Analyses of the electronic structures of FeFe-cofactors compared with those of FeMo- and FeV-cofactors and their P-clusters.

The electronic structures of FeFe-cofactors (FeFe-cos) in resting and turnover states, together with their PN clusters from iron-only nitrogenases, have been calculated using the bond valence method, and their crystallographic data were reported recently and deposited in the Protein Data Bank (PDB codes: 8BOQ and 8OIE). The calculated results have also been compared with those of their homologous Mo- and V-nitrogenases. For FeFe-cos in the resting state, Fe1/2/4/5/6/7/8 atoms are prone to Fe3+, while the Fe3 atom shows different degrees of mixed valences. The results support that the Fe8 atom at the terminal positions of FeFe-cos possesses the same oxidation states as the Mo3+/V3+ atoms of FeMo-/FeV-cos. In the turnover state, the overall oxidation state of FeFe-co is slightly reduced than those in the resting species, and its electronic configuration is rearranged after the substitution of S2B with OH, compatible with those found in CO-bound FeV-co. Moreover, the calculations give the formal oxidation states of 6Fe2+-2Fe3+ for the electronic structures of PN clusters in Fe-nitrogenases. By the comparison of Mo-, V- and Fe-nitrogenases, the overall oxidation levels of 7Fe atoms (Fe1-Fe7) for both FeFe- and FeMo-cos in resting states are found to be higher than that of FeV-co. For the PN clusters in MoFe-, VFe- and FeFe-proteins, they all exhibit a strong reductive character.

3D Gas Sensing with Multiple Nano Aerial Vehicles: Interference Analysis, Algorithms and Experimental Validation.

Within the scope of the ongoing efforts to fight climate change, the application of multi-robot systems to environmental mapping and monitoring missions is a prominent approach aimed at increasing exploration efficiency. However, the application of such systems to gas sensing missions has yet to be extensively explored and presents some unique challenges, mainly due to the hard-to-sense and expensive-to-model nature of gas dispersion. For this paper, we explored the application of a multi-robot system composed of rotary-winged nano aerial vehicles to a gas sensing mission. We qualitatively and quantitatively analyzed the interference between different robots and the effect on their sensing performance. We then assessed this effect, by deploying several algorithms for 3D gas sensing with increasing levels of coordination in a state-of-the-art wind tunnel facility. The results show that multi-robot gas sensing missions can be robust against documented interference and degradation in their sensing performance. We additionally highlight the competitiveness of multi-robot strategies in gas source location performance with tight mission time constraints.

Development and Feasibility of a Primary Care Provider Training Intervention to Improve Atrial Fibrillation Management.

The disparities in atrial fibrillation (AF) care are partially attributed to inadequate access to providers with specialized training in AF. Primary care providers (PCPs) are often the sole providers of AF care in under-resourced regions. As such, we sought to create a virtual education intervention for PCPs and to evaluate its impact on the use of stroke risk reduction strategies in patients with AF. A multidisciplinary team mentored PCPs on AF management over 6 months using a virtual case-based training format. Surveys of participant knowledge and confidence in AF care were compared before and after the intervention. Hierarchical logistic regression modeling was used to evaluate change in oral anticoagulation (OAC) therapy in the patients seen by participants before or after training. Of 41 participants trained, 49% worked in family medicine, 41% internal medicine, and 10% general cardiology. Participants attended a mean of 14 1-hour sessions. Overall, the appropriate use of OAC (for CHA2DS2-VASc score ≥1 man, ≥2 women) increased from 37% to 46% (p <0.001) comparing the patients seen before (n = 1,739) versus after (n = 610) intervention. The factors independently associated with appropriate OAC use included participant training (odds ratio [OR] 1.4, p = 0.002) and participant competence in AF management. The factors associated with decreased OAC use included patient age (OR 0.8 per 10 year, p = 0.008) and nonwhite race (OR 0.7, p = 0.028). Provider knowledge and confidence in AF care improved (p <0.001). In conclusion, we show that a virtual PCP training intervention improves the use of stroke risk reduction therapy in outpatients with AF and could be a widely scalable intervention to improve AF care in under-resourced communities.

Efficacy, Safety, and Tolerability of Oral Furosemide Among Patients Receiving Hemodialysis: A Pilot Study.

Introduction: Diuretic use may reduce volume-related complications in hemodialysis. We evaluated the efficacy, safety, and tolerability of furosemide in patients with hemodialysis-dependent kidney failure. Methods: We conducted an open label, single-arm, 18-week, dose titration pilot study of oral furosemide (maximum dose 320 mg/day) among patients receiving maintenance hemodialysis who reported at least 1 cup of urine output per day. The primary efficacy outcome was an increase from baseline to a specified threshold of 24-hour urine volume, with the threshold based on baseline urine volume (<200 ml/day vs. ≥200 ml/day). Safety outcomes included hypokalemia and hypomagnesemia, and tolerability was assessed by prespecified patient-reported symptoms. Results: Of the 39 participants, 28 (72%) received the expected furosemide dose, 3 (8%) underwent dose reduction, 5 (12%) discontinued furosemide without dose reduction, and 3 (8%) underwent dose reduction and subsequently discontinued furosemide. The median (quartile 1, quartile 3) baseline 24-hour urine volume was 290 ml (110, 740), and the maximum, average daily study furosemide dose ranged from 69 mg/day to 320 mg/d. The urine output efficacy outcome was met by 12 (33%), 11 (33%), and 7 (22%) participants at weeks 5, 12, and 18, respectively, in the intention-to-treat analysis, and by 12 (39%), 9 (35%), and 7 (28%) participants at weeks 5, 12, and 18, respectively, in the on-treatment analysis. There were no electrolyte, furosemide level, or patient-reported hearing change safety events. Conclusion: Furosemide was generally safe and well tolerated, but only one-third of participants met the efficacy definition at week 5. The clinical importance of the efficacy findings is uncertain.

The genome of homosporous maidenhair fern sheds light on the euphyllophyte evolution and defences.

Euphyllophytes encompass almost all extant plants, including two sister clades, ferns and seed plants. Decoding genomes of ferns is the key to deep insight into the origin of euphyllophytes and the evolution of seed plants. Here we report a chromosome-level genome assembly of Adiantum capillus-veneris L., a model homosporous fern. This fern genome comprises 30 pseudochromosomes with a size of 4.8-gigabase and a contig N50 length of 16.22 Mb. Gene co-expression network analysis uncovered that homospore development in ferns has relatively high genetic similarities with that of the pollen in seed plants. Analysing fern defence response expands understanding of evolution and diversity in endogenous bioactive jasmonates in plants. Moreover, comparing fern genomes with those of other land plants reveals changes in gene families important for the evolutionary novelties within the euphyllophyte clade. These results lay a foundation for studies on fern genome evolution and function, as well as the origin and evolution of euphyllophytes.

The Genetic Diversity in Thereuonema tuberculata (Wood, 1862) (Scutigeromorpha: Scutigeridae) and the Phylogenetic Relationship of Scutigeromorpha Using the Mitochondrial Genome.

Based on morphological characteristics to make species identification, the cryptic species of the Scutigeromorpha can be greatly underestimated. The mitochondrial genome provides a desirable tool for the biological identifications and the discovery of the cryptic species. The capacity to acquire mitochondrial genome sequences has substantially improved in recent years using next-generation sequencing (NGS) technology. On the basis of the next-generation sequencing, we obtained four complete mitochondrial genomes of Thereuonema tuberculata (Wood, 1862) from Nanyang, Henan Province (NY), Nanchang, Jiangxi Province (NC), Jinan, Shandong Province (JN), and Dali, Yunnan Province (DL) in China with GenBank numbers OK513221, OL449685, ON058988 and ON058989, respectively. The lengths of the four mitochondrial genomes ranged from 14,903 to 14,909 bp. The composition and order of genes of the four mitochondrial genomes were identical to the published mitochondrial genome of Scutigera coleoptrata (Linnaeus, 1758) (Scutigeromorpha: Scutigerdae). It was the first time that the tandem repeats in the control region were detected in Scutigeromorpha. We also calculated the corrected pairwise genetic distance of four complete mitochondrial genomes of T. tuberculata, ranging from 7.7 to 15.2%. The results showed that the T.tuberculata NC belonged to the typical sample of T. tuberculata, and T. tuberculata DL was hypothesized as a cryptic species of T. tuberculata. Meanwhile, T. tuberculata NY and T. tuberculata JN were hypothesized as potential cryptic species of T. tuberculata in this study. In both BI and ML trees, the monophyly of Scutigeromorpha, Scolopendromorpha, Geophilomorpha, and Lithobiomorpha was forcefully advocated. Moreover, Scutigeromorpha was recovered as the sister clade of (Scolopendromorpha + (Lithobiomorpha + Geophilomorpha)). Four specimens of T. tuberculata were clustered into one clade, which was the sister to the clade of S. coleoptrata.

The complete mitochondrial genome of Leptomantella tonkinae (Hebard, 1920) (Mantodea: Leptomantellidae) and its phylogeny.

The complete mitochondrial (mt) genome of Leptomantella tonkinae (Hebard, 1920) was 15,527 bp in length and contained 13 protein-coding genes, 22 transfer RNAs, two ribosomal RNAs, and one control region. The gene arrangement of mt genome of L. tonkinae was identical to the primitive mantis. The overall AT content of the mt genome was 74%. In ML and BI phylogenetic analyses, the monophyly of Leptomantellidae was robustly supported and the clade of Leptomantellidae is a sister clade to the group of (Gonypetidae+(Leptomantellidae+(Amorphoscelidae+Nanomantidae))).

Statistical analysis of PN clusters in Mo/VFe protein crystals using a bond valence method toward their electronic structures.

Nowadays, large numbers of MoFe proteins have been reported and their crystal data obtained by X-ray crystallography and uploaded to the Protein Data Bank (PDB). By big data analysis using a bond valence method, we make conclusions based on 79 selected PN in all 119 P-clusters of 53 MoFe proteins and 10 P-clusters of 5 VFe proteins from all deposited crystallographic data of the PDB. In the condition of MoFe protein crystals, the resting state PN clusters are proposed to have the formal oxidation state of 2Fe(iii)6Fe(ii), hiding two oxidized electron holes with high electron delocalization. The calculations show that Fe1, Fe2, Fe5, Fe6 and Fe7 perform unequivocally as Fe2+, and Fe3 is remarkably prone to Fe(iii), while Fe4 and Fe8 have different degrees of mixed valences. For PN clusters in VFe protein crystals, Fe1, Fe2, Fe4, Fe5 and Fe6 tend to be Fe2+, but the electron distributions rearrange with Fe7 and Fe8 being more oxidized mixed valences, and Fe3 presenting a little more reductive mixed valence than that in MoFe proteins. In terms of spatial location, Fe3 and Fe6 in P-clusters of MoFe proteins are calculated as the most oxidized and reduced irons, which have the shortest distances from homocitrate in the FeMo-cofactor and [Fe4S4] cluster, respectively, and thus could function as potential electron transport sites. This work shows different electron distributions of PN clusters in Mo/VFe protein crystals, from those obtained from previous data from solution with excess reducing agent from which it was concluded that PN clusters are all ferrous according to Mössbauer and electron paramagnetic resonance spectra.

Mitochondrial gene expression in different organs of Hoplobatrachus rugulosus from China and Thailand under low-temperature stress.

BACKGROUND: Hoplobatrachus rugulosus (Anura: Dicroglossidae) is distributed in China and Thailand and the former can survive substantially lower temperatures than the latter. The mitochondrial genomes of the two subspecies also differ: Chinese tiger frogs (CT frogs) display two identical ND5 genes whereas Thai tiger frogs (TT frogs) have two different ND5 genes. Metabolism of ectotherms is very sensitive to temperature change and different organs have different demands on energy metabolism at low temperatures. Therefore, we conducted studies to understand: (1) the differences in mitochondrial gene expression of tiger frogs from China (CT frogs) versus Thailand (TT frogs); (2) the differences in mitochondrial gene expression of tiger frogs (CT and TT frogs) under short term 24 h hypothermia exposure at 25 °C and 8 °C; (3) the differences in mitochondrial gene expression in three organs (brain, liver and kidney) of CT and TT frogs. RESULTS: Utilizing RT-qPCR and comparing control groups at 25 °C with low temperature groups at 8 °C, we came to the following results. (1) At the same temperature, mitochondrial gene expression was significantly different in two subspecies. The transcript levels of two identical ND5 of CT frogs were observed to decrease significantly at low temperatures (P < 0.05) whereas the two different copies of ND5 in TT frogs were not. (2) Under low temperature stress, most of the genes in the brain, liver and kidney were down-regulated (except for COI and ATP6 measured in brain and COI measured in liver of CT frogs). (3) For both CT and TT frogs, the changes in overall pattern of mitochondrial gene expression in different organs under low temperature and normal temperature was brain > liver > kidney. CONCLUSIONS: We mainly drew the following conclusions: (1) The differences in the structure and expression of the ND5 gene between CT and TT frogs could result in the different tolerances to low temperature stress. (2) At low temperatures, the transcript levels of most of mitochondrial protein-encoding genes were down-regulated, which could have a significant effect in reducing metabolic rate and supporting long term survival at low temperatures. (3) The expression pattern of mitochondrial genes in different organs was related to mitochondrial activity and mtDNA replication in different organs.

Metabolite trajectories across the perinatal period and mental health: A preliminary study of tryptophan-related metabolites, bile acids and microbial composition.

Depression and anxiety during pregnancy and postpartum are common, but affected women differ in timing, trajectories, and extent of symptoms. The objective of this pilot, feasibility study is to analyze trajectories of serotonin and tryptophan-related metabolites, bile acid metabolites, and microbial composition, in relation to psychiatric history and current symptoms across the perinatal period. Serum and fecal samples were collected from 30 women at three times points in the perinatal period and assayed with LC-MS/MS and 16S sequencing respectively. We defined mean trajectories for each metabolite, clustered individuals by metabolite trajectories, tested associations between metabolites, and examined metabolite levels in relation to microbial composition. Findings of note include: (1) changes in kynurenine and the ratio of kynurenic acid to kynurenine from second trimester to third trimester were strongly associated with baseline primary and secondary bile acids. (2) Secondary bile acid UDCA and its conjugated forms were associated with lower bacterial diversity and levels of Lachnospiraceae, a taxa known to produce Short Chain Fatty Acids. (3) History of anxiety was associated with UDCA levels, but history of major depression was not associated with any of the bile acids. (4) There was a trend towards lower dietary fiber for those with history of anxiety or depression. Overall, our results reveal substantial temporal variation in tryptophan-related metabolites and in bile acid metabolites over the perinatal period, with marked inter-individual variability. Trajectories of TRP -related metabolites, primary and secondary bile acids, and the absence or presence of microbes that produce Short Chain Fatty Acids (SCFAs) considered in concert have the potential to differentiate individuals based on perinatal adaptations that may impact mental and overall health.

The complete mitochondrial genome of Rana johnsi (Smith, 2009) (Anura: Ranidae) and its phylogeny.

Rana johnsi (Smith 2009) firstly considered as the member of genus Pseudorana, has been moved into the genus Rana. In this study, we sequenced the complete mitochondrial (mt) genome of R. johnsi using the Sanger method. The circular mt genome was 17,873 bp in length and contains 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, two ribosome RNA genes, and one control region. The overall nucleotide composition in majority-strand was 28% A, 29% T, 29% C, and 14% G. We discussed the phylogenetic relationship of R. johnsi in genus Rana using ML and BI analyses based on 13 PCGs. Excluding the clade of subgenus Lithobates, Rana draytonii was the basal clade to all other Rana species, which included R. johnsi as the basal clade. The monophyly of genus Rana was supported, whereas Pseudorana was failed to support.

Isolated Mixed-Valence Iron Vanadium Malate and Its Metal Hydrates (M = Fe2+, Cu2+, Zn2+) with Reversible and Irreversible Adsorptions for Oxygen.

Isolated octanuclear iron-vanadium malate (NH4)3(CH3NH3)3[FeIII2VIV2VV4O11(mal)6]·7.5H2O (1; H3mal = malic acid) and its family of metal hydrates M'3n[MII(H2O)2]1.5n[FeIII2VIV2VV4O11(mal)6]n·xnH2O (2 or 2-Fe, M' = NH4+, M = Fe, x = 7.5; 3 or 3-Cu, M' = K+, M = Cu, x = 10; 4 or 4-Zn, M' = K+, M = Zn, x = 6.5) have been obtained by self-assembly in water. The cluster anion [Fe2V6O11(mal)6]6- (1a) shows an interesting iron bicapped-triangular-prismatic structure, which is bridged by M2+ hydrates (M = Fe, Cu, Zn) to construct isostructural metal organic frameworks (MOFs) 2-4. The mixed-valence vanadium systems in 1-4 were determined by theoretical bond valence calculations (BVS) and charge balance. The magnetic susceptibilities are further elucidated as high spin for Fe3+ in 1a and bridging Fe2+ in 2-Fe, respectively. A strong ferromagnetic interaction was also observed for 2-Fe at 3 K. 2-Fe, 3-Cu, and 4-Zn have similar hydrophilic channels with diameters of 6.8, 6.5, and 6.6 Å, respectively, which show obvious affinity for O2 in comparison with no adsorption of N2, H2, CO2, and CH4 at room temperature under different pressures. Moreover, 2-Fe and 4-Zn exhibit irreversible O2 absorptions, which may be attributed to charge transfer between O2 and open metal sites (OMSs) formed during vacuum heating pretreatment. UV-vis and EPR spectra show a change in electronic structure of 2-Fe after O2 adsorption. The reversible adsorption observed in 3-Cu suggests a weak interaction between O2 and Cu2+ due to the Jahn-Teller effect. The properties of gas adsorption provide an insight into the performances of small molecules in the channels constructed by synthetic octanuclear model compounds, which are related to the interactions between the gas substrate and the heterometal cluster in biology.

Novel bidentate oxovanadium(IV) glycolate, α-hydroxybutyrate and citrate with terpyridine and their conversions to nitrosyl products.

A series of monomeric α-hydroxycarboxylato oxovanadium(IV) complexes [VO(H2cit)(tpy)]·H2O (1) (H4cit = citric acid, tpy = 2,2':6',2-terpyridine), [VO(glyc)(tpy)]·5.5H2O (2) (H2glyc = glycolic acid) and [VO(α-hbut)(tpy)]·3H2O (3) (α-H2hbut = α-hydroxybutyratic acid) have been obtained from the reactions of vanadyl sulfate with α-hydroxycarboxylates and terpyridine in acidic solutions. These complexes feature bidentate citrate, glycolate or α-hydroxybutyrate respectively. The ligand chelates to vanadium atom through α-hydroxy (in 1) or α-alkoxy (in 2 and 3) and α-carboxy groups, while ß-carboxy groups of citrate in 1 are free to participate strong hydrogen bonds with neighboring citrate. With comparable chelation, 1 shares a similar V-Oα-hydroxy distance [2.168(1) Å] with that observed in FeV-cofactor [2.17 Å] [1]. Moreover, nitrosyl vanadium complexes [V(NO)(glyc)(tpy)]·3H2O (4) and [V(NO)(α-hbut)(tpy)]·4H2O (5) were obtained via reductions of synthetic solutions of 2 and 3 with hydroxylamine respectively. The terminal oxygen atoms were substituted by linear nitrosyl groups in 4 and 5. They were fully characterized by UV-vis, IR, EPR spectra, X-ray structural analyses and theoretical bond valence calculations.

Preliminary Assignment of Protonated and Deprotonated Homocitrates in Extracted FeMo-Cofactors by Comparisons with Molybdenum(IV) Lactates and Oxidovanadium Glycolates.

A similar pair of protonated and deprotonated mononuclear oxidovanadium glycolates [VO(Hglyc)(phen)(H2O)]Cl·2H2O (1) and [VO(glyc)(bpy)(H2O)] (2) and a mixed-(de)protonated oxidovanadium triglycolate (NH4)2[VO(Hglyc)2(glyc)]·H2O (3) were isolated and examined. The ≡C-O(H) (≡C-OH or ≡C-O) groups coordinated to vanadium were spectroscopically and structurally identified. The glycolate in 1 features a bidentate chelation through protonated α-hydroxy and α-carboxy groups, whereas the glycolate in 2 coordinates through deprotonated α-alkoxy and α-carboxy groups. The glycolates in 3 coordinate to vanadium through α-alkoxy or α-hydroxy and α-carboxy groups and thus have both protonated ≡C-OH and deprotonated ≡C-O bonds simultaneously. Structural investigations revealed that the longer protonated V-Oα-hydroxy bonds [2.234(2) Å and 2.244(2) Å] in 1 and 3 are close to those of FeV-cofactor (FeV-co) 2.17 Å1 (FeMo-co 2.17 Å2), while deprotonated V-Oα-alkoxy bonds [2, 1.930(2); 3, 1.927(2) Å] were obviously shorter. This shows a similar elongated trend as the Mo-O distances in the previously reported deprotonated vs protonated molybdenum lactates (Wang, S. Y. et al. Dalton Trans. 2018, 47, 7412-7421) and these vanadium and molybdenum complexes have the same local V/Mo-homocitrate structures as those of FeV/Mo-cos of nitrogenases. The IR spectra of these oxidovanadium and the previously synthesized molybdenum complexes including different substituted ≡C-O(H) model compounds show red-shifts for ≡C-OH vs ≡C-O alternation, which further assign the two IR bands of extracted FeMo-co at 1084 and 1031 cm-1 to ≡C-O and ≡C-OH vibrations, respectively. Although the structural data or IR spectra for some of the previously synthesized Mo/V complexes and extracted FeMo-co were measured earlier, this is the first time that the ≡C-O(H) coordinated peaks are assigned. The overall structural and IR results well suggest the coexistence of homocitrates coordinated with α-alkoxy (deprotonated) and α-hydroxy (protonated) groups in the extracted FeMo-co.

Wheel-Like Icosanuclear Peroxotitanate-A Stable Water-Soluble Catalyst for Oxygen Transfer Reactions.

Water-soluble wheel-like icosanuclear peroxotitanate K16[Ti20(µ-O)8(HO2)8(O2)12( R, R-tart)12]·52H2O (1) chelated by tartrate has been successfully isolated. As the largest peroxotitanate reported, {Ti20} features 20 (hydro)peroxo groups with three kinds of coordination modes in µ-η1:η2, µ-η2:η2, and η2 fashions. The cluster is stable in solution and solid states. It has been tested for the catalytic oxidations of methyl phenyl sulfide and pyridine with hydrogen peroxide, respectively, which shows reversible elimination and the addition of peroxo groups. This provides a rare example of well-characterized titanium peroxide for homogeneous catalysis and mechanism research.

Comparison of hydroxycarboxylato imidazole molybdenum(iv) complexes and nitrogenase protein structures: indirect evidence for the protonation of homocitrato FeMo-cofactors.

Glycolato and R,S-lactato imidazole molybdenum(iv) complexes [Mo3SO3(glyc)2(im)5]·im·H2O (1), Na2[Mo3SO3(R,S-lact)3(im)3]·10H2O (2), and [Mo6O10(R,S-lact)2(im)10]·16H2O (3) have been isolated and characterized (H2glyc = glycolic acid, H2lact = lactic acid, im = imidazole). α-Alkoxy coordination with molybdenum [Mo-Oα-alkoxy 1.993(7)av Å] in 1 and 2 showed obvious differences to their counterpart with α-hydroxy coordination [MoIV3S4(PPh3)3(Hlact)2(lact)] [2.204(4)av Å] as shown in M. N. Sokolov, S. A. Adonin, A. V. Virovets, P. A. Abramov, C. Vicent, R. Llusar and V. P. Fedin, Inorg. Chim. Acta, 2013, 395, 11-18. This was also true for the 36 reported structures of FeMo-cofactors in the RCSB protein data bank (Mo-Oav 2.272 Å), which can serve as indirect evidence for the protonation of homocitrate in FeMo-co. The C-OHα-hydroxy bonds were longer than the short C-Oα-alkoxy bonds. Trinuclear Mo3SO3 cores were stabilized by imidazoles and/or α-hydroxycarboxylates, whereas only two glycolates were present in 1. α-Hydroxycarboxylates in 1 and 2 acted as bidentate ligands of Mo(iv) atoms through α-alkoxy and α-carboxy groups, while the imidazoles coordinated monodentately with nitrogen atoms. The lactates in 3 coordinated with Mo(iv) atoms through two oxygen atoms of α-carboxy groups, leaving the α-hydroxy group free. Furthermore, novel hexanuclear oxomolybdenum(v) malate Na6[(Mo2O4)3(mal)4]·5H2O (4) was also isolated (H3mal = malic acid). Solid-state and solution 13C NMR resonances of carbon atoms in α-alkoxy groups appeared in a high-field region (71.6, 77.4 ppm), indicating that α-alkoxy groups were easy to protonate.