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Context Originally developed for treatment of human immunodeficiency virus (HIV), the antiviral combination lopinavir/ritonavir (LPV/r) is being repurposed for treating the novel coronavirus disease (COVID-19) despite minimal experience in this markedly different population and an in-vitro derived EC50 against SARS-CoV-2 several hundred-fold greater than for HIV. We present a case series including a case of severe hyponatremia and a 32-fold overdose raising safety and effectiveness concerns in COVID-19 patients. Methods We measured LPV trough concentrations in 12 patients and reviewed their clinical charts for side effects known to occur in HIV patients. Findings Compared to established LPV trough concentrations in HIV patients, concentrations in COVID-19 patients were 3-fold greater (19.37 ± 10.12 mcg/mL versus 6.25 mcg/mL). In addition, cholestasis and dyslipidemia toxicity thresholds were exceeded in 12/12 and 11/12 patients respectively. No patients achieved the presumed therapeutic concentration. Side effects included gastrointestinal symptoms (5/12), electrolyte imbalances (4/12), liver enzyme disturbances (5/12) and triglyceride elevations (2/12). Conclusion No patients reached presumed therapeutic LPV concentrations despite experiencing side effects and exceeding cholestasis and dyslipidemia toxicity thresholds. This raises concerns for the safety and effectiveness of LPV/r. Clinicians should consider closely monitoring for side effects and not necessarily attribute them to COVID-19.

Background Paracetamol is recommended as first-line treatment for an acute sore throat. However, in primary care, antibiotics are still frequently prescribed as first-line management for sore throat. Objectives We aimed to explore the views and experiences of general practitioners (GPs) and patients regarding paracetamol for sore throat to understand why guidelines are often not adhered to. Methods A descriptive qualitative study with semi-structured interviews was conducted with a purposive sample of eight GPs and nine patients in Antwerp (Belgium). Data was analysed using thematic content analysis. Results The mean age of GPs was 42.4 years and of patients 51.4 years. Patients want reassurance and pain relief. Many patients do not self-manage their acute sore throat with paracetamol before consulting their GP. GPs often wrongly assume that the patient has already used pain relief without actually exploring this. Patients who do use paracetamol, do not know how to use it effectively. This leads to the perception and beliefs that it is insufficient to treat acute sore throat and when prescribed will lead to dissatisfaction. Patients generally accept the GP’s recommended treatment when given a thorough explanation, since they trust their GP’s expertise. Conclusion GPs play a major role in educating patients about paracetamol as effective pain-relieving treatment in acute sore throat. By actively exploring the patients’ ideas, concerns and expectations (ICE), patients’ satisfaction and guideline adherence could be improved.

COVID-19 – related morbidity is associated with exaggerated inflammation and cytokine production in the lungs, leading to acute respiratory failure. The cellular mechanisms underlying these so-called ‘cytokine storms’ are regulated through the Toll-like receptor 4 (TLR4) signaling pathway and by ROS (Reactive Oxygen Species). Both light (Photobiomodulation) and magnetic fields (e.g., Pulsed Electro Magnetic Field) stimulation are noninvasive therapies known to confer anti-inflammatory effects and regulate ROS signaling pathways. Here we show that daily exposure to two 10-minute intervals of moderate intensity infra-red light significantly lowered the inflammatory response induced via the TLR4 receptor signaling pathway in human cell cultures. Anti-inflammatory effects were likewise achieved by electromagnetic field exposure of cells to daily 10-minute intervals of either Pulsed Electromagnetic Fields (PEMF), or to Low-Level static magnetic fields. Because current illumination and electromagnetic field therapies have no known side effects, and are already approved for some medical uses, we have here developed protocols for verification in clinical trials of COVID-19 infection. These treatments are affordable, simple to implement, and may help to resolve the acute respiratory distress of COVID-19 patients both in the home and in the hospital.

Unique features of elephant hematology are known challenges in analytical methodology like two types of monocytes typical for members of the Order Afrotheria and platelet counts of the comparatively small elephant platelet. To investigate WBC differential and platelet data generated by an impedance-based hematology analyzer without availability of validated species-specific software for recognition of elephant WBCs and platelets, compared to manual blood film review. Blood samples preserved in ethylenediaminetetraacetic acid (EDTA) of 50 elephants (n = 35 Elephas maximus and n = 15 Loxodonta africana) were used. A Mann-Whitney test for independent samples was used to compare parameters between methods and agreement was tested using Bland-Altman bias plots. All hematological variables, including absolute numbers of heterophils, lymphocytes, monocytes, eosinophils, basophils, and platelets, were significantly different (p

Context Total Glucosides of Paeony (TGP) capsule possesses various hepatoprotective activities. No study is available concerning TGP’s concentration–effect relationship on hepatoprotection. Objective To establish a pharmacokinetics–pharmacodynamics (PK-PD) modelling on TGP capsule’s hepatoprotection after a single oral administration in hepatic injury rats. Materials and methods Male Sprague-Dawley rats were divided into five groups (n = 6): control, model (hepatic injury), treated-H (2.82 g/kg), treated-M (1.41 g/kg), and treated-L (0.705 g/kg) groups. All treated groups rats were intragastrically administered a single dose. An LC-MS/MS method was applied to determine paeoniflorin (Pae) and albiflorin (Alb) in rat serum. The effects of single-dose TGP on serum alanine transaminase (ALT), aspartate transaminase (AST) and total bile acid (TBA) were evaluated in hepatic injury rats. Results Single dose (2.82, 1.41, or 0.705 g/kg) TGP capsule could real-time down-regulate serum TBA but not ALT and AST in hepatic injury rats within 20 h. An inhibitory effect Sigmoid Emax of PK-PD modelling was established using Pae and Alb as PK markers and serum TBA as effect index. Pharmacodynamic parameters were calculated. For treated-H, treated-M and treated-L group, respectively, E0 were 158.1, 226.9 and 245.4 μmol/L for Pae, 146.1, 92.9 and 138.4 μmol/L for Alb, Emax were 53.0, 66.0, and 97.1 μmol/L for Pae, 117.4, 249.7 and 60.0 μmol/L for Alb, and EC50 were 9.3, 5.2 and 2.7 μg/mL for Pae, 2.3, 0.8, and 0.8 μg/mL for Alb. Discussion and conclusions Serum TBA is a sensitive effect index for TGP’s single dose PK-PD modelling, and it is potential for further multi-dose studies of TGP’ effect on hepatic injury. The study provides valuable information for TGP’s mechanistic research and rational clinical application.

In this paper, a set of 3-methylquniazolinone derivatives were designed, synthesised, and studied the preliminary structure-activity relationship for antiproliferative activities. All target compounds performed significantly inhibitory effects against wild type epidermal growth factor receptor tyrosine kinase (EGFRwt-TK) and tumour cells (A431, A549, MCF-7, and NCI-H1975). In particular, compound 4d 3-fluoro-N-(4-((3-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)methoxy)phenyl)benzamide showed higher antiproliferative activities against all tumour cells than Gefitinib (IC50 of 3.48, 2.55, 0.87 and 6.42 μM, respectively). Furthermore, compound 4d could induce apoptosis of MCF-7 cells and arrest in G2/M phase at the tested concentration. Molecular docking and ADMET studies showed that compound 4d could closely form many hydrogen bonds with EGFRwt-TK. Therefore, compound 4d is potential to develop as novel anti-cancer drug.

Microtubules (MTs) control cell shape and intracellular cargo transport. The role of MT turnover in the migration of slow-moving cells through endothelial barriers remains unclear. To irreversibly interfere with MT disassembly, we have used the MT-stabilizing agent zampanolide (ZMP) in Β16F10 melanoma as amodel of slow-moving cells. ZMP-treated B16 cells failed to follow chemotactic gradients across rigid confinements and could not generate stable sub-endothelial pseudopodia under endothelial monolayers. In vivo, ZMP-treated Β16 cells failed to extravasate though lung capillaries. In contrast to melanoma cells, the chemotaxis and transendothelial migration of ZMP-treated Tcells were largely conserved. This is afirst demonstration that MT disassembly is akey checkpoint in the directional migration of cancer cells but not of lymphocytes.

Insectivorous bats capture their prey in flight with impressive success. They rely on the echoes of their own ultrasonic vocalization that yield acoustic snapshots, which enable target tracking on a rapid time scale. This task requires the use of intermittent information to navigate a dynamically changing environment. Bats may solve this challenging task by building internal models that estimate target velocity to anticipate the future location of a prey item. This has been recently tested empirically in perched bats tracking a target moving across their acoustic field. In this report, we build on past work to propose a new model that describes bat flight trajectories employing predictive strategies. Furthermore, we compare this model with a previous model of bat target interception that has also been employed by some visually guided animals: parallel navigation. Abbreviations: HTTP, Hybrid Target Trajectory Prediction; CATD, Constant Absolute Target Direction; CB, Constant Bearing; PN, Parallel Navigation

RT-QuIC is a shaking-based cyclic amplification technique originally developed in the prion field to detect minute amounts of scrapie prion protein (PrPSc). In this study, we applied the RT-QuIC assay to investigate a-synuclein (a-syn) seeding activity in brains of Dementia with Lewy Body (DLB) patients and in brains of G2-3 transgenic mice expressing human a-syn with A53T mutation. The results show that a-syn seeding activity varies between patients with detectable dilutions ranging from 10−3 to 10−8 dilutions of brain tissue and is stable under exposures to the cycles of freezing, thawing and sonication. A53T a-syn aggregates from G2-3 transgenic mice greatly favoured A53T recombinant human a-syn as substrates in comparison to wild-type a-syn, suggesting that conformations for wild-type a-syn to be able to adopt are not compatible with that of A53T aggregates from G2-3.

PRNP genotypes, number of octarepeats (PHGGGWGQ) and indels in the PRNP promoter can influence the progression of prion disease in mammals. We found no relationship between presence of promoter indels in white-tailed deer and mule deer from Nebraska and CWD presence. White-tailed deer with the 95 H allele and G20D mule deer were more likely to be CWD-free, but unlike other studies white-tailed deer with the 96S allele(s) were equally likely to be CWD-free. We provide the first information on PRNP genotypes and indels in the promoter for Key deer (all homozygous 96SS) and Coues deer (lacked 95 H and 96S alleles, but possessed a uniquely high frequency of 103 T). All deer surveyed were homozygous for three tandem octarepeats.

Analysis of the literature data reveals that while inhibition of cancer-related carbonic anhydrase IX and XII isoforms continues to be an important enrichment factor for designing anticancer agent development libraries, exclusive reliance on the in vitro inhibition of these two recombinant isozymes in nominating candidate compounds for evaluation of their effects on cancer cells may lead not only to identifying numerous compounds devoid of the desired cellular efficacy but also to overlooking many promising candidates which may not display the best potency in biochemical inhibition assay. However, SLC-0111, now in phase Ib/II clinical trials, was developed based on the excellent agreement between the in vitro, in vivo and more recently, in-patient data.

A novel series of cyclin-dependent kinases (CDKs) inhibitors, which play critical roles in the cell cycle control and regulation of cell transcription, were synthesised. A systematic study of enzymatic and cellular assays led to the identification of compound X22 with a nanomolar potency against CDK4 and CDK9 and potent antiproliferative activities against a panel of tumour cell lines. X22 could induce cell cycle arrest and cell apoptosis in cancer cell lines. X22 dose-dependently inhibits signalling pathways downstream of CDKs in cancer cells. In vivo antitumor activity assays, oral administration of X22 led to significant tumour regression in mouse model without obvious toxicity. Superior anti-cancer efficacy in vitro and in vivo of X22 demonstrated combined depletion of cell cycle and transcriptional CDK all contributed to antitumor activity. Taken together, concomitant inhibition of cell cycle and transcriptional CDK activities provided valuable guide for further structural optimisation.

Elastase and tyrosinase are important targets both for cosmetics and for dermatological disorders. In this work, ninety herbal products were tested as inhibitors of these two enzymes. Eleven extracts resulted strongly active. Four out of them (Camellia sinensis, Ginkgo biloba, Rhodiola rosea, Vitis vinifera) inhibited both enzymes, five (Glycyrrhiza glabra, Ribes nigrum, Rheum officinale, Salvia officinalis, Tilia platyphyllos) were active against tyrosinase only, and two (Ceterach officinarum and Cinnamomum zeylanicum) proved selectively active against elastase. The IC50 ranged from 3.1 to 104.9 μg/mL and 19.3 to 164.3 μg/mL, against elastase and tyrosinase, respectively. The most active extracts resulted enriched in flavonoids (from 1.47 to 56.47 mg RE/g of extract) and phenolics (from 37.43 to 123.56 mg GAE/g of extract), indicating also an antioxidant potential. Finally, a positive correlation between enzymatic bioactivities and phenolic content was also established.

A series of compounds incorporating 3-(3-(2/3/4-substituted phenyl)triaz-1-en-1-yl) benzenesulfonamide moieties were synthesised and their chemical structure was confirmed by physico-chemical methods. Carbonic anhydrase (CA, EC 4.2.1.1) inhibitory effects of the compounds were evaluated against human isoforms hCA I and II. KI values of these sulphonamides were in the range of 21 ± 4–72 ± 2 nM towards hCA I and in the range of 16 ± 6–40 ± 2 nM against hCA II. The 4-fluoro substituted derivative might be considered as an interesting lead due to its effective inhibitory action against both hCA I and hCA II (KIs of 21 nM), a profile rarely seen among other sulphonamide CA inhibitors, making it of interest in systems where the activity of the two cytosolic isoforms is dysregulated. © 2019, © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group., TYL-2019-7137, This research was supported by the Ataturk University Research Fund (Project number: TYL-2019-7137).

The present study describes the synthesis of a novel series of thiazolidin-4-one and thiazinan-4-one using 1-(2-aminoethyl)pyrrolidine as amine precursor. All compounds were synthesised by one-pot three component cyclocondensation reaction from the amine, a substituted benzaldehyde and a mercaptocarboxylic acid. The compounds were obtained in moderate to good yields and were identified and characterised by 1H, 13 C, 2 D NMR and GC/MS techniques. The compounds also were screened for their in vitro acetylcholinesterase (AChE) activity in hippocampus and cerebral cortex on Wistar rats. The six most potent compounds have been investigated for their cytotoxicity by cell viability assay of astrocyte primary culture, an important cell of central nervous system. We highlighted two compounds (6a and 6k) that had the lowest IC50 in hippocampus (5.20 and 4.46 µM) and cerebral cortex (7.40 and 6.83 µM). These preliminary and important results could be considered a starting point for the development of new AChE inhibitory agents.

The analysis of monoclonal antibodies (mAbs) by a middle-down mass spectrometry (MS) approach is a growing field that attracts the attention of many researchers and biopharmaceutical companies. Usually, liquid fractionation techniques are used to separate mAbs polypeptides chains before MS analysis. Gas-phase fractionation techniques such as high-field asymmetric waveform ion mobility spectrometry (FAIMS) can replace liquid-based separations and reduce both analysis time and cost. Here, we present a rapid FAIMS tandem MS method capable of characterizing the polypeptide sequence of mAbs light and heavy chains in an unprecedented, easy, and fast fashion. This new method uses commercially available instruments and takes ~24 min, which is 40-60% faster than regular liquid chromatography-MS/MS analysis, to acquire fragmentation data using different dissociation methods.

Seed germination is a vital initial stage in the life cycle of a plant, which determines subsequent vegetative growth and reproduction. Melatonin acts as a plant's master regulator and is also involved in the process of seed germination. In a recent study, we show that the high concentration melatonin inhibited seed germination in Arabidopsis. Transcriptome and phenotype analysis implied that melatonin-mediated seed germination interacted with phytohormones abscisic acid (ABA), gibberellin (GA), and auxin. In this short communication, we discuss the mechanism of phytomelatonin that inhibits seed germination through ABA, GA, and IAA in Arabidopsis.

Extreme environments constitute the largest habitat on earth, but our understanding of life in such environments is rudimentary. The hostility of extreme environments such as the deep sea, earth’s crust, and toxic lakes limits the sampling, culturing, and studying of extremophiles, the organisms that live in these habitats. Thus, in terms of ecological research, extreme environments are the earth’s final frontier. A growing body of data suggests that nematodes are the most common animal taxon in different types of extreme settings such as the deep-subsurface and sediments in the deep sea. Notably, the reasons for the abundance of nematodes in extreme habitats remain mostly unknown. I propose that a unique combination of several characteristics of nematodes may explain, additively or synergistically, their successful adaptation to extreme habitats. Novel functional genetic and genomic approaches are expected to reveal molecular mechanisms of adaptation of nematodes to the many fascinating extreme environments on earth.

The study investigated how sprouted-papaya seed meal (SPSM) a total of affected the growth and carcase traits of broilers. Based on a completely randomized design, 390 day-old Lohmann broiler chicks were allotted to CONT (chicks provided with control diet), SEED25 (diet containing 2.5% papaya seed meal), GERM1 (diet containing 1% SPSM), GERM25 (diet containing 2.5% SPSM) and GERM5 (diet containing 5% SPSM). Body weight and feed intake of chickens were weekly recorded from 14 to 36 days of age, while birds (six birds per treatment group; 30 birds in total) were slaughtered at day 36. Feeding SPSM up to 5% did not impair (p > 0.05) broilers’ growth or feed intake. At 5%, SPSM compromised (p 0.05) detrimental effects, while papaya seed meal at the same proportion lowered (p

Phosphorus (P), which is taken up by plants as inorganic phosphate (Pi), is one of the most important macronutrients for plant growth and development. Meanwhile, it determines plant architecture in several ways, including leaf inclination. However, the molecular basis underlying the crosstalk between the signaling pathways of plant P homeostasis and architecture maintenance remains elusive. We recently characterized a WRKY transcription factor, OsWRKY108, in rice (Oryza sativa). It functions redundantly with OsWRKY21 to promote Pi uptake in response to Pi supply. Overexpression of either OsWRKY108 or OsWRKY21 led to up-regulation of Pi transporter genes and thus enhanced Pi accumulation. By contrast, transgenic rice plants expressing OsWRKY21-SRDX (a fusion protein transforming OsWRKY21 from an activator into a dominant repressor) but not the OsWRKY108-SRDX fusion showed decreased Pi accumulation under Pi-replete conditions. Here, we report that OsWRKY108 acts as a positive regulator of leaf inclination. OsWRKY108 overexpressors showed increased leaf inclination and OsWRKY108-SRDX plants showed an erect-leaf phenotype, irrespective of the Pi regimes. Nevertheless, the response of leaf inclination to Pi starvation was largely impaired upon OsWRKY108 overexpression. Moreover, in both OsWRKY108-SRDX plants and OsWRKY108 overexpressors, the ‘percentage of leaf angle alteration relative to wild-type’ under Pi-starvation condition was more significant than that under Pi-replete condition. These results suggest that the regulation of OsWRKY108 on leaf inclination is in part dependent on Pi availability. Altogether, our findings demonstrate that OsWRKY108 is an integrative regulator of P homeostasis and leaf inclination, serving as a link between plant nutrient signaling and developmental cues.

Aroma is a critical factor influencing consumer acceptability of ripe fruit. When fruit are eaten, the aroma travels retronasally from the mouth into the olfactory receptors located in the nose after exhaling. In kiwifruit (Actinidia spp.), terpene volatiles such as α-terpinolene and 1,8-cineole have been shown to contribute to the characteristic aroma of ripe fruit. Notably, 1,8-cineole contributes a key floral/eucalyptus note to the aroma of ripe A. chinensis ‘Hort16A’ kiwifruit, based on sensory descriptive and discriminant analysis. Emission of α-terpinolene and 1,8-cineole in kiwifruit is induced by ethylene, and production peaks when fruit are at eating ripeness. Two monoterpene synthase TPS-b family genes have been isolated from the fruit of A. arguta and A. chinensis that produce α-terpinolene and 1,8-cineole, respectively. Here we discuss terpene volatiles with respect to fruit aroma and consumer sensory evaluation, analyze the gene structure and conserved motifs of TPS-b genes in published kiwifruit genomes and then construct a transcriptional regulatory network based on Actinidia TPS-b. These data provide further insights into the potential molecular mechanisms underlying signature monoterpene synthesis to improve flavor in kiwifruit.

CFP/YFP-paired FRET is routinely used to estimate intracellular Ca(2+) concentrations in vivo. This system, however, is excited with blue light, which is likely to invoke unexpected responses in plant cells. This report describes a new green light-excitable FRET system with an mKO2/mCherry pair. Plant cells expressing this newly constructed FRET system demonstrated its ability to monitor changes in cytosolic free calcium concentration. The new system is likely to find applications in studies of plant cells where undesirable blue light responses must be avoided.

Tomato is an important crop for its high nutritional and medicinal properties. The role of salicylic acid (SA) in 1-aminocyclopropane-1-carboxylate synthase (ACS), sodium-hydrogen exchanger (NHX1), salt overly sensitive 1 (sos1) and high-affinity K(+) transporter (HKT1;2) transcripts, and ACS enzyme activity and ethylene (ET) production, and growth and physiological attributes was evaluated in tomato cv. Pusa Ruby under salinity stress. Thirty days-old seedlings treated with 0 mM NaCl, 250 mM NaCl, 250 mM NaCl plus 100 µM SA were assessed for different growth and physiological parameters at 45 DAS. Results showed ACS, NHX1, sos1 and HKT1;2 transcripts were significantly changed in SA treated plants. The ACS enzyme activity and ET content were considerably decreased in SA treated plants. Shoot length (SL), root length (RL), number of leaves (NL), leaf area per plant (LA), shoot fresh weight (SFW) and root fresh weight (RFW) were also improved under SA treatment. Conversely, the electrolyte leakage and sodium ion (Na(+)) content were significantly reduced in SA treated plants. In addition, the endogenous proline and potassium ion (K(+)) content, and K(+)/Na(+) ratio were considerably increased under SA treatment. Likewise, antioxidant enzymes (SOD, CAT, APX and GR) profile were better in SA treated plant. The present findings suggest that SA reverse the negative effects of salinity stress and stress induced ET production by modulating ACS, NHX, sos1 and HKT1;2 transcript level, and improving various growth and physiological parameters, and antioxidants enzymes profile. This will contribute to a better understanding of salinity stress tolerance mechanisms of tomato plants involving SA and ET cross talk and ions homeostasis to develop more tolerant plant.

Objective: The aim of this study was to compare the fit measurements from the 3 D triple-scan protocol and the impression replica technique, by measuring the fit of three-unit tooth-supported fixed dental prostheses. Materials and methods: The results from an earlier study using the triple-scan protocol were compared to results from the impression replica technique for absolute marginal gap, cervical area gap and internal gap. Results: There were no differences for cervical area gap or internal gap, but for absolute marginal gap the impression replica technique obtained significantly smaller fit values. Conclusion: The impression replica technique and the triple-scan protocol may both be used to measure the fit of tooth-supported restorations. However, the scanner used for the triple-scan protocol must be able to obtain scan points at the outermost edge of the restorations when used for absolute marginal gap.

Introduction: Transmissible mink encephalopathy (TME) is a fatal neurologic prion disease of farmed mink. Epidemiologic and experimental evidence following a Wisconsin outbreak in 1985 has linked TME to low-type bovine spongiform encephalopathy (BSE-L). Evidence suggests that farmed mink were likely exposed through feeding of BSE-L infected downer cattle. The interspecies transmission of TME to cattle has been documented. Recently, we demonstrated the susceptibility of sheep to cattle passaged TME by intracranial inoculation. The aim of the present study was to compare ovine passaged cattle TME to other prion diseases of food-producing animals. Using a bovine transgenic mouse model, we compared the disease phenotype of sheep TME to BSE-C and BSE-L. Materials and Methods: Separate inoculants of sheep passaged TME were derived from animals with the VRQ/VRQ (VV136) and ARQ/VRQ (AV136) prion protein genotype. Transgenic bovinized mice (TgBovXV) were intracranially inoculated with 20 µl of 1% w/v brain homogenate. The disease phenotypes were characterized by comparing the attack rates, incubation periods, and vacuolation profiles in TgBovXV mice. Results: The attack rate for BSE-C (13/13), BSE-L (18/18), and TMEVV (21/21) was 100%; whereas, the TMEAV group (15/19) had an incomplete attack rate. The average incubation periods were 299, 280, 310, and 541 days, respectively. The vacuolation profiles of BSE-L and TMEVV were most similar with mild differences observed in the thalamus and medulla. Vacuolation profiles from the BSE-C and TMEAV experimental groups were different than TMEVV and BSE-L. Conclusion: Overall the phenotype of disease in TME inoculated transgenic mice was dependent on the sheep donor genotype (VV vs AV). The results of the present study indicate that TME isolated from VRQ/VRQ sheep is similar to BSE-L with regards to incubation period, attack rate, and vacuolation profile. Our findings are in agreement with previous research that found phenotypic similarities between BSE-L and cattle passaged TME in an ovine transgenic rodent model. In this study, the similarities between ovine TME and BSE-L are maintained after multiple interspecies passages.

International audience; Soil-transmitted helminth (STH) infections carry the highest number of disability adjusted life years among all neglected tropical diseases, disproportionately affecting low-income countries such as Madagascar. This study describes the epidemiology of STH and S. stercoralis infections in twelve remote villages surrounding Ranomafana National Park (RNP), Ifanadiana, Madagascar. Questionnaires and stool samples were collected from 574 subjects from random households. The Kato-Katz method and spontaneous sedimentation technique were used to examine stool samples for evidence of infection. Infection prevalence rates were 71.4% for Ascaris lumbricoides (95% CI: 67.7–75.1), 74.7% for Trichuris trichiura (95% CI: 71.1–78.2), 33.1% for hookworm (95% CI: 29.2–36.9), and 3.3% for Strongyloides stercoralis (95% CI: 1.84–4.77). Participants who were older in age (OR = 0.96; 95% CI: 0.95–0.99) and who had a high school education (OR = 0.17; 95% CI: 0.04–0.77) were less likely to be infected with a STH. Females were less likely to be infected with A. lumbricoides (OR = 0.52; 95% CI: 0.33–0.82). Participants living in villages further from the main road were more likely to be infected with a STH (F = 4.00, p = 0.02). Overall, this study found that 92.5% (95% CI: 90.3–94.6) of the people living in rural regions near RNP have at least one STH infection. This calls into question the current preventative chemotherapy (PC) program in place and suggests that further medical, socioeconomic, and infrastructural deveopments are needed to reduce STH prevalence rates among this underserved population.

Snail2 is a repressor of E-cadherin during carcinogenesis; however, the specific mechanisms involved in this process remain largely unknown. Here, we determined that Snail2 was highly increased during TGF-β-induced EMT process in lung cells. H3K9 methylation was up-regulated and H3K4/H3K56 acetylation were down-regulated at the E-cadherin promoter. Snail2 interacted with G9a and HDACs to exert suppression of E-cadherin transcription. Overexpression of Snail2 enhanced the migration and invasion ability, whereas G9a and HDACs inhibition significantly reversed this effect. Our study demonstrated the importance of G9a- and HDACs-mediated regulation during Snail2-induced E-cadherin repression and metastasis during LC progression.

Human thioredoxin reductase 1 (TrxR1) is a selenocysteine-containing enzyme which plays a crucial role in regulating numerous redox signalling pathways within the cell. While its functioning is important in all cells, levels of TrxR1 expression are higher in cancer cells, possibly as an adaptation to much higher levels of reactive oxygen species and the need for more extensive DNA synthesis. This makes TrxR1 an attractive target for cancer therapy development. Inspired by the structure of disulphide compounds which have advanced through various stages of clinical development, we designed a series of dithiodiglycolic acid derivatives. These were prepared from respective thiol synthons using an iodine- or benzotriazolyl chloride-promoted oxidative disulphide bond formation. Inhibition of TrxR present in cell lysates from human neuroblastoma cells (SH-SY5Y) and rat liver cells indicated several compounds with a potential for TrxR inhibition. Some of these compounds were also tested for growth inhibition against two human cancer cell lines and normal human keratinocytes., Graphical Abstract

To develop multifunctional aldose reductase (AKR1B1) inhibitors for anti-diabetic complications, a novel series of 2-phenoxypyrido[3,2-b]pyrazin-3(4H)-one derivatives were designed and synthesised. Most of the derivatives were found to be potent and selective against AKR1B1, and 2-(7-chloro-2-(3,5-dihydroxyphenoxy)-3-oxopyrido[3,2-b]pyrazin-4(3H)-yl) acetic acid (4k) was the most active with an IC50 value of 0.023 µM. Moreover, it was encouraging to find that some derivatives showed strong antioxidant activity, and among them, the phenolic 3,5-dihydroxyl compound 4l with 7-bromo in the core structure was proved to be the most potent, even comparable to that of the well-known antioxidant Trolox. Thus the results suggested success in the construction of potent and selective AKR1B1 inhibitors with antioxidant activity.

We describe herein the design, multicomponent synthesis and biological studies of new donepezil + chromone + melatonin hybrids as potential agents for Alzheimer’s disease (AD) therapy. We have identified compound 14n as promising multitarget small molecule showing strong BuChE inhibition (IC = 11.90 ± 0.05 nM), moderate hAChE (IC = 1.73 ± 0.34 μM), hMAO A (IC = 2.78 ± 0.12 μM), and MAO B (IC = 21.29 ± 3.85 μM) inhibition, while keeping a strong antioxidant power (3.04 TE, ORAC test). Consequently, the results reported here support the development of new multitarget Donepezil + Chromone + Melatonin hybrids, such as compound 14n, as a potential drug for AD patients cure., LI thanks the Regional Council of Franche-Comté [2016YC-04540 and 04560] for financial support. JMC and MJOG thank Universidad Camilo José Cela (UCJC) for support [Grants 2015–12 and 2015–21]. RA and KM were supported by ERDF/ESF project PharmaBrain [no. CZ.02.1.01/0.0/0.0/16_025/0007444] and University of Hradec Kralove [no. IRP1902/2018, VT2201/2018].

The soils beneath and surrounding mature Artocarpus mariannensis, Elaeocarpus joga, and Serianthes nelsonii trees were studied in northern Guam limestone forests to determine the role of these trees in maintaining spatial heterogeneity of biogeochemistry. The soils beneath S. nelsonii were nutrient-enriched compared to soils away from S. nelsonii. The soils beneath A. mariannensis were depauperate for some nutrients or were not different from the soils away from A. mariannensis for other nutrients. The soils beneath E. joga exhibited increases in some nutrients such as nitrogen, carbon, and phosphorus, but decreases in other nutrients such as potassium and calcium when compared to the soils away from E. joga trees. These three tree species influenced spatial heterogeneity in soil nutrient status in the order A. mariannensis < E. joga < S. nelsonii and their presence added greatly to surface soil heterogeneity. Iron, manganese, and pH exhibited the least variation within the paired sites. Calcium, magnesium, potassium, and zinc exhibited the greatest variation among the paired sites. These findings indicate that continuing loss of these trees from Guam’s forests will diminish the associated biogeochemical spatial heterogeneity.

The aim of the presented study was to reveal the frequency of insomnia spells in E200K genetic Creutzfeldt–Jakob disease (gCJD) patients. Clinical records of 22 subjects diagnosed with E200K gCJD were retrospectively reviewed. The patients w/wo insomnia (n = 4, 18%/n = 18, 82%) did not differ in age, sex and the duration of the symptomatic phase. Analysis of the clinical features in the groups yielded differences in the clinical signs in the early phase of the disorder, proportion of homozygotes (Met/Met) at codon 129, MRI changes in the thalamus and the typical EEG abnormality. The study suggests that apart from traditional clinical features, the insomnia is not a rare early symptom in phenotype of E200K gCJD based on early thalamic involvement.

Context: The dried fruits of Arctium lappa L. have been used in two forms in traditional Chinese medicine; crude and stir-heating Fructus Arctii. However, its processed product possesses better activity. Objective: In this study, the chemical constituents of both crude and processed Fructus Arctii and their antiproliferative activities were evaluated. Materials and methods: The seven main active components in crude and various processed Fructus Arctii were quantitatively determined using high-performance liquid chromatography (HPLC). According to the actual amount in crude and five processed samples, seven single components were combined as multi-component combinations with six different proportions. The antiproliferative activities of these compatibility component groups were examined using the CCK-8 assay. Results: During the heating process, the proportion of the seven main components changed dynamically. The contents of 3-caffeoylquinic acid (3-CQA), 3,5-dicaffeoylquinic acid (3,5-diCQA), and arctiin (ARC) declined, while the contents of 4-caffeoylquinic acid (4-CQA), 3,4-dicaffeoylquinic acid (3,4-diCQA), 4,5-dicaffeoylquinic acid (4,5-diCQA), and arctigenin (ARG) increased very significantly. Discussion and conclusions: The results also indicated that seven components in the processed samples had higher cytotoxic profiles against HL-60 cells than those in the crude sample. Therefore, the heating process may enhance the antitumor activity of Fructus Arctii by changing the proportion of active components.

Newcastle disease (ND) remains an important enzootic disease in chickens in several parts of the world. With the increasing reports of virulence and genetic diversity of the causative agent; Newcastle disease virus (NDV), there is a need to identify the circulating NDV in specific regions. In Oman, to this moment, such information is still lacking. The aim of this study was to isolate and characterize the NDV from ND outbreaks from commercial farms in Oman. Following suspected outbreaks of ND in three commercial farms in 2017, a total of 30 carcasses (10 from each flock) of adult chickens were subjected to necropsy for gross and histopathological examination, virus isolation and molecular methods. Specifically, haemagglutination inhibition (HI) test and reverse transcription-polymerase chain reaction (RT-PCR) assay were used for the virus detection and confirmation, respectively. Lesions were suggestive of viscerotropic velogenic form of ND based on gross and histopathological examinations. Isolation of NDV was present in 4 cases and further confirmed by RT-PCR following the target of the partial fusion protein gene of the viral genome. The sequence of the partial fusion gene was determined and phylogenetic tree was constructed based on the partial length F gene of 4 Omani isolates and 65 previously published NDVs. The findings predicted that the Omani isolates had high homology (99%) with the isolate from Pakistan belonging to genotype VII. Subsequently, the isolated pathotype was identified as the virulent NDV. This study serves as a basic work for further research on the analysis and phenotyping of NDV in the Sultanate of Oman. Improved monitoring and surveillance of the disease is important for proper preventive measures. Keywords: Genotype, Phylogenetic tree, Poultry, Virulent

Graphical abstract, Grape pomace obtained as a byproduct of industrial processing of grapes retains nutrients and substances with anthelmintic potential such as saponins, tannins, and flavonoids. Therefore, this study evaluated the in vitro ovicidal and larvicidal activity of hydroalcoholic grape pomace extract against gastrointestinal nematodes of sheep. The anthelmintic evaluation was performed by in vitro assays with eggs and larvae of nematodes obtained from naturally infected donor sheep. The grape pomace extract showed high in vitro ovicidal and larvicidal activity with LD50 values of 0.30 mg/mL for egg hatching inhibition, 1.01 mg/mL for larval development inhibition and 100% efficacy in larval migration inhibition assays at all concentrations evaluated. The effect of tannins was evaluated by the addition of 50 mg/mL polyvinyl polypyrrolidone to grape pomace extract at the concentration of 12.5 mg/mL. The in vitro ovicidal activity of grape pomace was reduced by only 15% after polyvinyl polypyrrolidone addition, indicating that other phytochemicals also contribute to the ovicidal activity displayed by the extract. Our results demonstrate that grape pomace exhibits in vitro anthelmintic activity, suggesting that, beyond its nutritional potential, this pomace can also be an ally for gastrointestinal nematode control in sheep.

The aim of this article is to present a research-based rationale for NETfacts, a newly developed integrated approach at the individual and the community level in order to mitigate the mental and social sequelae of war and crisis. To this end, we provide a selective review of relevant literature from neuroscience, clinical psychology, and social science. In psychotraumatology, individual avoidance describes the effort to prevent exposure to trauma reminders. Among patients with post-traumatic stress disorder (PTSD), this becomes pathological, exacerbating distress and preventing recovery. This silence resonates in traumatized communities and consequently taboo builds – ultimately to the advantage of the perpetrators. The resulting collective avoidance leads to a fragmented collective memory about trauma or human rights violations in the community so that a shared account of the group’s history becomes impossible. The deficient collective memory promotes ambiguous truths and anxiety, enabling a reactive construction of safety based on selective information that leads to an endorsement of extreme opinions. Ongoing insecurity, violence and crime lead to increasing anxiety and fear. The self-interest of the perpetrators and the abnormal behaviour of survivors leads to an escalation in stigma and social exclusion resulting in the prevention or limitation of community exposure to traumatic material, i.e., to reduce tension and protect the construction of safety. The exposure to and recognition of traumatic facts subject to avoidance is key to a coherent collective memory and sense of communion, and to prevent further cycles of violence. The NETfacts health system combines individual and community-based intervention to treat the structure of memory at both the individual and collective levels. Abbreviations: NET: narrative exposure therapy; FORNET: narrative exposure therapy for forensic offender rehabilitation; NETfacts: facts derived from narrative exposure therapy, HIGHLIGHTS The article provides selected neuroscientific, clinical, and social science research to introduce the theoretical rationale of NETfacts; a newly developed integrated approach at the individual and the community level to mitigate the mental and social sequelae of crisis.

Background: Couple HOPES (Helping Overcome PTSD and Enhance Satisfaction) was created to help overcome a range of barriers to accessing psychotherapy for posttraumatic stress disorder (PTSD) and commonly associated intimate relationship problems. Objective: Couple HOPES is a guided, online self-help intervention adapted from Cognitive-Behavioural Conjoint Therapy for PTSD that aims to improve PTSD and enhance relationship satisfaction. Method/Results: This paper describes the processes and principles used to develop the Couple HOPES intervention platform as well as the coaching model and manual used to promote engagement and adherence to the intervention. Conclusions: Current research and future directions in testing Couple HOPES are outlined., HIGHLIGHTS Couple HOPES is a guided, online self-help intervention adapted from Cognitive-Behavioural Conjoint Therapy for PTSD. It was created to overcome the many barriers to established in-person evidence-based psychotherapies.

Background: Intensive treatment could be effective for patients with post-traumatic stress disorder (PTSD). Objective: The aim of the study was to test the feasibility of an 8-day (2-week) intensive outpatient treatment for PTSD. Method: Treatment each day consisted of individual Prolonged Exposure (PE), Eye Movement Desensitization and Reprocessing (EMDR), and psychoeducation and physical activity in groups. Patients met different therapists from session to session. Results: Six patients started and completed treatment. Levels of attendance of sessions was high. Patients reported that they were satisfied with the treatment, describing it as emotionally taxing, but meaningful. Therapists also described several positive aspects of the treatment format. There were large reductions in PTSD symptoms. Conclusions: Given these promising, but preliminary findings on the programme’s feasibility, future research should investigate this treatment format using larger samples and controlled designs., HIGHLIGHTS This 8-day (2-week) intensive outpatient treatment programme was feasible for patients suffering from severe PTSD. Treatment combined two types of trauma-focused treatment (PE and EMDR), psychoeducation, physical activity, and therapist rotation. All patients completed treatment and described it as emotionally taxing, but manageable and meaningful. Patients reported to be satisfied with the treatment, and there were large reductions in PTSD symptoms.

Background: University and college students are not usually identified as a population at risk during the COVID-19 pandemic. Yet, there is growing evidence of their specific distress associated with facing multiple abrupt changes and the need for rapid adaptation to a variety of academic, social, and financial challenges. The extent of their exposure to COVID-19 media and the associated media-related stress may further impair students’ perceived coping. Objective: This study assessed COVID-19-related functional difficulties and perceived coping among higher education students in Israel and explored the moderating role played by media coverage of the pandemic in inducing stress and exacerbating COVID-19-related difficulties in perceived coping among students. Method: Data was collected from 7,446 students from seven academic centres in Israel through online questionnaires about four to six weeks after the outbreak of the pandemic in Israel. Results: The findings showed positive associations between COVID-19-related difficulties, media exposure, media-related stress, and decreased levels of perceived coping with the pandemic. Moreover, media-related stress (but not the level of media exposure) moderated the relationship between COVID-19-related difficulties and perceived coping: the associations were significantly stronger for students reporting high media-related stress in comparison to individuals reporting low media-related stress. Conclusions: These results highlight the specific role of media-related stress and the need to distinguish this risk factor from the global impact of exposure to media coverage. The need for self-monitoring of the subjective level of stress associated with media exposure should be part of the psychoeducation efforts provided by public health authorities for promoting self-care during the COVID-19 pandemic., HIGHLIGHTS This study assessed COVID-19-related functional difficulties and perceived coping among 7,446 higher education students and explored the moderating role played by media coverage of the pandemic in inducing stress and exacerbating COVID-19-related difficulties in perceived coping.

Cognitive-behavioural conjoint therapy (CBCT) for PTSD has been shown to improve PTSD, relationship adjustment, and the health and well-being of partners. MDMA (3,4-methylenedioxymethamphetamine) has been used to facilitate an individual therapy for PTSD. This study was an initial test of the safety, tolerability, and efficacy of MDMA-facilitated CBCT. Six couples with varying levels of baseline relationship satisfaction in which one partner was diagnosed with PTSD participated in a condensed version of the 15-session CBCT protocol delivered over 7 weeks. There were two sessions in which both members of the couple were administered MDMA. All couples completed the treatment protocol, and there were no serious adverse events in either partner. There were significant improvements in clinician-assessed, patient-rated, and partner-rated PTSD symptoms (pre- to post-treatment/follow-up effect sizes ranged from d = 1.85–3.59), as well as patient depression, sleep, emotion regulation, and trauma-related beliefs. In addition, there were significant improvements in patient and partner-rated relationship adjustment and happiness (d =.64–2.79). These results are contextualized in relation to prior results from individual MDMA-facilitated psychotherapy and CBCT for PTSD alone. MDMA holds promise as a facilitator of CBCT to achieve more robust and broad effects on individual and relational functioning in those with PTSD and their partners., HIGHLIGHTS • MDMA was combined with cognitive-behavioural conjoint therapy for PTSD in six couples revealing significant improvements in PTSD, depression, sleep, emotion regulation, trauma beliefs, and relationship satisfaction.• Controlled studies are planned based on these promising results.

Background: The ability of coronavirus SARS-CoV-2 to spread is one of the determinants of the COVID-19 pandemic status. Until June 2020, global COVID-19 cases surpassed 10 million. Asymptomatic patients, with no respiratory impairment, are believed to be responsible for more than 80% of the transmission. Other viruses have been consistently detected in periodontal tissues. Objective: The aim of this study was to investigate the presence of SARS-CoV-2 in periodontal tissue. Methods: We conducted video-endoscope minimally invasive post-mortem biopsy in seven fatal cases of COVID-19, using a regular endoscope video system associated with a smartphone to locate periodontal tissue. We analyzed the samples using RT-PCR, to identify the SARS-CoV-2 RNA and histopathological analysis. Results: The seven studied autopsies with positive laboratory tests for COVID-19 included 57.14% of female patients at the average age of 47.4 (range 8 to 74). In five cases, periodontal tissue was positive for SARS-CoV-2 (RT-PCR). Histopathologic analyses showed morphologic alterations in the keratinocytes of the junctional epithelium, a vacuolization of the cytoplasm and nucleus and nuclear pleomorphism. Conclusion: We presented a biomolecular analysis obtained from minimally invasive autopsies. This is the first study to demonstrate the presence of SARS-CoV-2 in periodontal tissue in COVID-19 positive patients.

As an important transcription factor family, GROWTH-REGULATING FACTORs (GRFs) are involved in central development processes, including growth regulation, insect and disease resistance, and stress response. The OsGRF7 has recently been shown involving in modulating leaf angle through regulating GA and IAA metabolism. Interestingly, we found that OsGRF7 negatively regulates the tiller number. However, the detailed molecular mechanisms of OsGRF7 underlying the tiller number determination are still not understood. Here, we report that OsGRF7 directly targets the promoter of the NODULATION SIGNALING PATHWAY2 (OsNSP2), a key factor involving in the strigolactone synthesis. Correspondingly, OsGRF7 alters the expression level of OsNSP2 and the endogenous strigolactone content, which rendered repression of the outgrowth of the axillary buds. These findings unveil a novel function of OsGRF7 in rice tillering determination.

Hydrogen sulfide (H(2)S) is an important gas signal molecule, but little is known about its signal mechanism. Ca(2+) is an important second messenger in plant cells, and its fluctuation in the cytoplasm causes downstream physiological responses. Our previous study found that H(2)S can induce the accumulation of hydrogen peroxide (H(2)O(2)). We also found that reactive oxygen species (ROS) can further induce the Ca(2+) influx in guard cells by noninvasive micro-teat technology (NMT). This study confirmed that the accumulation of reactive oxygen species to induce Ca(2+) signal in guard cells, resulting in stomatal closure. Thus, revealing a novel mechanism of H(2)S promoting stomatal closure.

Our submission is responsive to the urgent need for public mental health action prompted by the escalating COVID-19 pandemic. In it, we review the evidence calling for urgent public mental health action, propose a mental health equivalent fo the World Health Organization's 'Do the Five' concept, and describe the 'REACH for Mental Health' public health measure we have launched at the Harvard T.H. Chan School of Public Health.Nuestra presentación responde a la necesidad urgente de acciones en la salud mental pública debido a la creciente pandemia de COVID-19. En esta presentación revisamos la evidencia que exige acciones urgentes de la salud mental pública, proponemos un equivalente de salud mental del concepto ‘Haz los cinco’ de la Organización Mundial de la Salud, y describimos la intervención de salud pública ‘REACH (por sus siglas en ingles) para Salud Mental’ que hemos lanzado en la Escuela T.H. Chan de Salud Pública de Harvard.本文是对因COVID-19大流行升级而急需采取公共精神卫生行动的回应。在本文中, 我们综述了呼吁采取紧急公共精神卫生行动的证据, 提出了与世界卫生组织的‘做到五点 (Do the Five)’概念相当的心理健康措施, 并描述了我们在哈佛大学陈水清公共卫生学院共同发起的‘为精神卫生提供REACH心理健康’公共卫生干预措施。我们描述了这种干预措施以支持必要的公共卫生行动, 以防止随着COVID-19大流行的全面展开而引发的广泛精神卫生危机。.

Given the rapid spread of the COVID-19 pandemic and the huge negative impacts it is causing, researching on COVID-19-related issues is very important for designing proactive and comprehensive public health interventions to fight against the pandemic. We describe the characteristics of COVID-19 patients detected in the two phases of the epidemic in Vietnam. Data used in this paper were mainly obtained from the official database of the Ministry of Health of Vietnam. Descriptive statistics were carried out using Stata 16 software. As of 18 May 2020, the cumulative number of COVID-19 cases detected in Vietnam was 324, 16 cases from 4 cities and provinces in the first phase (during 20 days, 0.8 cases detected per day) and 308 cases from 35 cities, provinces in the second phase (during 76 days, 4.1 cases detected per day). Vietnam has mobilized its entire political system to fight the COVID-19 and achieved some initial successes. We found both similarities and differences between the two phases of the COVID-19 epidemic in Vietnam. We demonstrated that the situation of the COVID-19 epidemic in Vietnam is getting more complicated and unpredictable.

Population growth, socio-cultural and economic changes as well as technological progress have an immediate impact on the environment and human health in particular. Our steadily rising needs of resources increase the pressure on the environment and narrow down untainted habitats for plants and wild animals. Balance and resilience of ecosystems are further threatened by climate change, as temperature and seasonal shifts increase the pressure for all species to find successful survival strategies. Arctic and subarctic regions are especially vulnerable to climate change, as thawing of permafrost significantly transforms soil structures, vegetation and habitats. With rising temperature, the risk of zoonotic diseases in the Republic of Sakha (Yakutia) has also increased. As vegetation periods prolong and habitats broaden, zoonotic pathogens and their vectors find more favourable living conditions. Moreover, permafrost degradation may expose historic burial grounds and allow for reviving the vectors of deadly infections from the past. To assess the current state of knowledge and emerging risks in the light of the “One Health” concept, a German-Russian Symposium took place on 13 August 2018 in Yakutsk, Russian Federation. This symposium report presents the main findings generated from presentations and discussions.

Background While there are several curricula using patients as educators, little has been published on how they affect student learning and professional development. Objective To explore what 1st year medical students learn about professional values from a patient-led educational experience and how it affects their professional development. Design We piloted a pediatric patient and family-led educational session during the molecular medicine course, with the goal of sharing the experience of caring for a child with a chronic illness. Following the session, students were required to submit a written reflection on what they learned and the impact the session had on them. All reflections from one academic year were qualitatively analyzed by two investigators and organized using HyperRESEARCH software. A content analysis approach was used to generate codes and emergent themes. Two theoretical lenses guided the analyses: Arnold’s framework on professional values and the lens of professional identity formation, described as a process by which health care professionals “think, act and feel like a physician. Results Students gained an appreciation of professional values, especially humanism and excellence, and how clinician role models reinforce these values. Reflective writings demonstrated recognition among learners that their identity involved being active participants in health care delivery and not just as passive classroom learners. Students were motivated to study diligently and be patient advocates; some questioned their skills in dealing with ambiguity and with the health-care system, resulting in a sense of helplessness. Conclusion Students learn the importance of professional attributes and of clinician role models through a pediatric family teaching experience. They are motivated, displaying glimpses of their future role as caregivers and patient advocates; however, some also express fear and doubt their own abilities. Based on this, a debriefing session has been introduced to prevent a negative effect on learner self-efficacy.

Phagocytosis plays important roles both in homeostasis and under pathological conditions. Fcγ receptor-mediated phagocytosis has been exploited as an integral mechanism for antibody-based therapies. Unlike Fcγ receptor-mediated phagocytosis, MerTK-mediated phagocytic clearance is immunologically silent. Here, we describe a bispecific antibody approach to harness MerTK for targeted clearance without inducing proinflammatory cytokine release associated with Fcγ receptor engagement. We generated bispecific antibodies targeting live B cells or amyloid beta aggregates to demonstrate the feasibility and versatility of this new approach.

This study aimed to evaluate vascular endothelial growth factor (VEGF) and pentraxin 3 (PTX-3) as predictive and diagnostic markers in differentiating severe dengue from non-severe dengue. The study was conducted in Ampang Health Clinic, Ampang Hospital and Serdang Hospital. The plasma levels of VEGF and PTX-3 were compared between severe dengue and non-severe dengue by ELISA from the day of presentation until discharged. Multiple logistic regression was used to develop predictive and diagnostic models by incorporating other clinical parameters. The receiver operating characteristics (ROC) analysis was used to assess the accuracy of the biomarkers and the developed models. Eighty-two patients were recruited, 29 with severe dengue and four died. The Area Under the Curve (AUC) was statistically significant in VEGF as diagnostic marker at Day 2 and 3 of illness with sensitivity of 80.00%-100.00% and specificity of 76.47%-80.00%. The predictive model with AUC of 0.84 (p

Arabidopsis roots sense the moisture gradient in soils and grow toward an area with higher water potential – a process called hydrotropism. Our previous study has shown that the apoplastic proton extrusion in root tips is influenced by brassinosteroids (BRs) receptor BR-INSENSITIVE1 (BRI1) and is crucial for hydrotropic response in Arabidopsis. Here we show that BRI1 interacts directly not only with Arabidopsis plasma membrane H+-ATPase 2 (AHA2) but also with Arabidopsis plasma membrane H+-ATPase 7 (AHA7). Therefore, BRI1 may affect hydrotropic response via regulating the activities of AHA2 and AHA7.