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Halide perovskite materials have recently been recognised as powerful ferroelectric and piezoelectric materials with applications in the energy harvesting arena, but their experimental proof is very limited. We achieved strong intrinsic piezoelectricity in the lead-free inorganic double perovskite Cs2AgBiBr6 at room temperature and utilized it for mechanical energy harvesting, with a piezoelectric co-efficient (d33) of 12.7 pC N-1. Hysteresis loop and structural analyses offered further validation for the substantial ferroelectric features of the as-synthesised double perovskite. Density functional theory (DFT) calculations revealed the presence of anharmonic phonon soft modes in tetragonal Cs2AgBiBr6 due to dynamic instability, which resulted in piezoelectricity. Under an optimal pressure of ≈25 kPa, a Cs2AgBiBr6 thin film-based piezoelectric nanogenerator device delivered instantaneous output values of ≈45 V and ≈200 nA. The strain-sensitive responses of the device were also exemplified to identify specific body motions from the detected instantaneous output values. The energy obtained from the device is shown to be effective for capacitor charging and commercial light-emitting diode (LED) lighting. Our study provides significant insights into the dielectric behaviour of materials as well as piezo- and ferroelectric behaviours, which are crucial for the development of modern electronic and energy harvesting devices.
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Three cardinal two-dimensional semiconductorsviz., AlC3, BC3and C3N, closely resembling the graphene structure, are intriguing contenders for emerging optoelectronic and thermomechanical applications. Starting from a critical stability analysis, this density functional theory study delves into a quantitative assessment of structural, mechanical, electronic, optical, vibrational and thermodynamical properties of these monolayers as a function of biaxial strain(ε)in a sublinear regime(-2%⩽ε⩽4%)of elastic deformation. The structures with cohesive energies slightly smaller than graphene, manifest exceptional mechanical stiffness, flexibility and breaking stress. The mechanical parameters have been deployed to further cultivate acoustic attributes and thermal conductivity. The hexagonal structures with mixed ionic-covalent molecular bonds have indirect electronic band-gap and work-function acutely sensitive toε. Dispersions of optical dielectric function, energy loss, refractive index, extinction coefficient, reflectivity, absorption coefficient and conductivity are deciphered in the UV-Vis-NIR regime against strain, where particular frequency bands featuring high polarization, dissipation, absorbance or reflectance are identified. Phonon band-structure and density of states testify dynamic stability in the ground state for all systems except the compressed ones. A comprehensive group theoretical analysis is performed to cultivate rotational; infrared and Raman-active modes, and the nature of molecular vibrations is delineated. The red-shifting of phonon bands andE2g/A1gRaman peaks with increasingε, associates estimation of Grüneisen parameter. Finally, strain-induced alterations of thermodynamic quantities such as entropy, enthalpy, free energy, heat capacity and Debye temperature are studied, followed by a molecular dynamics-based stability assessment under canonical ensemble.
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Malaria eradication is still a global challenge due to the lack of a broadly effective vaccine and the emergence of drug resistance to most of the currently available drugs as part of the mainline artemisinin-based combination therapy. A variety of experimental approaches are quite successful in identifying and synthesizing new promising pharmacophore hybrids with distinct mechanisms of action. Based on our recent findings, the current study demonstrates the reinvestigation of a series of diphenylmethylpiperazine and pyrazine-derived molecular hybrids. Pyrazine-derived molecular hybrids were screened to investigate the antiplasmodial activity on drug-susceptible Pf3D7 and drug-resistant PfW2 strains. The selected compounds were shown to be potent dual inhibitors of cysteine protease PfFP2 and PfFP3. Time-course parasitic development study demonstrated that compounds were able to arrest the growth of the parasite at the early trophozoite stage. The compounds did not show hemolysis of red blood cells and showed selectivity to the parasite compared with the mammalian Vero and A5489 cell lines. The study underlined HR5 and HR15 as a new class of Plasmodial falcipain inhibitors with an IC50 of 6.2 µM and 5.9 µM for PfFP2 and 6.8 µM and 6.4 µM for PfFP3, respectively. Both compounds have antimalarial efficacy with IC50 values of 3.05 µM and 2.80 µM for the Pf3D7 strain, and 4.35 µM and 3.39 µM for the PfW2 strain, respectively. Further structural optimization may turn them into potential Plasmodial falcipain inhibitors for malaria therapeutics.
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OBJECTIVES: To evaluate the effectiveness of robot-assisted therapy (RAT) followed by activities of daily living (ADL) training in comparison with conventional rehabilitation therapy (CRT) and ADL training in individuals with subacute stroke. DESIGN: A single-blind, 2-arm, parallel-group, open-level, randomized controlled trial. SETTING: A tertiary care teaching hospital in India. PARTICIPANTS: Forty-four persons (n=44) with first-ever stroke (in subacute stage) were enrolled from August 2021 to July 2023. INTERVENTION: Participants in the RAT group (n=22) received RAT for 30 minutes, followed by ADL training for 30 minutes. In contrast, participants in the CRT group (n=22) received CRT (30 minutes) followed by ADL training (30 minutes). Both groups received allocated interventions for 15 days over 3 weeks (5 days/week, 3 weeks). MAIN OUTCOME MEASURES: Primary outcome: Motor domain score of the Fugl-Meyer Assessment scale for upper extremity (FMA-UE). SECONDARY OUTCOMES: the other domains scores of FMA-UE (UL -sensation, -joint motions, -joint pain); Modified Ashworth Scale (MAS) (spasticity); hand-function (HF) and ADL-domain scores of the stroke impact scale (SIS); WHOQQL-BREF questionnaires (QOL). Participants were assessed at enrolment and follow-up at 3, 6, and 12 weeks. RESULTS: Persons who received RAT and ADL training reported significant improvement (P<.05) in UL motor function (mean difference [MD]=3.54;(95% confidence interval [CI]: 1.28 to 5.79]), UL passive joint motions (MD=2.54; [95% CI: 1.56 to 3.52]), SIS-HF (MD=6.37;[95% CI: 4.75 to 7.99]), SIS-ADL (MD=7.13 [95% CI: 3.52 to 8.74]), and in all domains of WHOQOL-BREF (except environmental domain) compared with persons who received CRT and ADL training at 12 weeks. CONCLUSIONS: The findings indicate that RAT followed by ADL training is more effective than CRT followed by ADL training in motor improvement, SIS-HF, SIS-ADL, and QOL at 12 weeks.
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Atividades Cotidianas , Recuperação de Função Fisiológica , Robótica , Reabilitação do Acidente Vascular Cerebral , Extremidade Superior , Humanos , Reabilitação do Acidente Vascular Cerebral/métodos , Masculino , Feminino , Método Simples-Cego , Pessoa de Meia-Idade , Extremidade Superior/fisiopatologia , Idoso , Índia , AdultoRESUMO
INTRODUCTION: Organophosphorus compounds (OPC) are one of the most commonly used pesticides worldwide and are often misused for suicidal poisoning due to their easy availability. Acute manifestations and management of organophosphorus (OP) poisoning have been reported several times. Organophosphorus-induced delayed neurotoxicity (OPIDN) is a rare delayed presentation of OP poisoning that involves central-peripheral distal axonopathy. CASE PRESENTATION: In this study, we report two cases of OPIDN developed after a few weeks of OP poisoning. Clinical features, electrodiagnostic study findings, and rehabilitative measures adopted for the patients and their follow-up have been described in the report. DISCUSSION: Organophosphorus (OP) poisoning may rarely produce features of delayed neurotoxicity, which may gradually appear after acute cholinergic symptoms. This report shows the importance of considering the delayed presentation of possible OPC toxicity in patients with neurological symptoms and a history of OPC exposure.
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Síndromes Neurotóxicas , Intoxicação por Organofosfatos , Humanos , Intoxicação por Organofosfatos/complicações , Intoxicação por Organofosfatos/diagnóstico , Compostos Organofosforados/toxicidade , Síndromes Neurotóxicas/diagnóstico , Síndromes Neurotóxicas/etiologiaRESUMO
Emerging resistance against artemisinin (ART) poses a major challenge in controlling malaria. Parasites with mutations in PfKelch13, the major marker for ART resistance, are known to reduce hemoglobin endocytosis, induce unfolded protein response (UPR), elevate phosphatidylinositol-3-phosphate (PI3P) levels, and stimulate autophagy. Nonetheless, PfKelch13-independent resistance is also reported, indicating extensive complementation by reconfiguration in the parasite metabolome and transcriptome. These findings implicate that there may not be a single 'universal identifier' of ART resistance. This review sheds light on the molecular, transcriptional, and metabolic pathways associated with ART resistance, while also highlighting the interplay between cellular heterogeneity, environmental stress, and ART sensitivity.
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Antimaláricos , Artemisininas , Malária Falciparum , Humanos , Plasmodium falciparum/genética , Plasmodium falciparum/metabolismo , Malária Falciparum/tratamento farmacológico , Malária Falciparum/parasitologia , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Mutação , Resistência a Medicamentos/genética , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismoRESUMO
Malaria is a widespread infectious disease, causing nearly 247 million cases in 2021. The absence of a broadly effective vaccine and rapidly decreasing effectiveness of most of the currently used antimalarials are the major challenges to malaria eradication efforts. To design and develop novel antimalarials, we synthesized a series of 4,7-dichloroquinoline and methyltriazolopyrimidine analogues using a multi-component Petasis reaction. The synthesized molecules (11-31) were screened for in-vitro antimalarial activity against drug-sensitive and drug-resistant strains of Plasmodium falciparum with an IC50 value of 0.53 µM. The selected compounds were screened to evaluate in-vitro and in-silico enzyme inhibition efficacy against two cysteine proteases, PfFP2 and PfFP3. The compounds 15 and 17 inhibited PfFP2 with an IC50 = 3.5 and 4.8 µM, respectively and PfFP3 with an IC50 = 4.9 and 4.7 µM, respectively. Compounds 15 and 17 were found equipotent against the Pf3D7 strain with an IC50 value of 0.74 µM, whereas both were displayed IC50 values of 1.05 µM and 1.24 µM for the PfW2 strain, respectively. Investigation of effect of compounds on parasite development demonstrated that compounds were able to arrest the growth of the parasites at trophozoite stage. The selected compounds were screened for in-vitro cytotoxicity against mammalian lines and human red-blood-cell (RBC), which demonstrated no significant cytotoxicity associated with the molecules. In addition, in silico ADME prediction and physiochemical properties supported the drug-likeness of the synthesized molecules. Thus, the results highlighted the diphenylmethylpiperazine group cast on 4,7-dichloroquinoline and methyltriazolopyrimidine using Petasis reaction may serve as models for the development of new antimalarial agents.
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Antimaláricos , Cisteína Proteases , Malária , Animais , Humanos , Antimaláricos/química , Malária/tratamento farmacológico , Plasmodium falciparum , Eritrócitos , MamíferosRESUMO
Despite several initiatives to subside the global malaria burden, the spread of artemisinin-resistant parasites poses a big threat to malaria elimination. Mutations in PfKelch13 are predictive of ART resistance, whose underpinning molecular mechanism remains obscure. Recently, endocytosis and stress response pathways such as the ubiquitin-proteasome machinery have been linked to artemisinin resistance. With Plasmodium, however, ambiguity persists regarding a role in ART resistance for another cellular stress defence mechanism called autophagy. Therefore, we investigated whether, in the absence of ART treatment, basal autophagy is augmented in PfK13-R539T mutant ART-resistant parasites and analyzed whether PfK13-R539T endowed mutant parasites with an ability to utilize autophagy as a pro-survival strategy. We report that in the absence of any ART treatment, PfK13-R539T mutant parasites exhibit increased basal autophagy compared to PfK13-WT parasites and respond aggressively through changes in autophagic flux. A clear cytoprotective role of autophagy in parasite resistance mechanism is evident by the observation that a suppression of PI3-Kinase (PI3K) activity (a master autophagy regulator) rendered difficulty in the survival of PfK13-R539T ART-resistant parasites. In conclusion, we now show that higher PI3P levels reported for mutant PfKelch13 backgrounds led to increased basal autophagy that acts as a pro-survival response to ART treatment. Our results highlight PfPI3K as a druggable target with the potential to re-sensitize ART-resistant parasites and identify autophagy as a pro-survival function that modulates ART-resistant parasite growth.
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With the contemplations of ecological and environmental issues related to energy harvesting, piezoelectric nanogenerators (PNGs) may be an accessible, sustainable, and abundant elective wellspring of energy in the future. The PNGs' power output, however, is dependent on the mechanical energy input, which will be intermittent if the mechanical energy is not continuous. This is a fatal flaw for electronics that need continuous power. Here, a self-charging flexible supercapacitor (PSCFS) is successfully realized that can harvest sporadic mechanical energy, convert it to electrical energy, and simultaneously store power. Initially, chemically processed multimetallic oxide, namely, copper cobalt nickel oxide (CuCoNiO4) is amalgamated within the poly(vinylidene fluoride) (PVDF) framework in different wt % to realize high-performance PNGs. The combination of CuCoNiO4 as filler creates a notable electroactive phase inside the PVDF matrix, and the composite realized by combining 1 wt % CuCoNiO4 with PVDF, coined as PNCU 1, exhibits the highest electroactive phase (>86%). Under periodic hammering (â¼100 kPa), PNGs fabricated with this optimized composite film deliver an instantaneous voltage of â¼67.9 V and a current of â¼4.15 µA. Furthermore, PNG 1 is ingeniously integrated into a supercapacitor to construct PSCFS, using PNCU 1 as a separator and CuCoNiO4 nanowires on carbon cloth (CC) as the positive and negative electrodes. The self-charging behavior of the rectifier-free storage device was established under bending deformation. The PSCFS device exhibits â¼845 mV from its initial open-circuit potential â¼35 mV in â¼220 s under periodic bending of 180° at a frequency of 1 Hz. The PSCFS can power up various portable electronic appliances such as calculators, watches, and LEDs. This work offers a high-performance, self-powered device that can be used to replace bulky batteries in everyday electronic devices by harnessing mechanical energy, converting mechanical energy from its environment into electrical energy.
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Malaria is the most lethal parasitic infections in the world. To address the emergence of drug resistance to current antimalarials, here we report the design and synthesis of new series of tetrahydrobenzothieno[2,3-d]pyrimidine-acetamide hybrids by using multicomponent Petasis reaction as the key step and evaluated in vitro for their antimalarial effectiveness. The structure of all the compounds were confirmed by NMR Spectroscopy and mass spectrometry. Most of the compounds showed potent antimalarial activity against both CQ-sensitive (3D7) and CQ-resistant (W2) strains. A8, A5, and A4 are the most potent compounds that showed excellent anti-plasmodial activity against CQ-resistant strain in the nanomolar range with IC50 values 55.7â¯nM, 60.8â¯nM, and 68.0â¯nM respectively. To assess the parasite selectivity, the in vitro cytotoxicity of selected compounds (A3-A6, A8) was tested against HPL1D cells, demonstrating low cytotoxicity with high selectivity indices. Furthermore, these compounds were also evaluated on two additional human cancerous cell lines (A549 and MDA-MB-231), confirming their anticancer effectiveness. The in vitro hemolysis assay also showed the non-toxicity of these compounds on normal uninfected human RBCs. The interaction of these hybrids was also investigated by the molecular docking studies in the binding site of wild type Pf-DHFR-TS and quadruple mutant Pf-DHFR-TS. The in silico ADMET profiling also revealed promising physicochemical and pharmacokinetic parameters for the most active hybrids, which provide strong vision for further development of potential antimalarials.
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Antimaláricos , Plasmodium , Humanos , Antimaláricos/química , Simulação de Acoplamento Molecular , Plasmodium falciparum/metabolismo , Pirimidinas/químicaRESUMO
The emergence of Plasmodium falciparum resistance raises an urgent need to find new antimalarial drugs. Here, we report the rational repurposing of the anti-hepatitis C virus drug, alisporivir, a nonimmunosuppressive analog of cyclosporin A, against artemisinin-resistant strains of P. falciparum. In silico docking studies and molecular dynamic simulation predicted strong interaction of alisporivir with PfCyclophilin 19B, confirmed through biophysical assays with a Kd value of 354.3 nM. Alisporivir showed potent antimalarial activity against chloroquine-resistant (PfRKL-9 with resistance index [Ri] 2.14 ± 0.23) and artemisinin-resistant (PfKelch13R539T with Ri 1.15 ± 0.04) parasites. The Ri is defined as the ratio between the IC50 values of the resistant line to that of the sensitive line. To further investigate the mechanism involved, we analyzed the expression level of PfCyclophilin 19B in artemisinin-resistant P. falciparum (PfKelch13R539T). Semiquantitative real-time transcript, Western blot, and immunofluorescence analyses confirmed the overexpression of PfCyclophilin 19B in PfKelch13R539T. A 50% inhibitory concentration in the nanomolar range, together with the targeting of PfCyclophilin 19B, suggests that alisporivir can be used in combination with artemisinin. Since artemisinin resistance slows the clearance of ring-stage parasites, we performed a ring survival assay on artemisinin-resistant strain PfKelch13R539T and found significant decrease in parasite survival with alisporivir. Alisporivir was found to act synergistically with dihydroartemisinin and increase its efficacy. Furthermore, alisporivir exhibited antimalarial activity in vivo. Altogether, with the rational target-based Repurposing of alisporivir against malaria, our results support the hypothesis that targeting resistance mechanisms is a viable approach toward dealing with drug-resistant parasite.
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Antimaláricos , Artemisininas , Malária Falciparum , Malária , Humanos , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Ciclosporina/farmacologia , Ciclosporina/uso terapêutico , Reposicionamento de Medicamentos , Resistência a Medicamentos , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Malária/tratamento farmacológico , Malária Falciparum/tratamento farmacológico , Plasmodium falciparumRESUMO
PURPOSE: The objective of the study was to assess the efficacy of autologous platelet-rich plasma (PRP) injections in the treatment of patellar tendinopathy. METHODS: The PubMed, MEDLINE, EMBASE, CINAHL, and Cochrane Central Register of Controlled Trials databases were searched for clinical trials which compared PRP injection with other 'active treatment' interventions ('Non-PRP' injection and 'No-injection' treatments) or 'No-active treatment' interventions. Randomized and non-randomized clinical trials that had been published up to 15 November 2021, were included in the meta-analysis. The primary outcome, pain relief, was measured on a 'visual analog scale.' Secondary outcomes were knee functional activities and quality of life (QoL). The PRISMA guidelines were followed throughout the study. RESULTS: Eight comparative studies were identified for inclusion in the meta-analysis. Assessment of these studies revealed that there were no significant differences in pain relief, functional outcomes, and QoL in the short, medium, and long term between PRP injection and Non-PRP injection interventions. Similarly, comparison of PRP injection to the No-active treatment intervention showed no differences in short- and medium-term pain relief. However, when PRP injection was compared to the No-injection treatment intervention extracorporeal shock wave therapy (ECWT), the former was found to be more effective in terms of pain relief in the medium term (mean difference [MD] - 1.50; 95% confidence interval [CI] - 2.72 to - 0.28) and long term (MD - 1.70; 95% CI, - 2.90 to - 0.50) and functional outcomes in the medium term (MD 13.0; 95% CI 3.01-22.99) and long term (MD 13.70; 95% CI 4.62-22.78). CONCLUSIONS: In terms of pain relief and functional outcomes, the PRP injection did not provide significantly greater clinical benefit than Non-PRP injections in the treatment of patellar tendinopathy. However, in comparison with ESWT, there was a significant benefit in favor of PRP injection.
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The artemisinin-resistant mutations in Plasmodium falciparum (PfKelch13) identified worldwide are mostly confined to the Broad-complex, tramtrack and bric-à-brac/poxvirus and zinc-finger (BTB/POZ) and Kelch-repeat propeller (KRP) domains. To date, only two crystal structures of the BTB/POZ-KRP domains as tight dimers are available, which limits structure-based predictions and interpretation of its role(s) in inducing clinical artemisinin resistance. Our solution Small-Angle X-ray Scattering (SAXS) data analysis and shape restoration brought forth that: (a) PfKelch13 forms a stable hexamer in P6 symmetry, (b) interactions of the N-termini drive the hexameric assembly, and (c) the six KRP domains project independently in space, forming a cauldron-like architecture. We further deduce that the artemisinin-sensitive mutant A578S is packed like the wild-type protein, however, hexameric assemblies of the predominant artemisinin-resistant mutants R539T and C580Y displayed detectable differences in the spatial positioning of their BTB/POZ-KRP domains. Lastly, mapping of mutations known to enable artemisinin resistance suggested evolutionary pressure in the selection for mutations in the BTB/POZ-KRP domains. These mutations appear non-detrimental to the hexameric assembly of proteins, and yet somehow alter the flux of downstream events essential for the susceptibility to artemisinin.
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Antimaláricos , Artemisininas , Malária Falciparum , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Resistência a Medicamentos/genética , Humanos , Malária Falciparum/tratamento farmacológico , Mutação , Plasmodium falciparum/genética , Plasmodium falciparum/metabolismo , Proteínas de Protozoários/metabolismo , Espalhamento a Baixo Ângulo , Difração de Raios XRESUMO
Objectives: The objectives of the study were to investigate the neuromusculoskeletal complications of Type 2 diabetes mellitus (T2DM) and their associated factors, including the level of physical activity (PA) and clinicodemographic characteristics. Materials and Methods: In this cross-sectional analysis, we included 370 participants diagnosed with T2DM for no <1 year who satisfied the inclusion and exclusion criteria. Demographic and clinical characteristics were noted and a thorough clinical examination was performed on all the participants. International PA Questionnaire-Short Form was used to evaluate the level of PA of the participants. The continuous data is presented as mean ± SD and the categorical data is presented as the number of participants (n) and percentage (%). A logistic regression model was used to investigate the predictors for the prevalence of the complications. Results: The mean duration of T2DM was 7.32 ± 5.53 years and the mean hemoglobin A1C (HbA1c) level (%) was 8.16±1.67. A majority of the participants were having uncontrolled diabetes with an HbA1c level ≥7.5% (n = 190; 51.35%). The level of PA was low in a substantial proportion of the participants (n = 276; 74.59%). A total of 162 (43.78%) participants were diagnosed with neuromusculoskeletal complications. Low back pain was the most common complication and degenerative disk disease was the most common diagnosis overall. Longer duration of diabetes, poor glycemic control, and low PA were associated with the prevalence of neuromusculoskeletal complications (P < 0.05). Conclusion: Neuromusculoskeletal complications of T2DM are common and can result in significant disability in this population. Low PA is very common among T2DM patients and an important contributor to the development of complications. Health-care providers should consider PA an integral component of the management protocol for T2DM patients.
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Tail-anchored (TA) proteins are defined by the absence of N-terminus signal sequence and the presence of a single transmembrane domain (TMD) proximal to their C-terminus. They play fundamental roles in cellular processes including vesicular trafficking, protein translocation and quality control. Some of the TA proteins are post-translationally integrated by the Guided Entry of TA (GET) pathway to the cellular membranes; with their N-terminus oriented towards the cytosol and C-terminus facing the organellar lumen. The TA repertoire and the GET machinery have been extensively characterized in the yeast and mammalian systems, however, they remain elusive in the human malaria parasite Plasmodium falciparum. In this study, we bioinformatically predicted a total of 63 TA proteins in the P. falciparum proteome and revealed the association of a subset with the P. falciparum homolog of Get3 (PfGet3). In addition, our proximity labelling studies either definitively identified or shortlisted the other eligible GET constituents, and our in vitro association studies validated associations between PfGet3 and the corresponding homologs of Get4 and Get2 in P. falciparum. Collectively, this study reveals the presence of proteins with hallmark TA signatures and the involvement of evolutionary conserved GET trafficking pathway for their targeted delivery within the parasite.
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Membrana Celular/metabolismo , Malária Falciparum/metabolismo , Proteínas de Membrana/metabolismo , Plasmodium falciparum/metabolismo , Domínios e Motivos de Interação entre Proteínas , Proteínas de Protozoários/metabolismo , Sequência de Aminoácidos , Retículo Endoplasmático , Humanos , Malária Falciparum/parasitologia , Transporte Proteico , Saccharomyces cerevisiae/metabolismo , Homologia de Sequência de AminoácidosRESUMO
ABSTRACT: The objective of this review was to analyze the existing data on acute inflammatory myelopathies associated with coronavirus disease 2019 infection, which were reported globally in 2020. PubMed, CENTRAL, MEDLINE, and online publication databases were searched. Thirty-three acute inflammatory myelopathy cases (among them, seven cases had associated brain lesions) associated with coronavirus disease 2019 infection were reported. Demyelinating change was seen in cervical and thoracic regions (27.3% each, separately). Simultaneous involvement of both regions, cervical and thoracic, was seen in 45.4% of the patients. Most acute inflammatory myelopathy disorders reported sensory motor and bowel bladder dysfunctions. On cerebrospinal fluid analysis, pleocytosis and increased protein were reported in 56.7% and 76.7% of the patients, respectively. Cerebrospinal fluid severe acute respiratory syndrome coronavirus 2 reverse transcriptase-polymerase chain reaction was positive in five patients. On T2-weighted imaging, longitudinally extensive transverse myelitis and short-segment demyelinating lesions were reported in 76% and 21%, respectively. Among the patients with longitudinally extensive transverse myelitis, 61% reported "moderate to significant" improvement and 26% demonstrated "no improvement" in the motor function of lower limbs. Demyelinating changes in the entire spinal cord were observed in three patients. Most of the patients with acute inflammatory myelopathy (including brain lesions) were treated with methylprednisolone (81.8%) and plasma-exchange therapy (42.4%). An early treatment, especially with intravenous methylprednisolone with or without immunoglobulin and plasma-exchange therapy, helped improve motor recovery in the patients with acute inflammatory myelopathy associated with coronavirus disease 2019.
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COVID-19/complicações , Doenças da Medula Espinal/diagnóstico , Doenças da Medula Espinal/virologia , Diagnóstico por Imagem , Glucocorticoides/uso terapêutico , Humanos , Metilprednisolona/uso terapêutico , Pandemias , SARS-CoV-2 , Doenças da Medula Espinal/tratamento farmacológicoRESUMO
BACKGROUND: Despite numerous efforts to eradicate the disease, malaria continues to remain one of the most dangerous infectious diseases plaguing the world. In the absence of any effective vaccines and with emerging drug resistance in the parasite against the majority of anti-malarial drugs, the search for new drugs is urgently needed for effective malaria treatment. METHODS: The goal of the present study was to examine the compound library, based on indoles generated through diversity-oriented synthesis belonging to four different architecture, i.e., 1-aryltetrahydro/dihydro-ß-carbolines and piperidine/pyrrolidine-fused indole derivatives, for their in vitro anti-plasmodial activity. Trifluoroacetic acid catalyzed transformation involving tryptamine and various aldehydes/ketones provided the library. RESULTS: Among all the compounds screened, 1-aryltetrahydro-ß-carbolines 2 and 3 displayed significant anti-plasmodial activity against both the artemisinin-sensitive and artemisinin-resistant strain of Plasmodium falciparum. It was observed that these compounds inhibited the overall parasite growth in intra-erythrocytic developmental cycle (IDC) via reactive oxygen species-mediated parasitic death and thus could be potential anti-malarial compounds. CONCLUSION: Overall the compounds 2 and 3 identified in this study shows promising anti-plasmodial activity that can kill both artemisinin-sensitive and artemisinin-resistant strains of P. falciparum.
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Antimaláricos/farmacologia , Artemisininas/farmacologia , Resistência a Medicamentos , Indóis/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Antimaláricos/química , Indóis/químicaRESUMO
The incorporation of vacancies in a system is considered a proficient method of defect engineering in general catalytic modulation. Among two-dimensional materials, the deficiency of surface active sites and a high band gap restrict the catalytic activity of hexagonal boron nitride (hBN) material towards the oxygen reduction reaction (ORR), which hinders its applicability in fuel cells. A bane to boon strategy has been introduced here by coupling two sluggish ORR materials (hBN & MoS2) by a probe-sonication method to form a heterostructure (termed HBPS) which fosters four electron pathways to assist the reduction of oxygen. Theoretical and experimental studies suggest the kinetically and thermodynamically favorable formation of boron vacancies (B-vacancies) in the presence of MoS2, which act as active sites for oxygen adsorption in HBPS. B-vacancy induced uneven charge distribution together with band gap depression promote rapid electron transfer from the valance band to the conduction band which prevails over the kinetic limitation of pure hBN nanosheets towards ORR kinetics. The formed B-vacancy induced HBPS further exhibits a low Tafel slope (66 mV dec-1), and a high onset potential (0.80 V vs. RHE) with an unaltered electrochemically active surface area (ESCA) after long-term cycling. Thus, vacancy engineering in hBN has proved to be an efficient approach to unlock the potential of catalytic performance enhancement.
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Magnetite (Fe3O4), a representative relaxor multiferroic material, possesses fundamentally appealing multifaceted size-dependent properties. Herein, to evaluate a prototype spinel transition metal oxide (STMO), monodispersed and highly water-dispersible spherical magnetite nanoparticles (MNPs) with an enormous size range (3.7-242.8 nm) were synthesized via a facile microwave-assisted and polyol-mediated solvothermal approach at a controlled temperature and pressure using unique crystallite growth inhibitors. The excellent long-term colloidal stability of the MNPs in a polar environment and increase in their zeta potential confirmed the coordinative effect of the carboxylate groups derived from the covalent surface functionalization, which was also validated by FTIR spectroscopy, TGA and XPS analysis. The optical bandgap (Eg) between the crystal field split-off bands, which was calculated using the absorption spectra, increased gradually with a decrease in size of the MNPs within a broad UV-Vis range (1.59-4.92 eV). The red-shifting of the asymmetric Raman peaks with a smaller size and short-range electron-phonon coupling could be explained by the modified phonon confinement model (MPCM), whereas ferrimagnetic nature rejigged by superparamagnetism was verified from Mössbauer analysis. These stoichiometric, non-toxic, polar and magnetic nanocrystals are not only ideal for biomedical applications, but also suitable as electroactive porous host networks. Finally, the size-modulated MNPs were incorporated in poly(vinylidene fluoride) [PVDF]-based polytype nanogenerators as an electret filler to demonstrate their piezoelectric performance (VOCâ¼115.95 V and ISCâ¼1.04 µA), exhibiting substantial electromagnetic interference shielding.