UiO-66-NH2 and Zeolite-Templated Carbon Composites for the Degradation and Adsorption of Nerve Agents.

Composites of metal-organic frameworks and carbon materials have been suggested to be effective materials for the decomposition of chemical warfare agents. In this study, we synthesized UiO-66-NH2/zeolite-templated carbon (ZTC) composites for the adsorption and decomposition of the nerve agents sarin and soman. UiO-66-NH2/ZTC composites with good dispersion were prepared via a solvothermal method. Characterization studies showed that the composites had higher specific surface areas than pristine UiO-66-NH2, with broad pore size distributions centered at 1-2 nm. Owing to their porous nature, the UiO-66-NH2/ZTC composites could adsorb more water at 80% relative humidity. Among the UiO-66-NH2/ZTC composites, U0.8Z0.2 showed the best degradation performance. Characterization and gas adsorption studies revealed that beta-ZTC in U0.8Z0.2 provided additional adsorption and degradation sites for nerve agents. Among the investigated materials, including the pristine materials, U0.8Z0.2 also exhibited the best protection performance against the nerve agents. These results demonstrate that U0.8Z0.2 has the optimal composition for exploiting the degradation performance of pristine UiO-66-NH2 and the adsorption performance of pristine beta-ZTC.

Small-molecule binding of the axin RGS domain promotes ß-catenin and Ras degradation.

Both the Wnt/ß-catenin and Ras pathways are aberrantly activated in most human colorectal cancers (CRCs) and interact cooperatively in tumor promotion. Inhibition of these signaling may therefore be an ideal strategy for treating CRC. We identified KY1220, a compound that destabilizes both ß-catenin and Ras, via targeting the Wnt/ß-catenin pathway, and synthesized its derivative KYA1797K. KYA1797K bound directly to the regulators of G-protein signaling domain of axin, initiating ß-catenin and Ras degradation through enhancement of the ß-catenin destruction complex activating GSK3ß. KYA1797K effectively suppressed the growth of CRCs harboring APC and KRAS mutations, as shown by various in vitro studies and by in vivo studies using xenograft and transgenic mouse models of tumors induced by APC and KRAS mutations. Destabilization of both ß-catenin and Ras via targeting axin is a potential therapeutic strategy for treatment of CRC and other type cancers activated Wnt/ß-catenin and Ras pathways.

Discovery of phosphonic acid natural products by mining the genomes of 10,000 actinomycetes.

Although natural products have been a particularly rich source of human medicines, activity-based screening results in a very high rate of rediscovery of known molecules. Based on the large number of natural product biosynthetic genes in microbial genomes, many have proposed "genome mining" as an alternative approach for discovery efforts; however, this idea has yet to be performed experimentally on a large scale. Here, we demonstrate the feasibility of large-scale, high-throughput genome mining by screening a collection of over 10,000 actinomycetes for the genetic potential to make phosphonic acids, a class of natural products with diverse and useful bioactivities. Genome sequencing identified a diverse collection of phosphonate biosynthetic gene clusters within 278 strains. These clusters were classified into 64 distinct groups, of which 55 are likely to direct the synthesis of unknown compounds. Characterization of strains within five of these groups resulted in the discovery of a new archetypical pathway for phosphonate biosynthesis, the first (to our knowledge) dedicated pathway for H-phosphinates, and 11 previously undescribed phosphonic acid natural products. Among these compounds are argolaphos, a broad-spectrum antibacterial phosphonopeptide composed of aminomethylphosphonate in peptide linkage to a rare amino acid N(5)-hydroxyarginine; valinophos, an N-acetyl l-Val ester of 2,3-dihydroxypropylphosphonate; and phosphonocystoximate, an unusual thiohydroximate-containing molecule representing a new chemotype of sulfur-containing phosphonate natural products. Analysis of the genome sequences from the remaining strains suggests that the majority of the phosphonate biosynthetic repertoire of Actinobacteria has been captured at the gene level. This dereplicated strain collection now provides a reservoir of numerous, as yet undiscovered, phosphonate natural products.

Structural and functional insight into an unexpectedly selective N-methyltransferase involved in plantazolicin biosynthesis.

Plantazolicin (PZN), a polyheterocyclic, N(α),N(α)-dimethylarginine-containing antibiotic, harbors remarkably specific bactericidal activity toward strains of Bacillus anthracis, the causative agent of anthrax. Previous studies demonstrated that genetic deletion of the S-adenosyl-L-methionine-dependent methyltransferase from the PZN biosynthetic gene cluster results in the formation of desmethylPZN, which is devoid of antibiotic activity. Here we describe the in vitro reconstitution, mutational analysis, and X-ray crystallographic structure of the PZN methyltransferase. Unlike all other known small molecule methyltransferases, which act upon diverse substrates in vitro, the PZN methyltransferase is uncharacteristically limited in substrate scope and functions only on desmethylPZN and close derivatives. The crystal structures of two related PZN methyltransferases, solved to 1.75 Å (Bacillus amyloliquefaciens) and 2.0 Å (Bacillus pumilus), reveal a deep, narrow cavity, putatively functioning as the binding site for desmethylPZN. The narrowness of this cavity provides a framework for understanding the molecular basis of the extreme substrate selectivity. Analysis of a panel of point mutations to the methyltransferase from B. amyloliquefaciens allowed the identification of residues of structural and catalytic importance. These findings further our understanding of one set of orthologous enzymes involved in thiazole/oxazole-modified microcin biosynthesis, a rapidly growing sector of natural products research.

Underestimation of Rhinogenic Causes in Patients Presenting to the Emergency Department with Acute Headache.

OBJECTIVES: Differential diagnosis is essential, since secondary headache due to paranasal sinus lesions are similar in headache characteristics to primary headache. However, since patients visiting the emergency department due to acute severe headache are primarily treated by neurologists, paranasal sinuses lesions and anatomical variations of the nasal cavity causing the headache are commonly overlooked because of the clinician's lack of knowledge about rhinosinugenic headache. This study investigated the prevalence of paranasal sinus lesions and anatomical variations that may cause secondary headaches in patients who were diagnosed as primary headache and treated by neurologists in the emergency room. METHODS: A retrospective study was done involving 1235 patients who visited the emergency department from January 2008 to December 2012 and who were diagnosed with primary headache. From the axial view of brain computed tomography, examination of sinusitis, mucosal contact points, concha bullosa, isolated sphenoid lesion, and osteoma were done, and location and morphology was analyzed. METHODS: Three hundred fifty-five of 1235 (28.7%) patients had sinusitis, mucosal contact points, concha bullosa, isolated sphenoid lesion, and osteoma as possible causes for secondary headaches. CONCLUSION: Differential diagnosis of primary headaches requires knowledge of paranasal sinus lesions including rhinosinusitis or anatomical variations. Also, interdisciplinary evaluation of acute headache presenting to the emergency room is necessary for accurate diagnosis and proper management.

Cyanohydrin phosphonate natural product from Streptomyces regensis.

Streptomyces regensis strain WC-3744 was identified as a potential phosphonic acid producer in a large-scale screen of microorganisms for the presence of the pepM gene, which encodes the key phosphonate biosynthetic enzyme phosphoenolpyruvate phosphonomutase. (31)P NMR revealed the presence of several unidentified phosphonates in spent medium after growth of S. regensis. These compounds were purified and structurally characterized via extensive 1D and 2D NMR spectroscopic and mass spectrometric analyses. Three new phosphonic acid metabolites, whose structures were confirmed by comparison to chemically synthesized standards, were observed: (2-acetamidoethyl)phosphonic acid (1), (2-acetamido-1-hydroxyethyl)phosphonic (3), and a novel cyanohydrin-containing phosphonate, (cyano(hydroxy)methyl)phosphonic acid (4). The gene cluster responsible for synthesis of these molecules was also identified from the draft genome sequence of S. regensis, laying the groundwork for future investigations into the metabolic pathway leading to this unusual natural product.

Effect of laser intensity on the characteristic of inkjet-printed silver nanoparticles during continuous laser sintering.

The variation in electric conductivity was examined for laser irradiation with various beam intensities. A 532-nm continuous wave laser was irradiated onto inkjet-printed silver lines on a glass substrate and the electrical resistance was measured in situ during the irradiation. The results demonstrate that electrical conductivity varies nonlinearly with laser intensity, and has a minimum specific resistance of 3.1 x 10(-8) Ωm at 4 kW/cm2 irradiation. These results are interesting because the specific resistance achieved by the present laser irradiation was approximately 1.9 times lower than the best value obtainable by oven heating, even though it was still higher by 1.9 times than that of bulk silver. It is also demonstrated that the irradiation time required to complete the sintering process decreases with laser intensity. The numerical simulation of laser heating shows that the heating temperature could be as high as 250 degrees C for laser sintering, while it is limited to 250 degrees C for oven sintering. The characteristics of sintering with laser intensity based on the results of field emission scanning electron microscope images are discussed.

Use of a phosphonate methyltransferase in the identification of the fosfazinomycin biosynthetic gene cluster.

Natural product discovery has been boosted by genome mining approaches, but compound purification is often still challenging. We report an enzymatic strategy for "stable isotope labeling of phosphonates in extract" (SILPE) that facilitates their purification. We used the phosphonate methyltransferase DhpI involved in dehydrophos biosynthesis to methylate a variety of phosphonate natural products in crude spent medium with a mixture of labeled and unlabeled S-adenosyl methionine. Mass-guided fractionation then allowed straightforward purification. We illustrate its utility by purifying a phosphonate that led to the identification of the fosfazinomycin biosynthetic gene cluster. This unusual natural product contains a hydrazide linker between a carboxylic acid and a phosphonic acid. Bioinformatic analysis of the gene cluster provides insights into how such a structure might be assembled.

Bayesian predictive modeling for gas purification using breakthrough curves.

This study proposes a predictive model for assessing adsorber performance in gas purification processes, specifically targeting the removal of chemical warfare agents (CWAs) using breakthrough curve analysis. Conventional parameter estimation methods, such as Brunauer-Emmett-Teller analysis, encounter challenges due to the limited availability of kinetic and equilibrium data for CWAs. To overcome these challenges, we implement a Bayesian parametric inference method, facilitating direct parameter estimation from breakthrough curves. The model's efficacy is confirmed by applying it to H2S purification in a fixed-bed setup, where predicted breakthrough curves aligned closely with previous experimental and numerical studies. Furthermore, the model is applied to sarin with ASZM-TEDA carbon, estimating key parameters that could not be assessed through conventional experimental techniques. The reconstructed breakthrough curves closely match actual measurements, highlighting the model's accuracy and robustness. This study not only enhances filter performance prediction for CWAs but also offers a streamlined approach for evaluating gas purification technologies under limited experimental data conditions.

Nonintrusive thermal-wave sensor for operando quantification of degradation in commercial batteries.

Monitoring real-world battery degradation is crucial for the widespread application of batteries in different scenarios. However, acquiring quantitative degradation information in operating commercial cells is challenging due to the complex, embedded, and/or qualitative nature of most existing sensing techniques. This process is essentially limited by the type of signals used for detection. Here, we report the use of effective battery thermal conductivity (keff) as a quantitative indicator of battery degradation by leveraging the strong dependence of keff on battery-structure changes. A measurement scheme based on attachable thermal-wave sensors is developed for non-embedded detection and quantitative assessment. A proof-of-concept study of battery degradation during fast charging demonstrates that the amount of lithium plating and electrolyte consumption associated with the side reactions on the graphite anode and deposited lithium can be quantitatively distinguished using our method. Therefore, this work opens the door to the quantitative evaluation of battery degradation using simple non-embedded thermal-wave sensors.

Influence of Mechanical Fatigue at Different States of Charge on Pouch-Type Li-Ion Batteries.

Since flexible devices are being used in various states of charge (SoCs), it is important to investigate SoCs that are durable against external mechanical deformations. In this study, the effects of a mechanical fatigue test under various initial SoCs of batteries were investigated. More specifically, ultrathin pouch-type Li-ion polymer batteries with different initial SoCs were subjected to repeated torsional stress and then galvanostatically cycled 200 times. The cycle performance of the cells after the mechanical test was compared to investigate the effect of the initial SoCs. Electrochemical impedance spectroscopy was employed to analyze the interfacial resistance changes of the anode and cathode in the cycled cells. When the initial SoC was at 70% before mechanical deformation, both electrodes well maintained their initial state during the mechanical fatigue test and the cell capacity was well retained during the cycling test. This indicates that the cells could well endure mechanical fatigue stress when both electrodes had moderate lithiation states. With initial SoCs at 0% and 100%, the batteries subjected to the mechanical test exhibited relatively drastic capacity fading. This indicates that the cells are vulnerable to mechanical fatigue stress when both electrodes have high lithiation states. Furthermore, it is noted that the stress accumulated inside the batteries caused by mechanical fatigue can act as an accelerated degradation factor during cycling.

Ultralight and Ultrathin Electrospun Membranes with Enhanced Air Permeability for Chemical and Biological Protection.

With the growing interest in chemical and biological warfare agents (CWAs/BWAs), the focus has shifted toward aerosol protection using protective clothing. However, compared to air-permeable membranes, those with water vapor permeability have been investigated more extensively. Filtering membranes without air permeability have limited practical usage in personal protective suits and masks. In this study, polyacrylonitrile membranes with tightly attached activated carbon and doped copper(II) oxide were prepared via electrospinning. The nanofibers with uniformly controlled diameters and smooth morphologies enable water/air breathability and protection against aerosol (100 nm polystyrene nanobeads similar to SARS-CoV-2) penetration. The uniformly distributed and tightly attached activated carbon and doped copper(II) oxide particles enhance the sorptive performance of the membranes by blocking gaseous CWAs, including soman, nerve chemical agents, and BWAs. Such dual-purpose membranes can be implemented in protective equipment owing to their high performance and easy processing.

Using marine natural products to discover a protease that catalyzes peptide macrocyclization of diverse substrates.

Small N-C terminally cyclic ribosomal peptides are common in nature, yet the mechanisms underlying their biosyntheses remain largely unknown. We recently identified candidate peptide cyclase genes in the metagenomes of marine animals. Here we report that PatG, a protease discovered in this analysis, cleaves variables, short peptides out of a precursor protein, and cyclizes these peptides in vivo and in vitro.

Roles of dark energy perturbations in dynamical dark energy models: can we ignore them?

We show the importance of properly including the perturbations of the dark energy component in the dynamical dark energy models based on a scalar field and modified gravity theories in order to meet with present and future observational precisions. Based on a simple scaling scalar field dark energy model, we show that observationally distinguishable substantial differences appear by ignoring the dark energy perturbation. By ignoring it the perturbed system of equations becomes inconsistent and deviations in (gauge-invariant) power spectra depend on the gauge choice.

A Ras destabilizer KYA1797K overcomes the resistance of EGFR tyrosine kinase inhibitor in KRAS-mutated non-small cell lung cancer.

The epidermal growth factor receptor (EGFR) inhibitors such as erlotinib and gefitinib are widely used for treatment of non-small cell lung cancer (NSCLC), but they have shown limited efficacy in an unselected population of patients. The KRAS mutations, which are identified in approximately 20% of NSCLC patients, have shown to be associated with the resistance to the EGFR tyrosine kinase inhibitors (TKIs). Currently, there is no clinically available targeted therapy which can effectively inhibit NSCLC tumors harboring KRAS mutations. This study aims to show the effectiveness of KYA1797K, a small molecule which revealed anti-cancer effect in colorectal cancer by destabilizing Ras via inhibiting the Wnt/ß-catenin pathway, for the treatment of KRAS-mutated NSCLC. While erlotinib fail to have anti-transforming effect in NSCLC cell lines harboring KRAS mutations, KYA1797K effectively inhibited the Ras-ERK pathway in KRAS-mutant NSCLC cell lines. As a result, KYA1797K treatment suppressed the growth and transformation of KRAS mutant NSCLC cells and also induced apoptosis. Furthermore, KYA1797K effectively inhibited Kras-driven tumorigenesis in the KrasLA2 mouse model by suppressing the Ras-ERK pathway. The destabilization of Ras via inhibition of the Wnt/ß-catenin pathway is a potential therapeutic strategy for KRAS-mutated NSCLC that is resistant to EGFR TKI.

Oxygen-enriched air for co-incineration of organic sludges with municipal solid waste: a pilot plant experiment.

Pilot-plant experiments were performed to evaluate the effect of oxygen enrichment on the co-incineration of MSW and organic sludge from a wastewater treatment facility. Combustion chamber temperatures, stack gas concentrations, i.e., CO(2) and CO, and the residual oxygen were measured. The maximum ratio of organic sludge waste to total waste input was 30 wt.%. Oxygen-enriched air, 22 vol.% (dry basis) oxygen, was used for stable combustion. As the co-incineration ratio of the sludge increased, the primary and secondary combustion chamber temperatures were decreased to 900 and 750 degrees C, respectively, approximately 100 degrees C below the proper incineration. However, if the supplied air was enriched with 22 vol.% (dry basis) oxygen content, the incinerator temperature was high enough to burn the waste mixture containing 30 wt.% moisture sludge, with an estimated heating value of 6.72 MJ/kg. There are two main benefits of using oxygen enrichment in the co-incineration. First, the sensible heat can be reduced as the quantity of nitrogen in the flue gas will be decreased. Second, the unburned carbon formation is reduced due to the oxygen-enriched burning of the waste, despite an increase in the sludge co-incineration ratio.

Life-threatening paraspinal muscle hematoma after percutaneous vertebroplasty.

Bleeding and hematoma formation is rarely reported in percutaneous vertebroplasty procedure. An 84 year old male presented with a large paraspinal muscle hematoma after a percutaneous vertebroplasty. The patient had neither any prior bleeding disorder nor any anticoagulant treatment. Vital signs of the patient were unstable, and his hemoglobin level decreased daily. After a month of conservative treatment, including transfusion, cryotherapy, pain control and bed rest, his hemoglobin level remained stable and he showed relief from pain. Four months later, hematoma resolved spontaneously and he could walk without back pain.

Isolated volar fracture-dislocation of the base of the second metacarpal bone by indirect injury.

Isolated volar fracture-dislocation of the second carpometacarpal joint is extremely rare, and no case of indirect injury has been reported. We are presenting a case of indirect injury, treated by open reduction with volar approach. Three-dimensional computed tomography was helpful for confirming and making surgical plan for this injury.

Risk factors for mortality of severe trauma based on 3 years' data at a single Korean institution.

PURPOSE: This study aimed to determine the mortality rate in patients with severe trauma and the risk factors for trauma mortality based on 3 years' data in a regional trauma center in Korea. METHODS: We reviewed the medical records of severe trauma patients admitted to Ajou University Hospital with an Injury Severity Score (ISS) > 15 between January 2010 and December 2012. Pearson chi-square tests and Student t-tests were conducted to examine the differences between the survived and deceased groups. To identify factors associated with mortality after severe trauma, multivariate logistic regression was performed. RESULTS: There were 915 (743 survived and 172 deceased) enrolled patients with overall mortality of 18.8%. Age, blunt trauma, systolic blood pressure (SBP) at admission, Glasgow Coma Scale (GCS) at admission, head or neck Abbreviated Injury Scale (AIS) score, and ISS were significantly different between the groups. Age by point increase (odds ratio [OR], 1.016; P = 0.001), SBP ≤ 90 mmHg (OR, 2.570; P < 0.001), GCS score ≤ 8 (OR, 6.229; P < 0.001), head or neck AIS score ≥ 4 (OR, 1.912; P = 0.003), and ISS by point increase (OR, 1.042; P < 0.001) were significant risk factors. CONCLUSION: In severe trauma patients, age, initial SBP, GCS score, head or neck AIS score, and ISS were associated with mortality.