ABSTRACT
Semiconducting MXenes are an intriguing two-dimensional (2D) material class with promising electronic and optoelectronic properties. Here, we focused on recently prepared Hf-based MXenes, namely, Hf3C2O2 and Hf2CO2. Using the first-principles calculation and excited state corrections, we proved their dynamical stability, reconciled their semiconducting behavior, and obtained fundamental gaps by using the many-body GW method (indirect 1.1 and 2.2 eV; direct 1.4 and 3.5 eV). Using the Bethe-Salpeter equation, we subsequently provided optical gaps (0.9 and 2.7 eV, respectively), exciton binding energies, absorption spectra, and other properties of excitons in both Hf-based MXenes. The indirect character of both 2D materials further allowed for a significant decrease of excitation energies by considering indirect excitons with exciton momentum along the Γ-M path in the Brillouin zone. The first bright excitons are strongly delocalized in real space while contributed by only a limited number of electron-hole pairs around the M point in the k-space from the valence and conduction band. A diverse range of excitonic states in Hf3C2O2 MXene lead to a 4% and 13% absorptance for the first and second peaks in the infrared region of absorption spectra, respectively. In contrast, a prominent 28% absorptance peak in the visible region appears in Hf2CO2 MXene. Results from radiative lifetime calculations indicate the promising potential of these materials in optoelectric devices requiring sustained and efficient exciton behavior.
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OBJECTIVE: To report six cases of Rhizopus homothallicus rhino-orbital-cerebral mucormycosis in North India between April 2021 and July 2021. CASE DETAILS: All six patients had diabetes, concomitant SARS-CoV-2 infection, a history of oxygen requirement and steroid intake. Among these six cases 4 were female. All patients presented with sinus pain and peri-orbital swelling. COVID-19-associated mucormycosis (CAM) was diagnosed based on microbiological examination of the biopsied tissue, and its staging was determined radiologically by CT and MRI. Three patients were in stage III-C, the others were in stage II-C, II-D and IV-A. A multidisciplinary team treated the patients with extensive surgical debridement of the affected tissue, correction of predisposing comorbidities and administration of an antifungal agents. Patients were followed up for 6 months with routine direct nasal endoscopy to check the sinonasal cavity for any recurrence. All the six patients survived at 6 months of follow-up. CONCLUSION: A timely initiated multidisciplinary team-based approach can reduce the mortality in rhino-orbital-cerebral mucormycosis cases caused by R. homothallicus.
Subject(s)
COVID-19 , Mucormycosis , Humans , Female , Male , Mucormycosis/diagnostic imaging , Mucormycosis/therapy , Tertiary Care Centers , SARS-CoV-2 , Antifungal Agents/therapeutic use , IndiaABSTRACT
Disparities in cancer patient responses have prompted widespread searches to identify differences in sensitive vs. nonsensitive populations and form the basis of personalized medicine. This customized approach is dependent upon the development of pathway-specific therapeutics in conjunction with biomarkers that predict patient responses. Here, we show that Cdk5 drives growth in subgroups of patients with multiple types of neuroendocrine neoplasms. Phosphoproteomics and high throughput screening identified phosphorylation sites downstream of Cdk5. These phosphorylation events serve as biomarkers and effectively pinpoint Cdk5-driven tumors. Toward achieving targeted therapy, we demonstrate that mouse models of neuroendocrine cancer are responsive to selective Cdk5 inhibitors and biomimetic nanoparticles are effective vehicles for enhanced tumor targeting and reduction of drug toxicity. Finally, we show that biomarkers of Cdk5-dependent tumors effectively predict response to anti-Cdk5 therapy in patient-derived xenografts. Thus, a phosphoprotein-based diagnostic assay combined with Cdk5-targeted therapy is a rational treatment approach for neuroendocrine malignancies.
Subject(s)
Neoplasms/drug therapy , Neoplasms/metabolism , Neuroectodermal Tumors/drug therapy , Phosphoproteins/metabolism , Protein Kinase Inhibitors/administration & dosage , Animals , Biomarkers/analysis , Biomarkers/metabolism , Cyclin-Dependent Kinase 5/antagonists & inhibitors , Cyclin-Dependent Kinase 5/genetics , Cyclin-Dependent Kinase 5/metabolism , Heterografts , Humans , Mice , Neoplasms/genetics , Neuroectodermal Tumors/genetics , Neuroectodermal Tumors/metabolism , Phosphoproteins/analysis , Phosphoproteins/genetics , PhosphorylationABSTRACT
Drought is one of the most serious abiotic stressors in the environment, restricting agricultural production by reducing plant growth, development, and productivity. To investigate such a complex and multifaceted stressor and its effects on plants, a systems biology-based approach is necessitated, entailing the generation of co-expression networks, identification of high-priority transcription factors (TFs), dynamic mathematical modeling, and computational simulations. Here, we studied a high-resolution drought transcriptome of Arabidopsis. We identified distinct temporal transcriptional signatures and demonstrated the involvement of specific biological pathways. Generation of a large-scale co-expression network followed by network centrality analyses identified 117 TFs that possess critical properties of hubs, bottlenecks, and high clustering coefficient nodes. Dynamic transcriptional regulatory modeling of integrated TF targets and transcriptome datasets uncovered major transcriptional events during the course of drought stress. Mathematical transcriptional simulations allowed us to ascertain the activation status of major TFs, as well as the transcriptional intensity and amplitude of their target genes. Finally, we validated our predictions by providing experimental evidence of gene expression under drought stress for a set of four TFs and their major target genes using qRT-PCR. Taken together, we provided a systems-level perspective on the dynamic transcriptional regulation during drought stress in Arabidopsis and uncovered numerous novel TFs that could potentially be used in future genetic crop engineering programs.
Subject(s)
Arabidopsis , Arabidopsis/genetics , Arabidopsis/metabolism , Gene Regulatory Networks , Droughts , Transcription Factors/metabolism , Systems Biology , Gene Expression Regulation, Plant , Stress, Physiological/geneticsABSTRACT
Biological networks are often large and complex, making it difficult to accurately identify the most important nodes. Node prioritization algorithms are used to identify the most influential nodes in a biological network by considering their relationships with other nodes. These algorithms can help us understand the functioning of the network and the role of individual nodes. We developed CentralityCosDist, an algorithm that ranks nodes based on a combination of centrality measures and seed nodes. We applied this and four other algorithms to protein-protein interactions and co-expression patterns in Arabidopsis thaliana using pathogen effector targets as seed nodes. The accuracy of the algorithms was evaluated through functional enrichment analysis of the top 10 nodes identified by each algorithm. Most enriched terms were similar across algorithms, except for DIAMOnD. CentralityCosDist identified more plant-pathogen interactions and related functions and pathways compared to the other algorithms.
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The surging demand of value-added products has steered the transition of laboratory microbes to microbial cell factories (MCFs) for facilitating production of large quantities of important native and non-native biomolecules. This shift has been possible through rewiring and optimizing different biosynthetic pathways in microbes by exercising frameworks of metabolic engineering and synthetic biology principles. Advances in genome and metabolic engineering have provided a fillip to create novel biomolecules and produce non-natural molecules with multitude of applications. To this end, numerous MCFs have been developed and employed for production of non-natural nucleic acids, proteins and different metabolites to meet various therapeutic, biotechnological and industrial applications. The present review describes recent advances in production of non-natural amino acids, nucleic acids, biofuel candidates and platform chemicals.
Subject(s)
Nucleic Acids , Biosynthetic Pathways/genetics , Biotechnology , Metabolic Engineering , Synthetic BiologyABSTRACT
Of all the nutrients, vitamin A has been the most extensively evaluated for its impact on immunity. There are three main forms of vitamin A, retinol, retinal and retinoic acid (RA) with the latter being most biologically active and all-trans-RA (ATRA) its main derivative. Vitamin A is a key regulator of the functions of various innate and adaptive immune cells and promotes immune-homeostasis. Importantly, it augments the interferon-based innate immune response to RNA viruses decreasing RNA virus replication. Several clinical trials report decreased mortality in measles and Ebola with vitamin A supplementation.During the Covid-19 pandemic interventions such as convalescent plasma, antivirals, monoclonal antibodies and immunomodulator drugs have been tried but most of them are difficult to implement in resource-limited settings. The current review explores the possibility of mega dose vitamin A as an affordable adjunct therapy for Covid-19 illness with minimal reversible side effects. Insight is provided into the effect of vitamin A on ACE-2 expression in the respiratory tract and its association with the prognosis of Covid-19 patients. Vitamin A supplementation may aid the generation of protective immune response to Covid-19 vaccines. An overview of the dosage and safety profile of vitamin A is presented along with recommended doses for prophylactic/therapeutic use in randomised controlled trials in Covid-19 patients.
Subject(s)
COVID-19/immunology , COVID-19/prevention & control , Vitamin A/administration & dosage , Animals , COVID-19/virology , Humans , Immunity/drug effects , Immunomodulation/drug effects , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Vitamin A/analysisABSTRACT
PURPOSE: To analyze the effect of fluid on visual acuity in cases of Type 3 macular neovascularization. METHODS: This multicentric, retrospective cohort study included eyes with treatment-naïve Type 3 macular neovascularization. Analysis of fluid in different compartments was performed. Group A included eyes with isolated intraretinal fluid, whereas Group B included eyes with intraretinal fluid in conjunction with subretinal fluid and/or sub retinal pigment epithelial fluid. RESULTS: Eyes in Group A (31, 55.3%) had better best-corrected visual acuity of 20/50 snellen equivalent (0.42 ± 0.31 logarithm of the minimum angle of resolution) at baseline and 20/50 snellen equivalent (0.40 ± 0.28 logarithm of the minimum angle of resolution) at complete resolution compared with Group B with visual acuity of 20/80 snellen equivalent (0.64 ± 0.35 logarithm of the minimum angle of resolution) (P = 0.0181) at baseline and 20/100 snellen equivalent (0.70 ± 0.40 logarithm of the minimum angle of resolution) (P = 0.0021) at complete resolution. Subfoveal atrophy was more in Group B (82.6% 19/23) at complete resolution in comparison to Group A (16/31, 51.6%). Eyes in Group B needed more anti-vascular endothelial growth factor injections (10.3 ± 9.0) for complete resolution compared with Group A (5.7 ± 4.8). CONCLUSION: Intraretinal fluid may be associated with good visual acuity in Type 3 macular neovascularization in contrast to other forms of neovascular age related macular degeneration. Furthermore, intraretinal fluid in isolation may need fewer injections and could probably be associated with less subfoveal atrophy.
Subject(s)
Fluorescein Angiography/methods , Macula Lutea/diagnostic imaging , Retinal Neovascularization/diagnosis , Subretinal Fluid , Tomography, Optical Coherence/methods , Aged , Aged, 80 and over , Female , Follow-Up Studies , Fundus Oculi , Humans , Male , Middle Aged , Prognosis , Retinal Neovascularization/physiopathology , Retrospective Studies , Visual AcuityABSTRACT
PURPOSE: To critically review data published in the recent past to scrutinize a causal relationship between retinal vascular occlusion and COVID-19. METHOD: A comprehensive literature search was performed on Pubmed with the key words retinal vascular occlusion, retinal vein occlusion, retinal artery occlusion, and COVID-19. RESULTS: A total of 17 case reports were published during this period, and 10 were on retinal vein occlusion and 7 on retinal artery occlusion. Most of the published reports lacked convincing evidences in one or the other aspects, such as insufficient laboratory workup or presence of multiple confounding risk factors. CONCLUSION: In this index article, strength of the data is insufficient to establish a definitive cause-and-effect relationship of retinal vascular occlusive disorders with COVID-19. Hence, clinicians can continue to manage these cases according to the standard guidelines until there are more robust evidences to support this association to alter the diagnostic and treatment modalities.
Subject(s)
COVID-19/complications , Eye Infections, Viral/etiology , Retinal Artery Occlusion/virology , Retinal Vein Occlusion/virology , SARS-CoV-2 , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , MythologyABSTRACT
AIM: This study examines Pakistan nurses' emotional labour and stress in health care emergencies, specifically their emotional exhaustion and availability of support of organization and management to alleviate the effects. BACKGROUND: As COVID-19 pandemic has been declared a global outbreak and many countries have enacted medical emergencies, this has increased job demands and expected desired emotional expressions from frontline workers. Such high levels of job demand contribute to various stress reactions among employees. METHODS: Authors applied a longitudinal design, using an experimental approach, to collect data from 319 nurses serving in 107 government hospitals in Pakistan. The authors surveyed nurses at two time points with the interval of 3 months by using an online questionnaire tool. At one time, they asked nurses to report on emotional labour, stress and exhaustion. In the second phase, after providing supports (during interval phase) at different levels, the authors repeated the same scales from same participants in addition to instrumental support and coaching leadership. Data were processed using SPSS-Amos for elementary analysis and SPSS-process macro software for robustness and hypotheses testing. RESULTS: The findings indicate that job stress fully mediates the relationship between surface acting and emotional exhaustion in controlled phase and partially mediates in intervention phase. Furthermore, in intervention phase, instrumental support moderates and alleviates positive effects of emotional labour on job stress, and coaching leadership moderates and lessens positive effects of job stress on emotional exhaustion. CONCLUSION: This research concludes that health care organizations can alleviate emotional exhaustion caused by emotional labour and job stress amid emergencies by providing support at different levels: organizational and managerial. However, the effectiveness of these supports depends on high to low levels. IMPLICATIONS FOR NURSING MANAGEMENT: This study demonstrates that to handle and support emotional labour and job stress to avoid emotional exhaustion in health care emergencies, organizational supports matter. Support at organizational level can include instrumental support. At managerial level, holding a coaching leadership style can foster external facets of management while uplifting the internal support qualities of confidence and self-awareness that improve the individuals' ability to lead; work with paradox and uncertainty.
Subject(s)
Burnout, Professional , COVID-19 , Mentoring , Nurses , Occupational Stress , Humans , Leadership , Job Satisfaction , COVID-19/epidemiology , Emergencies , Pandemics , Occupational Stress/complications , Surveys and Questionnaires , Burnout, Professional/etiology , Burnout, Professional/psychologyABSTRACT
The thermodynamic stability of III-nitride monolayers is calculated using the phonon band structure. Electronic properties are computed using the generalized gradient approximation-Perdew-Burke-Ernzerhof exchange-correlation potentials, which show the semiconducting behavior with bandgap 0.59 eV, 2.034 eV, and 2.906 eV for InN, GaN, and AlN monolayers, respectively. The biaxial tensile and compressive strains are used as external stimuli to understand their impact on the optoelectronic properties of these monolayers. The thermodynamic stability of strained monolayers is investigated to explore the maximum possible strains, i.e. flexibility limit, these monolayers can sustain. These monolayers are more sensitive to compressive strains, showing thermodynamic instability even at 1% compressive strain for all the considered monolayers. Further, the III-nitride monolayers are more robust with the tensile strain. InN, GaN, and AlN monolayers can sustain up to 4%, 16%, and 18% tensile strain, respectively. More interestingly, the electronic transitions, such as direct to indirect and semiconducting to metallic, are noticed with strain in the considered monolayers. The optical properties also exhibit strong strain dependency at the different transition points.
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OBJECTIVE: To analyze the role of intravitreal anti-vascular endothelial growth factor (anti-VEGF) or steroid injection for the management of Irvine Gass syndrome. METHODS: It is an interventional, retrospective, multicenter study. One hundred and thirty-two injections were given in 79 eyes of 72 patients with Irvine Gass syndrome. Patients were treated with at least one intravitreal injection of either anti-VEGF or steroid. Outcomes were measured at 12 months (± 1 week). [Ranibizumab (Lucentis; Genentech, South San Francisco, CA) (Razumab; Intas Pharmaceutical Ltd, Ahmedabad, India) Bevacizumab (Avastin; Genentech, South San Francisco, CA) or Aflibercept (Eylea; Regeneron, Tarrytown, NY)] or steroids [Dexamethasone implant (Ozurdex, Allergan Inc, Irvine, CA) or intravitreal triamcinolone)]. RESULTS: Intravitreal injections were initiated in (67.6%) of eyes within 14 weeks of diagnosis. Intravitreal dexamethasone implant was used as the initial intravitreal therapy in (73.4%) of eyes. More than fifty percent (54.5%) of the patients were switched from anti-VEGF to Intravitreal dexamethasone implant. Reduction in the mean CMT was 336.7 ± 191.7 and 160.1 ± 153.1 microns in eyes treated within four weeks and more than 14 weeks from diagnosis (p = 0.005). Mean ETDRS letter gain was 16.7 ± 12.9 and 5.2 ± 9.2 in eyes treated within 4 weeks and more than 14 weeks from diagnosis (p = 0.004). Three eyes injected with intravitreal dexamethasone implant reported an intraocular pressure spike of > 25 mmHg which was controlled with topical medications. No other ocular or systemic adverse events were observed. CONCLUSION: Study results suggest that physicians tend to introduce intravitreal therapy within 14 weeks of diagnosis. The most common therapy at initiation and for the switch is intravitreal dexamethasone implant. Patients treated early (within 4 weeks) respond better in terms of structure and function.
Subject(s)
Macular Edema , Bevacizumab/therapeutic use , Dexamethasone/therapeutic use , Drug Implants , Glucocorticoids/therapeutic use , Humans , India , Intravitreal Injections , Macular Edema/drug therapy , Retrospective Studies , Visual AcuityABSTRACT
Systems biology is an inclusive approach to study the static and dynamic emergent properties on a global scale by integrating multiomics datasets to establish qualitative and quantitative associations among multiple biological components. With an abundance of improved high throughput -omics datasets, network-based analyses and machine learning technologies are playing a pivotal role in comprehensive understanding of biological systems. Network topological features reveal most important nodes within a network as well as prioritize significant molecular components for diverse biological networks, including coexpression, protein-protein interaction, and gene regulatory networks. Machine learning techniques provide enormous predictive power through specific feature extraction from biological data. Deep learning, a subtype of machine learning, has plausible future applications because a domain expert for feature extraction is not needed in this algorithm. Inspired by diverse domains of biology, we here review classic systems biology techniques applied in plant immunity thus far. We also discuss additional advanced approaches in both graph theory and machine learning, which may provide new insights for understanding plant-microbe interactions. Finally, we propose a hybrid approach in plant immune systems that harnesses the power of both network biology and machine learning, with a potential to be applicable to both model systems and agronomically important crop plants.
Subject(s)
Host-Pathogen Interactions , Machine Learning , Systems Biology , Algorithms , Gene Regulatory Networks , Models, BiologicalABSTRACT
Cyanobacteria are one of the ancient bacterial species occupying a variety of habitats with diverse metabolic preferences. RNA regulators like riboswitches play significant role in controlling the gene expression in prokaryotes. The taxonomic distribution of riboswitches suggests that they might be one of the oldest mechanisms of gene control system. In this paper, we analyzed the distribution of different riboswitch families in various cyanobacterial genomes. It was observed that only four riboswitch classes were abundant in cyanobacteria, B12-element (Cob)/AdoCbl/AdoCbl-variant riboswitch being the most abundant. The analysis suggests that riboswitch mode of regulation is present in cyanobacterial species irrespective of their habitat types. A large number of unidentified genes regulated by riboswitches listed in this analysis indicate the wide range of targets for these riboswitch families. The analysis revealed a large number of genes regulated by riboswitches which may assist in elaborating the diversity among the cyanobacterial species.