were registered, 45 cases are dual primary (26 females, 19 males) of which 64.4% are synchronous and 35.6% metachronous cases. Seventy-nine percent received cancer-directed treatment for synchronous and 87% for metachronous. The most common sites of the primary tumor were breast (33%), head and neck (22.2%), gynecological sites (11%), prostate (9%), esophagus (4%), and remaining other tumors (20.8%). Most common sites for second malignancies were gastrointestinal (GI) tract (31%), gynecological sites (18%), head and neck (16%), hematological malignancies (7%), soft tissue sarcoma (4%), breast (2%), and other sites (22%). Conclusion More than 70% of cases of primary tumors were in breast, head and neck, gynecological, and prostate. Of these, more than 60% of the second malignancy was found in the GI tract, gynecological, and head and neck sites. Around two-thirds of dual tumors are synchronous. Breast cancer cases have higher incidence of second malignancy. Regular follow-up is necessary to assess the survival of the second primary.

Comparative analysis of drug-salt-polymer interactions by experiment and molecular simulation improves biopharmaceutical performance.

The propensity of poorly water-soluble drugs to aggregate at supersaturation impedes their bioavailability. Supersaturated amorphous drug-salt-polymer systems provide an emergent approach to this problem. However, the effects of polymers on drug-drug interactions in aqueous phase are largely unexplored and it is unclear how to choose an optimal salt-polymer combination for a particular drug. Here, we describe a comparative experimental and computational characterization of amorphous solid dispersions containing the drug celecoxib, and a polymer, polyvinylpyrrolidone vinyl acetate (PVP-VA) or hydroxypropyl methylcellulose acetate succinate, with or without Na+/K+ salts. Classical models for drug-polymer interactions fail to identify the best drug-salt-polymer combination. In contrast, more stable drug-polymer interaction energies computed from molecular dynamics simulations correlate with prolonged stability of supersaturated amorphous drug-salt-polymer systems, along with better dissolution and pharmacokinetic profiles. The celecoxib-salt-PVP-VA formulations exhibit excellent biopharmaceutical performance, offering the prospect of a low-dosage regimen for this widely used anti-inflammatory, thereby increasing cost-effectiveness, and reducing side-effects.

Critical nanomaterial attributes of iron-carbohydrate nanoparticles: Leveraging orthogonal methods to resolve the 3-dimensional structure.

Intravenous iron-carbohydrate nanomedicines are widely used to treat iron deficiency and iron deficiency anemia across a wide breadth of patient populations. These colloidal solutions of nanoparticles are complex drugs which inherently makes physicochemical characterization more challenging than small molecule drugs. There have been advancements in physicochemical characterization techniques such as dynamic light scattering and zeta potential measurement, that have provided a better understanding of the physical structure of these drug products in vitro. However, establishment and validation of complementary and orthogonal approaches are necessary to better understand the 3-dimensional physical structure of the iron-carbohydrate complexes, particularly with regard to their physical state in the context of the nanoparticle interaction with biological components such as whole blood (i.e. the nano-bio interface).

Microbially influenced corrosion and rust tubercle formation on sheet piles in freshwater systems.

The extent of how complex natural microbial communities contribute to metal corrosion is still not fully resolved, especially not for freshwater environments. In order to elucidate the key processes, we investigated rust tubercles forming massively on sheet piles along the river Havel (Germany) applying a complementary set of techniques. In-situ microsensor profiling revealed steep gradients of O2 , redox potential and pH within the tubercle. Micro-computed tomography and scanning electron microscopy showed a multi-layered inner structure with chambers and channels and various organisms embedded in the mineral matrix. Using Mössbauer spectroscopy we identified typical corrosion products including electrically conductive iron (Fe) minerals. Determination of bacterial gene copy numbers and sequencing of 16S rRNA and 18S rRNA amplicons supported a densely populated tubercle matrix with a phylogenetically and metabolically diverse microbial community. Based on our results and previous models of physic(electro)chemical reactions, we propose here a comprehensive concept of tubercle formation highlighting the crucial reactions and microorganisms involved (such as phototrophs, fermenting bacteria, dissimilatory sulphate and Fe(III) reducers) in metal corrosion in freshwaters.

Stabilization of mineral-associated organic carbon in Pleistocene permafrost.

Ice-rich Pleistocene-age permafrost is particularly vulnerable to rapid thaw, which may quickly expose a large pool of sedimentary organic matter (OM) to microbial degradation and lead to emissions of climate-sensitive greenhouse gases. Protective physico-chemical mechanisms may, however, restrict microbial accessibility and reduce OM decomposition; mechanisms that may be influenced by changing environmental conditions during sediment deposition. Here we study different OM fractions in Siberian permafrost deposited during colder and warmer periods of the past 55,000 years. Among known stabilization mechanisms, the occlusion of OM in aggregates is of minor importance, while 33-74% of the organic carbon is associated with small, <6.3 µm mineral particles. Preservation of carbon in mineral-associated OM is enhanced by reactive iron minerals particularly during cold and dry climate, reflected by low microbial CO2 production in incubation experiments. Warmer and wetter conditions reduce OM stabilization, shown by more decomposed mineral-associated OM and up to 30% higher CO2 production. This shows that considering the stability and bioavailability of Pleistocene-age permafrost carbon is important for predicting future climate-carbon feedback.

Kinetics of Arf1 inactivation regulates Golgi organisation and function in non-adherent fibroblasts.

Arf1 belongs to the Arf family of small GTPases that localise at the Golgi and plasma membrane. Active Arf1 plays a crucial role in regulating Golgi organisation and function. In mouse fibroblasts, loss of adhesion triggers a consistent drop (∼50%) in Arf1 activation that causes the Golgi to disorganise but not fragment. In suspended cells, the trans-Golgi (GalTase) disperses more prominently than cis-Golgi (Man II), accompanied by increased active Arf1 (detected using GFP-ABD: ARHGAP10 Arf1 binding domain) associated with the cis-Golgi compartment. Re-adhesion restores Arf1 activation at the trans-Golgi as it reorganises. Arf1 activation at the Golgi is regulated by Arf1 Guanine nucleotide exchange factors (GEFs), GBF1, and BIG1/2. In non-adherent fibroblasts, the cis-medial Golgi provides a unique setting to test and understand the role GEF-mediated Arf1 activation has in regulating Golgi organisation. Labelled with Man II-GFP, non-adherent fibroblasts treated with increasing concentrations of Brefeldin-A (BFA) (which inhibits BIG1/2 and GBF1) or Golgicide A (GCA) (which inhibits GBF1 only) comparably decrease active Arf1 levels. They, however, cause a concentration-dependent increase in cis-medial Golgi fragmentation and fusion with the endoplasmic reticulum (ER). Using selected BFA and GCA concentrations, we find a change in the kinetics of Arf1 inactivation could mediate this by regulating cis-medial Golgi localisation of GBF1. On loss of adhesion, a ∼50% drop in Arf1 activation over 120 min causes the Golgi to disorganise. The kinetics of this drop, when altered by BFA or GCA treatment causes a similar decline in Arf1 activation but over 10 min. This causes the Golgi to now fragment which affects cell surface glycosylation and re-adherent cell spreading. Using non-adherent fibroblasts this study reveals the kinetics of Arf1 inactivation, with active Arf1 levels, to be vital for Golgi organisation and function.

Nano-vaccination Strategies: Applications and Challenges for Intranasal Immunization.

The nasal route, a subgroup of mucosal delivery systems, constitutes a lucrative and encouraging substitute for administering drugs and vaccines. Over the years, a lot of research has been done in this area, and scientists have successfully explored this pathway using novel formulations to combat several infections. This review article aims to address the pathways of mucosal immunization, the dominance of the nasal route over other mucosal routes for immunization, and the mechanism of generation of immunogenic response via nasal route and nanotechnology-based approaches for intranasal vaccination. The immunotherapeutic and vaccinations for intranasal administration available in the market are also discussed, along with a brief overview of the products in the pipeline. It can also be assumed that such an approach can prove to be favorable in designing vaccinations for the current uncertain times. In spite of some dubious views on this.

Longitudinal Assessment of Calcium and Magnesium Levels in Women with Preeclampsia.

The present study reports the levels of maternal serum calcium and magnesium from early pregnancy until delivery, along with cord levels, in women who developed preeclampsia (PE) and compares them with those without PE. A total of 324 pregnant women (216 non-PE and 108 PE women) were included in this retrospective case-control study of prospectively collected data nested in an observational cohort study. Maternal blood was collected at 4 time points during pregnancy (V1 = 11-14 weeks, V2 = 18-22 weeks, V3 = 26-28 weeks, and V4 = at delivery) and umbilical cord blood at delivery. Independent t tests were used to compare calcium, magnesium, and their ratio between two groups, and their associations with PE were studied using regression models. Calcium levels were similar between groups at all time points. Magnesium levels were lower (p = 0.021) at V2 in PE group as compared with non-PE group. Maternal calcium and magnesium levels were negatively associated, with blood pressure in early pregnancy. In fully adjusted logistic regression analysis, lower magnesium levels were associated with an increased risk of PE at V2 (OR 0.25 [95% CI 0.07, 0.94] p = 0.04). Lower magnesium in mid-pregnancy was associated with higher risk of PE. These changes were observed before the diagnosis of PE, thereby suggesting that they may have a role in the etiology of PE.

Environmental Risk of Arsenic Mobilization from Disposed Sand Filter Materials.

Arsenic (As)-bearing water treatment residuals (WTRs) from household sand filters are usually disposed on top of floodplain soils and may act as a secondary As contamination source. We hypothesized that open disposal of these filter-sands to soils will facilitate As release under reducing conditions. To quantify the mobilization risk of As, we incubated the filter-sand, the soil, and a mixture of the filter-sand and soil in anoxic artificial rainwater and followed the dynamics of reactive Fe and As in aqueous, solid, and colloidal phases. Microbially mediated Fe(III)/As(V) reduction led to the mobilization of 0.1-4% of the total As into solution with the highest As released from the mixture microcosms equaling 210 µg/L. Due to the filter-sand and soil interaction, Mössbauer and X-ray absorption spectroscopies indicated that up to 10% Fe(III) and 32% As(V) were reduced in the mixture microcosm. Additionally, the mass concentrations of colloidal Fe and As analyzed by single-particle ICP-MS decreased by 77-100% compared to the onset of reducing conditions with the highest decrease observed in the mixture setups (>95%). Overall, our study suggests that (i) soil provides bioavailable components (e.g., organic matter) that promote As mobilization via microbial reduction of As-bearing Fe(III) (oxyhydr)oxides and (ii) As mobilization as colloids is important especially right after the onset of reducing conditions but its importance decreases over time.

Insights into the Role of Compendial/Biorelevant Media on the Supersaturation Behaviour of Drug Combination (Drug-Drug Interaction) and Precipitation Inhibition by Polymers.

Combination drug therapy (CDT) plays an immense role in the treatment of various diseases such as malaria, hypertension, cancer, HIV-AIDS, helminthiasis, and many more. However, in vitro drug-drug interaction (DDI) is not well reported for better efficacy of CDT. In DDI one drug may enhance the precipitation of other drugs thereby reducing the advantage of CDT. Herein, we report DDI in terms of in vitro precipitation of drugs with albendazole and mebendazole. This may be the first report to propensate the possibility of either drug precipitation in the combination. These drugs are categorized into BCS class II weak base and hence have tendency to precipitate in the gastrointestinal tract. The objective of this study is to find precipitation of drug combinations in different compendial and biorelevant media (deionized water, phosphate buffer pH 6.8, FaSSIF, and FeSSIF) and screening of the polymers for precipitation inhibition. Nine polymers were investigated at three different concentrations in terms of their drug-polymer solubility, in vitro precipitation behavior, induction time, SHC, and droplet size. Although, all the polymers inhibit the precipitation of drugs, the extent of precipitation inhibition for Soluplus is high. The obtained drug-polymer precipitates were filtered, dried, and analyzed for amorphous/partial amorphous form using polarised light microscopy (PLM), differential scanning calorimetry (DSC), and powder X-ray diffractometry (PXRD). The drug-polymer interaction was examined using Fourier transform infrared (FTIR) spectroscopy and nuclear magnetic resonance (NMR) revealing the effect of polymers on drug precipitation. These insights may further be used in the formulation of CDT for helminthiasis management.

Temperature dependence of nitrate-reducing Fe(II) oxidation by Acidovorax strain BoFeN1 - evaluating the role of enzymatic vs. abiotic Fe(II) oxidation by nitrite.

Fe(II) oxidation coupled to nitrate reduction is a widely observed metabolism. However, to what extent the observed Fe(II) oxidation is driven enzymatically or abiotically by metabolically produced nitrite remains puzzling. To distinguish between biotic and abiotic reactions, we cultivated the mixotrophic nitrate-reducing Fe(II)-oxidizing Acidovorax strain BoFeN1 over a wide range of temperatures and compared it to abiotic Fe(II) oxidation by nitrite at temperatures up to 60°C. The collected experimental data were subsequently analyzed through biogeochemical modeling. At 5°C, BoFeN1 cultures consumed acetate and reduced nitrate but did not significantly oxidize Fe(II). Abiotic Fe(II) oxidation by nitrite at different temperatures showed an Arrhenius-type behavior with an activation energy of 80±7 kJ/mol. Above 40°C, the kinetics of Fe(II) oxidation were abiotically driven, whereas at 30°C, where BoFeN1 can actively metabolize, the model-based interpretation strongly suggested that an enzymatic pathway was responsible for a large fraction (ca. 62%) of the oxidation. This result was reproduced even when no additional carbon source was present. Our results show that at below 30°C, i.e. at temperatures representing most natural environments, biological Fe(II) oxidation was largely responsible for overall Fe(II) oxidation, while abiotic Fe(II) oxidation by nitrite played a less important role.

Idiopathic chronic pancreatitis: Beyond antioxidants.

Chronic pancreatitis (CP) is a complex disease associated with gene-gene or gene-environment interactions. The incidence of idiopathic CP has shown an increasing trend, withits phenotypeshaving changed considerably in the last two decades. The diseaseitself can be regulated before it reaches the stage of established CP; however, the etiopathogenesis underlying idiopathic CP remains to be established, making the condition difficult to cure. Unfortunately, there also remains a lack of consensus regarding the beneficial effects of antioxidant therapiesfor CP. It is known that antioxidant therapy does not reduce inflammatory and fibrotic cytokines, making it unlikely that they could modulate the disease process. Although antioxidants are safe, very few studies to date have reported the long-term beneficial effects in patients with CP. Thus, studies are being performed to identify drugs that can improve symptoms and alter the natural history of CP. Statins, with their numerous pleiotropic effects, may play a role in the treatment of CP, butin 2006, their use was found to be associated with the undesirable side effect of promoting pancreatitis. Latter studies showed favourable effects of statins in CP, highlighting the particular benefits of lipophilic statins, such as lovastatin and simvastatin, over the hydrophilic statins, such as rosuvastatin. Ultimately, studies to repurpose N-acetylcysteine as a CP therapy areyielding very promising results.

Explicating the molecular level drug-polymer interactions at the interface of supersaturated solution of the model drug: Albendazole.

Supersaturation as a formulation principle relates to the aqueous solubility of poorly soluble drugs in solution . However, supersaturation state of drugs tends to crystallize because of its thermodynamic instability thereby compromising the solubility and biopharmaceutical performance of drugs. The present study aims to investigate the supersaturation potential of albendazole (ABZ) and its precipitation via nucleation and crystal growth. We hypothesized the use of polymers will avoid ABZ precipitation by interacting with drug molecules. The drug polymer interactions are characterized using conventional methods of Fourier transform infrared (FTIR), Nuclear magnetic resonance (NMR) and Polarized light microscopy (PLM). We have used a novel approach of sum frequency generation (SFG) vibrational spectroscopic in exploring the drug polymer interactions at air-water interface. Recently we have reported the SFG for e rifaximin-polymer interactions (Singh et al., 2021). The supersaturation assay, saturation solubility studies and nucleation induction time analysis revealed polyvinyl alcohol (PVA) and polyvinyl pyrrolidone (PVP K30) as effective precipitation inhibitors thereby enhancing the ABZ equilibrium solubility and in vitro supersaturation maintenance of ABZ. Further, modification in the solid state of ABZ has confirmed the influence of polymers on its precipitation behaviour. We conclude that PVA and PVP K30 act as nucleation and crystal growth inhibitor, respectively for the precipitation inhibition of ABZ.

Organic Matter from Redoximorphic Soils Accelerates and Sustains Microbial Fe(III) Reduction.

Microbial reduction of Fe(III) minerals is a prominent process in redoximorphic soils and is strongly affected by organic matter (OM). We herein determined the rate and extent of microbial reduction of ferrihydrite (Fh) with either adsorbed or coprecipitated OM by Geobacter sulfurreducens. We focused on OM-mediated effects on electron uptake and alterations in Fh crystallinity. The OM was obtained from anoxic soil columns (effluent OM, efOM) and included-unlike water-extractable OM-compounds released by microbial activity under anoxic conditions. We found that organic molecules in efOM had generally no or only very low electron-accepting capacity and were incorporated into the Fh aggregates when coprecipitated with Fh. Compared to OM-free Fh, adsorption of efOM to Fh decelerated the microbial Fe(III) reduction by passivating the Fh surface toward electron uptake. In contrast, coprecipitation of Fh with efOM accelerated the microbial reduction, likely because efOM disrupted the Fh structure, as noted by Mössbauer spectroscopy. Additionally, the adsorbed and coprecipitated efOM resulted in a more sustained Fe(III) reduction, potentially because efOM could have effectively scavenged biogenic Fe(II) and prevented the passivation of the Fh surface by the adsorbed Fe(II). Fe(III)-OM coprecipitates forming at anoxic-oxic interfaces are thus likely readily reducible by Fe(III)-reducing bacteria in redoximorphic soils.

Amorphous Salts Solid Dispersions of Celecoxib: Enhanced Biopharmaceutical Performance and Physical Stability.

Numerous amorphous solid dispersion (ASD) formulations of celecoxib (CEL) have been attempted for enhancing the solubility, dissolution rate, and in vivo pharmacokinetics via high drug loading, polymer combination, or by surfactant addition. However, physical stability for long-term shelf life and desired in vivo pharmacokinetics remains elusive. Therefore, newer formulation strategies are always warranted to address poor aqueous solubility and oral bioavailability with extended shelf life. The present investigation elaborates a combined strategy of amorphization and salt formation for CEL, providing the benefits of enhanced solubility, dissolution rate, in vivo pharmacokinetics, and physical stability. We generated amorphous salts solid dispersion (ASSD) formulations of CEL via an in situ acid-base reaction involving counterions (Na+ and K+) and a polymer (Soluplus) using the spray-drying technique. The generated CEL-Na and CEL-K salts were homogeneously and molecularly dispersed in the matrix of Soluplus polymer. The characterization of generated ASSDs by differential scanning calorimetry revealed a much higher glass-transition temperature (Tg) than the pure amorphous CEL, confirming the salt formation of CEL in solid dispersions. The micro-Raman and proton nuclear magnetic resonance spectroscopy further confirmed the formation of salt at the -S═O position in the CEL molecules. CEL-Na-Soluplus ASSD exhibited a synergistic enhancement in the aqueous solubility (332.82-fold) and in vivo pharmacokinetics (9.83-fold enhancement in the blood plasma concentration) than the crystalline CEL. Furthermore, ASSD formulations were physically stable for nearly 1 year (352 days) in long-term stability studies at ambient conditions. Hence, we concluded that the ASSD is a promising strategy for CEL in improving the physicochemical properties and biopharmaceutical performance.

Microbial processes during deposition and diagenesis of Banded Iron Formations.

Banded Iron Formations (BIFs) are marine chemical sediments consisting of alternating iron (Fe)-rich and silica (Si)-rich bands which were deposited throughout much of the Precambrian era. BIFs represent important proxies for the geochemical composition of Precambrian seawater and provide evidence for early microbial life. Iron present in BIFs was likely precipitated in the form of Fe3+ (Fe(III)) minerals, such as ferrihydrite (Fe(OH)3), either through the metabolic activity of anoxygenic photoautotrophic Fe2+ (Fe(II))-oxidizing bacteria (photoferrotrophs), by microaerophilic bacteria, or by the oxidation of dissolved Fe(II) by O2 produced by early cyanobacteria. However, in addition to oxidized Fe-bearing minerals such as hematite (FeIII 2O3), (partially) reduced minerals such as magnetite (FeIIFeIII 2O4) and siderite (FeIICO3) are found in BIFs as well. The presence of reduced Fe in BIFs has been suggested to reflect the reduction of primary Fe(III) minerals by dissimilatory Fe(III)-reducing bacteria, or by metamorphic (high pressure and temperature) reactions occurring in presence of buried organic matter. Here, we present the current understanding of the role of Fe-metabolizing bacteria in the deposition of BIFs, as well as competing hypotheses that favor an abiotic model for BIF deposition. We also discuss the potential abiotic and microbial reduction of Fe(III) in BIFs after deposition. Further, we review the availability of essential nutrients (e.g. P and Ni) and their implications on early Earth biogeochemistry. Overall, the combined results of various ancient seawater analogue experiments aimed at assessing microbial iron cycling pathways, coupled with the analysis of the BIF rock record, point towards a strong biotic influence during BIF genesis.