Populus trichocarpa is an ecologically important tree species and economically important biofeedstock. Belowground, P. trichocarpa interacts with diverse microorganisms in the rhizosphere and root endosphere. These plant–microbe interactions can bolster a variety of plant processes, ranging from pathogen suppression to drought tolerance, yet we know little about the impact of chronic drought stress on P. trichocarpa’s belowground microbiomes. To investigate the interactive effect of chronic drought on belowground microbial communities across genetically different P. trichocarpa hosts, we assessed archaeal/bacterial and fungal communities within the root endosphere, rhizosphere, and surrounding bulk soil of selected genotypes in a long-term drought experiment in Boardman, OR, U.S.A. We sequenced the 16S ribosomal RNA and internal transcribed spacer 2 gene region on samples collected from 16 distinct P. trichocarpa genotypes in plots with full or reduced irrigation. Eight of these genotypes have been previously identified as drought tolerant while the other eight genotypes were drought susceptible. Although reduced irrigation influenced the composition of every archaeal or bacterial microbiome compartment, fungal communities were only affected in the rhizosphere and bulk soil compartments. Drought-tolerant bacteria such as Actinobacteria were differentially abundant in reduced irrigation across all belowground microbiomes. Host drought tolerance influenced plant-associated microbiome compartments but had little impact on the bulk soil compartment. Drought-tolerant trees were enriched for potential growth-promoting microorganisms in the root endosphere and rhizosphere, including Sphingomonas bacteria and ectomycorrhizal fungi. Overall, associations of growth-promoting microbes in drought-resistant P. trichocarpa genotypes can be leveraged to improve biofeedstock productivity in regions prone to periodic drought.

Iron reduction and sulfate reduction are two of the major biogeochemical processes that occur in anoxic sediments. Microbes that catalyze these reactions are therefore some of the most abundant organisms in the subsurface, and some of the most important. Due to the variety of mechanisms that microbes employ to derive energy from these reactions, including the use of soluble electron shuttles, the dynamics between iron- and sulfate-reducing populations under changing biogeochemical conditions still elude complete characterization. Here, we amended experimental bioreactors comprised of freshwater aquifer sediment with ferric iron, sulfate, acetate, and the model electron shuttle AQDS (9,10-anthraquinone-2,6-disulfonate) and monitored both the changing redox conditions as well as changes in the microbial community over time. The addition of the electron shuttle AQDS did increase the initial rate of FeIII reduction; however, it had little effect on the composition of the microbial community. Our results show that in both AQDS- and AQDS+ systems there was an initial dominance of organisms classified as Geobacter (a genus of dissimilatory FeIII-reducing bacteria), after which sequences classified as Desulfosporosinus (a genus of dissimilatory sulfate-reducing bacteria) came to dominate both experimental systems. Furthermore, most of the ferric iron reduction occurred under this later, ostensibly "sulfate-reducing" phase of the experiment. This calls into question the usefulness of classifying subsurface sediments by the dominant microbial process alone because of their interrelated biogeochemical consequences. To better inform models of microbially-catalyzed subsurface processes, such interactions must be more thoroughly understood under a broad range of conditions.

A major challenge of quantifying feedback between microbial communities and climate is the vast diversity of microbial communities and the intricacy of soil biogeochemical processes they mediate. We overcome this challenge by simplifying the representation of diverse enzyme functions from metagenomics data. We developed a dynamic allocation scheme for enzyme functional classes (EFCs) based on the premise that microbial communities act to maximize acquisition of limiting resources while minimizing energy expenditure for acquiring unlimited resources. We incorporated this scheme into a biogeochemical model to explicitly represent microbial functional diversity and simulate responses of microbially-mediated soil biogeochemical processes to varying environmental and nutrient conditions. Representing microbial functional diversity and environmental acclimation improved predictions of the stoichiometry of microbial biomass and mitigated the sensitivity of soil organic carbon to warming in nutrient-deficient regions. Our results indicate the importance of microbial functional diversity and environmental acclimation for projecting climate feedbacks of nutrient-limited soils.

BACKGROUND:Precisely engineered mesoporous silica has been shown to induce weight loss in mice, but whether it is safe to use in humans have not investigated. OBJECTIVE:The aim was to determine whether oral dosing, up to 9 grams/day, of precisely engineered mesoporous silica as a food additive can be used safely in male humans. DESIGN:This single blinded safety study consisted of two study arms including 10 males each (18-35 years). One arm consisted of participants with normal weight and one with obesity. After a placebo run-in period, all subjects were given porous silica three times daily, with increasing dose up to 9 grams/day (Phase 1). Subjects with obesity continued the study with highest dose for additional 10 weeks (Phase 2). RESULTS:All participants completed Phase 1 and 90% completed Phase 2, with approximately 1% missed doses. Participants reported no abdominal discomfort, and changes in bowel habits were minor and inconsistent. The side effects observed were mild and tolerable, biomarkers did not give any safety concern, and no severe adverse events occurred. CONCLUSION:Mesoporous silica intake of up to 9 grams/day can be consumed by males without any major adverse events or safety concerns.

Aim: Obesity is a risk factor for cardiovascular disease and diabetes. We aimed to elucidate the effects of distinct mesoporous silica particles (MSPs) supplemented in food on metabolic parameters in obesity. Materials & methods: MSPs with precisely controlled pore size were synthesized, characterized and compared with a control in a C57Bl/6 mouse diet-induced obesity model, studying weight, adiposity, metabolic regulation and food efficiency. Results: The most effective MSPs reduced adipose tissue formation to 6.5 ± 0.5 g compared with 9.4 ± 1.2 g, leptin levels nearly halved from 32.8 ± 7.4 to 16.9 ± 1.9 ng/ml and a 33% reduction of food efficiency. Control MSP showed no effects. Conclusion: Results demonstrate potential of distinct MSPs to improve metabolic risk factors. Further studies investigating mechanism of action and confirming human safety are needed.

In article number 202000057, Tore Bengtsson and co-workers report that oral intake of mesoporous silica particles (MSP) reduce glycated hemoglobin and low-density lipoprotein in healthy individuals with obesity. Preclinical investigations show sequestration of pancreatic a-amylase and lipase by MSP, suggesting that MSP lowers digestive enzymes availability in the small intestine, resulting in decreased digestion of macronutrients and reduced caloric uptake.

Engineered mesoporous silica particles (MSP) are thermally and chemically stable porous materials composed of pure silica and have attracted attention for their potential biomedical applications. Oral intake of engineered MSP is shown to reduce body weight and adipose tissue in mice. Here, clinical data from a first-in-humans study in ten healthy individuals with obesity are reported, demonstrating a reduction in glycated hemoglobin (HbA1c) and low-density lipoprotein cholesterol, which are well-established metabolic and cardiovascular risk factors. In vitro investigations demonstrate sequestration of pancreatic  α-amylase and lipase in an MSP pore-size dependent manner. Subsequent ex vivo experiments in conditions mimicking intestinal conditions and in vivo experiments in mice show a decrease in enzyme activity upon exposure to the engineered MSP, presumably by the same mechanism. Therefore, it is suggested that tailored MSP act by lowering the digestive enzyme availability in the small intestine, resulting in decreased digestion of macronutrient and leading to reduced caloric uptake. This novel MSP based mechanism-of-action, combined with its excellent safety in man, makes it a promising future agent for prevention and treatment of metabolic diseases.

The standard of care for persons with prediabetes is lifestyle intervention, however in real-life less than 20% of people are able to adopt a healthier living. There is an unmet need for safe and effective treatment options for persons with prediabetes. We have developed unique mesoporous silica particles (MSP) with tailored characteristics (SiPore15) that sequesters pancreatic amylase and lipase locally in the gut, resulting in decreased digestion of carbohydrates and fats. A first-in-man safety-trial in healthy and obese volunteers (clinicaltrials.org ID no. NCT03667430) showed a good safety profile for SiPore15 and an exploratory analysis revealed a reduction in HbA1c. In the present efficacy-trial 43 subjects were enrolled, 33 persons with prediabetes (HbA1c 39 mmol/mol or above) and 10 persons newly diagnosed with diabetes type 2. All subjects were treated with SiPore15, 3 gm-TID with meals, for 12 weeks (clinicaltrials.org ID no. NCT03823027). A manufacturing error resulted in 26 subjects receiving the correct MSP for half of the treatment period and 9 subjects for the full period. An exploratory analysis revealed that the long-term blood glucose marker HbA1c was statistically reduced after 6 weeks (1 mmol/mol) and further reduced at 12 weeks (1.4 mmol/mol). Among the subjects who received the correct material, 0 subjects had a serious AE and the AEs reported were mild to moderate, indicating a favorable safety profile. The magnitude in HbA1c reduction was comparable to what has been observed with metformin in prediabetic clinical trials, translating to significant risk reduction in developing diabetes type 2. SiPore15’s novel ingestible device concept, combined with the preliminary demonstration of efficacy and safety indicates that SiPore15 is an exciting approach for prevention and treatment of diabetes and merits further clinical investigation. Disclosure E.V. Johnston: None. M.N. Iqbal: None. G. Robert-Nicoud: Employee; Self; Sigrid Therapeutics. M.Z. Lindgren: None. E.R. Waara: None. A. Udden: None. K. Pietiläinen: None. T. Bengtsson: Board Member; Self; Atrogi, Sigrid Therapeutics.

Mesoporous silica particles (MSPs) are thermally and chemically stable porous materials composed exclusively of silicon dioxide. Here we report the results of a First-in-Man clinical trial evaluating engineered MSPs with controlled surface area, pore volume, pore size, particle size and morphology, named SiPore, in obese but otherwise healthy male volunteers (n=20). SiPore is orally ingested and passes through the body without being absorbed and is safely eliminated via the feces. The clinical effects of SiPore were significant reduction in several metabolic and cardiovascular risk factors. HbA1c was reduced by 5% and LDL-C by 15% on average from baseline, both clinically meaningful reductions. Adverse events observed were mild and transient. These promising effects led to further investigations into SiPore’s mode of action. We hypothesized that SiPore acts as a molecular sieve by sequestration of biomolecules in the gastrointestinal tract, which could explain the observed clinical results. This merited a more detailed analysis of the interaction between SiPore and digestive enzymes. SiPore significantly sequestered amylase and lipase in vitro while MSPs with smaller pore size had no effect. Lipase and amylase were depleted by SiPore from more complex biological matrices, such as porcine pancreatin and mouse intestinal fluid. Moreover, SiPore inhibited the activity of human salivary amylase in human saliva. Further studies of amylase depletion in vitro indicated that the availability of pores of a certain pore size is a critical parameter for enzyme sequestration. This innovative mode of action, combined with SiPore’s promising safety profile, makes SiPore an exciting candidate for treatment or prevention of metabolic diseases, particularly prediabetes and type 2 diabetes (T2D). SiPore is currently being investigated in an ongoing clinical trial in 40 prediabetic or newly diagnosed T2D subjects (NCT03823027). Disclosure M.E. Lindgren: Employee; Self; Sigrid Therapeutics AB. E. Rollman Waara: Employee; Self; Sigrid Therapeutics AB. B. Benziane: Employee; Self; Sigrid Therapeutics. H. Vallhov: Employee; Self; Sigrid Therapeutics. N. Iqbal: None. E.V. Johnston: None. T. Bengtsson: Other Relationship; Self; Atrogi, Sigrid Therapeutics. Funding Vinnova (2015-02023)

The highly active ruthenium-based water oxidation catalyst [Ru-X(mcbp)(OHn)(py)(2)] [mcbp(2-)=2,6-bis(1-methyl-4-(carboxylate)benzimidazol-2-yl)pyridine; n=2, 1, and 0 for X=II, III, and IV, respectively], can be generated in a mixture of Ru-III and Ru-IV states from either [Ru-II(mcbp)(py)(2)] or [Ru-III(Hmcbp)(py)(2)](2+) precursors. The precursor complexes are isolated and characterized by single-crystal X-ray analysis, NMR, UV/Vis, EPR, and FTIR spectroscopy, ESI-HRMS, and elemental analysis, and their redox properties are studied in detail by electrochemical and spectroscopic methods. Unlike the parent catalyst [Ru(tda) (py)(2)] (tda(2-)=[2,2:6,2-terpyridine]-6,6-dicarboxylate), for which full transformation into the catalytically active species [Ru-IV(tda)(O)(py)(2)] could not be carried out, stoichiometric generation of the catalytically active Ru-aqua complex [Ru-X(mcbp)(OHn)(py)(2)] from the Ru-II precursor was achieved under mild conditions (pH7.0) and short reaction times. The redox properties of the catalyst were studied and its activity for electrocatalytic water oxidation was evaluated, reaching a maximum turnover frequency (TOFmax) of around 40000s(-1) at pH9.0 (from foot-of-the-wave analysis), which is comparable to the activity of the state-of-the-art catalyst [Ru-IV(tda)(O)(py)(2)].

Liquid chromophores constitute a rare but intriguing class of molecules that are in high demand for the design of luminescent inks, liquid semiconductors, and solar energy storage materials. The most common way to achieve liquid chromophores involves the introduction of long alkyl chains, which, however, significantly reduces the chromophore density. Here, strategy is presented that allows for the preparation of liquid chromophores with a minimal increase in molecular weight, using the important class of perylenes as an example. Two synergistic effects are harnessed: (1) the judicious positioning of short alkyl substituents, and (2) equimolar mixing, which in unison results in a liquid material. A series of 1-alkyl perylene derivatives is synthesized and it is found that short ethyl or butyl chains reduce the melting temperature from 278 °C to as little as 70 °C. Then, two low-melting derivatives are mixed, which results in materials that do not crystallize due to the increased configurational entropy of the system. As a result, liquid chromophores with the lowest reported molecular weight increase compared to the neat chromophore are obtained. The mixing strategy is readily applicable to other π-conjugated systems and, hence, promises to yield a wide range of low molecular weight liquid chromophores.

The β-subunit of human thyroid stimulating hormone (hTSH) has been synthesized as a single glycoform bearing a chitobiose disaccharide at the native glycosylation site. Key to the successful completion of this synthesis was the introduction of an arginine-tagged acetamidomethyl group, which served to greatly facilitate handling of a glycopeptide fragment with poor aqueous solubility. This general solution to the challenge of working with intractable peptides is expected to find wide use in protein synthesis.

Herein, we describe the straightforward synthesis and thorough characterization of a magnetically-separable heterogeneous catalyst comprised of 1-3nm-sized Pd nanoparticles immobilized on a mesoporous silica-magnetite composite (Pd-0-AmP-SMC). Catalytic evaluations were conducted using Suzuki-Miyaura cross-couplings as the model reactions, for which this Pd nanocatalyst exhibited high performance in an environmentally-friendly solvent mixture. Additionally, this Pd nanocatalyst could be re-used up to five cycles without any observable loss of activity, and separation of the catalyst could be conveniently done by a magnet.

Ring opening of cyclic carbonates with unprotected amino acids in water – a route to highly functional carbamates.

All in water – functional cyclic carbonates as a versatile and renewable protection/deprotection platform.

Herein, we report on the facile synthesis of a heterogeneous copper nanocatalyst and its combination with 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) for the aerobic oxidation of alcohols to their corresponding carbonyl compounds. This low cost copper nanocatalyst was found to exhibit excellent recyclability, making it a highly attractive catalytic system from an economical and environmental point of view. Extensive characterization of the catalyst by a number of techniques revealed that it was comprised of well-dispersed Cu(I/II) nanoparticles with an average size of around 6nm.

Herein we report the synthesis of mesoporous ruthenium oxide (MP-RuO2) using a template-based approach. The catalytic efficiency of the prepared MP-RuO2 was compared to commercially available ruthenium oxide nanoparticles (C-RuO2) as heterogeneous catalysts for water oxidation. The results demonstrated superior performance of MP-RuO2 for oxygen evolution compared to the C-RuO2 with respect to recyclability, amount of generated oxygen, and stability over several catalytic runs.

Herein, a design of a biohybrid catalyst is described, consisting of Pd nanoparticles and a cross-linked network of aggregated lipase B enzyme of Candida antarctica (CalB CLEA) functioning as an active support for the Pd nanoparticles. Both entities of the hybrid catalyst showed good catalytic activity. The applicability was demonstrated in a one-pot reaction, where the Pd-catalyzed cycloisomerization of 4-pentynoic acid afforded a lactone that serves as an acyl donor in a subsequent selective enzymatic kinetic resolution of a set of sec-alcohols. The catalyst proved to be robust and could be recycled five times without a significant loss of activity.