This brief is concerned with a new problem of designing a robust adaptive backstepping controller for nonlinear systems where state constraints are an explicit function of time and state variables, ...i.e., pure state constraints. Furthermore, a disturbance observer is designed to cope with the disturbances in the systems. Finally, a numerical example is demonstrated to show the efficacy of the proposed theoretical results.
Glutaredoxins (Grxs) are a family of small multifunctional proteins involved in various cellular functions, including redox regulation and protection under oxidative stress. Despite the high number ...of Grx genes in plant genomes (48 Grxs in rice), the biological functions and physiological roles of most of them remain unknown. Here, the functional characterization of the two arsenic-responsive rice Grx family proteins, OsGrx_C7 and OsGrx_C2.1 are reported. Over-expression of OsGrx_C7 and OsGrx_C2.1 in transgenic Arabidopsis thaliana conferred arsenic (As) tolerance as reflected by germination, root growth assay, and whole plant growth. Also, the transgenic expression of OsGrxs displayed significantly reduced As accumulation in A. thaliana seeds and shoot tissues compared to WT plants during both AsIII and AsV stress. Thus, OsGrx_C7 and OsGrx_C2.1 seem to be an important determinant of As-stress response in plants. OsGrx_C7 and OsGrx_C2.1 transgenic showed to maintain intracellular GSH pool and involved in lowering AsIII accumulation either by extrusion or reducing uptake by altering the transcript of A. thaliana AtNIPs. Overall, OsGrx_C7 and OsGrx_C2.1 may represent a Grx family protein involved in As stress response and may allow a better understanding of the As induced stress pathways and the design of strategies for the improvement of stress tolerance as well as decreased As content in crops.
Introduction: In December 2019, a cluster of atypical cases of pneumonia was reported in Wuhan, China, which was later designated as Coronavirus disease 2019 (COVID-19) by the World Health ...Organization (WHO) on Feb 11, 2020. We all are facing a global pandemic, and it is very important to be clear that there is no correct roadmap to navigate this difficult situation. It is imperative to state that this global pandemic impacted the spine care services of our institute. In the present study, we have assessed the spine surgeries performed by orthopedic surgeons in terms of volume and etiologies during the COVID-19 pandemic and compared the data with a pre-COVID period. Materials and Methods: We retrospectively collected data from all patients who underwent spinal surgeries at our institute under the department of orthopedics from August 20, 2019 to August 20, 2020 (a total of 12 months duration). The data was then divided into two groups-pre-COVID period (August 20, 2019-February 19, 2020-6 months) and during the COVID pandemic (February 20, 2020-August 20, 2021-6 months). Results: A total of 140 patients underwent surgery at our institute from August 20, 2019 to August 20, 2020. Of these, 91 patients underwent surgery during the pre-COVID period, and 49 patients underwent surgery during the COVID pandemic. In this devastating phase of the pandemic, our department's total number of surgeries significantly declined to 46.15%. The routine surgeries performed during the pandemic phase show a steep fall from 59.34% in the pre-COVID period to 10.20%. Conclusion: This paper is meant to focus attention on the exorbitant reduction in the operative workflow of the spine patients during the COVID-19 pandemic at a tertiary healthcare institute. It is the need of the hour that orthopedic surgeons maintain equilibrium while providing the best possible treatment to their patients and limiting the spread of the COVID-19 pandemic.
Aldehyde dehydrogenase 1 (ALDH1A1), an oxidoreductase class of enzymes, is overexpressed in various types of cancer cell lines and is the major cause of resistance to the Food and Drug Administration ...(FDA)‐approved drug, cyclophosphamide (CP). In cancer conditions, CP undergoes a sequence of biotransformations to form an active metabolite, aldophosphamide, which further biotransforms to its putative cytotoxic metabolite, phosphoramide mustard. However, in resistant cancer conditions, aldophosphamide is converted into its inactive metabolite, carboxyphosphamide, via oxidation with ALDH1A1. Herein, to address the issue of ALDH1A1 mediated CP resistance, we report a series of benzodoxazol‐2(3H)‐one and 2‐oxazolo4,5‐bpyridin‐2(3H)‐one derivatives as selective ALDH1A1 inhibitors. These inhibitors were designed using a validated 3D‐quantitative structure activity relationship (3D‐QSAR) model coupled with scaffold hopping. The 3D‐QSAR model was developed using reported indole‐2,3‐diones based ALDH1A1 inhibitors, which provided field points in terms of electrostatic, van der Waals and hydrophobic potentials required for selectively inhibiting ALDH1A1. The most selective indole‐2,3‐diones‐based compound, that is, cmp 3, was further considered for scaffold hopping. Two top‐ranked bioisosteres, that is, benzodoxazol‐2(3H)‐one and 2‐oxazolo4,5‐bpyridin‐2(3H)‐one, were selected for designing new inhibitors by considering the field pattern of 3D‐QSAR. All designed molecules were mapped perfectly on the 3D‐QSAR model and found to be predictive with good inhibitory potency (pIC50 range: 7.5–6.8). Molecular docking was carried out for each designed molecule to identify key interactions that are required for ALDH1A1 inhibition and to authenticate the 3D‐QSAR result. The top five inhibitor‐ALDH1A1 complexes were also submitted for molecular dynamics simulations to access their stability. In vitro enzyme assays of 21 compounds suggested that these compounds are selective toward ALDH1A1 over the other two isoforms, that is, ALDH2 and ALDH3A1. All the compounds were found to be at least three and two times more selective toward ALDH1A1 over ALDH2 and ALDH3A1, respectively. All the compounds showed an IC50 value in the range of 0.02–0.80 μM, which indicates the potential for these to be developed as adjuvant therapy for CP resistance.
A series of benzodoxazol‐2(3H)‐one and 2‐oxazolo4,5‐bpyridin‐2(3H)‐one derivatives were designed as selective aldehyde dehydrogenase 1 (ALDH1A1) inhibitors, using a validated 3D‐QSAR model coupled with scaffold hopping. All compounds were found to be at least 2–3 times more selective toward ALDH1A1 than ALDH2 and ALDH3A1. Based on their IC50 values, all the compounds showed the potential to be developed as adjuvant therapy for cyclophosphamide resistance.
Abstract
BACKGROUND
Vertebral hemangiomas are benign, highly vascular lesions of the vertebra, rarely seen in the pediatric age group.
OBJECTIVE
To analyze the long-term (>3 yr) outcome of patients ...of pediatric vertebral hemangioma presenting with myelopathy and to describe our surgical strategy to treat such cases.
METHODS
All patients up to 18 yr of age with a symptomatic vertebral hemangioma treated at our hospital from May 2003 to August 2016, with at least 3-yr follow-up were included. Functional clinical outcomes were measured using American Spinal Injury Association (ASIA) score.
RESULTS
There were 7 male and 7 female patients. All hemangiomas were located in the thoracic spine with single-level involvement. Upper thoracic spine involvement was more common (12 cases: 85.71%) than lower thoracic spine involvement (2 cases: 14.29%). All patients had features of myelopathy. The mean age was 14.57 yr, ranging from 10 to 18 yr. The mean follow-up was 62.21 mo, ranging from 36 to 90 mo. All patients had improvement in motor strength of both lower limbs postoperatively. Local pain, which was present in 1 patient, resolved, and the bladder symptoms present in 5 patients also resolved.
CONCLUSION
Our experience in treating symptomatic pediatric vertebral hemangiomas, along with the long-term follow-up data, suggests that good postoperative results can be achieved with minimal complications in carefully selected patients.
Graphical Abstract
Graphical Abstract
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•Juglans regia L. fruit is commonly used as nutraceuticals especially for development of brain tissue.•Isoprenaline administration produces oxidative damage, reduced antioxidant ...status and cholinergic crisis along with histopathological alterations in rat brain.•Hull extract administration reduced the lipid and protein peroxidation, restored antioxidant status and histopathological changes in brain induced by isoprenaline.
The study was aimed at assessing isoprenaline (ISO) induced oxidative damage in brain of Wistar rats and its protection by hydroethanolic hull extract of Juglans regia. Administration of ISO significantly increases catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), malondialdehyde (MDA) and advanced oxidation protein product (AOPP) levels and significantly reduced activities of antioxidant status (TAS), total thiols (TTH), acetylcholinesterase (AChE), arylesterase (AE), and glutathione peroxidase (GPx) in rat brain. Histopathologically, neuronal degeneration, spongiosis and gliosis were seen in cerebral cortex after ISO administration. Pretreatment with hull extract restored TAS, TTH, AChE, CAT and SOD values. Additionally, significant reductions were noted in levels of MDA, AOPP, and severity of histomorphological changes in cerebral cortex following hull extract treatment. Altered antioxidant biomarkers along with histopathological changes indicate oxidative injury in rat brain following ISO administration. Repeated administration of J. regia hull extract demonstrating presence of neuroprotective properties against ISO induced oxidative damage in rat brain.
Background & Aims: ARID1A is postulated to be a tumor suppressor gene owing to loss-of-function mutations in human pancreatic ductal adenocarcinomas (PDAC). However, its role in pancreatic ...pathogenesis is not clear despite recent studies using genetically engineered mouse (GEM) models. We aimed at further understanding of its direct functional role in PDAC, using a combination of GEM model and PDAC cell lines. Methods: Pancreas-specific mutant Arid1a-driven GEM model (Ptf1a-Cre; KrasG12D; Arid1af/f or “KAC”) was generated by crossing Ptf1a-Cre; KrasG12D (“KC”) mice with Arid1af/f mice and characterized histologically with timed necropsies. Arid1a was also deleted using CRISPR-Cas9 system in established human and murine PDAC cell lines to study the immediate effects of Arid1a loss in isogenic models. Cell lines with or without Arid1a expression were developed from respective autochthonous PDAC GEM models, compared functionally using various culture assays, and subjected to RNA-sequencing for comparative gene expression analysis. DNA damage repair was analyzed in cultured cells using immunofluorescence and COMET assay. Results: Retention of Arid1a is critical for early progression of mutant Kras-driven pre-malignant lesions into PDAC, as evident by lower Ki-67 and higher apoptosis staining in “KAC” as compared to “KC” mice. Enforced deletion of Arid1a in established PDAC cell lines caused suppression of cellular growth and migration, accompanied by compromised DNA damage repair. Despite early development of relatively indolent cystic precursor lesions called intraductal papillary mucinous neoplasms (IPMNs), a subset of “KAC” mice developed aggressive PDAC in later ages. PDAC cells obtained from older autochthonous “KAC” mice revealed various compensatory (“escaper”) mechanisms to overcome the growth suppressive effects of Arid1a loss. Conclusions: Arid1a is an essential survival gene whose loss impairs cellular growth, and thus, its expression is critical during early stages of pancreatic tumorigenesis in mouse models. In tumors that arise in the setting of ARID1A loss, a multitude of “escaper” mechanisms drive progression.
A BSTRACT Aim: To study psychiatric co-morbidities, anxiety, depression, and quality of life in patients of chronic obstructive pulmonary disease (COPD). Materials and Methods: A cross-sectional, ...case-control study was conducted on 122 cases of COPD and equal number of age- and sex-matched controls in a tertiary care hospital. They were assessed with the Mini-International Neuropsychiatric Interview (MINI), depression, anxiety stress scale-42 (DASS-42), St. George Respiratory Questionnaire (SGRQ), and COPD Assessment Test (CAT). Results: COPD patients and control subjects were matched with respect to age, sex, education, employment, domicile, and socioeconomic status. Psychiatric disorders were diagnosed in 56% of cases and 14% of controls. Major depressive disorder, alcohol dependence, and anxiety disorders were the most common psychiatric diagnoses. There was significantly higher prevalence of smoking in cases with COPD compared to control subjects suicidality was present in two patients. The mean scores on depression, anxiety, and stress on DASS-42 of COPD patients were significantly higher than normal controls. On the CAT majority of the COPD patients belonged to the high-impact group followed by the very high-impact group. Mean scores on the SGRQ were in the range expected in COPD patients. A multiple regression analysis revealed that significant predictors of SGRQ scores were age, gender, economic status, domicile, alcohol habits, depression, anxiety, and stress. Conclusion: COPD patients have a significantly higher prevalence of psychiatric co-morbidities compared to healthy controls. Common psychiatric disorders were major depression, alcohol dependence, and anxiety disorders along with smoking.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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