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Diffusion dysfunction in severe convalescent COVID-19 patients of 6 to 9 months follo...
YU WANG
Yanfen Tang

YU WANG

and 8 more

April 06, 2022
Objective: To explore the long-term effects of SARS-Cov-2 infection on the pulmonary function in convalescent COVID-19 patients of 6 to 9 months follow-up in Beijing, China. Methods: 64 cases of COVID-19 patients were recruited for the study, discharged from the Beijing Ditan Hospital, Capital Medical University for 6 to 9 months. COVID-19 patients were divided into mild, moderate and severe groups. The pulmonary function tests, the novel coronavirus antibody (IgM and IgG), chest CT and blood tests were investigated during follow-up. Results: 31.2% (20/64) patients had pulmonary ventilation dysfunction and 35.9% (23/64) had diffusion dysfunction. In the severe group, 56.50% (13/23) individuals showed decreased diffusion function. The diffusion dysfunction of severe group was significant decreased than the moderate (P=0.021). Among 56 cases, the positive rate of IgG titers was 73.2% (41/56). The result of chest CT showed 55.4% (31/56) cases in nodules, 44.6% (25/56) in strip-like changes, 37.5% (21/56) in ground glass shadow. Patients were tended to have ground glass changes in the severe group, while nodules in the moderate group. Conclusion: For the 6 to 9 months in convalescent COVID-19 patients, 56.50% (13/23) severe patients had pulmonary diffusion dysfunction. In the convalescent COVID-19 patients, especially those with severe illness, should have their pulmonary function tested regularly.
A systematic literature review to identify ethical, legal and social responsibilities...
Vasiliki Rahimzadeh
Susan Wolfert

Vasiliki Rahimzadeh

and 7 more

April 06, 2022
Nonprofit organizations (NPOs) play critical roles as funding sources, research partners, and disseminators of emerging drug developments in pediatric cancer, yet the literature offers limited understanding or guidance of ethical best practices and processes. We conducted a systematic search for peer reviewed articles, commentaries, newsletters, and white papers indexed in the PubMed and Web of Science databases to identify the ethical, legal, and social responsibilities of NPOs to i) patients/families, ii) researchers, iii) sponsors, and iv) donors when funding clinical trials. Fifty-four articles met the inclusion criteria. Minimizing conflicts of interest, ensuring transparent reporting of trial endpoints, and communicating with families about trial opportunities emerged as key themes. We identified critical gaps in the literature related to negotiating research partnerships, setting trial priorities and establishing best ethical practices in the emerging field of venture philanthropy. Results informed points to consider for NPOs when funding pediatric cancer clinical trials going forward.
Ultrasound-guided totally implantable venous access ports placement via right brachio...
Wei Ding
Lu Qiu

Wei Ding

and 8 more

April 06, 2022
Background and objectives: To investigate the feasibility and safety of ultrasound-guided totally implantable venous access ports (TIVAPs) via the right brachiocephalic vein (BCV) in pediatric patients. Methods: A single institutional retrospective review was performed on 35 pediatric patients with hematological malignancies who underwent TIVAPs implantation via ultrasound-guided right BCV approach from July 2018 to June 2021. Technical success rate, procedural information and TIVAP related complications were evaluated. Results: All the pediatric TIVAP devices were successfully implanted via right BCV access. Venous access was successful by first attempt in 32 children (91.42%); two cases (5.71%) required a second attempt; one patient (2.86%) required a third attempt. The mean procedural time was 44.63 ± 6.41 mins (range, 34-62 mins). No intraoperative complications occurred. The average TIVAP indwelling time was 563.51 ± 208.47 days (range, 193-1014 days) with a cumulative 19,723 catheter-days. The incidence of postoperative complications was 11.43% (4/35), corresponding to a rate of 0.20 complications per 1000 catheter-days. Two cases of local hematoma and two catheter dysfunctions occurred in three patients. No other complications such as wound dehiscence, delayed incision healing, catheter-related thrombosis (CRT), catheter malposition/fracture, surgical site infection, catheter-related bloodstream infection (CRBSI), pinch-off syndrome and drug extravasation were observed during follow-up. Conclusions: Ultrasound-guided right BCV access for TIVAPs placement in pediatric patients appears to be technically feasible, safe and effective. Further large-sample, prospective studies are warranted.
Global regularity for the 2D magnetic B\’{e}nard system with fractional partial dissi...
yujun Liu

yujun Liu

April 06, 2022
In this paper, we considered the global regularity for the 2D incompressible anisotropic magnetic B\’{e}nard system with fractional partial dissipation. More precisely, we established the global existence and regularity for the 2D incompressible anisotropic magnetic B\’{e}nard system with only vertical hyperdiffusion $\Lambda_{2}^{2\beta}b_1$ and horizontal hyperdiffusion $\Lambda_{1}^{2\beta}b_2$ and $(-\Delta)^{\alpha}\theta$, where $\Lambda_{1}$ and $\Lambda_{2}$ are directional Fourier multiplier operators with the symbols being $|\xi_1|$ and $|\xi_2|$, respectively. We prove that, for $\beta>1$ and $0<\alpha<1$, this system always possesses a unique global-in-time classical solution when the initial data is sufficiently smooth.
Zinc Finger Protein 384 (ZNF384) Impact on Childhood Mixed Phenotype Acute Leukemia a...
Tugce Sudutan
Yucel Erbilgin

Tugce Sudutan

and 11 more

April 06, 2022
B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a heterogeneous malignancy and consists of several genetic abnormalities. Some of these abnormalities are used in clinic for risk calculation and treatment decision. ZNF384 rearrangements are one of the new oncogenic subtypes that have been identified in BCP-ALL by recent studies. Also patients with ZNF384 fusions have been reported in with mixed phenotypic acute leukemia (MPAL). In this study, we screened 133 pediatric patients with ALL for the most common ZNF384 fusions; ZNF384-TCF3, ZNF384-EP300 and ZNF384-TAF15 by using qPCR. The total frequency of ZNF384 gene rearrangements was 8.2% in the cohort. We identified ZNF384 fusions in 9.5% of mixed phenotypic leukemia and 7.6% of BCP-ALL groups. Moreover, a novel breakpoint was identified in ZNF384-TCF3 fusion. Patients with MPAL showed significantly higher ZNF384 expression than BCP-ALL and controls. Patients with ZNF384 rearrangements had intermediate survival rates based on other subtypes.
A rare case of drug resistant adult-onset temporal lobe epilepsy due to a focal corti...
Chokote Eric
Leonard Ngarka

Chokote Eric

and 11 more

April 06, 2022
This case suggests that clinicians should consider seizures as a differential diagnosis of paroxystic cough with loss of consciousness. Focal cortical dysplasia should equally be screened for with MRI scans even in adults with epilepsy in sub-saharan Africa.
Actinomycosis of the middle turbinate
Malek Mnejja
Imen Achour

Malek Mnejja

and 7 more

April 06, 2022
Actinomycosis in an uncommon bacterial disease caused by actinomyces. Cervicofacial infection accounts for more than 60% of all cases. However, nasal and paranasal sinus involvement has rarely been described. We report here in a case of a patient presenting with a middle turbinate actinomycosis.
Anti-inflammatory and immune-mediated therapy for a case of febrile infection-related...
Tomonori Kurimoto
Tsuyoshi Matsuoka

Tomonori Kurimoto

and 6 more

April 06, 2022
Febrile infection-related epilepsy syndrome (FIRES) is a disease of unknown etiology, characterized by refractory frequent focal seizures, which require prolonged intensive care. We successfully treated a boy with FIRES with anti-inflammatory and immunosuppressive therapy. This case suggests that an autoimmune mechanism may play a role in the development of FIRES
Vesico-umbilical fistula caused by persistent opening of the urachal duct: about two...
Augustin  Mukakala
Daniel Safari Nteranya

Augustin Mukakala

and 11 more

April 06, 2022
Urachal disorders are as uncommon as they are mysterious. Mastering the diagnostic and therapeutic approach of various urachal illnesses, as well as a better understanding of the embryological development of the urinary system, is critical for surgeons (urologists, pediatric surgeons, general surgeons, and general practitioners).
Ablation Index-guided high-power ablation for superior vena cava isolation
luqian cui
shujuan dong

luqian cui

and 6 more

April 06, 2022
Objectives: The ablation index (AI)-guided high-power ablation for pulmonary vein isolation (PVI) apears to be a novel strategy in treating atrial fibrillation (AF). This study aimed to evaluate the feasibility and safety of superior vena cava isolation (SVCI) by using AI-guided high-power ablation strategy among patients with AF after PVI. Methods: Data from 53 patients with AF were collected. Mapping and ablation of SVC was performed after PVI. The ablation power was set to 45 W and the ablation procedure was guided by AI. The SVC was divided into six segments in a cranial view. Applications and locations of radiofrenquency (RF) was recorded. The RF applications and AI value in different SVC walls were compared and analyzed. Results: SVCI was performed in 46 patients and electrical SVCIs were successfully achieved in all patients with a mean of 7.6 ± 2.9 RF applications. The mean time of SVCI procedure was 9.5±4.5 min. RF applications at anteroseptal wall was 38 (10.8%) points in 20 (43.5%) patients, posteroseptal wall was 74 (21.0%) points in 38 (82.6%) patients, posteral wall was 81 (22.9%%) points in 40 (87.0%%) patients, anteroseptal wall was 72 (20.4%) points in 37 (80.4%%) patients, anterolateral wall was 45 (12.7%) points in 27 (58.7%) patients, anteroseptal wall was 43 (12.2%) points in 23 (50.0%) patients. The mean AI value in septal, posterior and anterior walls was higher than that of lateral wall. There was no complication in any cases. Conclusion: AI-guided high-power ablation is feasible and safe strategy in performing SVCI. The RF applications and AI value in different SVC walls varied.
Wong Type Oscillation Criteria for Nonlinear Impulsive Differential Equations
A. Zafer
Sibel Dogru Akgol

A. Zafer

and 1 more

April 06, 2022
We present Wong-type oscillation criteria for nonlinear impulsive differential equations having discontinuous solutions and involving both negative and positive coefficients. We use a technique that involves the use of a nonprincipal solution of the associated linear homogeneous equation. The existence of principal and nonpricipal solutions was recently obtained by the present authors in [J. Math. Anal. Appl. 503 (2021) 125311]. As special cases, we have superlinear and sublinear Emden-Fowler equations under impulse effects. It is shown that the oscillation behavior changes due to impulses, in particular impulses acting on the solution itself, not on its derivative. An example is also given to illustrate the importance of the results.
Blockchain Based Renewable Energy P2P Trading in Smart Grid
MISHAAL AHMED
Abid khan

MISHAAL AHMED

and 2 more

April 06, 2022
the dramatic increase in demand of global electricity utilization has introduced various environmental and sustainability concerns for Conventional Energy Systems (CES) based on fossil fuels, which driving the global energy manufacturers to adapt new efficient and resilient energy systems. Presently the focus of the scientist and researchers is on the Renewable Energy based and Smart Grid system, which has potential to address the contemporary problems found in conventional energy systems. On the other side , Smart is a new technology, which allows the integration of clean energy sources such as wind, solar, geothermal, hydro, biomass, and tidal energy systems, ensuring energy availability at all times. The quintessential purpose of renewable technologies is to contrive a sustained community. Nevertheless, it has become a challenging concern for centralized energy systems or Smart Grid to integrate and coordinate enormous consignment of expanding users and connections. Consequently, blockchain has emerged as a resilient technology in various industries offering data integrity, trust between parties, data immutability, and secure communication, making it an auspicious technology for decentralized SG and RE criterion. In this research article, a blockchain based energy trade based modal on Peer-to-Peer transactions management presented. The main goal of the research work is to describe energy-trading model based on crypto wallets as a digital currency using smart grid and renewable energies. Moreover, electrical grid technologies, which implemented in blockchain energy based systems, will be analyze. Furthermore, contemporary challenges of industrial and commercial communities employing Renewable Energy found in conventional and centralized energy systems will be address.
Remote Programming of CIED Based On 5G Cloud Follow-up App
Caiyan Cui
Lin Tong

Caiyan Cui

and 4 more

April 06, 2022
Regular follow-up of patients with cardiovascular implantable electronic devices (CIEDs) is a necessary part to optimize the CIED system performance and longevity, which can assess the outcome of CIED, its working conditions and the timely identification of device dysfunction and arrhythmias. Traditional follow-up includes in-person evaluation and remote monitoring. With the development of the 5G cloud support platform, the “5G Cloud Follow-up APP” was designed to realize remote programming of CIEDs, thereby realizing emergency intervention for patients and supplementing deficiencies of traditional follow-up methods. We summarize the utilization, safety, and implications of CIED remote programming.
Trophic diversification and parasitic invasion as ecological niche modulators for gut...
Elena Kashinskaya
Evgeniy Simonov

Elena Kashinskaya

and 7 more

April 06, 2022
The impact of parasites on gut microbiota of the host is well documented, but the role of the relationship between the parasite and the host in the formation of the microbiota is poorly understood. Using 16S amplicon sequencing and newly developed methodological approaches, we characterize the gut microbiota of the sympatric pair of whitefish Coregonus lavaretus complex and the associated microbiota of cestodes parasitizing their intestine. The essence of the proposed approaches is, firstly, to use the method of successive washes of the microbiota from the cestode’s surfaces to analyze the degree of bacterial association to the tegument of the parasite. Secondly, to use a method combining the sampling of intestinal content and mucosa with the wash-out procedure from the mucosa to understand the real structure of the fish gut microbiota. Our results demonstrate that the trophic diversification of a sympatric pair of whitefish predetermines a segregation by ecological niches of their respective microbial communities within their intestine. Additional environmental niches for settlement of bacteria in the intestine are formed by the parasitic helminths that caused the restructuring of the bacterial community in infected fish compared to those uninfected. Using the desorption method in Ringer’s solution, we have demonstrated that Proteocephalus sp. cestodes possess their own microbial community which is put together from “surface” bacteria received from the host, bacteria which are weakly and strongly associated with the tegument, and microbiota obtained after removal of the tegument from the cestodes.
Response to Letter to the Editor regarding ‘Characteristics and outcomes of ventricul...
Fouad Khalil
Ammar Killu

Fouad Khalil

and 1 more

April 06, 2022
We would like to thank the authors for their letter and interest in our manuscript. We appreciate their valuable comments. The authors have raised the following important points: 1. The heterogenicity of our cohort with mitral valve surgery (MVS) 2. Elucidating the characteristics and causes of ventricular arrhythmias (VA) in patients with primary versus secondary mitral disease as well as in those with ischemic versus non-ischemic heart disease 3. The paucity of cardiac magnetic resonance imaging (MRI) as a limitation of the study 4. The need for careful evaluation of patients prior to ablation since most arrhythmias did not originate from the perimitral area.
Fatty acid β-oxidation targeted metastatic growth inhibition in triple negative breas...
Bhuban Ruidas
Neha Choudhury

Bhuban Ruidas

and 8 more

April 06, 2022
Background and purpose Carnitine palmitoyltransferase I (CPT1), an integral outer mitochondrial protein and prime decider of fatty acid β-oxidation (FAO) has been considered to be a key therapeutic target against triple negative breast cancer (TNBC) progression and survival. Herein, we have introduced a biotin-functionalized copolymer, (Py-P(PDSMA-co-PEGMA)-b-P(Bt-PEGMA)), CP4 which can actively target CPT1 and block FAO in metastatic TNBC. Experimental Approach CP4 were synthesized using reversible addition fragmentation chain transfer or RAFT polymerization. In silico computation modelling predicted the active binding of CP4 with CPT1. Cell-based Seahorse energy efflux assay investigated the mitochondrial respiration, glycolytic function and overall ATP production rate. FACS analysis checked the mitochondrial membrane potential (ΔΨm), reactive oxygen species (ROS) and cell apoptosis. Real-time quantitative reverse transcription PCR (qRT-PCR) analysed FAO-related protein expression profiles. Antitumor activities were confirmed in female breast cancer (BALB/c) mice model. Key results Negative docking score and Ramachandran plot analyses affirmed the active targeting of CP4 to CPT1. Beside, CP4 has remarkably switched the ΔΨm and produced excessive ROS followed by the reduction in glycolytic function, mitochondrial oxidative phosphorylation, FAO and thereby limited excessive ATP production. In turn, it induced metastatic growth inhibition and apoptotic cell death in TNBC cells. Importantly, CP4 has significantly improved the altered lipid and oxidative stress profiles following excellent tumor regression, and thereby advocated plausible FAO-targeted anticancer therapies. Conclusion and Implications CP4 has the potentiality of being a new age FAO-targeted anticancer therapeutics that may open up a new treatment strategy against breast cancer soon.
Ab-initio study of hypothetical Ti3AlB2 and two new designed layered ordered double-t...
Shiquan Feng
Feng Guo

Shiquan Feng

and 5 more

April 06, 2022
We have designed Ti3AlB2 and two new layered ordered double-transition metals MAX compound Ti2ZrAlB2 based on the structure of Ti3AlC2. By first-principles calculations with density functional theory, their structure, phase stability, elastic properties, electronic properties and thermal properties have been further investigated. Results show that they are all energetic, thermodynamically and mechanically stable. The bulk modulus, shear modulus, Young's modulus, Poisson's ratio and Debye temperature were computed to discuss their elastic and thermal properties. Results show that they are all good ductile materials with high melting points. Density of states and electron localization function of these three phases were presented to research the chemical bonds and explore the reason limiting their melting points.
Assessment of Channel Migration of Koshi River in Nepal Using Remote Sensing and GIS
Raju Chauhan
Suchana Baniya

Raju Chauhan

and 2 more

April 06, 2022
River channel shifting is the geomorphological process involving the lateral movement of an [alluvial](https://en.wikipedia.org/wiki/Alluvial) [river channel](https://en.wikipedia.org/wiki/Channel_(geography)) across its [floodplain](https://en.wikipedia.org/wiki/Floodplain). Koshi river is characterized by high planform dynamics, especially in the lower reaches. We studied the dynamics of channel planform and shifting through systematic analysis and interpretation of diverse channel configurations using multidate satellite images from 1999 to 2019 of the Koshi River from Chatara to the Nepal-India border. Remote sensing techniques and GIS environment was used for change analysis based on imageries of 1999, 2009 and 2019. The channel shifting was determined by assessing and calculating the transient changes in the planform from the temporal satellite data. The result shows that over the stretch of 48 km, the Koshi River is highly braided with no distinct sub-channel observed. Both the river stretch and braiding are greatest within the southern portion compared to the northern part. Between 1999 and 2019, the area of the water channel is reduced by 24.08 km 2 whereas, the channel bars have increased by 68.08 km 2. The river has experienced a clear shift of the channel toward the west in recent years. The average annual rate of shifting was estimated to be 21.6 m year -1 towards the west and 0.8 m year -1 towards the east, with the overall expansion of the river flood plains. Monitoring of river planform helps in effective river management. This result can be utilized for developing integrated river and land management plans in the Koshi basin.
A Semi-Empirical correlation for stratified two-phase flow friction factors
Pouya Ranjbari
Mohammad Emamzadeh

Pouya Ranjbari

and 1 more

April 05, 2022
The optimal design of two-phase flow pipes depends on various variables. Pressure drop and liquid hold-up are essential parameters in the appropriate design of pipes. These parameters can be estimated by numerical simulation of pipes. However, the simulation strongly depends on both phase frictions. Frictions are commonly calculated using friction factors, and various empirical correlations have been proposed to calculate friction factors, but most of these correlations are dependent on the experimental conditions. The present study proposes a semi-empirical friction factor model by modifying an existing model in the literature for stratified two-phase flows. Experimental data from various laboratories are taken to validate the interface shear stress, velocity profile and pressure gradient. Compared with previous models, the predicted velocity profiles and shear stresses are in better agreement with the experimental data.
A Finite Element Analysis of the behaviour of 3D printing equipment in the event of a...

Dan Claudiu Negrău

and 2 more

April 14, 2022
Practising and solving practical problems often require knowledge and sometimes advanced problem-solving skills in several disciplines simultaneously. The issue generated during the research was developed, involves an understanding of the phenomena of fluid flow, knowledge of the principles and methods of solving heat transfer problems, coupled with those of heat stress, a high level of proficiency and solving the problems of advanced technologies, i.e. solving the issues of the state of tensions and micro-and macro-dimensional deformations. Thus, the problem to be solved here, we have structured it, virtually, in three sub-categories of related issues: Finite Element Analysis of the behaviour of the printing equipment in case of a constant heat flow, having as a subject of study the volume of hot air, in stationary flow as well as in non-stationary flow, using COMSOL MULTIPHYSICS®.
Multiple targeting CO2 laser ablation for the treatment of vaginal intraepithelial ne...
Dongli Kong
Ruqi Chen

Dongli Kong

and 10 more

April 05, 2022
Objective To investigate the detailed procedure and efficacy of multiple targeting CO2 laser ablation (MTLA-CO2) for the treatment of vaginal intraepithelial neoplasia (VaIN) and to obtain a stably high cure rate and low complication incidence. Design Patients with VaIN were recruited and received MTLA. After follow-up, we aimed to find the risk factors affecting the efficacy. Setting Obstetrics & Gynecological outpatients’ department of Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology. Population Fifty-seven cases of LSIL(VaIN1) and 160 cases of HSIL(VaIN2,3). Methods Patients with VaIN were recruited and received MTLA. The detailed clinical data were recorded and the risk factors were analyzed. Main Outcome Measures The pathological cure and HPV clearance. Results The cumulative pathological cure rate was 92.0% and 96.0%, and the cumulative HPV negative rate was 77.5% and 75.5%, for the HSIL(VaIN2,3) and LSIL(VaIN1) groups respectively. Larger areas of lesions (p =0.083) and history of hysterectomy (p =0.037) were independent risk factors for pathological persistence. Menopause (p =0.006) and immunosuppression (p =0.059) were independent risk factors for HR-HPV persistent infection. Condemn use (p =0.002) was a protective factor against HR-HPV infection. It was proposed 3~5 times of laser ablation for HSIL(VaIN2,3) and 2~3 times of laser ablation for LSIL(VaIN1). Conclusions The MTLA for VaIN was effective and well-tolerated. The schematization of MTLA was decided according to the characteristics of VaIN lesions, high-risk factors and surveillance. Funding The National Natural Science Foundation of China (81974410, 81572571, 81630060, 82002769, 81230038). Keywords Laser ablation, targeting, VaIN
Glycine at the third position of TM3 determines the action of fluralaner on insect an...
Qiu Tang Huang
Cheng Wang Sheng

Qiu Tang Huang

and 6 more

April 05, 2022
BACKGROUND AND PURPOSE Fluralaner is a novel isoxazoline insecticide with broad insect spectrum, and mainly acts on the insect GABA receptor with unique binding action, but its molecular interaction with insect GABA receptor has not been deeply identified on molecular level according to its selectivity between target (insect) and non-target (mammal) organisms. EXPERIMENTAL APPOACH The potential binding residues (I258T and L275I in TM1; V288I, M298N, G303N and A304S in TM2; G3’M/S, A327S, G336N, M338I and A339F in TM3; M473V and I477D in TM4) were predicted by SYBYL-X 2.1 software, and verified respectively by the site-directed mutagenesis and two-electrode voltage clamp (TEVC) technique. KEY RESULTS In the 11 predicted amino acids, the G3’M has the strongest ability to reduce the sensitivity of recombinant rice stem borer RDL homomeric channel to fluralaner. Compared with the wild-type (WT)-RDL, the G3’M mutation almost completely abolish the binding of fluralaner and avermectin, but not fipronil on recombinant homomeric channel of RDL from several orders of insects in vitro. In addition, the M3’G on rat Mus musculus β2 improved the sensitivity of recombinant heteromeric Mmα1β2-M3’G channel to fluralaner. Our results demonstrated that the glycine at the third position of TM3 determines the action of fluralaner and should be the binding site of fluralaner with RDL. CONCLUSION AND IMPLICATIONS These results would contribute to understanding the molecular interaction of fluralaner with RDL homomeric channel and may be used to guide future modification of isoxazolines to achieve highly selective control of pests with minimal effects on non-targeted organisms.
Cold stress combined with salt or abscisic acid supplementation enhances lipogenesis...
David Fierli
Maria Elena Barone

David Fierli

and 3 more

April 05, 2022
Microalgae have attracted interests from a range of biotechnology fields due to the variety of valuable bioactive metabolites some species can synthesise. Compounds such as ω3-fatty acids or carotenoid pigments are commercially exploited to provide the materials necessary for product formulations within the pharmacology, nutraceutical or cosmetic sectors. The co-stimulation of several compounds of interest may as such improve the cost-effectiveness of microalgal biorefinery pipelines. This study focused on the microalgal biological model species Phaeodactylum tricornutum (marine diatom) to investigate the effects on lipogenesis and carotenogenesis of combined stressors, here cold temperature shock (from 20 to 10°C) and addition of NaCl salt (5 mg/ml) or the phytohormone abscisic acid (4 mg/l), applied using a two-stage cultivation strategy. Results showed that cold stress with NaCl or phytohormone addition increased the neutral lipid content of the biomass (20 to 35%). These treatments also enhanced the proportions of EPA (22% greater than control) in the fatty acid profile of biomass extracts. In addition, these treatments had a stimulatory effect on carotenogenesis, especially the combination of cold stress with NaCl addition, which returned the highest production of fucoxanthin (33% increase). The gene expression of diacylglycerol acyltransferase (DGAT) and the ω-3 desaturase precursor (PTD15), as determined by real time PCR, were enhanced 4- and 16-fold relative to the control, respectively. In addition, zeaxanthin epoxidase 3 (ZEP3), involved in the xanthophyll cycle, was downregulated at low temperature when combined with abscisic acid. These results highlight the benefits of applying a combination of low temperature and salinity stress, as part of a two-stage cultivation process, to simultaneously enhance the yields of the valuable metabolites EPA and fucoxanthin in Phaeodactylum tricornutum.
Mechanism of αO-Conotoxin GeXIVA[1,2], a Novel Nonaddictive Analgesic, Based on In Vi...
Xiaoyu Zhu
mei yuan

Xiaoyu Zhu

and 6 more

April 05, 2022
Background and purpose: αO-conotoxin GeXIVA[1,2], a natural peptide discovered by our laboratory from Conus generalis in the South China Sea, is a novel nonaddictive analgesic targeting the α9α10 nicotinic acetylcholine receptor (nAChR). This study aimed to elucidate the underlying mechanisms by the disposition and modelling of GeXIVA[1,2]. Experimental approach: The pharmacokinetics (PK) of GeXIVA[1,2] and tissue distribution in rats and dogs were studied. A population pharmacokinetics model and a pharmacokinetic-pharmacodynamic model were developed based on animal data and used to predict the efficacious dose in humans and explain the mechanism. Key results: The intramuscular bioavailability of GeXIVA[1,2] was 11.47% and 13.37% in rats and dogs, respectively. Across experimental doses, the plasma exposure increased approximately in proportion to dose, and the half-life of GeXIVA[1,2] ranged from 5.37±0.99 to 19.65±6.21 min. GeXIVA[1,2] had less extensive tissue distribution. The bound fractions differed in human, rat, and dog plasma, ranging from 55.85±5.10% to 87.64±7.49%. The one-compartment model with the first-order absorption PPK model estimated an efficacious dose of 11.9-30.8 μg·kg-1 in a 70 kg human with bodyweight as a covariant. The inhibitory loss indirect response model combined with an effect compartment adequately described PK-PD relationships. Conclusion and implications: We speculated that GeXIVA[1,2] exerts analgesia by inhibiting the elimination of certain endogenous substances, which may be a key pharmacodynamic biomarker. This is the first report of the disposition of conotoxin-derived therapeutic agents and possible analgesic mechanisms of α9α10 nAChR, which were elucidated by PK studies and modelling approaches.
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