bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and properties of novel poly(ether ketone ketone)s containing 1,4‐naphthylene units by electrophilic solution copolycondensation
Authors: Wei Li , Wang Guixia , Cai Mingzhong
Published: January 2021

Semicrystalline poly(aryl ether ketone)s (PAEKs) represent an industrially important class of high‐performance engineering thermoplastics with excellent physicochemical and mechanical properties, and the synthesis of PAEKs with enhanced glass transition temperatures (Tg) and moderate melting temperatures (Tm) is highly desirable. In the work reported, novel poly(ether ketone ketone)s (PEKKs) containing 1,4‐naphthylene units in main chains were synthesized by Friedel–Crafts solution copolycondensation of terephthaloyl chloride with a mixture of diphenyl ether and 1,4‐di(4‐phenoxybenzoyl)naphthalene (1,4‐DPOBN). The polymerization proceeded smoothly in 1,2‐dichloroethane in the presence of anhydrous AlCl3andN‐methylpyrrolidone under mild conditions and afforded polymers having inherent viscosities of 0.66–0.98 dL g−1. The polymers with 5–30 mol% 1,4‐DPOBN are semicrystalline and have obviously enhancedTgover commercial poly(ether ether ketone)s and PEKKs due to the incorporation of rigid and bulky 1,4‐naphthylene moieties into the main chain. The polymers with 20–30 mol% 1,4‐DPOBN not only have highTgof 175–177 °C, but also relatively lowTmof 331–336 °C, having high potential for melt processing. The polymers with 20–30 mol% 1,4‐DPOBN also exhibit excellent thermal stability and good mechanical and solvent‐resistance properties. © 2021 Society of Chemical Industry
Photosynthesis of polymer networks with controlled properties by dimerization of cinnamoyl groups
Authors: Gadek Magdalena , Strachota Beata , Matějka Libor
Published: January 2021

Photosensitive monomers/polymers/copolymers containing a variable amount of cinnamoyl (Ci) groups ranging from 3 up to 480 per molecule were synthesized. These precursors were photocrosslinked by irradiation with UV light of wavelength 320–380 nm via the photodimerization of the Ci units. The evolution of conversion, gel fraction, modulus and Tg during irradiation was followed. Two types of photosensitive systems were studied: (i) a blend of photosensitive precursors of different functionality fCi and (ii) copolymers with a different content of Ci units and Tg. The control of the precursors' structure and composition as well as photocuring time period make it possible to finely tune the properties of the formed polymer network films. The prepared photocrosslinked networks show a very broad range of thermomechanical properties with Tg from −25 °C up to 135 °C and moduli over a range of three orders of magnitude. © 2021 Society of Chemical Industry
Template‐free electrochemically polymerized polypyrrole nanowires and their application in flexible solid‐state supercapacitors
Authors: Chen Ruyi , Zhong Jiang , Zhu Huifang , Tang Chunmi , Qiao Yongluo , Fu Changqing , Wang Jinglan , Shen Liang , He Haifeng , Gao Fei
Published: January 2021

Treated carbon cloths combined with polypyrrole (PPy) nanowires (TCC@PPyW) were fabricated by template‐free electrochemical deposition of pyrrole in the presence of sodium citrate dihydrate and sodium perchlorate. The morphologies and electrochemical performances of the samples were studied using scanning electron microscopy, cyclic voltammetry, galvanostatic charge–discharge measurements and electrochemical impedance spectroscopy. The morphologies of PPy nanostructure were controlled by regulating interfacial pH, deposition time and concentration of sodium perchlorate. PPy nanorods were generated with the aid of water oxidation when the pH of pyrrole solution was 7.9, and PPy nanowires could be obtained by increasing the deposition time or the concentration of sodium perchlorate. The resulting PPy nanowires were about 100 nm in diameter and up to 600 nm in length. TCC@PPyW electrodes provided a large contact area for electrolyte, which facilitated the rapid delivery of electric charge. As a result, the TCC@PPyW electrodes exhibited a high areal specific capacitance of 841.2 mF cm−2 at 0.4 mA cm−2 and a high energy density of 420.6 μWh cm−2 at a power density of 0.2 mW cm−2. An all‐solid‐state flexible symmetric supercapacitor without any binder, incorporated with TCC@PPyW as electrodes and poly(vinyl alcohol)–LiCl gel as gel electrolyte, is also reported. The TCC@PPyW supercapacitor displayed excellent flexibility and rate capability. © 2021 Society of Chemical Industry
Trans‐limonenedioxide, a promisingbio‐basedepoxy monomer
Authors: Schutz Louis , Kazemi Forouzan , Mackenzie Elby , Bergeron Jean‐Yves , Gagnon Eric , Claverie Jerome P.
Published: January 2021

Vast quantities of the natural terpene (R)‐limonene can be collected from food waste. Epoxidation of its two double bonds provides limonene dioxide (LDO), a difunctional epoxy monomer. However, LDO is a mixture of four isomers, two of which (trans‐LDO) are actually difunctional while the others (cis‐LDO) have one epoxide group which is significantly less reactive, as revealed by Fourier transformed infrared spectroscopic analysis of formulations cross‐linked with polyethylene imine. These results are also confirmed when preparing epoxy formulations using respectivelycisortransisomers. From DFT calculations, the reactivity of each epoxide group of LDO has been assessed in model reactions with primary and secondary amines, in the presence of amine or alcohol hydrogen‐bond donors. The kinetics of cross‐linking has also been probed by differential scanning calorimetry. As measured by dynamic mechanical analysis, the resulting epoxy resins based ontransisomers have a storage modulus ofca1GPa at room temperature and a glass transition temperature (Tg) of 70°C. These results demonstrate thattransLDO is a promising bio‐based epoxy monomer, which could be used as an alternative to petroleum‐based epoxy monomers.
Longitudinal predictors of caregiver resilience outcomes at the end of childhood cancer treatment
Authors: Barakat Lamia P. , Madden Rebecca E. , Vega Gabriela , Askins Martha , Kazak Anne E.
Published: January 2021

Objective

Caregiver resilience in the context of childhood cancer treatment has been described using cross‐sectional and retrospective studies, but little is known about prospective predictors of resilience outcomes. We examined associations of demographics, cancer‐related variables, and intrapersonal and interpersonal factors at diagnosis (family psychosocial risk, perceived social support, and healthcare self‐efficacy) and psychosocial services provided during treatment with caregiver resilience outcomes at the end of treatment.

Methods

For a study validating a family psychosocial risk screener, 314 primary caregivers completed the measures at diagnosis of their child (aged 0–17 years) and when cancer treatment ended. Resilience outcomes were ratings of distress, posttraumatic stress, and posttraumatic growth. Multiple regression analyses evaluated the relative contribution of hypothesized predictors.

Results

Caregivers endorsed clinically significant distress, moderate posttraumatic growth, and low posttraumatic stress based on norms. Posttraumatic growth was not associated with posttraumatic stress or distress, which were significantly associated with each other. Over and above resilience at diagnosis, family psychosocial risk was associated with resilience at the end of treatment. Perceived social support, healthcare self‐efficacy, and psychosocial services provided demonstrated associations with resilience in univariate analyses, but demographics and cancer‐related variables did not.

Conclusions

Resilience and family psychosocial risk at diagnosis were the strongest predictors of caregiver resilience outcomes at the end of the treatment. Intrapersonal and interpersonal predictors were weaker and varied by resilience measure. Consistent with psychosocial standards of care, broad evaluation of caregiver risks, resources, and resilience processes and outcomes is recommended at diagnosis and through the treatment trajectory including the end of treatment.
Entering the era of highly effective modulator therapies
Authors: Dave Kavita , Dobra Rebecca , Scott Sandra , Saunders Clare , Matthews Jess , Simmonds Nicholas J. , Davies Jane C.
Published: January 2021

Since the discovery of the gene responsible for cystic fibrosis (CF) in 1989, hopes have been pinned on a future with novel therapies tackling the basis of the disease rather than its symptoms. These have become a reality over the last decade with the development through to the clinic of CF transmembrane conductance regulator (CFTR) modulators. These are oral drugs which improve CFTR protein function through either increasing the time the channel pore is open (potentiators) or facilitating its trafficking through the cell to its location on the cell membrane (correctors). The first potentiator, ivacaftor, is now licensed and available clinically in many parts of the world. It is highly effective with impressive clinical impact in the lungs and gastrointestinal tract; longer‐term data from patient registries show fewer exacerbations, a slower rate of lung function loss and reduced need for transplantation in patients receiving ivacaftor. However, as a single drug, it is suitable for only a small minority of patients. The commonest CFTR mutation, F508del, requires both correction and potentiation for clinical efficacy. Two dual‐agent drugs (lumacaftor/ivacaftor and tezacaftor/ivacaftor) have progressed through to licensing, although their short term impact is more modest than that of ivacaftor; this is likely due to only partial correction of protein misfolding and trafficking. Most recently, triple compounds have been developed: two different corrector molecules (elexacaftor and tezacaftor) which, by addressing different regions in the misfolded F508del protein, more effectively improve trafficking. In addition to large improvements in clinical outcomes in people with two copies of F508del, the combination is sufficiently effective that it works in patients with only one copy of F508del and a second, nonmodulator responsive mutation. For the first time, we thus have a drug suitable for around 85% of people with CF. Even more gains are likely to be possible when these drugs can be used in younger children, although more sensitive outcome measures are needed for this age group. Special consideration is needed for people with very rare mutations; those with nonmodulatable mutation combinations will likely require gene or messenger RNA‐based therapeutic approaches, many of which are being explored. Although this progress is hugely to be celebrated, we still have more work to do. The international collaboration between trials networks, pharma, patient organizations, registries, and people with CF is something we are all rightly proud of, but innovative trial design and implementation will be needed if we are to continue to build on this progress and further develop drugs for people with CF.
Tracheal anomalies associated with Down syndrome: A systematic review
Authors: Fockens M. Matthijs , Hölscher Michiel , Limpens Jacqueline , Dikkers Frederik G.
Published: January 2021

Introduction

Airway anomalies are accountable for a substantial part of morbidity and mortality in children with Down syndrome (DS). Although tracheal anomalies occur more often in DS children, a structured overview on the topic is lacking. We systematically reviewed the characteristics of tracheal anomalies in DS children.

Methods

A MEDLINE and EMBASE search for DS and tracheal anomalies was performed. Tracheal anomalies included tracheal stenosis, complete tracheal ring deformity (CTRD), tracheal bronchus, tracheomalacia, tracheal web, tracheal agenesis or atresia, laryngotracheoesophageal cleft type 3 or 4, trachea sleeve, and absent tracheal rings.

Results

Fifty‐nine articles were included. The trachea of DS children is significantly smaller than non‐DS children. Tracheomalacia and tracheal bronchus are seen significantly more often in DS children. Furthermore, tracheal stenosis, CTRD, and tracheal compression by vascular structures are seen regularly in children with DS. These findings are reflected by the significantly higher frequency of tracheostomy and tracheoplasty performed in DS children.

Conclusion

In children with DS, tracheal anomalies occur more frequently and tracheal surgery is performed more frequently than in non‐DS children. When complaints indicative of tracheal airway obstruction like biphasic stridor, dyspnea, or wheezing are present in children with DS, diagnostic rigid laryngotracheobronchoscopy with special attention to the trachea is indicated. Furthermore, imaging studies (computed tomography, magnetic resonance imaging, and ultrasound) play an important role in the workup of DS children with airway symptoms. Management depends on the type, number, and extent of tracheal anomalies. Surgical treatment seems to be the mainstay in severe cases.
Heart failure is not a determinant of central sleep apnea in the pediatric population
Authors: Wheeler Jonathan A. , Tutrow Kaylee D. , Ebenroth Eric S. , Gaston Benjamin , Bandyopadhyay Anuja
Published: January 2021

Background/Objectives

Adults with heart failure (HF) have high prevalence of central sleep apnea (CSA). While this has been repeatedly investigated in adults, there is a deficiency of similar research in pediatric populations. The goal of this study was to compare prevalence of CSA in children with and without HF and correlate central apneic events with heart function.

Methods

Retrospective analysis of data from children with and without HF was conducted. Eligible children were less than 18 years old with echocardiogram and polysomnogram within 6 months of each other. Children were separated into groups with and without HF based on left ventricular ejection fraction (LVEF). Defining CSA as central apnea‐hypopnea index (CAHI) more than 1/hour, the cohort was also classified into children with and without CSA for comparative study.

Results

A total of 120 children (+HF: 19, −HF: 101) were included. The +HF group was younger, with higher prevalence of trisomy 21, muscular dystrophy, oromotor incoordination, and structural heart disease. The +HF group had lower apnea‐hypopnea index (median: 3/hour vs. 8.6/hour) and lower central apnea index (CAI) (median: 0.2/hour vs. 0.55/hour). Prevalence of CSA was similar in both groups (p = .195). LogCAHI was inversely correlated to age (Pearson correlation coefficient: −0.245, p = .022). Children with CSA were younger and had higher prevalence of prematurity (40% vs. 5.3%). There was no significant difference in LVEF between children with and without CSA. After excluding children with prematurity, relationship between CAHI and age was no longer sustained.

Conclusions

In contrast to adults, there is no difference in prevalence of CSA in children with and without HF. Unlike in adults, LVEF does not correlate with CAI in children. Overall, it appears that central apneic events may be more a function of age and prematurity rather than of heart function.
Necrotizing pneumonia among Italian children in the pneumococcal conjugate vaccine era
Authors: Carloni Ines , Ricci Silvia , Rubino Chiara , Cobellis Giovanni , Rinaldelli Giampaolo , Azzari Chiara , de Benedictis Fernando M.
Published: January 2021

Background

Necrotizing pneumonia (NP) is a severe complication of community‐acquired pneumonia. The impact of 13‐valent pneumococcal conjugate vaccine (PCV13) on the epidemiology of NP in children has not been assessed.

Patients and methods

Medical records of children less than 18 years admitted with NP to two pediatric hospitals in Italy between 2005 and 2019 were reviewed. The following four periods were defined: 2005–2010 (pre‐PCV13), 2011–2013 (early post‐PCV13), 2014–2016 (intermediate post‐PCV13), and 2017–2019 (late post‐PCV13).

Results

Forty‐three children (median age, 44 months) were included. Most of them (93%) were previously healthy. No differences in age, sex, season of admission, comorbidity, clinical presentation, or hospital course were identified between pre‐PCV13 and post‐PCV13 periods. A significant decrease in the rate of NP‐associated hospitalizations was found between the early (1.5/1000 admissions/year) and the intermediate (0.35/1000 admissions/year) post‐PCV13 period (p = .001). An increased trend in admissions was found thereafter. Streptococcus pneumoniae was the most common agent detected in both periods (pre‐PCV13: 11/18, 61%; post‐PCV13: 13/25, 52%). Serotype 3 was the most common strain in both periods (pre‐PCV13: 3/11, 27%; post‐PCV13; 4/13, 31%). There were no changes in the etiology over time, but most patients with Streptococcus pyogenes or Staphylococcus aureus infection were admitted during the post‐PCV13 period.

Conclusions

The hospitalization rate for NP in children decreased a few years after the implementation of PCV13 immunization in Italy. However, an increased trend in admissions was found thereafter. S. pneumoniae was the most frequent causal agent in both pre‐ and post‐PCV13 periods. Pneumococcal serotypes were mainly represented by Strain 3.
Human SARS CoV‐2 spike protein mutations
Authors: Guruprasad Lalitha
Published: January 2021

The human spike protein sequences from Asia, Africa, Europe, North America, South America, and Oceania were analyzed by comparing with the reference severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) protein sequence from Wuhan‐Hu‐1, China. Out of 10333 spike protein sequences analyzed, 8155 proteins comprised one or more mutations. A total of 9654 mutations were observed that correspond to 400 distinct mutation sites. The receptor binding domain (RBD) which is involved in the interactions with human angiotensin‐converting enzyme‐2 (ACE‐2) receptor and causes infection leading to the COVID‐19 disease comprised 44 mutations that included residues within 3.2 Å interacting distance from the ACE‐2 receptor. The mutations observed in the spike proteins are discussed in the context of their distribution according to the geographical locations, mutation sites, mutation types, distribution of the number of mutations at the mutation sites and mutations at the glycosylation sites. The density of mutations in different regions of the spike protein sequence and location of the mutations in protein three‐dimensional structure corresponding to the RBD are discussed. The mutations identified in the present work are important considerations for antibody, vaccine, and drug development.
Mycobacterium tuberculosis puromycin hydrolase displays a prolyl oligopeptidase fold and an acyl aminopeptidase activity
Authors: Zhao YuanHao , Feng Qiaoli , Zhou Xiao , Zhang Yan , Lukman Maxwell , Jiang Jie , Ruiz‐Carrillo David
Published: January 2021

Puromycin‐hydrolizing peptidases have been described as members of the prolyl oligopeptidase peptidase family. These enzymes are present across all domains of life but still little is known of the homologs found in the pathogenic bacterium Mycobacterium tuberculosis. The crystal structure of a M. tuberculosis puromycin hydrolase peptidase has been determined at 3 Angstrom resolution, revealing a conserved prolyl oligopeptidase fold, defined by α/β‐hydrolase and β‐propeller domains with two distinctive loops that occlude access of large substrates to the active site. The enzyme displayed amino peptidase activity with a substrate specificity preference for hydrophobic residues in the decreasing order of phenylalanine, leucine, alanine and proline. The enzyme's active site is lined by residues Glu564 for the coordination of the substrates amino terminal moiety and His561, Val608, Tyr78, Trp306, Phe563 and Ty567 for the accommodation of hydrophobic substrates. The availability of a crystal structure for puromycin hydrolase of M. tuberculosis shall facilitate the development of inhibitors with therapeutic applications.
The photocatalytic antibacterial molecular mechanisms towards Pseudomonas syringae pv. tabaci by g‐C3N4 nanosheets: insights from the cytomembrane, biofilm and motility disruption
Authors: Cai Lin , Jia Huanyu , He Lanying , Wei Xuefeng , Feng Hui , Fan Guangjin , Ma Xiaozhou , Ma Guanhua , Sun Xianchao
Published: January 2021

BACKGROUND

Antibacterial photocatalytic therapy has been employed as a promising strategy to combat antibiotic‐resistant bacteria in the water disinfection field, especially some non‐metal inorganic nanomaterials. However, their antibacterial activities on plant phytopathogens are poorly understood. Here, the photocatalytic antibacterial mechanism of the urea‐synthesized graphitic carbon nitride nanosheets (g‐C3N4 nanosheets) against Pseudomonas syringae pv. tabaci was systematically investigated in vitro and in vivo.

RESULTS

The g‐C3N4 nanosheets exhibited remarkable concentration‐dependent and irradiation‐time‐dependent antibacterial properties, and the 0.5 mg mL−1 concentration ameliorated tobacco wildfire disease in host plants. Specifically, under visible irradiation, g‐C3N4 nanosheets produced numerous reactive oxygen species (ROS), supplementing the plentiful extracellular and intracellular ROS in bacteria. After exposing light‐induced g‐C3N4 nanosheets for 1 h, 500 genes were differentially expressed, according to transcriptome analyses. Notably, the expression of genes related ‘antioxidant activity’ and ‘membrane transport’ was sharply upregulated, and those related to ‘bacterial chemotaxis’, ‘biofilm formation’, ‘energy metabolism’ and ‘cell motility’ were downregulated. After exposure for over 2 h, the longer‐time pressure on the target bacteria cause the decreased biofilm formation and flagellum motility, further injuring the cell membranes leading to cytoplasm leakage and damaged DNA, eventually resulting in the bacterial death. Concomitantly, the attachment of g‐C3N4 nanosheets was a synergistic physical antibacterial pathway. The infection capacity assessment also supported the earlier supposition.

CONCLUSION

These results provide novel insights into the photocatalytic antibacterial mechanisms of g‐C3N4 nanosheets at the transcriptome level, which are expected to be useful for dissecting the response pathways in antibacterial activities and for improving g‐C3N4‐based photocatalysts practices in plant disease control. © 2021 Society of Chemical Industry
Yacon as an alternative host plant for Encarsia formosa mass‐rearing: validating a multinomial theorem for bootstrap technique in life table research
Authors: Zhao Yue , Zhao Chun‐Li , Yang Xiangbing , Chi Hsin , Dai Peng , Desneux Nicolas , Benelli Giovanni , Zang Lian‐Sheng
Published: January 2021

BACKGROUND

Yacon (Smallanthus sonchifolius) is a broadleaf host plant suitable for rearing the greenhouse whitefly, Trialeurodes vaporariorum (Westwood). Here, the possibility of using yacon as an alternative host plant for production of the parasitoid, Encarsia formosa Gahan, one of the most important natural enemies of whiteflies, was explored. Data on the demographic characteristics, parasitism rate, and host‐feeding rate were collected and analyzed using the TWOSEX‐MSChart, CONSUME‐MSChart, and TIMING‐MSChart computer programs, and then contrasted with comparable data from the more commonly utilized host plant, tobacco.

RESULTS

Higher fecundity (F) (190.13 eggs/female) and more oviposition days (Od) (16.60 days) were observed in E. formosa when yacon was used as the host plant for rearing T. vaporariorum, compared with when tobacco was used (F = 150.13 eggs/female, Od = 15.27 days). The intrinsic rate of increase (r), finite rate of increase (λ), and net reproduction rate (R0) were significantly higher in E. formosa parasitizing T. vaporariorum reared on yacon compared with those parasitizing tobacco‐reared T. vaporariorum. Furthermore, the net host‐feeding rate (C0 = 40.87 prey/parasitoid), net killing rate (Z0 = 239.73 prey/parasitoid), and finite killing rate ( = 0.2560/day) for E. formosa on yacon‐reared whiteflies were significantly higher than those from tobacco‐reared whiteflies.

CONCLUSION

Our results showed that yacon is more suitable than tobacco as a host plant for mass‐rearing E. formosa for biological control programs to manage whiteflies. An innovative application of the multinomial theorem for calculating the exact probability of bootstrap samples in life table research was also introduced. © 2021 Society of Chemical Industry
Field validation of biocontrol strategies to control brown rot on stone fruit in several European countries
Authors: Casals Carla , Guijarro Belén , De Cal Antonieta , Torres Rosario , Usall Josep , Perdrix Víctor , Hilscher Ulrike , Ladurner Edith , Smets Tom , Teixidó Neus
Published: January 2021

BACKGROUND

Brown rot caused by Monilinia spp. is the most significant disease of stone fruit. New approaches to fruit production have necessitated the development of control strategies that are more eco‐ and consumer‐friendly. An efficient field strategy to control brown rot was previously designed based on the application of two biocontrol agents (BCAs), Bacillus amyloliquefaciens CPA‐8 (CPA‐8) or Penicillium frequentans 909 (Pf909), with calendar‐based treatment. In the present study, the strategy was validated on different stone fruit hosts in four producing countries over two seasons.

RESULTS

The results obtained were reported according to three different scenarios: Scenario 1, in which there was no presence of disease in the field; Scenario 2, in which high disease pressure occurred in the field and treatments (biologicals or chemicals) were not effective; and Scenario 3, with low or medium to high disease presence. The results were successful because, in general, BCA strategies were shown to control brown rot to a similar extent as chemicals strategies. We found that most of the trials conducted in this study were classed under Scenario 3 (62.5%), with only 12.5% and 25% of the trials classed under Scenarios 1 and 2, respectively.

CONCLUSION

These novel findings allowed the formulation of CPA‐8 and Pf909 as valuable tools for farmers to produce stone fruits more competitively and meet consumer demand for safer and more environmentally friendly products. © 2021 Society of Chemical Industry
Net charge tuning modulates the antiplasmodial and anticancer properties of peptides derived from scorpion venom
Authors: Pedron Cibele Nicolaski , Silva Adriana Farias , Torres Marcelo Der Torossian , Oliveira Cyntia Silva de , Andrade Gislaine Patricia , Cerchiaro Giselle , Pinhal Maria Aparecida Silva , de la Fuente‐Nunez Cesar , Oliveira Junior Vani Xavier
Published: January 2021

VmCT1, a linear helical antimicrobial peptide isolated from the venom of the scorpion Vaejovis mexicanus, displays broad spectrum antimicrobial activity against bacteria, fungi, and protozoa. Analogs derived from this peptide containing single Arg‐substitutions have been shown to increase antimicrobial and antiparasitic activities against Trypanossoma cruzi. Here, we tested these analogs against malaria, an infectious disease caused by Plasmodium protozoa, and assessed their antitumoral properties. Specifically, we tested VmCT1 synthetic variants [Arg]3‐VmCT1‐NH2, [Arg]7‐VmCT1‐NH2, and [Arg]11‐VmCT1‐NH2, against Plasmodium gallinaceum sporozoites and MCF‐7 mammary cancer cells. Our screen identified peptides [Arg]3‐VmCT1‐NH2 and [Arg]7‐VmCT1‐NH2 as potent antiplasmodial agents (IC50 of 0.57 and 0.51 μmol L−1, respectively), whereas [Arg]11‐VmCT1‐NH2 did not show activity against P. gallinaceum sporozoites. Interestingly, all peptides presented activity against MCF‐7 and displayed lower cytotoxicity toward healthy cells. We demonstrate that increasing the net positive charge of VmCT1, through arginine substitutions, modulates the biological properties of this peptide family yielding novel antiplasmodial and antitumoral molecules.
Tensile Creep Behavior and Microstructure Evolution of As‐Cast Mg–9.82Gd–0.38Zr Alloy at 250 °C
Authors: Qin He , Yang Guangyu , Zhang Lei , Ouyang Shuxia , Wang Chunhui , Jie Wanqi
Published: January 2021

Herein the tensile creep behavior and microstructure evolution of an as‐cast Mg–9.82Gd–0.38Zr alloy under different stresses at 250 °C are investigated. The results of creep test show that the creep strain and steady creep rate increase with the creep stress at 250 °C. The fitted stress exponent n value (4.4) and transmission electron microscopy analysis suggest that the steady creep is dominated by the dislocation climb and glide mechanisms together. At the primary stage, due to the segregation of the Gd content, a fine‐strengthening β′ phase precipitates near the α‐Mg grain boundary. Then the transformation of β′ precipitates to a needle‐like β phase, coarsening, and growth of the β phase toward the intragranular direction gradually deteriorate the creep resistance of the experimental alloy. Moreover, two kinds of precipitate‐free zones (PFZs) appear at the end of the secondary creep stage and the PFZs nearly perpendicular to the applied stress direction widen gradually because of the directional diffusion. The nucleation and propagation of creep crack along the cracked eutectic phase and PFZs lead to the greatly rising creep rate at the end of the tertiary creep stage, which eventually results in the intergranular creep fracture of the experimental alloy.
A weighted log‐rank test and associated effect estimator for cancer trials with delayed treatment effect
Authors: Yu Chang , Huang Xiang , Nian Hui , He Philip
Published: January 2021

The standard log‐rank test has been extended by adopting various weight functions. Cancer vaccine or immunotherapy trials have shown a delayed onset of effect for the experimental therapy. This is manifested as a delayed separation of the survival curves. This work proposes new weighted log‐rank tests to account for such delay. The weight function is motivated by the time‐varying hazard ratio between the experimental and the control therapies. We implement a numerical evaluation of the Schoenfeld approximation (NESA) for the mean of the test statistic. The NESA enables us to assess the power and to calculate the sample size for detecting such delayed treatment effect and also for a more general specification of the non‐proportional hazards in a trial. We further show a connection between our proposed test and the weighted Cox regression. Then the average hazard ratio using the same weight is obtained as an estimand of the treatment effect. Extensive simulation studies are conducted to compare the performance of the proposed tests with the standard log‐rank test and to assess their robustness to model mis‐specifications. Our tests outperform theGρ,γclass in general and have performance close to the optimal test. We demonstrate our methods on two cancer immunotherapy trials.
Oridonin interrupts cellular bioenergetics to suppress glioma cell growth by down‐regulating PCK2
Authors: Lin Jianhu , Wu Shanshan , Ye Sisi , Papa Akuetteh Percy David , Yang Jianjing , Huang Shengwei , Arthur Gifty , Zhuge Qichuan , Zhang Yu
Published: January 2021

We aim to evaluate the tumor metabolic suppressive activity of Oridonin (extract of Rabdosia rubescens) in glioma and elucidate its potential mechanism. Effects of Oridonin on U251/U87 cells were determined by CCK8, RTCA, colony formation, flow cytometry, wound healing, and Transwell assay. Xenograft tumor model to evaluate the effect of Oridonin on glioma cells in vivo. Cellular bioenergetics were measured by Seahorse. RNA‐seq was performed to screen potential biological pathways in Oridonin treated cells. Bioinformatics analysis of PCK2 in glioma was performed based on TCGA/CGGA. Endogenous PCK2 was knocked‐down by lentivirus packaged shRNA. We found Oridonin significantly inhibited cell growth in U251/U87 in vitro and in vivo. Both oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were decreased in Oridonin‐treated U251/U87 cells. Oridonin treatment led to PCK2 down‐regulation. Additionally, PCK2 was up‐regulated in higher grade glioma and correlated with poor outcomes. Furthermore, PCK2 depletion significantly inhibited cell growth and decreased OCR/ECAR in U251/U87 which coincided with the effects of Oridonin. Therefore, we evaluated the potent anti‐tumor property of Oridonin in glioma. Importantly, we demonstrated that PCK2 might be a novel target of Oridonin on glioma by inducing energy crisis and increasing oxidative stress.
An aqueous extract of Prunella vulgaris L. inhibits the growth of papillary thyroid carcinoma by inducing autophagy in vivo and in vitro
Authors: Song Jia , Zhang Zhengbao , Hu Youkun , Li Ziyin , Wan Yu , Liu Jiafei , Chu Xinwei , Wei Qinzhi , Zhao Min , Yang Xingfen
Published: January 2021

The continued global rise in papillary thyroid carcinoma (PTC) combined with potential adverse effects of regular treatments calls for an alternative therapy. Prunella vulgaris L. (PV) is commonly used as a herbal remedy for thyroid diseases in China, but its influence on PTC is unclear. This study investigated the effect of PV aqueous extract on PTC and its underlying mechanism using a mouse xenograft model and the human PTC cell line K1. PV suppressed tumor growth in PTC‐bearing mice at 0.05 and 0.1 g/kg bw, accompanied by improvements in autophagy‐related protein expressions in xenografts. In K1 cells, PV inhibited cell growth and induced autophagic flux, manifesting as changes in autophagy‐related proteins, the presence of autophagosomes, and a further increase in LC3‐II by co‐incubation with bafilomycin A1. Autophagy inhibitor 3‐methyladenine ameliorated the autophagic cell death caused by PV. The mammalian target of rapamycin (mTOR) activator MHY1485 blocked the antiproliferative activity of PV by regulating mTOR, unc‐51‐like autophagy activating kinase 1 (ULK1), autophagosomes formation, and autophagy‐related proteins. The adenosine monophosphate‐activated protein kinase (AMPK) inhibitor compound C attenuated PV‐induced inhibition of mTOR. Our results suggest that PV inhibits the growth of PTC in vivo and in vitro via autophagy, which is associated with the AMPK/mTOR/ULK1 pathway. Thus, PV has the potential to function as a therapeutic agent against PTC.
Comparison of acute and chronic effects of Bacopa monnieri, Ginkgo biloba, and Lavandula angustifolia and their mixture on learning and memory in mice
Authors: Rehman Mujeeb Ur , Ali Niaz , Jamal Muhammad , Kousar Rehana , Ishaq Muhammad , Awan Abdul Aleem , Hussain Iftekhar , Sherkheli Muhammad Azhar , ul Haq Rizwan
Published: January 2021

Forty‐seven million people are living with memory‐related disorders worldwide. Phytomedicines are gaining extensive interest in the treatment of these ailments. Memory‐enhancing (acute and chronic) potentials of commercial grade extracts of Bacopa monnieri (200 mg/kg, po), Ginkgo biloba (150 mg/kg, po), and Lavandula angustifolia (200 mg/kg, po) and their mixture (B. monnieri 100 mg/kg, G. biloba 75 mg/kg, and L. angustifolia 100 mg/kg, po) were compared for their synergistic/additive effects on the Morris water maze (MWM) test and elevated plus maze (EPM) test in scopolamine‐induced amnesia in mice. Escape latency and accumulative path length were significantly reduced both in acute (up to day 6) and chronic trials (days 8–14) in B. monnieri‐, G. biloba‐, and L. angustifolia‐treated animals and their mixtures (n = 8, p < .05) in MWM. Furthermore, in probe trials (acute on day 7 and chronic on day 15), the number of crossing‐overs at platform position and time spent in platform quadrant were significantly increased, while transfer latency in EPM was decreased in treated animals as compared to the saline group (n = 8, p < .05). The mixture showed synergistic effects on memory enhancement as compared to each extract individually in mice. Further studies may be carried out on the active compounds of B. monnieri at the cellular and molecular levels.
Rapid and direct detection of artificially aged papers employing easy ambient sonic‐spray ionization mass spectrometry
Authors: Oliveira Luan Felipe Campos , de Morais Damila Rodrigues , Correa Deleon Nascimento , de Morais Campêlo Jacqueline , Sussulini Alessandra , Eberlin Marcos Nogueira , Santos Jandyson Machado
Published: January 2021

Rationale

The effort to make fake documents look real leads to the use of crickets and beverages to produce artificially aged papers, as land titles, based on yellowing caused by the use of these methods. An old practice in Brazil, called “cricketing”, has led to the misappropriation of Brazilian land using these documents. We propose a rapid, simple, instantaneous and non‐destructive method to identify artificially aged papers by easy ambient sonic‐spray ionization mass spectrometry (EASI‐MS) analysis.

Methods

Three typical aging procedures were used to obtain artificially aged papers using coffee, cola drink, and crickets, with the papers being analyzed by EASI‐MS. Multivariate statistical analyses were performed on the data to find the sample groups and to study the most relevant ions of each ageing procedure. High‐resolution MS (HRMS) was used to obtain the exact masses and attribute formulae to relevant ions present in the samples.

Results

The combination of EASI‐MS and multivariate statistical analyses allowed us to identify the most relevant ions to classify the adulteration of documents and HRMS identified most of these relevant ions. TMS fingerprinting in combination with multivariate analysis also demonstrated that this approach can qualitatively differentiate all the examined paper samples.

Conclusions

We developed a cheap, fast and easy method that can help to elucidate counterfeit documents that have been artificially aged, helping to identify chemical additives and one that can be used in forensic laboratories.
Reagent and analyte ion hydrates in secondary electrospray ionization mass spectrometry (SESI‐MS), their equilibrium distributions and dehydration in an ion transfer capillary: Modelling and experiments
Authors: Dryahina Kseniya , Som Suman , Smith David , Španěl Patrik
Published: January 2021

Rationale

Secondary electrospray ionization (SESI) in a water spray environment at atmospheric pressure involves the reactions of hydrated hydronium reagent ions, H3O+(H2O)n, with trace analyte compounds in air samples. Understanding the formation and dehydration of reagent and analyte ions is the foundation for meaningful quantification of trace compounds by SESI‐mass spectrometry (MS).

Methods

A numerical model based on gas‐phase ion thermochemistry is developed that describes equilibria in H3O+(H2O)nreagent cluster ion distributions and ligand switching reactions with polar NH3molecules leading to equilibrated hydrated ammonium ions NH4+(H2O)m. The model predictions are compared with experimental results obtained using a cylindrical SESI source coupled to an ion‐trap mass spectrometer via a heated ion transfer capillary. Non‐polar isoprene, C5H8, was used to further probe the nature of the reagent ions.

Results

Equilibrium distributions of H3O+(H2O)nions and their reactions with NH3molecules have been characterized by the model in the near‐atmospheric pressure SESI source. NH3analyte molecules displace H2O ligands from the H3O+(H2O)nions at the collisional rate forming NH4+(H2O)mions, which travel through the heated ion transfer capillary losing H2O molecules. The data for variable NH3concentrations match the model predictions and the C5H8test substantiates the notion of dehydration in the heated capillary.

Conclusions

Large cluster ions formed in the SESI region are dehydrated to H3O+(H2O)1,2,3and NH4+(H2O)1,2while passing through the heated capillary, and considerable diffusion losses also occur. This phenomenon is also predicted for other polar analyte molecules, A, that can undergo similar switching reactions, thus forming AH+and AH+(H2O)manalyte ions.
The impact of phthalate on reproductive function in women with endometriosis
Authors: Chou Ya‐Ching , Tzeng Chii‐Ruey
Published: January 2021

Background

Endometriosis is a common gynecological condition in which stromal or glandular epithelium is implanted in extrauterine locations. Endometriosis causes detrimental effects on the granulosa cells, and phthalate interferes with the biological and reproductive function of endometrial cells at a molecular level.

Methods

This article retrospectively reviewed the studies on phthalate exposure and its relationship with endometriosis. A literature search was performed for scientific articles using the keywords “phthalate and endometriosis,” “endometriosis and granulosa cells,” “phthalate and granulosa cells,” and “phthalates and endometrial cells.”

Results

Endometriosis can affect cytokine production, steroidogenesis, cell cycle progression, expression of estrogen receptor‐α (ER‐α)/progesterone receptor (PR), and cause endoplasmic reticulum stress, senescence, apoptosis, autophagy, and oxidative stress in the granulosa cells. Mono‐n‐butyl phthalate (MnBP) alters the expression of cytokines, cell cycle‐associated genes, ovarian stimulation, steroidogenesis, and progesterone production. Several in vitro studies have demonstrated that phthalate caused inflammation, invasion, change in cytokines, increased oxidative stress, viability, resistance to hydrogen peroxide, and proliferation of endometrial cells.

Conclusion

This might provide new insights about the impact of phthalate on the pathogenesis of endometriosis and its consequences on the ovarian function.
Potential detrimental role of soluble ACE2 in severe COVID‐19 comorbid patients
Authors: Rahman Mohammad Mahmudur , Hasan Maruf , Ahmed Asif
Published: January 2021

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) enters the host cell by binding to angiotensin‐converting enzyme 2 (ACE2) receptor. Other important proteins involved in this process include disintegrin and metalloproteinase domain‐containing protein 17 (ADAM17) also known as tumour necrosis factor‐α‐converting enzyme and transmembrane serine protease 2. ACE2 converts angiotensin II (Ang II) to angiotensin (1–7), to balance the renin angiotensin system. Membrane‐bound ACE2 ectodomain shedding is mediated by ADAM17 upon viral spike binding, Ang II overproduction and in several diseases. The shed soluble ACE2 (sACE2) retains its catalytic activity, but its precise role in viral entry is still unclear. Therapeutic sACE2 is claimed to exert dual effects; reduction of excess Ang II and blocking viral entry by masking the spike protein. Nevertheless, the paradox is why SARS‐CoV‐2 comorbid patients struggle to attain such benefit in viral infection despite having a high amount of sACE2. In this review, we discuss the possible detrimental role of sACE2 and speculate on a series of events where protease primed or non‐primed virus–sACE2 complex might enter the host cell. As extracellular virus can bind many sACE2 molecules, sACE2 level could be reduced drastically upon endocytosis by the host cell. A consequential rapid rise in Ang II level could potentially aggravate disease severity through Ang II‐angiotensin II receptor type 1 (AT1R) axis in comorbid patients. Hence, monitoring sACE2 and Ang II level in coronavirus disease 2019 comorbid patients are crucial to ensure safe and efficient intervention using therapeutic sACE2 and vaccines.
Online learning‐based model predictive control with Gaussian process models and stability guarantees
Authors: Maiworm Michael , Limon Daniel , Findeisen Rolf
Published: January 2021

Model predictive control allows to provide high performance and safety guarantees in the form of constraint satisfaction. These properties, however, can be satisfied only if the underlying model, used for prediction, of the controlled process is sufficiently accurate. One way to address this challenge is by data‐driven and machine learning approaches, such as Gaussian processes, that allow to refine the model online during operation. We present a combination of an output feedback model predictive control scheme and a Gaussian process‐based prediction model that is capable of efficient online learning. To this end, the concept of evolving Gaussian processes is combined with recursive posterior prediction updates. The presented approach guarantees recursive constraint satisfaction and input‐to‐state stability with respect to the model–plant mismatch. Simulation studies underline that the Gaussian process prediction model can be successfully and efficiently learned online. The resulting computational load is significantly reduced via the combination of the recursive update procedure and by limiting the number of training data points while maintaining good performance.
Tracking control for lower limb rehabilitation robots based on polynomial nonlinear uncertain models
Authors: Li Ying , Ke Jin , Zeng Jianping
Published: January 2021

This paper aims to propose a novel idea for the modeling and trajectory tracking control of a lower limb rehabilitation robot. A polynomial nonlinear uncertain model is established to deal with the difficulty of accurate modeling for the lower limb rehabilitation robot with complex dynamic characteristics. A high‐order nonlinear disturbance observer (HONDO) is utilized to estimate the lumped disturbance with fast time‐varying and the corresponding observer gain matrix is obtained byH∞performance. Then an HONDO‐based composite tracking controller is designed to achieve good tracking performance of the lower limb rehabilitation robot. In addition, all solvability conditions can be directly handled by sum of squares programming, effectively avoiding the calculation problem. Finally, numerical simulations are conducted to verify the validity of the proposed method.
Fusion of neural networks, for LIDAR‐based evidential road mapping
Authors: Capellier Edouard , Davoine Franck , Cherfaoui Véronique , Li You
Published: January 2021

LIDAR sensors are usually used to provide autonomous vehicles with three‐dimensional representations of their environment. In ideal conditions, geometrical models could detect the road in LIDAR scans, at the cost of a manual tuning of numerical constraints, and a lack of flexibility. We instead propose an evidential pipeline, to accumulate road detection results obtained from neural networks. First, we introduce RoadSeg, a new convolutional architecture that is optimized for road detection in LIDAR scans. RoadSeg is used to classify individual LIDAR points as either belonging to the road, or not. Yet, such point‐level classification results need to be converted into a dense representation, that can be used by an autonomous vehicle. We thus second present an evidential road mapping algorithm, that fuses consecutive road detection results. We benefitted from a reinterpretation of logistic classifiers, which can be seen as generating a collection of simple evidential mass functions. An evidential grid map that depicts the road can then be obtained, by projecting the classification results from RoadSeg into grid cells, and by handling moving objects via conflict analysis. The system was trained and evaluated on real‐life data. A python implementation maintains a 10 Hz framerate. Since road labels were needed for training, a soft labeling procedure, relying lane‐level HD maps, was used to generate coarse training and validation sets. An additional test set was manually labeled for evaluation purposes. So as to reach satisfactory results, the system fuses road detection results obtained from three variants of RoadSeg, processing different LIDAR features.
An alternative formulation of Coxian phase‐type distributions with covariates: Application to emergency department length of stay
Authors: Rizk Jean , Walsh Cathal , Burke Kevin
Published: January 2021

In this article, we present a new methodology to model patient transitions and length of stay in the emergency department using a series of conditional Coxian phase‐type distributions, with covariates. We reformulate the Coxian models (standard Coxian, Coxian with multiple absorbing states, joint Coxian, and conditional Coxian) to take into account heterogeneity in patient characteristics such as arrival mode, time of admission, and age. The approach differs from previous research in that it reduces the computational time, and it allows the inclusion of patient covariate information directly into the model. The model is applied to emergency department data from University Hospital Limerick in Ireland, where we find broad agreement with a number of commonly used survival models (parametric Weibull and log‐normal regression models and the semiparametric Cox proportional hazards model).