High Tolerance Research Articles

Exploring genotypic variation and gene expression associated to cadmium accumulation in bread wheat

Cadmium (Cd) contamination poses significant risks to agricultural productivity and human health, particularly through its accumulation in staple crops such as bread wheat (Triticum aestivum L.). This study evaluated Cd accumulation and tolerance among six bread wheat cultivars exposed to six Cd concentrations (0, 2.5, 5, 10, 15, 20, and 25 mg kg−1 soil). Phenotypic assessments and quantitative real-time PCR (qRT-PCR) were conducted to analyze the expression patterns of TaNRAMP and TaZIP genes in various tissues and developmental stages of wheat, which play crucial roles in Cd uptake and transport. Results demonstrated significant variability in Cd accumulation. The Barat cultivar exhibited the lowest accumulation in grain (ranging from 0.21 to 8.8 mg kg−1) and the highest tolerance. In contrast, Kavir and Pishtaz displayed elevated Cd levels in both grain and straw, while Parsi accumulated more Cd in straw at lower concentrations (56.9 mg kg−1 in Cd concentration of 10 mg kg−1 soil). The gene expression analysis revealed that most cultivars showed increased expression of TaNRAMP genes, particularly TaNRAMP2 in Cd concentration of 10 mg kg−1 soil, which facilitates Cd uptake from the soil, and TaZIP genes, such as TaZIP4 and TaZIP7, involved in transporting Cd within the plant. Notably, the expression of TaZIP1 was significantly lower in cultivars with high Cd accumulation, suggesting a potential regulatory mechanism for Cd tolerance. Furthermore, cultivars exhibiting higher Cd levels correlated with increased expression of stress-responsive genes, indicating a broader response to Cd stress. These findings highlight Barat’s potential for bread-making applications due to its low Cd accumulation, while Morvarid and Pishtaz which show reduced Cd content in the straw even under high Cd exposure are better suited for animal feed. This research underscores the genetic variability of wheat cultivars in response to Cd stress and provides essential insights into the molecular mechanisms underlying Cd accumulation, offering valuable information for breeding programs aimed at developing Cd-tolerant varieties to ensure food security in contaminated regions.

Susceptibility of Bemisia tabaci Gennadius (Hemiptera: Aleyrodidae) Mediterranean Populations Found in São Paulo, Brazil to 11 Insecticides and Characterization of Their Endosymbionts.

The silverleaf whitefly, Bemisia tabaci Gennadius (Hemiptera: Aleyrodidae), is a significant agricultural pest worldwide, impacting a variety of crop yields. Since the introduction of B. tabaci Mediterranean (MED) species in Brazil, limited research has measured the relative efficacy of the primary insecticides used in whitefly management. This study evaluated the susceptibility of three distinct B. tabaci MED populations to 11 insecticide active ingredients and characterized the bacterial endosymbionts within each population. The insecticides tested were acetamiprid, bifenthrin, cyantraniliprole, diafenthiuron, spiromesifen, imidacloprid, pymetrozine, pyriproxyfen, sulfoxaflor, and thiamethoxam. Results showed varying LC50 and LC90 values among tested insecticides and populations. Notably, populations varied in response to imidacloprid and thiamethoxam with some populations having a 6× higher tolerance. Sequencing data of endosymbionts revealed that individuals from the most susceptible B. tabaci population harbored Rickettsia and Arsenophonus, whereas these bacteria were not detected in the resistant populations. These findings highlight the need for frequent insecticide toxicity bioassays of distinct B. tabaci populations and the adoption of integrated pest management strategies to preserve the efficacy of insecticides for B. tabaci control. Additionally, the role of infection by endosymbionts to alter susceptibility should be further explored.

Prospective Approaches of Herbal Novel Delivery System with Special Reference to the Herbal Nanosciences

: Medicinal and culinary uses of plants date back centuries. Projects on a global scale are conducting laboratory research to identify plants with therapeutic properties, with the ultimate goal of developing such compounds into medicines with acceptable drug delivery mechanisms and bringing them to market. Non-synthetic medications derived from plant or herbal sources have attracted a lot of interest because of their high tolerability and low likelihood of adverse medication reactions. All diseases, the theory goes, can be cured by something found in nature. Medicines can be taken in a wide variety of forms, including tablets, capsules, powders, semi-liquid extracts, tinctures, decoctions, medicinal teas, solutions, and more. Longer release, patient adherence, and other objectives necessitate adjustments to herbal medications. Researchers into novel drug delivery systems had hitherto overlooked herbal remedies due to a lack of scientific validation and the challenges inherent in processing, standardizing, extracting, and identifying them. Transdisciplinary research and cuttingedge isolation, purification, and identification techniques have led to the development of novel herbal compositions. Bioactive plant extracts and phytoconstituents are used in a wide variety of Nano- Emulsions, microspheres, transferosomes, implants, and ethosomes. Compared to herbal remedies, novel formulations fared better. Among these advantages are increased solubility, bioavailability, toxicity, pharmacological activity, stability, delivery duration, and resistance to physical and chemical degradation. As a result, the pharmacokinetic and pharmacodynamic properties of herbal medications can be enhanced by the use of novel drug delivery systems, making them safer and more effective. : This article aims to provide a concise description of the many new drug delivery techniques that have been created for the administration of herbal medications. The ultimate goal is to increase the efficacy of therapies and to learn more about their significance and worldwide appeal.

Infected nursery stock and poor silvicultural practices contribute to development of Ceratocystis manginecans wilt and canker disease in Eucalyptus pellita

In Indonesia and Malaysia, Eucalyptus pellita has replaced large areas of Acacia mangium plantations as the latter species is highly susceptible to C. manginecans. This strategy may not be effective in the long term as E. pellita is also susceptible to Ceratocystis wilt and canker disease though it has higher tolerance than A. mangium. Furthermore, the pathogen has the capacity to evolve and adapt to new hosts. To highlight the need for careful sanitation in nurseries and the potential impact of wounding during silvicultural operations, two experiments were conducted to (i) demonstrate the ability of cryptic Ceratocystis infections in nursery plants to develop into Ceratocystis wilt and canker disease after planting out and (ii) assess the risk of Ceratocystis infection and disease development from different wound types. In the nursery, three-month-old mini-cuttings of seven E. pellita clones were artificially wounded and inoculated with two isolates of Ceratocystis manginecans near the base of the stem. The disease incidence and lesion length were measured one month later, just prior to planting out. After four months of growth in the plantation, the trees were harvested and stems sliced longitudinally to measure the length of xylem discolouration. Six of 36 ramets of susceptible clones died and the length of xylem discolouration was significantly greater in susceptible clones than in tolerant clones. The second experiment was based on inoculation of 12-month-old plantation-grown trees of one clone of E. pellita with one isolate of C. manginecans using six different wounding methods. The inoculated wounds on the trees all produced xylem discolouration, except for those that only penetrated the outer bark. Disease incidence was greater at stem heights of 30 to 90 cm than on the basal stem or branch stub. The experiment emphasised the importance of minimising the risk of C. manginecans infection following wounding in the nursery and in the field as the discolouration is an indication of xylem blockage that can lead to tree mortality.

Development and Testing of HTS Coil With Ceramic Coated REBCO Conductor for High Radiation Tolerance

Development and Testing of HTS Coil With Ceramic Coated REBCO Conductor for High Radiation Tolerance

Mesoporous Silica-Based Membranes in Transdermal Drug Delivery: The Role of Drug Loss in the Skin.

Compared to other forms of drug administration, the use of Transdermal Drug Delivery Systems (TDDSs) offers significant advantages, including uniform drug release profiles that contribute to lower side effects and higher tolerability, avoidance of direct exposure to the gastrointestinal tract, better patient compliance due to their non-invasive means of application and others. Mesoporous silica membranes are of particular interest in this regard, due to their chemical stability and their tunable porous system, with adjustable pore sizes, pore volumes and surface chemistries. While this allows for fine-tuning and, thus, the development of optimized TDDSs with high loading capacities and the desired release profile of a given drug, its systemic availability also relies on skin penetration. In this paper, using a TDDS based on mesoporous silica membranes in Franz cell experiments on porcine skin, we demonstrate surprisingly substantial drug loss during skin penetration. Drug passage through porcine skin was found to be dependent on the age and pre-treatment of the skin. pH and temperature were major determinants of drug recovery rates as well, indicating drug loss in the skin by enzymatic metabolization. Regarding the TDDS, higher loading obtained by SO3H surface modification of the mesoporous silica membranes reduced drug loss. Still, high loss rates in the skin were determined for different drugs, including anastrozole, xylazine and imiquimod. We conclude that, beyond the fine-tuned drug release profiles from the mesoporous silica membrane TDDS, remarkably high drug loss in the skin is a major issue for achieving desired skin penetration and, thus, the systemic availability of drugs. This also poses critical requirements for defining an optimal TDDS based on mesoporous silica membranes.

Performance de crescimento do feijão caupi sob diferentes concentrações iônicas da solução nutritiva

ABSTRACT: Cowpea is a food crop representing an important source of proteins and income, mainly for people living in the north and northeast of Brazil. This study aimed to evaluate the growth performance of two cowpea cultivars under four different ionic concentrations of the growth solution. Thus, a pot experiment was performed using the sand culture technique and set up in a completely randomized design with a 2 x 4 factorial scheme, using four replications and one plant per plot. After the period of growth, the parameters such as length of the shoot, stem diameter, number of leaves, number of secondary branches, number of pods, fresh weight of the stem, stem dry mass, leaf dry mass, shoot dry mass, and root/shoot ratio were obtained. The results pointed out that there was a significant interaction effect on parameters like stem diameter, leaf dry mass, shoot dry mass, and number of leaves. Both cultivars were strongly responsive to changes in ionic concentration, indicating a greater biomass production at ionic concentrations of 90% and 120%. A greater growth performance for BRS Rouxinol than BRS Itaim was observed, while the second cultivar indicated a high tolerance as exposed to the highest ionic concentrations.

Expression of the alfalfa gene MsMDHAR in Arabidopsis thaliana increases water stress tolerance.

The ascorbate-glutathione pathway plays an essential role in the physiology of vascular plants, particularly in their response to environmental stresses. This pathway is responsible for regulating the cellular redox state, which is critical for maintaining cell function and survival under adverse conditions. To study the involvement of the alfalfa monodehydroascorbate reductase (MsMDHAR) in water stress processes, Arabidopsis thaliana plants constitutively expressing the sequence encoding MsMDHAR were developed. Transgenic events with low and high MsMDHAR expression and ascorbate levels were selected for further analysis of drought and waterlogging tolerance. Under water stress, Arabidopsis transgenic plants generated higher biomass, produced more seeds, and had larger roots than wild type ones. This higher tolerance was associated with increased production of waxes and chlorophyll a at the basal level, greater stomatal opening and stability in regulating the relative water content and reduced H2O2 accumulation under stress conditions in transgenic plants. Overall, these results show that MsMDHAR is involved in plant tolerance to abiotic stresses. The data presented here also emphasises the potential of the MsMDHAR enzyme as a plant breeding tool to improve water stress tolerance.

Efficacy and tolerability of initial triple combination therapy with metformin, dapagliflozin and saxagliptin compared with stepwise add-on therapy in drug-naïve patients with type 2 diabetes (TRIPLE-AXEL study): A multicentre, randomized, 104-week, open-label, active-controlled trial.

To evaluate the efficacy and tolerability of an initial triple combination therapy (TCT) compared with conventional stepwise add-on therapy (SAT) in patients with newly diagnosed type 2 diabetes (T2D). This multicentre, randomized, 104-week, open-label trial randomized 105 patients with drug-naïve T2D (with HbA1c level ≥ 8.0%, < 11.0%) to the TCT (1000 mg of metformin, 10 mg of dapagliflozin and 5 mg of saxagliptin once daily) or SAT (initiated with metformin, followed by glimepiride and sitagliptin) groups. The primary outcome was the proportion of patients who achieved an HbA1c level of less than 6.5% without hypoglycaemia, weight gain of 5% or higher, or discontinuation of drugs because of adverse events at week 104. HbA1c reduction from baseline at week 104 was similar between the groups (the least squares mean change was -2.56% in the TCT group vs. -2.75% in the SAT group). The primary outcome was achieved in 39.0% and 17.1% of the TCT and SAT groups, respectively, with a risk difference of 22.0 (95% confidence interval 3.0, 40.8; P = .027). HbA1c level less than 6.5% at week 104 was 46.3% in both the TCT and SAT groups, whereas the incidence of hypoglycaemia, weight gain, or discontinuation of drugs was 16.7% and 62.0% in the TCT and SAT groups, respectively (P < .001). TCT was well-tolerated and had fewer adverse events than SAT. Among newly diagnosed patients with T2D, initial TCT effectively lowered HbA1c levels with higher tolerability and safety than SAT for 104 weeks, suggesting a novel strategy for initial combination therapy in T2D patients.

P‐18: A Novel Ultra Low‐loading Gate Driver Circuit for 14‐inch 2.8K OLED Display

Recently there is an increasingly high demand for OLED (organic light‐emitting diode) panel to develop corresponding shift register driver circuits for pixel circuits, which has become an important research in the field of OLED panel design. This paper proposes 10 TFTs(thin film transistors )and 2 capacitor component driver circuits that has higher tolerance and better reliability regarding fluctuations such as display screen process, IC power signal noise, long‐term operation, etc..

An Exceptional Valorization of CuO Nanoparticles in Ionic Liquids as an Efficient Medium for the Electrophilic Substitution of Indole Towards the Formation of Bis(indolyl)methanes

Aim: Ionic liquids are promising green solvents with simple but unique structure-related physical properties such as negligible vapour pressure, exceptional thermal conductivity, remarkable thermal stability and their suitability and inertness towards a broad range of catalytic applications. CuO NPs have been addressed as a cost-effective and a reagent of a choice that necessitates only mild reaction conditions to offer a high yield of the desired products with exceptional selectivity in a short duration of time. Therefore, in the present work, attempts have been made to explore the catalytic potentials of CuO NPs in an ionic liquid medium to synthesize biologically important bis(indolyl)methanes. Background: Catalytic explorations of metal oxide nanoparticles in ionic liquids offers a cooperative effect that has a significant impact on the kinetics as well as on the outcome of the reaction. Therefore, such catalytic systems in the present times have seized the scientific community's interest from the perspectives of sustainable development in synthetic organic chemistry. The combination of metal oxide nanoparticles with highly tunable ionic liquids is not only used to synthesize simple organic molecules but also explored in the synthesis of complex organic molecules of high commercial and biological relevance. Objectives: The current work offers a rapid and robust protocol for synthesizing bis(indolyl)methanes via electrophilic substitution reaction between indole and various aldehydes in the presence of a CuO nanoparticles-ionic liquid system. The discussion focuses on the high tolerance of different functionalities by the catalytic system leading to the synthesis of bis(indolyl)methanes. Methods: CuO NPs have been synthesized via the co-precipitation method using ionic liquid. The applicability of metal oxide nanoparticles-IL matrix was further investigated in synthesizing bis(indolyl)methanes. Results: The FT-IR absorption below 600 cm-1 and the XRD pattern showing all the peaks in the diffraction diagram revealed the formation of CuO NPs. FESEM images show the flake-shaped morphology of CuO NPs and are found to be separated from the agglomerated clusters Conclusion: Ionic liquid-CuO NPs matrix reveals good to exceptional catalytic properties, and their advancements as a catalytic system at room temperature open new avenues for synthetic organic chemists.

Systematic review and network meta-analysis of agomelatine for the treatment of generalized anxiety disorder in adult patients.

This systematic literature review aimed to assess the efficacy and tolerability of agomelatine versus approved medications for the treatment of generalized anxiety disorder (GAD) in adult patients. We selected randomized controlled trials on various medications used to treat GAD in adult patients. An existing systematic literature review (Kong et al., 2020) was used to identify relevant studies published before 2020. Outcomes of remission and discontinuation due to adverse events (AEs) were analyzed, following a random-effects network meta-analysis approach. Of 25 identified studies, 20 and 22 studies were included in the network meta-analysis for studying the remission and discontinuation (due to AEs) outcomes, respectively. A statistically significant difference in the remission rate was observed between agomelatine and pregabalin [odds ratio (OR), 2.22; 95% confidence interval (CI), 1.19-4.21]. For the other comparators, the results were nonsignificant; however, all the point estimates were in favor of agomelatine. Similarly, for discontinuation because of AEs, the point estimates leaned consistently toward agomelatine suggesting its higher tolerability. The probabilities of agomelatine having the highest remission rate and lowest discontinuation (due to AEs) rate were 67% and 68%, respectively. Based on its demonstrated effectiveness and tolerability, agomelatine can be considered as a drug of choice for the treatment of GAD.

Structural underpinnings and long-term effects of resilience in Parkinson’s disease

Resilience in neuroscience generally refers to an individual’s capacity to counteract the adverse effects of a neuropathological condition. While resilience mechanisms in Alzheimer’s disease are well-investigated, knowledge regarding its quantification, neurobiological underpinnings, network adaptations, and long-term effects in Parkinson’s disease is limited. Our study involved 151 Parkinson’s patients from the Parkinson’s Progression Marker Initiative Database with available Magnetic Resonance Imaging, Dopamine Transporter Single-Photon Emission Computed Tomography scans, and clinical information. We used an improved prediction model linking neuropathology to symptom severity to estimate individual resilience levels. Higher resilience levels were associated with a more active lifestyle, increased grey matter volume in motor-associated regions, a distinct structural connectivity network and maintenance of relative motor functioning for up to a decade. Overall, the results indicate that relative maintenance of motor function in Parkinson’s patients may be associated with greater neuronal substrate, allowing higher tolerance against neurodegenerative processes through dynamic network restructuring.

Photocatalytic Functionalization of Dehydroalanine-Derived Peptides in Batch and Flow.

Unnatural amino acids, and their synthesis by the late-stage functionalization (LSF) of peptides, play a crucial role in areas such as drug design and discovery. Historically, the LSF of biomolecules has predominantly utilized traditional synthetic methodologies that exploit nucleophilic residues, such as cysteine, lysine or tyrosine. Herein, we present a photocatalytic hydroarylation process targeting the electrophilic residue dehydroalanine (Dha). This residue possesses an α,β-unsaturated moiety and can be combined with various arylthianthrenium salts, both in batch and flow reactors. Notably, the flow setup proved instrumental for efficient scale-up, paving the way for the synthesis of unnatural amino acids and peptides in substantial quantities. Our photocatalytic approach, being inherently mild, permits the diversification of peptides even when they contain sensitive functional groups. The readily available arylthianthrenium salts facilitate the seamless integration of Dha-containing peptides with a wide range of arenes, drug blueprints, and natural products, culminating in the creation of unconventional phenylalanine derivatives. The synergistic effect of the high functional group tolerance and the modular characteristic of the aryl electrophile enables efficient peptide conjugation and ligation in both batch and flow conditions.

Temporal Changes in Biochemical Responses to Salt Stress in Three Salicornia Species.

Halophytes adapt to salinity using different biochemical response mechanisms. Temporal measurements of biochemical parameters over a period of exposure to salinity may clarify the patterns and kinetics of stress responses in halophytes. This study aimed to evaluate short-term temporal changes in shoot biomass and several biochemical variables, including the contents of photosynthetic pigments, ions (Na+, K+, Ca2+, and Mg2+), osmolytes (proline and glycine betaine), oxidative stress markers (H2O2 and malondialdehyde), and antioxidant enzymes (superoxide dismutase, peroxidase, catalase, and ascorbate peroxidase) activities of three halophytic Salicornia species (S. persica, S. europaea, and S. bigelovii) in response to non-saline, moderate (300 mM NaCl), and high (500 mM NaCl) salinity treatments at three sampling times. Salicornia plants showed maximum shoot biomass under moderate salinity conditions. The results indicated that high Na+ accumulation in the shoots, coupled with the relative retention of K+ and Ca2+ under salt stress conditions, contributed significantly to ionic and osmotic balance and salinity tolerance in the tested Salicornia species. Glycine betaine accumulation, both constitutive and salt-induced, also seems to play a crucial role in osmotic adjustment in Salicornia plants subjected to salinity treatments. Salicornia species possess an efficient antioxidant enzyme system that largely relies on the ascorbate peroxidase and peroxidase activities to partly counteract salt-induced oxidative stress. The results also revealed that S. persica exhibited higher salinity tolerance than S. europaea and S. bigelovii, as shown by better plant growth under moderate and high salinity. This higher tolerance was associated with higher peroxidase activities and increased glycine betaine and proline accumulation in S. persica. Taking all the data together, this study allowed the identification of the biochemical mechanisms contributing significantly to salinity tolerance of Salicornia through the maintenance of ion and osmotic homeostasis and protection against oxidative stress.

Meiobenthos and ocean acidification: Effects on meiobenthic communities inhabiting Mediterranean cold shallow CO2-vents

Ocean acidification is causing major changes in marine ecosystems, with varying levels of impact, depending both on the habitat and the studied organisms. Here, we investigated for the first time the meiobenthos and nematode fauna inhabiting the sediments around Castello Aragonese (Ischia, Italy), characterized by variable pH values due to coastal volcanic CO2 venting. In this scenario, nematode functional diversity changed according to different pH levels and grain size: maturity index was higher at most acidic stations and trophic composition spanned from the dominance of predators in the acidic stations, to the high abundance of non-selective deposit feeders and epistrate feeders in the ambient-pH stations. Overall, the present study revealed a relatively high tolerance of meiobenthos and nematodes to lower pH conditions. However, an in-depth analysis of nematode fauna showed differences in their assemblages at different pH levels with few nematode genera rather adapted to the extreme environmental conditions at the acidic stations.

Abstract 4528: Improving carboplatin therapy: A novel albumin-targeted platinum(IV) prodrug with superior anticancer activity in vivo

Abstract Platinum(II)-based chemotherapeutics are among the most commonly used anticancer drugs and are part of nearly every second treatment scheme. However, they lack in tumor specificity, causing severe sides effects, dose-dependent toxicity as well as drug resistance development. Due to their higher tolerability, platinum(IV) prodrugs are currently in the focus of interest. However, comparable to their platinum(II) counterparts, they show insufficient tumor accumulation and are frequently prematurely activated. A promising strategy to improve tumor targeting of anticancer drugs is to exploit the enhanced consumption and accumulation of albumin in the malignant tissue. Thus, we developed a new albumin-targeted maleimide-containing platinum(IV) prodrug, which releases carboplatin in a highly tumor-specific manner. The maleimide moieties enable the drug to selectively bind the endogenous albumin via its free thiol of cysteine 34. The aim of this study was to in-depth characterize the pharmacological behavior and anticancer activity in vivo of the new prodrug. To this end, several xenograft and allograft experiments were performed. To investigate tissue distribution and pharmacokinetics serum, urine, tumor and organ samples of mice were collected after drug treatment and were evaluated by (size-exclusion chromatography) inductively-coupled plasma mass spectrometry and immunohistochemistry (e.g cleaved caspase-3). These experiments revealed that the new prodrug fast and selectively binds to the serum albumin after intravenous injection, leading to an enhanced plasma half-life and an increased tumor accumulation in comparison to its corresponding platinum(II) drug carboplatin. Additionally, the new complex resulted in superior anticancer activity and prolonged overall survival based on the distinctly improved pharmacokinetic profile and enhanced apoptosis induction. In conclusion, these data support that albumin binding is a potent tool to increase the tumor specificity of platinum(IV) drugs and prevent their premature activation in other body compartments. Consequently, this very promising prodrug will be further developed towards clinical phase I testing. Citation Format: Hemma Schueffl, Regina Weinmuellner, Nadine Sommerfeld, Bernhard K. Keppler, Walter Berger, Christian R. Kowol, Petra Heffeter. Improving carboplatin therapy: A novel albumin-targeted platinum(IV) prodrug with superior anticancer activity in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4528.

Engineering diaryl alcohol dehydrogenase KpADH reveals importance of retaining hydration shell in organic solvent tolerance.

Alcohol dehydrogenases (ADHs) are synthetically important biocatalysts for the asymmetric synthesis of chiral alcohols. The catalytic performance of ADHs in the presence of organic solvents is often important since most prochiral ketones are highly hydrophobic. Here, the organic solvent tolerance of KpADH from Kluyveromyces polyspora was semi-rationally evolved. Using tolerant variants obtained, meticulous experiments and computational studies were conducted to explore properties including stability, activity and kinetics in the presence of various organic solvents. Compared with WT, variant V231D exhibited 1.9-fold improvement in ethanol tolerance, while S237G showed a 6-fold increase in catalytic efficiency, a higher , as well as 15% higher tolerance in 7.5% (v/v) ethanol. Based on 3 × 100 ns MD simulations, the increased tolerance of V231D and S237G against ethanol may be ascribed to their enhanced ability in retaining water molecules and repelling ethanol molecules. Moreover, 6.3-fold decreased KM value of V231D toward hydrophilic ketone substrate confirmed its capability of retaining hydration shell. Our results suggest that retaining hydration shell surrounding KpADH is critical for its tolerance to organic solvents, as well as catalytic performance. This study provides useful guidance for engineering organic solvent tolerance of KpADH and other ADHs.

HFIP-promoted synthesis of imidazo [1,2-a]pyridines containing CF3-substituted tertiary alcohols at room temperature

Herein, we introduce a facile and efficient method for the synthesis of imidazo [1,2-a]pyridines containing CF3-substituted tertiary alcohol moieties using trifluoropyruvates as synthons under metal-free reaction conditions. The reaction promoted by the HFIP proceeds well at room temperature, displaying good to satisfactory yields and high functional group tolerance. Some advantages of the protocol are mild reaction conditions, simple operation and ready scalability.

Iodosylbenzene-Promoted Glycosylation with Selenoglycosides: Application in One-Pot Glycosylation.

A novel method for the glycosylation of selenoglycosides activated by iodosylbenzene was developed. The glycosylation reaction conditions were mild, fast, and efficient, with a high tolerance to diverse protecting groups and a wide substrate scope, which is advantageous for synthesizing complex glycosides. In addition, selenoglycosides were shown to be orthogonal to thioglycosides under the promotion of iodosylbenzene. Notably, a high yield of the poorly reactive glucuronidation reaction product was obtained by acetyl-protected selenoglycoside. Finally, the orthogonal one-pot synthesis of β-(1→6) oligoglucans demonstrated the usefulness of this method in oligosaccharide synthesis.