The structure and biosynthesis of heinamides A1-A3 and B1-B5, antifungal members of the laxaphycin lipopeptide family

Laxaphycins are a family of cyclic lipopeptides with synergistic antifungal and antiproliferative activities. They are produced by multiple cyanobacterial genera and comprise two sets of structurally unrelated 11- and 12-residue macrocyclic lipopeptides. Here, we report the discovery of new antifungal laxaphycins from Nostoc sp. UHCC 0702, which we name heinamides, through antimicrobial bioactivity screening. We characterized the chemical structures of eight heinamide structural variants A1-A3 and B1-B5. These variants contain the rare non-proteinogenic amino acids 3-hydroxy-4-methylproline, 4-hydroxyproline, 3-hydroxy-d-leucine, dehydrobutyrine, 5-hydroxyl beta-amino octanoic acid, and O-carbamoyl-homoserine. We obtained an 8.6-Mb complete genome sequence from Nostoc sp. UHCC 0702 and identified the 93 kb heinamide biosynthetic gene cluster. The structurally distinct heinamides A1-A3 and B1-B5 variants are synthesized using an unusual branching biosynthetic pathway. The heinamide biosynthetic pathway also encodes several enzymes that supply non-proteinogenic amino acids to the heinamide synthetase. Through heterologous expression, we showed that (2S,4R)-4-hydroxy-l-proline is supplied through the action of a novel enzyme LxaN, which hydroxylates l-proline. 11- and 12-residue heinamides have the characteristic synergistic activity of laxaphycins against Aspergillus flavus FBCC 2467. Structural and genetic information of heinamides may prove useful in future discovery of natural products and drug development.Peer reviewe

Biochemical characterization of a cyanobactin arginine-N-prenylase from the autumnalamide biosynthetic pathway

Cyanobactins are linear and cyclic post-translationally modified peptides. Here we show that the prenyl-D-Arg-containing autum-nalamide A is a member of the cyanobactin family. Biochemical assays demonstrate that the AutF prenyltransferase targets the guanidinium moiety in arginine and homoarginine and is a useful tool for biotechnological applications.Peer reviewe

Ventricular flow analysis and its association with exertional capacity in repaired tetralogy of Fallot: 4D flow cardiovascular magnetic resonance study

Background: Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) allows quantification of biventricular blood flow by flow components and kinetic energy (KE) analyses. However, it remains unclear whether 4D flow parameters can predict cardiopulmonary exercise testing (CPET) as a clinical outcome in repaired tetralogy of Fallot (rTOF). Current study aimed to (1) compare 4D flow CMR parameters in rTOF with age- and gender-matched healthy controls, (2) investigate associations of 4D flow parameters with functional and volumetric right ventricular (RV) remodelling markers, and CPET outcome. Methods: Sixty-three rTOF patients (14 paediatric, 49 adult; 30 ± 15 years; 29 M) and 63 age- and gender-matched healthy controls (14 paediatric, 49 adult; 31 ± 15 years) were prospectively recruited at four centers. All underwent cine and 4D flow CMR, and all adults performed standardized CPET same day or within one week of CMR. RV remodelling index was calculated as the ratio of RV to left ventricular (LV) end-diastolic volumes. Four flow components were analyzed: direct flow, retained inflow, delayed ejection flow and residual volume. Additionally, three phasic KE parameters normalized to end-diastolic volume (KEi EDV), were analyzed for both LV and RV: peak systolic, average systolic and peak E-wave. Results: In comparisons of rTOF vs. healthy controls, median LV retained inflow (18% vs. 16%, P = 0.005) and median peak E-wave KEi EDV (34.9 µJ/ml vs. 29.2 µJ/ml, P = 0.006) were higher in rTOF; median RV direct flow was lower in rTOF (25% vs. 35%, P < 0.001); median RV delayed ejection flow (21% vs. 17%, P < 0.001) and residual volume (39% vs. 31%, P < 0.001) were both greater in rTOF. RV KEi EDV parameters were all higher in rTOF than healthy controls (all P < 0.001). On multivariate analysis, RV direct flow was an independent predictor of RV function and CPET outcome. RV direct flow and RV peak E-wave KEi EDV were independent predictors of RV remodelling index. Conclusions: In this multi-scanner multicenter 4D flow CMR study, reduced RV direct flow was independently associated with RV dysfunction, remodelling and, to a lesser extent, exercise intolerance in rTOF patients. This supports its utility as an imaging parameter for monitoring disease progression and therapeutic response in rTOF. Clinical Trial Registrationhttps://www.clinicaltrials.gov. Unique identifier: NCT03217240

W6+ & Br- codoped Li4Ti5O12 anode with super rate performance for Li-ion batteries

We report a novel Li4Ti5-xWxO12-xBrx (x = 0.025, 0.050 and 0.100) anode material simultaneously doped with W6+ and Br- ions prepared by a simple solid-state reaction in air, aiming to significantly improve electrical conductivity of Li4Ti5O12. Our theoretical calculation predicts that codoping with W6+ on the Ti4+ site and Br- on the O2- site can remarkably narrow down the band gap, and thus facilitate the electron transport in the lattice of LTO. The comparative experiments prove that W & Br-codoped LTO exhibits higher electrical conductivity compared with undoped LTO as expected, thus leading to improved rate capability and specific capacity. Particularly, Li4Ti5 xWxO12 xBrx (x = 0.05) exhibits the best rate capability and cycling stability with an outstanding capacity retention of 88.7% even at 10 C rate after 1000 cycles. This codoping strategy with high valence transition metal and halide ions holds promise to be applied to other insulating cathode materials suffering from inferior electrical conductivity

Ginsenoside Rh3 Inhibits Lung Cancer Metastasis by Targeting Extracellular Signal-Regulated Kinase: A Network Pharmacology Study

Lung cancer has a high mortality rate and is very common. One of the main reasons for the poor prognosis of patients with lung cancer is the high incidence of metastasis. Ginsenoside Rh3, a rare ginsenoside extracted from Panax notoginseng, exhibits excellent anti-inflammatory and anti-tumor effects. Nonetheless, the inhibitory potential of Rh3 against lung cancer remains unknown. The target genes of Rh3 were screened by the PharmMapper database; the proliferation of lung cancer cells was detected by MTT assay; the migration and invasion of cells were detected by the Transwell method; and the expression of extracellular signal-regulated kinase (ERK) and EMT-related proteins in vivo and in vitro were detected by Western blotting. In addition, we established a lung metastasis model in nude mice using A549 cells to assess the effect of Rh3 on NSCLC tumor metastasis in vivo. Our findings suggest that Rh3 significantly inhibited lung cancer metastasis both in vivo and in vitro. It was determined by flow cytometry analysis that Rh3 notably inhibited cell proliferation by blocking the G1 phase. In addition, Rh3 inhibited metastasis in lung cancer cells and regulated the expression of metastasis-related proteins under hypoxia. Mechanistic studies suggested that Rh3 targeted ERK to inhibit lung cancer metastasis. The ERK inhibitor U0126 or siRNA-mediated knockdown of ERK had an enhanced effect on Rh3&rsquo;s ability to inhibit lung cancer metastasis. The studies revealed that the inhibitory effect of Rh3 on the metastatic ability of lung cancer cells may be supported by ERK-related signaling pathways

Vitamin D Status and Related Factors in Newborns in Shanghai, China

With the increasing recognition of the importance of the non-skeletal effects of vitamin D (VitD), more and more attention has been drawn to VitD status in early life. However, the VitD status of newborns and factors that influence VitD levels in Shanghai, China, remain unclear. A total of 1030 pregnant women were selected from two hospitals in Shanghai, one of the largest cities in China located at 31 degrees north latitude. Umbilical cord serum concentrations of 25-hydroxy vitamin D [25(OH)D] were measured by LC-MS-MS, and questionnaires were used to collect information. The median cord serum 25(OH)D concentration was 22.4 ng/mL; the concentration lower than 20 ng/mL accounted for 36.3% of the participants, and the concentration lower than 30 ng/mL for 84.1%. A multivariable logistic regression model showed that the determinants of low 25(OH)D status were being born during autumn or winter months and a lack of VitD-related multivitamin supplementation. The relative risk was 1.7 for both autumn (95% CI, 1.1–2.6) and winter (95% CI, 1.1–2.5) births (p &lt; 0.05). VitD-related multivitamin supplementation more than once a day during pregnancy reduced the risk of VitD deficiency [adjusted OR (aOR) = 0.6, 95% CI (0.45–1.0) for VitD supplementation] (p &lt; 0.05). VitD deficiency and insufficiency are common in newborns in Shanghai, China, and are independently associated with season and VitD supplementation. Our findings may assist future efforts to correct low levels of 25(OH)D in Shanghai mothers and their newborn children

Cardiac involvement in patients recovering from Delta Variant of COVID‐19: a prospective multi‐parametric MRI study

Abstract Aims The cardiac injury and sequelae of Delta Variant of coronavirus disease 2019 (COVID‐19) remain unknown. This study aimed to evaluate the presence of cardiac involvement in patients recovering from Delta Variant of COVID‐19 based on multi‐parametric cardiac magnetic resonance imaging (MRI). Methods and results We prospectively assessed patients recovering from Delta Variant of COVID‐19 using multi‐parametric cardiac magnetic resonance imaging (MRI) between June 2021 and July 2021. Comparison was made with 25 healthy controls. Forty‐four patients (median age 51 years, 28 women) recovering from Delta Variant were recruited and had a median time of 35 days between diagnosis and cardiac MRI. There were no patients with chest pain (0/44, 0%) and high sensitivity cardiac troponin T troponin elevation (median levels 2.20 pg/mL, IQR levels 0.85–4.40 pg/mL). Regarding the cardiac imaging findings, a total of 14 (32%) patients presented cardiac tissue feature abnormalities, and a total of 9 (20%) patients had a myocarditis‐like injury based on cardiac MRI 2018 Lake Louise criteria. When we further assessed the T1 and T2 mapping values for of patients' individual, abnormal raised global native T1, T2, and extracellular volume were seen in 6 (14%), 6 (14%), and 4 (9%) patients, respectively. Comparing with controls, the patients had lower LV global longitudinal strain and (−22.2 ± 2.8% vs. −24.6 ± 2.0%, P < 0.001) and global circumferential strain (−20.7 ± 6.8% vs. −24.3 ± 2.9%, P = 0.014), but higher global native T1 (1318.8 ± 55.5 ms vs. 1282.9 ± 38.1 ms, P = 0.006). Four (9%) patients presented myocardial late gadolinium enhancement with subepicardial pattern mostly common seen, and two (5%) patients presented pericardial enhancement. Conclusions The cardiac MRI could detect subclinical functional and myocardial tissue characteristic abnormalities in individuals who were recovering from Delta Variant without cardiac‐related clinical findings. The native T1 mapping and strain imaging may be a sensitive tool for the noninvasive detection of a subset of patients who are at risk for cardiac sequelae and more prone to myocardial damage in survivors with Delta Variant

Novel materials for Cr(VI)adsorption by magnetic titanium nanotubes coated phosphorene

The accumulation of Cr(VI)will cause mutagenic and carcinogenic effects on humans. Therefore, the standard regulations have been governed by the EPA to control the chromium content in the effluent and drinking water and have made it mandatory [1]. For the better recovery of the adsorbent; Magnetic nano particle based phosphorene titanium nano tubes were used for the first time in action which has been proven to be superior for the Chormium pollutants. MNP-PN-TNT (Magnetic nanoparticle-Phosphorene-Titanium nano tubes)was synthesized from hydrothermal method in this study. The prepared material is used for effective removal of Cr(VI)from the water by adsorption technique in acidic environment. The adsorption capacity was found to be 35 mg g −1 at the initial concentration of 50 mg L −1 maintainingthe temperature under 45 °C. The optimal operation condition is under pH 9, temperature of 25 °C, and dosage of 0.8 g L −1 obtained from RSM (Response Surface Methdology). The adsorption process of MNP-PN-TNT is conformed with a pseudo-second-order kinetic model. Cr(VI)adsorption behavior with MNP-PN-TNT, is spontaneous from the results of thermodynamics analysis. The adsorption mechanism of Cr(VI)with MNP-PN-TNT was evident by O1s, C1s, Cr 2p, Ti 2p, Fe 2p and P 2p of XPS. Cr(VI)is adsorbed with MNP-PN-TNT, in randomness during the adsorption process

Promoting Large-Area Slot-Die-Coated Perovskite Solar Cell Performance and Reproducibility by Acid-Based Sulfono-γ-AApeptide

Homogeneous and pinhole-free large-area perovskite films are required to realize the commercialization of perovskite modules and panels. Various large-area perovskite coatings were developed; however, at their film coating and drying stages, many defects were formed on the perovskite surface. Consequently, not only the devices lost substantial performance but also their long-term stability deteriorated. Here, we fabricated a compact and uniform large-area MAPbI3-perovskite film by a slot-die coater at room temperature (T) and at high relative humidity (RH) up to 40%. The control slot-die-coated perovskite solar cell (PSC) produced 1.082 V open-circuit voltage (Voc), 24.09 mA cm–2 short current density (Jsc), 71.13% fill factor (FF), and a maximum power conversion efficiency (PCE) of 18.54%. We systematically employed a multi-functional artificial amino acid (F-LYS-S) to modify the perovskite defects. Such amino acids are more inclined to bind and adhere to the perovskite defects. The amino, carbonyl, and carboxy functional groups of F-LYS-S interacted with MAPbI3 through Lewis acid–base interaction and modified iodine vacancies significantly. Fourier transform infrared spectroscopy revealed that the C═O group of F-LYS-S interacted with the uncoordinated Pb2+ ions, and X-ray photoelectron spectroscopy revealed that the lone pair of −NH2 coordinated with the uncoordinated Pb2+ and consequently modified the I– vacancies remarkably. As a result, the F-LYS-S-modified device demonstrated more than three-fold charge recombination resistance, which is one of the primary requirements to fabricate high-performance PSCs. Therefore, the device fabricated employing F-LYS-S demonstrated remarkable PCE of 21.08% with superior photovoltaic parameters of 1.104 V Voc, 24.80 mA cm–2 Jsc, and 77.00%. FF. Concurrently, the long-term stability of the PSCs was improved by the F-LYS-S post-treatment, where the modified device retained ca. 89.6% of its initial efficiency after storing for 720 h in air (T ∼ 27 °C and RH ∼ 50–60%)

Direct pathway cloning and expression of the radiosumin biosynthetic gene cluster

Radiosumins are a structurally diverse family of low molecular weight natural products that are produced by cyanobacteria and exhibit potent serine protease inhibition. Members of this family are dipeptides characterized by the presence of two similar non-proteinogenic amino acids. Here we used a comparative bioinformatic analysis to identify radiosumin biosynthetic gene clusters from the genomes of 13 filamentous cyanobacteria. We used direct pathway cloning to capture and express the entire 16.8 kb radiosumin biosynthetic gene cluster from Dolichospermum planctonicum UHCC 0167 in Escherichia coli. Bioinformatic analysis demonstrates that radiosumins represent a new group of chorismate-derived non-aromatic secondary metabolites. High-resolution liquid chromatography-mass spectrometry, nuclear magnetic resonance spectroscopy and chemical degradation analysis revealed that cyanobacteria produce a cocktail of novel radiosumins. We report the chemical structure of radiosumin D, an N-methyl dipeptide, containing a special Aayp (2-amino-3-(4-amino-2-cyclohexen-1-ylidene) propionic acid) with R configuration that differs from radiosumin A-C, an N-Me derivative of Aayp (Amyp) and two acetyl groups. Radiosumin C inhibits all three human trypsin isoforms at micromolar concentrations with preference for trypsin-1 and -3 (IC50 values from 1.7 mu M to >7.2 mu M). These results provide a biosynthetic logic to explore the genetic and chemical diversity of the radiosumin family and suggest that these natural products may be a source of drug leads for selective human serine proteases inhibitors.Peer reviewe