Essential regulation of cell bioenergetics by constitutive InsP3 receptor Ca2+ transfer to mitochondria.

Mechanisms that regulate cellular metabolism are a fundamental requirement of all cells. Most eukaryotic cells rely on aerobic mitochondrial metabolism to generate ATP. Nevertheless, regulation of mitochondrial activity is incompletely understood. Here we identified an unexpected and essential role for constitutive InsP(3)R-mediated Ca(2+) release in maintaining cellular bioenergetics. Macroautophagy provides eukaryotes with an adaptive response to nutrient deprivation that prolongs survival. Constitutive InsP(3)R Ca(2+) signaling is required for macroautophagy suppression in cells in nutrient-replete media. In its absence, cells become metabolically compromised due to diminished mitochondrial Ca(2+) uptake. Mitochondrial uptake of InsP(3)R-released Ca(2+) is fundamentally required to provide optimal bioenergetics by providing sufficient reducing equivalents to support oxidative phosphorylation. Absence of this Ca(2+) transfer results in enhanced phosphorylation of pyruvate dehydrogenase and activation of AMPK, which activates prosurvival macroautophagy. Thus, constitutive InsP(3)R Ca(2+) release to mitochondria is an essential cellular process that is required for efficient mitochondrial respiration and maintenance of normal cell bioenergetics.

Combined effects of smoking and alcohol consumption on the risk of liver cancer according to metabolic syndrome: A nested case-control study in South Korea.

Tobacco and alcohol may interact to increase the risk of liver cancer, which might be modified by other risk factors. Their combined effects in the context of metabolic syndrome (MetS) remain unclear. Given the increasing prevalence of MetS, this nested case-control study was conducted to evaluate the combined effects of smoking and alcohol consumption on liver cancer risk with stratification by MetS. We included 15,352 liver cancer patients and 92,112 matched controls who attended the nationwide general health examination during 2009-2019, using a customized database (N = 5,545,835) from the Korean National Health Insurance Service. Liver cancer risk according to smoking and alcohol consumption was estimated using conditional multivariable logistic regression. Additive and multiplicative interactions between these two factors were assessed. Results showed that in men, dual current users were at a significantly higher risk of liver cancer compared with dual nonusers, adjusted odds ratio (aOR) = 1.61, 95% confidence interval: (1.50, 1.72). Interactions were detected between light-to-moderate alcohol consumption (0.1-28 g/day) and heavy smoking (>20 pack-years) on additive scale, relative excess risk due to interaction = 0.34 (0.16, 0.51), attributable proportion = 0.22 (0.11, 0.33), synergy index = 2.75 (1.85, 3.66), and multiplicative scale, aOR for the product term = 1.28 (1.11, 1.49). An additive interaction was also revealed between light-to-moderate drinking and light-to-moderate smoking in the MetS subgroup. In women, light-to-moderate drinking/nonsmoking was negatively associated with the risk in the non-MetS subgroup. In conclusion, a holistic health promotion program should target male dual users of tobacco cigarettes and alcohol, including light-to-moderate users, especially those with MetS.

RetroGREAT signaling: The lessons we learn from yeast.

The mitochondrial retrograde signaling (RTG) pathway of communication from mitochondria to the nucleus was first studied in yeast Saccharomyces cerevisiae. It rewires cellular metabolism according to the mitochondrial state by reprogramming nuclear gene expression in response to mitochondrial triggers. The main players involved in retrograde signaling are the Rtg1 and Rtg3 transcription factors, and a set of positive and negative regulators, including the Rtg2, Mks1, Lst8, and Bmh1/2 proteins. Retrograde regulation is integrated with other processes, including stress response, osmoregulation, and nutrient sensing through functional crosstalk with cellular pathways such as high osmolarity glycerol or target of rapamycin signaling. In this review, we summarize metabolic changes observed upon retrograde stimulation and analyze the progress made to uncover the mechanisms underlying the integration of regulatory circuits. Comparisons of the evolutionary adaptations of the retrograde pathway that have occurred in the different yeast groups can help to fully understand the process.

Novel melanin-derived stationary phase for immobilized metal ion affinity chromatography in recombinant His-tagged protein purification.

The matrix of the stationary phase is a crucial element in affinity chromatography for protein purification. Various materials, including polymer or magnetic materials, have been employed as the matrix in the purification of His-tagged protein. Here, for the first time, we utilized a combination of melanin and alginate, both natural polymer materials, to synthesize Ni-melanin/alginate (Ni-M/A) beads for His-tagged protein purification. We investigated the binding of His-tagged Mpro on the Ni-M/A beads, referred to as Ni-M/A-Mpro, and assessed the elution efficiency of Mpro from the beads. Our examination involved FTIR, EDS, XRD, SDS-PAGE, and Western blotting methods. FTIR spectra revealed notable changes in the stretching patterns and intensities of hydroxyl, amine, carbonyl, imine and amide chemical groups, when Mpro protein was present in the Ni-M/A sample. XRD spectra demonstrated the occurrence of two Nickel peaks at 35-40 deg and 40-45 deg in Ni-M/A, but only one nickel peak at 35-40 deg in Ni-M/A-Mpro, indicating the binding of Mpro on the Nickel ions. EDS analysis reported a decrease in the concentration of Nickel on the surface of Ni-M/A from 16% to 7% when Mpro protein was loaded into the stationary phase. Importantly, our data indicated that the purity of the His-tagged protein Mpro after purification reached 97% after just one-step purification using the Ni-M/A stationary phase. Moreover, the binding capacity of Ni-M/A for Mpro was approximately 5.2 mg/g with recovery efficiency of 40%. Our results suggested Ni-M/A as a highly potential solid phase for affinity chromatography in the purification of His-tagged protein.

In vitro and in vivo anti-tumor effect of Trichobakin fused with urokinase-type plasminogen activator ATF-TBK.

BACKGROUND: Trichobakin (TBK), a member of type I ribosome-inactivating proteins (RIPs), was first successfully cloned from Trichosanthes sp Bac Kan 8-98 in Vietnam. Previous study has shown that TBK acts as a potential protein synthesis inhibitor; however, the inhibition efficiency and specificity of TBK on cancer cells remain to be fully elucidated. METHODS AND RESULTS: In this work, we employed TBK and TBK conjugated with a part of the amino-terminal fragment (ATF) of the urokinase-type plasminogen activator (uPA), which contains the Ω-loop that primarily interacts with urokinase-type plasminogen activator receptor, and can be a powerful carrier in the drug delivery to cancer cells. Four different human tumor cell lines and BALB/c mice bearing Lewis lung carcinoma cells (LLC) were used to evaluate the role of TBK and ATF-TBK in the inhibition of tumor growth. Here we showed that the obtained ligand fused RIP (ATF-TBK) reduced the growth of four human cancer cell lines in vitro in the uPA receptor level-dependent manner, including the breast adenocarcinoma MDA-MB 231 cells and MCF7 cells, the prostate carcinoma LNCaP cells and the hepatocellular carcinoma HepG2 cells. Furthermore, the conjugate showed anti-tumor activity and prolonged the survival time of tumor-bearing mice. The ATF-TBK also did not cause the death of mice with doses up to 48 mg/kg, and they were not significantly distinct on parameters of hematology and serum biochemistry between the control and experiment groups. CONCLUSIONS: In conclusion, ATF-TBK reduced the growth of four different human tumor cell lines and inhibited lung tumor growth in a mouse model with little side effects. Hence, the ATF-TBK may be a target to consider as an anti-cancer agent for clinical trials.

Associations between dietary diversity and dyslipidemia among Japanese workers: cross-sectional study and longitudinal study findings.

OBJECTIVE: The aim of this study was to determine the associations between dietary diversity and risk of dyslipidemia in Japanese workers. METHODS: The cross-sectional study included 1399 participants aged 20-63 years and the longitudinal study included 751 participants aged 20-60 years in 2012-2013 (baseline) who participated at least once from 2013 to 2017 with cumulative participation times of 4.9 times. Dietary intake was assessed using a food frequency questionnaire, and dietary diversity score (DDS) was determined using the Quantitative Index for Dietary Diversity. Dyslipidemia was diagnosed when at least one of the following conditions was met: hypertriglyceridemia, high LDL-cholesterol, low HDL-cholesterol, high non-HDL-cholesterol, and a history of dyslipidemia. Multivariable logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for dyslipidemia with control of confounding factors in cross-sectional analysis. Generalized estimating equations were used for calculating the ORs (95% CI) for dyslipidemia in the follow-up period according to the DDS at baseline with control of confounding factors in longitudinal analysis. RESULTS: Cross-sectional analysis showed that the highest DDS reduced the odds of dyslipidemia in men (OR [95% CI] in Tertile 3: 0.67 [0.48-0.95], p value = 0.023). In longitudinal analysis, a moderate DDS reduced the risk of dyslipidemia (OR [95% CI] in Tertile 2: 0.21 [0.07-0.60], p value = 0.003) in women. CONCLUSIONS: The results of cross-sectional analysis in this study suggest that the higher diversity of diet might reduce the presence of dyslipidemia in men and the results of longitudinal analysis suggest that a moderate DDS might reduce the risk of dyslipidemia in women. Further studies are needed since the results of cross-sectional and longitudinal analyses in this study were inconsistent.

Triple oxygen isotope evidence for limited mid-Proterozoic primary productivity.

The global biosphere is commonly assumed to have been less productive before the rise of complex eukaryotic ecosystems than it is today1. However, direct evidence for this assertion is lacking. Here we present triple oxygen isotope measurements (∆17O) from sedimentary sulfates from the Sibley basin (Ontario, Canada) dated to about 1.4 billion years ago, which provide evidence for a less productive biosphere in the middle of the Proterozoic eon. We report what are, to our knowledge, the most-negative ∆17O values (down to -0.88‰) observed in sulfates, except for those from the terminal Cryogenian period2. This observation demonstrates that the mid-Proterozoic atmosphere was distinct from what persisted over approximately the past 0.5 billion years, directly reflecting a unique interplay among the atmospheric partial pressures of CO2 and O2 and the photosynthetic O2 flux at this time3. Oxygenic gross primary productivity is stoichiometrically related to the photosynthetic O2 flux to the atmosphere. Under current estimates of mid-Proterozoic atmospheric partial pressure of CO2 (2-30 times that of pre-anthropogenic levels), our modelling indicates that gross primary productivity was between about 6% and 41% of pre-anthropogenic levels if atmospheric O2 was between 0.1-1% or 1-10% of pre-anthropogenic levels, respectively. When compared to estimates of Archaean4-6 and Phanerozoic primary production7, these model solutions show that an increasingly more productive biosphere accompanied the broad secular pattern of increasing atmospheric O2 over geologic time8.

New Solasodine-Type Glycoalkaloids Isolated from Solanum nigrum and Their Cytotoxic Activity.

Three undescribed solalodine-type glycoalkaloids, named solanigrinoside A-C (1-3), and six known compounds (4-9) were isolated from the whole plants of Solanum nigrum. Their structures were elucidated based on analysis of HR-ESI-MS, 1D- and 2D-NMR spectral data, and comparison with those reported in literatures. The solanigrinoside A-C (1-3), solasodine (4), and 3-acetoxysolasodine (5) exhibited cytotoxic effects against LU-1, Hep-G2, and MCF-7 cells with IC50 values in range from 4.6 µM to 56.2 µM. Compound 2 showed the significant cytotoxic activity with corresponding IC50 values of 5.7 µM, 7.9 µM, and 4.6 µM, respectively.

Four Steroidal Saponins from the Trunks of Dracaena cambodiana with Inhibition of NO Production in LPS Activated RAW264.7 Cells.

Dracaena cambodiana Pierre ex Gagnep. is well known as a medicinal plant and widely distributed in Vietnam. Phytochemical investigation on the trunks of D. cambodiana lead to the isolation of four undescribed compounds (1-4) together with seven known ones (5-11). Their structures were determined to be pennogenin-24-yl-O-ß-D-glucopyranoside (1), 17α-hydroxycambodianoside C (2), (25R)-27-hydroxypenogenin 3-O-α-L-rhamnopyranosyl-(1→3)-[α-L-rhamnopyranosyl-(1→2)]-ß-D-glucopyranoside (3), (3ß,25R)-17α,22α-dihydroxy-furost-5-en-3-yl-O-α-L-rhamnopyranosyl-(1→3)-[α-L-rhamnopyranosyl-(1→2)]-ß-D-glucopyranoside (4), dracagenin A (5), 1-O-ß-D-glucopyranosyl-2-hydroxy-4-allylbenzene (6), 1-O-α-L-rhamnopyranosyl-(1→6)-ß-D-glucopyranosyl-2-hydroxy-allylbenzene (7), 2-O-α-L-rhamnopyranosyl-(1→6)-ß-D-glucopyranosyl-1-hydroxy-allylbenzene (8), cinnamrutinoside A (9), icariside D1 (10), and seco-isolariciresinol 9-O-ß-glucopyranoside (11) by extensive spectroscopic investigation, HR-ESI-MS, 1D and 2D NMR spectra. The anti-inflammatory activity of the isolated compounds was evaluated on macrophages. Compounds 1-6 significantly inhibited nitric oxide production in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Among them, compound 1 showed the best inhibitory activity with an IC50 value of 8.90±0.56 µM.

Oleanane-Type Triterpene Glycosides from Camellia phanii and Their α-Glucosidase Inhibitory Activity.

Three new oleanane-type triterpene saponins, named camphanosides A-C (1-3), along with five known compounds, chikusetsusaponin IVa (4), spinasaponin A 28-O-glucoside (5), (-)-epicatechin (6), (-)-epicatechin 3-O-gallate (7), and (-)-epigallocatechin 3-O-gallate (8) were isolated from the leaves Camellia phanii Hakoda & Ninh. Their structures were established by 1D and 2D-NMR and mass spectral analysis and chemical methods. Moreover, compounds 1-5 were also evaluated for α-glucosidase inhibitory activity. Compounds 1-3 exhibited moderate α-glucosidase inhibitory activity with IC50 values of 230.7±18.0, 251.4±22.7, and 421.4±25.6 µM, respectively.

Growing propensity of internet addiction among Asian college students: meta-analysis of pooled prevalence from 39 studies with over 50,000 participants.

OBJECTIVES: Rapid internet penetration and technological advancements have facilitated accessibility to internet-enabled devices globally. Since Asia lacks comprehensive data on internet addiction among college students, this review aims to estimate its pooled prevalence. STUDY DESIGN: This was a systematic review and meta-analysis. METHODS: Searches were conducted in PubMed, Scopus, CINAHL, and MEDLINE from their inception through August 2022 using terms appropriate to internet addiction and Asian countries/territorial for publications in English peer-reviewed journals. The studies included those done on current college students and provided unambiguous indicators of the threshold of internet addiction. The pooled prevalence was calculated through a random-effects meta-analysis by RStudio software, and I2 statistic was used to assess heterogeneity. The Joanna Briggs Institute critical appraisal checklist was used for quality assessment. RESULTS: Overall, between 2007 and 2021, 39 papers comprising 45 effect sizes and totaling 58,058 participants met the inclusion criteria. The pooled prevalence of internet addiction among Asian college students was 24.3% (95% confidence interval: 19.8%-29.5%, Q = 6234, df = 44, τ2 = 0.79, I2 = 99.29%), and strikingly, this percentage increased over time. A high degree of heterogeneity was seen, and no publication bias was found. CONCLUSIONS: To our knowledge, this is the first comprehensive review report on Asian college students, which found that one-fifth suffer from internet addiction. The findings emphasize the significance of multidisciplinary prevention and management strategies to mitigate the harmful effects of internet addiction. Further research is warranted to develop a standardized diagnostic tool for a more precise estimation of internet addiction among this population.

Preliminary Characterization of an Active CMOS Pad Detector for Tracking and Dosimetry in HDR Brachytherapy.

We assessed the accuracy of a prototype radiation detector with a built in CMOS amplifier for use in dosimetry for high dose rate brachytherapy. The detectors were fabricated on two substrates of epitaxial high resistivity silicon. The radiation detection performance of prototypes has been tested by ion beam induced charge (IBIC) microscopy using a 5.5 MeV alpha particle microbeam. We also carried out the HDR Ir-192 radiation source tracking at different depths and angular dose dependence in a water equivalent phantom. The detectors show sensitivities spanning from (5.8 ± 0.021) × 10-8 to (3.6 ± 0.14) × 10-8 nC Gy-1 mCi-1 mm-2. The depth variation of the dose is within 5% with that calculated by TG-43. Higher discrepancies are recorded for 2 mm and 7 mm depths due to the scattering of secondary particles and the perturbation of the radiation field induced in the ceramic/golden package. Dwell positions and dwell time are reconstructed within ±1 mm and 20 ms, respectively. The prototype detectors provide an unprecedented sensitivity thanks to its monolithic amplification stage. Future investigation of this technology will include the optimisation of the packaging technique.

Evaluation of Dihydroartemisinin-Piperaquine Efficacy and Molecular Markers in Uncomplicated Falciparum Patients: A Study across Binh Phuoc and Dak Nong, Vietnam.

Background and Objectives: Malaria continues to be a significant global health challenge. The efficacy of artemisinin-based combination therapies (ACTs) has declined in many parts of the Greater Mekong Subregion, including Vietnam, due to the spread of resistant malaria strains. This study was conducted to assess the efficacy of the Dihydroartemisinin (DHA)-Piperaquine (PPQ) regimen in treating uncomplicated falciparum malaria and to conduct molecular surveillance of antimalarial drug resistance in Binh Phuoc and Dak Nong provinces. Materials and Methods: The study included 63 uncomplicated malaria falciparum patients from therapeutic efficacy studies (TES) treated following the WHO treatment guidelines (2009). Molecular marker analysis was performed on all 63 patients. Methods encompassed Sanger sequencing for pfK13 mutations and quantitative real-time PCR for the pfpm2 gene. Results: This study found a marked decrease in the efficacy of the DHA-PPQ regimen, with an increased rate of treatment failures at two study sites. Genetic analysis revealed a significant presence of pfK13 mutations and pfpm2 amplifications, indicating emerging resistance to artemisinin and its partner drug. Conclusions: The effectiveness of the standard DHA-PPQ regimen has sharply declined, with rising treatment failure rates. This decline necessitates a review and possible revision of national malaria treatment guidelines. Importantly, molecular monitoring and clinical efficacy assessments together provide a robust framework for understanding and addressing detection drug resistance in malaria.

DS86760016, a Leucyl-tRNA Synthetase Inhibitor, Is Active against Mycobacterium abscessus.

Benzoxaboroles are a new class of leucyl-tRNA synthetase inhibitors. Epetraborole, a benzoxaborole, is a clinical candidate developed for Gram-negative infections and has been confirmed to exhibit favorable activity against a well known pulmonary pathogen, Mycobacterium abscessus. However, according to ClinicalTrials.gov, in 2017, a clinical phase II study on the use of epetraborole to treat complicated urinary tract and intra-abdominal infections was terminated due to the rapid emergence of drug resistance during treatment. Nevertheless, epetraborole is in clinical development for nontuberculous mycobacteria (NTM) disease especially for Mycobacterium avium complex-related pulmonary disease (MAC-PD). DS86760016, an epetraborole analog, was further demonstrated to have an improved pharmacokinetic profile, lower plasma clearance, longer plasma half-life, and higher renal excretion than epetraborole in animal models. In this study, DS86760016 was found to be similarly active against M. abscessus in vitro, intracellularly, and in zebrafish infection models with a low mutation frequency. These results expand the diversity of druggable compounds as new benzoxaborole-based candidates for treating M. abscessus diseases.

MeRgeION: a Multifunctional R Pipeline for Small Molecule LC-MS/MS Data Processing, Searching, and Organizing.

Small molecule structure elucidation using tandem mass spectrometry (MS/MS) plays a crucial role in life science, bioanalytical, and pharmaceutical research. There is a pressing need for increased throughput of compound identification and transformation of historical data into information-rich spectral databases. Meanwhile, molecular networking, a recent bioinformatic framework, provides global displays and system-level understanding of complex LC-MS/MS data sets. Herein we present meRgeION, a multifunctional, modular, and flexible R-based toolbox to streamline spectral database building, automated structural elucidation, and molecular networking. The toolbox offers diverse tuning parameters and the possibility to combine various algorithms in the same pipeline. As an open-source R package, meRgeION is ideally suited for building spectral databases and molecular networks from privacy-sensitive and preliminary data. Using meRgeION, we have created an integrated spectral database covering diverse pharmaceutical compounds that was successfully applied to annotate drug-related metabolites from a published nontargeted metabolomics data set as well as reveal the chemical space behind this complex data set through molecular networking. Moreover, the meRgeION-based processing workflow has demonstrated the usefulness of a spectral library search and molecular networking for pharmaceutical forced degradation studies. meRgeION is freely available at: https://github.com/daniellyz/meRgeION2.

Dual and Sequential Locked/Unlocked Photochromic Effects on FRET Controlled Singlet Oxygen Processes by Contracted/Extended Forms of Diarylethene-Based [1]Rotaxane Nanoparticles.

Manipulations of singlet oxygen (1 O2 ) generations by the integration of both aggregation-induced emission luminogen (AIEgen) photosensitizer and photochromic moieties have diversified features in photodynamic therapy applications. Through Förster resonance energy transfer (FRET) pathway to induce red PL emissions (at 595 nm) for 1 O2 productions, [1]rotaxane containing photosensitive tetraphenylethylene (TPE) donor and photochromic diarylethene (DAE) acceptor is introduced to achieve dual and sequential locked/unlocked photoswitching effects by pH-controlled shuttling of its contracted/extended forms. Interestingly, the UV-enabled DAE ring closure speeds follow the reversed trend of DAE self-constraint degree as: contracted < extended < noninterlocked forms in [1]rotaxane analogues, thus FRET processes can be adjusted in contracted/extended forms of [1]rotaxane upon UV irradiations. Accordingly, the contracted form of [1]rotaxane is FRET-OFF locked and inert to UV exposure due to the larger bending conformation of DAE parallel (p-)conformer, compared with its extended and noninterlocked analogues possessing switchable FRET-OFF/ON behaviors activated by dual and sequential pH- and photoswitching. Owing to the advantages of 1 O2 productions tuned by multistimuli inputs (pH, UV, and blue light), an useful logic circuit for toxicity outputs of the surface modified [1]rotaxane nanoparticles (NPs) has been demonstrated to offer promising 1 O2 productions and managements based on mechanically interlocked molecules for future bioapplications.

Impact of chemical modifications on the antimicrobial and hemolytic activity of helical amphipathic peptide Lasioglossin LL-III.

Insect venom is abundant in potential antimicrobial peptides (AMPs), which can serve as novel alternatives to conventional antibiotics. Among them, Lasioglossin III LL-III) is a promising candidate with a broad spectrum against many fungi strains and both types of bacteria, whereas almost non-toxic to red blood cells. Many chemical approaches have been recently applied to improve its pharmacological properties and provide useful information regarding structure-activity relationships. Hence, this review focused on highlighting the lesson learned from each modification and supporting the future design of potent, selective, and metabolically stable AMPs.

Effect of substituting glutamine with lysine on structural and biological properties of antimicrobial peptide Polybia-MP1.

The natural antimicrobial peptide Polybia-MP1 is a promising candidate for developing new treatment therapy for infection and cancer. It showed broad-spectrum antimicrobial and anticancer activity with high safety on healthy cells. However, previous sequence modification usually resulted in at least one of two consequences: a notable increase in hemolytic activity or a considerable decrease in activity against Gram-negative bacteria and cancer cells. Herein, a new approach was applied by replacing the amino acid Glutamine at position 12 with Lysine and generating the MP1-Q12K analog. Our preliminary data suggested an enhancement in antibacterial and antifungal activity, whereas the anticancer and hemolytic activity of the two peptides were comparable. Moreover, MP1-Q12K was found to be less self-assembly than Polybia-MP1, which further supports the enhancement of antimicrobial properties. Hence, this study provides new information regarding the structure-activity relationships of Polybia-MP1 and support for the development of potent, selective antimicrobial peptides.

Ultrasensitive Monitoring of Cyanide Concentrations in Water Using a Aucore-Agshell Hybrid-Coating-Based Fiber Optical Sensor.

Cyanides, which are extremely toxic chemicals that are rapidly absorbed into the human body and interact with cytochrome oxidase, strongly inhibit cellular respiration to body death with convulsions. Cyanide ions that exist in many forms in nature such as those found in apricot kernels, cassava roots, and bamboo shoots as cyanogenic glycosides are inevitably used in various industries, including gold and silver mining as well as in dyes and plastic industries. In this study, for the sake of developing ultrahigh-sensitive sensors for cyanide monitoring in a simple manner, we chemically synthesize Aucore-Agshell hybrid nanomaterials of different core/shell thicknesses for colorimetric sensors and fiber optical sensors. Their sensing principle relies on the formation of the Ag/Au cyanocomplex upon cyanide injection. The generated metal cyanocomplex induced changes in refractive indices, causing changes in properties of localized surface plasmon resonance (LSPR), i.e., optical absorbance change for the colorimetric sensors. For fiber optical sensors, the hybrid metal nanoparticles were immobilized on the fiber core surface and the metal cyanocomplex formation induced changes in the fiber cladding refractive index, enabling quantitative cyanide detection with ultrahigh sensitivity. The LSPR-based colorimetric sensor provided the lowest detectable cyanide concentration of 5 × 10-6 M, whereas the value for the fiber-based sensor was 8 × 10-11 M.

Stabilization of Synthetic Collagen Triple Helices: Charge Pairs and Covalent Capture.

Collagen mimetic peptides are composed of triple helices. Triple helical formation frequently utilizes charge pair interactions to direct protein assembly. The design of synthetic triple helices is challenging due to the large number of competing species and the overall fragile nature of collagen mimetics. A successfully designed triple helix incorporates both positive and negative criteria to achieve maximum specificity of the supramolecular assembly. Intrahelical charge pair interactions, particularly those involved in lysine-aspartate and lysine-glutamate pairs, have been especially successful both in driving helix specificity and for subsequent stabilization by covalent capture. Despite this progress, the important sequential and geometric relationships of charged residues in a triple helical context have not been fully explored for either supramolecular assembly or covalent capture stabilization. In this study, we compare the eight canonical axial and lateral charge pairs of lysine and arginine with glutamate and aspartate to their noncanonical, reversed charge pairs. These findings are put into the context of collagen triple helical design and synthesis.