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Hantaviruses are single-stranded RNA viruses belonging to the family Bunyaviridae that causes hantavirus cardiopulmonary syndrome (HCPS) and hemorrhagic fever with renal syndrome (HFRS) worldwide. Currently, there is no effective vaccination or therapy available for the treatment of hantavirus, hence there is a dire need for research to formulate therapeutics for the disease. Computational vaccine designing is currently a highly accurate, time and cost-effective approach for designing effective vaccines against different diseases. In the current study, we shortlisted highly antigenic proteins i.e., envelope, and nucleoprotein from the proteome of hantavirus and subjected to the selection of highly antigenic epitopes to design of next-generation multi-epitope vaccine constructs. A highly antigenic and stable adjuvant was attached to the immune epitopes (T-cell, B-cell, and HTL) to design Env-Vac, NP-Vac, and Com-Vac constructs, which exhibit stronger antigenic, non-allergenic, and favorable physiochemical properties. Moreover, the 3D structures were predicted and docking analysis revealed robust interactions with the human Toll-like receptor 3 (TLR3) to initiate the immune cascade. The total free energy calculated for Env-Vac, NP-Vac, and Com-Vac was -50.02 kcal/mol, -24.13 kcal/mol, and -62.30 kcal/mol, respectively. In silico cloning, results demonstrated a CAI value for the Env-Vac, NP-Vac, and Com-Vac of 0.957, 0.954, and 0.956, respectively, while their corresponding GC contents were 65.1%, 64.0%, and 63.6%. In addition, the immune simulation results from three doses of shots released significant levels of IgG, IgM, interleukins, and cytokines, as well as antigen clearance over time, after receiving the vaccine and two booster doses. Our vaccines against Hantavirus were found to be highly immunogenic, inducing a robust immune response that demands experimental validation for clinical usage.
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Orthohantavírus , Vacinas Virais , Orthohantavírus/imunologia , Vacinas Virais/imunologia , Humanos , Vacinologia/métodos , Simulação de Acoplamento Molecular , Simulação por Computador , Epitopos/imunologia , Epitopos/química , Modelos Moleculares , Infecções por Hantavirus/prevenção & controle , Infecções por Hantavirus/imunologiaRESUMO
Objective The objective of this study was to compare K1, K2, Kmax, and pachymetry values from Pentacam and Galilei scans of corneal topography in order to assess their correlation and interchangeability in clinical practice. Methodology A total of 34 patients (68 eyes) were enrolled in the study. Corneal topography was performed using Pentacam and Galilei devices on the same day. K1, K2, Kmax, and pachymetry readings were obtained from the scans and analyzed using paired t-tests and Bland-Altman plots. Results There were minimal differences in clinical settings between Pentacam and Galilei for K1, K2, Kmax (>0.75 D), and pachymetry values (>15 um). However, there was a statistically significant difference found between Kmax and pachymetry, making their interchangeability questionable. Conclusion Pentacam and Galilei demonstrate a good correlation between corneal keratometric values (K1, K2, and Kmax) and pachymetry values in clinical settings, and they should be used interchangeably with caution.
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Cancer remains one of the major causes of morbidity and mortality worldwide. Scientists from different fields are working to devise an efficient treatment strategy in order to reduce the global burden of cancer. Commonly used treatment approaches for cancer treatment include chemotherapy, immunotherapy, photodynamic therapy, radiation, surgery, etc. These treatment procedures have several pitfalls, such as toxicity, limited bioavailability, rapid elimination, poor specificity, and high cost. On the other side, plant-derived anticancer compounds exhibit several advantages and can overcome these shortcomings. Plant-based anticancer compounds are safer, potent, easily available, and comparatively cost-effective. The current review discusses pure plant- based compounds that are used as a therapeutic remedy for anticancer application. The proposed mechanisms of action, through which these compounds inhibit cancer cell growth, tumor growth, angiogenesis, instigate apoptosis, cytotoxicity, mitochondrial membrane degradation, and reduce cell viability as well as cell cycle progression, are also reviewed. These naturally occurring compounds exhibit great therapeutic potential and could be used as candidate drugs in clinical applications.
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This paper proposes a circularly polarized ultra-thin flexible antenna with a flexible rectifier and power management unit (PMU) for smartwatch/wristband applications. The flexible antenna is compact (0.17λ0 × 0.20λ0 × 0.0004λ0) and has a stepped ground plane. A parasitic element is used at the substrate bottom to reduce the specific absorption rate (SAR) and enhance the gain up to 3.2 dBi, at the resonating frequency of WLAN/Wi-Fi (2.45 GHz). The SAR of the proposed design is also analysed at the resonating frequency, and it satisfies the guidelines of the International Commission on Non-Ionizing Radiation Protection (ICNIRP) and IEEE C95.1-2019 human safety standards. An impedance matching circuit is used between the antenna and the RF energy harvester to improve conversion efficiency. Polarization mismatch is avoided with the help of circular polarization, achieved by tuning stubs of size 0.02λ0 × 0.044λ0. The integration of the antenna and rectenna results in a good conversion efficiency of 78.2% at - 5 dBm of input power with a load resistance of 2 KΩ. The availability of RF signals allows the user to charge the smartwatch/wristband by connecting the PMU circuit with the RF energy harvester.
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Protocell fitness under extreme prebiotic conditions is critical in understanding the origin of life. However, little is known about protocell's survival and fitness under prebiotic radiations. Here we present a radioresistant protocell model based on assembly of two types of coacervate droplets, which are formed through interactions of inorganic polyphosphate (polyP) with divalent metal cation and cationic tripeptide, respectively. Among the coacervate droplets, only the polyP-Mn droplet is radiotolerant and provides strong protection for recruited proteins. The radiosensitive polyP-tripeptide droplet sequestered with both proteins and DNA could be encapsulated inside the polyP-Mn droplet, and form into a compartmentalized protocell. The protocell protects the inner nucleoid-like condensate through efficient reactive oxygen species' scavenging capacity of intracellular nonenzymic antioxidants including Mn-phosphate and Mn-peptide. Our results demonstrate a radioresistant protocell model with redox reaction system in response to ionizing radiation, which might enable the protocell fitness to prebiotic radiation on the primitive Earth preceding the emergence of enzyme-based fitness. This protocell might also provide applications in synthetic biology as bioreactor or drug delivery system.
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Células Artificiais , Células Artificiais/metabolismo , Peptídeos , Proteínas , MineraisRESUMO
Cornea plana (CP) is a rare ocular condition existing in two distinct clinical and hereditary forms: a milder, autosomal dominant type I and a more severe, autosomal recessive type II. The condition is more commonly found in Finnish, Saudi, and Czech families. We report three brothers from a consanguineous marriage that presented with complaints of decreased vision of varying degrees. All three of them have blue, thick, and hazy corneas with shallow anterior chamber depths. The additional features of CP type II were seen in the older two brothers including arcus lipoids, ill-demarcated limbus, and an accommodative squint. They were managed by the correction of refractive errors through spectacles and detailed counseling with follow-up visits to look for progressive complications. The management is mainly centered around optically or surgically correcting the developmental anomalies. This is complimented with proper genetic counseling and regular follow-up visits to look for and manage complications. There are, however, novel therapies that can be considered in these patients including corneal transplants or corneal stromal stem cellular therapies.
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Purtscher retinopathy (PR) is an occlusive vasculopathy of the retinal microvasculature that classically presents 24-48 hours after compressive chest trauma. Symptoms vary from mild to severe acute visual loss. Characteristic findings on fundus examination such as Purtscher flecken, cotton wool spots, and retinal hemorrhages may also be found. Here, we discuss a case of Purtscher retinopathy due to compressive chest trauma.
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Volatile organic compounds (VOCs) such as formaldehyde and benzene are among the key contributors to indoor air pollution. The current situation of environmental pollution is alarming, especially indoor air pollution is becoming a challenge as affecting plants and humans. VOCs are known to adversely affect indoor plants by causing necrosis and chlorosis. In order to withstand these organic pollutants, plants are naturally equipped with an antioxidative defense system. The current research study aimed to evaluate the combined effect of formaldehyde and benzene on the antioxidative response of selected indoor C3 plants including Chlorophytum comosum, Dracaena mysore, and Ficus longifolia. After the combined application of different levels (0, 0; 2, 2; 2, 4; 4, 2; and 4, 4 ppm) of benzene and formaldehyde respectively, in an airtight glass chamber, the enzymatic and non-enzymatic antioxidants were analyzed. Analysis of total phenolics showed a significant increase (10.72 mg GAE/g) in F. longifolia; C. comosum (9.20 mg GAE/g); and D. mysore (8.74 mg GAE/g) compared to their respective controls as 3.76, 5.39, and 6.07 mg GAE/g. Total flavonoids (724 µg/g) were reported in control plants of F. longifolia which were increased to 1545.72 µg/g from 724 µg/g (in control) followed by 322.66 µg/g in D. mysore (control having 167.11 µg/g). Total carotenoid content also increased in D. mysore (0.67 mg/g) followed by C. comosum (0.63 mg/g) in response to increasing the combined dose compared to their control plants having 0.62 and 0.24 mg/g content. The highest proline content was exhibited by D. mysore (3.66 µg/g) as compared to its respective control plant (1.54 µg/g) under a 4 ppm dose of benzene and formaldehyde. A significant increase in enzymatic antioxidants including total antioxidants (87.89%), catalase (59.21 U/mg of protein), and guaiacol peroxidase (52.16 U/mg of protein) was observed in the D. mysore plant under a combined dose of benzene (2 ppm) and formaldehyde (4 ppm) with respect to their controls. Although experimental indoor plants have been reported to metabolize indoor pollutants, the current findings indicate that the combined application of benzene and formaldehyde is also affecting the physiology of indoor plants as well.
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Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Compostos Orgânicos Voláteis , Humanos , Benzeno/análise , Poluentes Atmosféricos/análise , Antioxidantes/análise , Formaldeído/análise , Poluição do Ar em Ambientes Fechados/análise , Compostos Orgânicos Voláteis/análiseRESUMO
Microspherophakia is a rare congenital anomaly characterized by an abnormally small and spherical crystalline lens, which can be associated with several systemic syndromes. We present an extremely rare case of bilateral anteriorly displaced microspherophakia in a female child with Marfanoid habitus. The patient displayed phenotypic features resembling Marfan syndrome, including tall stature, muscle hypotonia, dolichostenomelia, and increased arm span than body length. However, unlike Marfan syndrome, Marfanoid habitus is not associated with mutations in the fibrillin-1 gene. The association between microspherophakia and Marfanoid habitus is a unique presentation that has not been reported in the literature. This case report aims to increase awareness of microspherophakia as a possible ocular association of Marfanoid habitus.
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Driver distraction is considered a main cause of road accidents, every year, thousands of people obtain serious injuries, and most of them lose their lives. In addition, a continuous increase can be found in road accidents due to driver's distractions, such as talking, drinking, and using electronic devices, among others. Similarly, several researchers have developed different traditional deep learning techniques for the efficient detection of driver activity. However, the current studies need further improvement due to the higher number of false predictions in real time. To cope with these issues, it is significant to develop an effective technique which detects driver's behavior in real time to prevent human lives and their property from being damaged. In this work, we develop a convolutional neural network (CNN)-based technique with the integration of a channel attention (CA) mechanism for efficient and effective detection of driver behavior. Moreover, we compared the proposed model with solo and integration flavors of various backbone models and CA such as VGG16, VGG16+CA, ResNet50, ResNet50+CA, Xception, Xception+CA, InceptionV3, InceptionV3+CA, and EfficientNetB0. Additionally, the proposed model obtained optimal performance in terms of evaluation metrics, for instance, accuracy, precision, recall, and F1-score using two well-known datasets such as AUC Distracted Driver (AUCD2) and State Farm Distracted Driver Detection (SFD3). The proposed model achieved 99.58% result in terms of accuracy using SFD3 while 98.97% accuracy on AUCD2 datasets.
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Condução de Veículo , Direção Distraída , Humanos , Acidentes de Trânsito/prevenção & controle , Redes Neurais de ComputaçãoRESUMO
Climate changes abruptly affect optimum growth temperatures, leading to a negative influence on plant physiology and productivity. The present study aimed to investigate the extent of low-temperature stress effects on date palm growth and physiological indicators under the exogenous application of silicon (Si). Date palm seedlings were treated with Si (1.0 mM) and exposed to different temperature regimes (5, 15, and 30 °C). It was observed that the application of Si markedly improved fresh and dry biomass, photosynthetic pigments (chlorophyll and carotenoids), plant morphology, and relative water content by ameliorating low-temperature-induced oxidative stress. Low-temperature stress (5 and 15 °C), led to a substantial upregulation of ABA-signaling-related genes (NCED-1 and PyL-4) in non Si treated plants, while Si treated plants revealed an antagonistic trend. However, jasmonic acid and salicylic acid accumulation were markedly elevated in Si treated plants under stress conditions (5 and 15 °C) in comparison with non Si treated plants. Interestingly, the upregulation of low temperature stress related plant plasma membrane ATPase (PPMA3 and PPMA4) and short-chain dehydrogenases/reductases (SDR), responsible for cellular physiology, stomatal conductance and nutrient translocation under silicon applications, was observed in Si plants under stress conditions in comparison with non Si treated plants. Furthermore, a significant expression of LSi-2 was detected in Si plants under stress, leading to the significant accumulation of Si in roots and shoots. In contrast, non Si plants demonstrated a low expression of LSi-2 under stress conditions, and thereby, reduced level of Si accumulation were observed. Less accumulation of oxidative stress was evident from the expression of superoxide dismutase (SOD) and catalase (CAT). Additionally, Si plants revealed a significant exudation of organic acids (succinic acid and citric acid) and nutrient accumulation (K and Mg) in roots and shoots. Furthermore, the application of Si led to substantial upregulation of the low temperature stress related soybean cold regulated gene (SRC-2) and ICE-1 (inducer of CBF expression 1), involved in the expression of CBF/DREB (C-repeat binding factor/dehydration responsive element binding factor) gene family under stress conditions in comparison with non Si plants. The current research findings are crucial for exploring the impact on morpho-physio-biochemical attributes of date palms under low temperature and Si supplementation, which may provide an efficient strategy for growing plants in low-temperature fields.
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Phoeniceae , Silício , Silício/farmacologia , Silício/metabolismo , Phoeniceae/genética , Phoeniceae/metabolismo , Antioxidantes/farmacologia , Temperatura , Estresse OxidativoRESUMO
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine produced and secreted by immune cells in response to an infection, often in response to interferon (IFN) stimulation. In cancer, it has also been shown that IFN stimulates the production of TRAIL, and it has been proposed that this TRAIL can induce apoptosis in an autocrine or paracrine manner in different cancer cells. Yet, the mechanism mediating TRAIL upregulation and the implications of TRAIL as an apoptotic molecule in cancer cells are still poorly understood. We show here that in certain cancer cells, TRAIL is upregulated by enhancer clusters, potent genomic regulatory regions containing densely packed enhancers that have combinatorial and additive activity and that are usually found to be associated with cancer-promoting genes. Moreover, we found that TRAIL upregulation by IFNα is mediated by these enhancer clusters in breast and lung cancer cells. Surprisingly, IFNα stimulation leads to the intracellular accumulation of TRAIL protein in these cancer cells. Consequently, this TRAIL is not capable of inducing apoptosis. Our study provides novel insights into the mechanism behind the interferon-mediated upregulation of TRAIL and its protein accumulation in cancer cells. Further investigation is required to understand the role of intracellular TRAIL or depict the mechanisms mediating its apoptosis impairment in cancer cells.
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Introduction Color vision testing was first seen as a parameter to be tested in the 1700s. Nowadays, it is a well-known phenomenon with significant quality-of-life implications. Structures involved in color vision include the lens, pupil, retinal cone photopigments, and several photoreceptor processes that translate the incoming spectrum of different light wavelengths into a processed colored image. An initial color vision assessment was made simply by comparing the color perception of the individual to that of the examiner. The most commonly used tools to screen for color vision defects today are color plates, such as the Ishihara color plates. In the modern age, smartphones have evolved to become an essential part of our everyday lives with applications such as Eye Handbook, which allow easier access to color vision testing using color plates displayed on smartphone screens. In this study, we compared color vision testing on Android and iOS devices to the standard Ishihara booklet. Materials and methods A cross-sectional validation study was performed on patients presenting to the Armed Forces Institute of Ophthalmology, Rawalpindi, Pakistan for six months. The sample size collected was 162 with a 95% confidence interval. The age range of the sample population was kept at 12-70 years. A patient was selected for participation in the study, and a color vision assessment was performed using the Ishihara color plates and Android and iOS smartphones. The collected data was then entered into IBM SPSS (Statistical Package for the Social Sciences) Statistics 25 for analysis, with the p-value being kept at 0.05. Results The sample size was 162, with the gender distribution being predominantly male (69.14%). The average age of the participants was 35.94 (SD = 12.04). The result of the two-tailed paired sample z-testwas not significant based on a p-value of 0.565, indicating the null hypothesis cannot be rejected. This finding suggests the difference between the mean of Ishihara and the mean of the iPhone was not significantly different from zero. Similar results were found for comparisons between Android smartphones and the Ishihara booklet. Conclusions Previous studies conducted showed nearly 60% of subjects with normal color vision correctly identified all colors on standard Ishihara color plates. The two-tailed paired sample t-test conducted in our study showed no significant difference between either of the smartphone groups (iPhone or Android) and the Ishihara booklet group, indicating that smartphones present a viable alternative to standard Ishihara booklet testing. However, there are certain limitations to our study. Different types of smartphone screens present a challenge in standardization while testing color vision, something that is not a problem when using the Ishihara booklet. However, smartphones are more widely available, more versatile, and present far greater ease of access. Both these factors should be considered when comparing the two in future studies.
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The selective anti-tumor activity and less toxic nature of hypoxia-activated prodrugs including tirapazamine (TPZ) are harbored by hypoxia levels in tumors, the inadequacy of which leads to failure in clinical trials. Thus, the development of effective clinical applications of TPZ requires advanced strategies to intensify hypoxia levels in tumors effectively and safely. In this study, we designed and fabricated a paclitaxel (PTX)-loaded dual-response delivery system with a low dose (e.g., 2 Gy) of X-ray and reactive oxygen species on the basis of diselenide block copolymers. Upon the external X-ray stimulus, the system accurately released encapsulated PTX at tumor sites and remarkably improved tumor hypoxia levels by causing severe damage to tumor blood vessels. Subsequently, these enhanced tumor hypoxia levels effectively activated the reduction of TPZ into benzotriazinyl free radicals, which significantly improved the antitumor efficacy of our system against 4T1 breast cancer cells with an initial tumor volume of 500 mm3. Moreover, the dual-stimulus coordinated and controlled release of PTX was found to largely avoid the off-target effects of PTX on normal cells while exhibiting very limited side effects in experimental mice. The current novel strategy for regulating tumor hypoxia levels offers an effective and safe way to activate TPZ for the treatment of large solid tumors.
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Antineoplásicos , Neoplasias , Animais , Camundongos , Tirapazamina/farmacologia , Tirapazamina/uso terapêutico , Espécies Reativas de Oxigênio/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Hipóxia Tumoral , Raios X , Neoplasias/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Hipóxia/tratamento farmacológico , Linhagem Celular TumoralRESUMO
Lung abscesses and empyemas are 2 forms of pulmonary infection that can present with similar clinical features. However, empyemas are associated with higher morbidity and mortality, necessitating the need to distinguish one from the other. Plain radiographs can sometimes provide clues to help differentiate the 2 pathologies but more often than not, a computed tomography scan is required to confirm the diagnosis. Correct diagnosis is essential, as the goal standard therapeutic intervention for empyemas may be contraindicated in patients with lung abscesses. Empyemas require percutaneous or surgical drainage in combination with antibiotics, while lung abscesses are generally treated with antibiotics alone as drainage can be associated with various complications. We present a case of a 65-year-old man with parapneumonic empyema diagnosed with characteristic findings on chest computed tomography and treated with surgical drainage and antibiotics. We hope to improve patient outcomes by highlighting the classical radiographic findings that help distinguish empyema and abscess.
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Empiema , Abscesso Pulmonar , Masculino , Humanos , Idoso , Abscesso Pulmonar/diagnóstico por imagem , Abscesso Pulmonar/terapia , Empiema/diagnóstico , Empiema/terapia , Empiema/complicações , Drenagem/métodos , Tomografia Computadorizada por Raios X/métodos , Antibacterianos/uso terapêuticoRESUMO
Mammarena viruses are emerging pathogenic agents and cause hemorrhagic fevers in humans. These viruses accomplish host immune system evasion to replicate and spread in the host. There are only few available therapeutic options developed for Mammarena Virus (also called MMV). Currently, only a single candidate vaccine called Candid#1 is available against Junin virus. Similarly, the effective treatment Ribavirin is used only in Lassa fever treatments. Herein, immune-informatics pipeline has been used to annotate whole proteome of the seven human infecting Mammarena strains. The extensive immune based analysis reveals specie specific epitopes with a crucial role in immune response induction. This was achieved by construction of immunogenic epitopes (CTL "Cytotoxic T-Lymphocytes", HTL "Helper T-Lymphocytes", and B cell "B-Lymphocytes") based vaccine designs against seven different Mammarena virus species. Furthermore, validation of the vaccine constructs through exploring physiochemical properties was performed to confirm experimental feasibility. Additionally, in-silico cloning and receptor based immune simulation was performed to ensure induction of primary and secondary immune response. This was confirmed through expression of immune factors such as IL, cytokines, and antibodies. The current study provides with novel vaccine designs which needs further demonstrations through potential processing against MMVs. Future studies may be directed towards advanced evaluations to determine the efficacy and safety of the designed vaccines through further experimental procedures.
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Arenaviridae , Vacinas Virais , Humanos , Vacinologia/métodos , Arenaviridae/genética , Epitopos de Linfócito B , Epitopos de Linfócito T , Proteoma , Ribavirina , Vacinas de Subunidades Antigênicas , Citocinas , Simulação de Acoplamento Molecular , Biologia ComputacionalRESUMO
Ocular coloboma is a rare congenital anomaly that arises due to an abnormality in embryogenesis. It occurs due to failed fusion of the embryonic fissure resulting in a persistent defect. Colobomas may present with vision loss but are most commonly asymptomatic and diagnosed incidentally. In this article, we present a case of asymptomatic chorioretinal coloboma diagnosed on routine screening. The patient was managed with prophylactic argon laser retinopexy to prevent complications leading to visual impairment in the future.
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Anti-melanoma differentiation-associated protein 5 (anti-MDA5) associated clinically amyopathic dermatomyositis (CADM) is a rare entity that is frequently associated with rapidly progressive interstitial lung disease. The disease is characterized by its association with a distinct myositis specific antibody, the lack of muscle involvement seen with other inflammatory myopathies, and a strong correlation with the development of rapidly progressive interstitial lung disease. Diagnosis is based on clinical findings and the presence of autoantibodies. Management generally involves combination immunosuppression therapy. However, the disease course is often aggressive and lends a poor prognosis. We report a case of a healthy 55-year-old male who presented with dyspnea, dry cough, and joint pain for 1 month. The patient was diagnosed with anti-MDA5 associated CADM with interstitial lung disease after a complete rheumatological workup found elevated titers of MDA5 antibodies and computed tomography of the chest without contrast revealed radiographic evidence of interstitial lung involvement. Disease course was complicated by the development of Pneumocystis pneumonia as a result of profound immunosuppression from combination immunosuppressant therapy. Our patient eventually succumbed to his illness approximately 10 weeks following initial symptom onset. This case highlights the aggressive nature of the disease and the challenges in management. Further research is warranted to establish more effective therapeutic options.
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Arsenic is a toxic metal abundantly present in agricultural, industrial, and pesticide effluents. To overcome arsenic toxicity and ensure safety for plant growth, silicon (Si) can play a significant role in its mitigation. Here, we aim to investigate the influence of silicon on date palm under arsenic toxicity by screening antioxidants accumulation, hormonal modulation, and the expression profile of abiotic stress-related genes. The results showed that arsenic exposure (As: 1.0 mM) significantly retarded growth attributes (shoot length, root length, fresh weight), reduced photosynthetic pigments, and raised reactive species levels. Contrarily, exogenous application of Si (Na2SiO3) to date palm roots strongly influenced stress mitigation by limiting the translocation of arsenic into roots and shoots as compared with the arsenic sole application. Furthermore, an enhanced accumulation of polyphenols (48%) and increased antioxidant activities (POD: 50%, PPO: 75%, GSH: 26.1%, CAT: 51%) resulted in a significant decrease in superoxide anion (O2â¢-: 58%) and lipid peroxidation (MDA: 1.7-fold), in silicon-treated plants, compared with control and arsenic-treated plants. The Si application also reduced the endogenous abscisic acid (ABA: 38%) under normal conditions, and salicylic acid (SA: 52%) and jasmonic acid levels (JA: 62%) under stress conditions as compared with control and arsenic. Interestingly, the genes; zeaxanthin epoxidase (ZEP) and 9-cis-epoxycarotenoid dioxygenase (NCED-1) involved in ABA biosynthesis were upregulated by silicon under arsenic stress. Likewise, Si application also upregulated gene expression of plant plasma membrane ATPase (PMMA-4), aluminum-activated malate transporter (ALMT) responsible for maintaining cellular physiology, stomatal conductance, and short-chain dehydrogenases/reductases (SDR) involved in nutrients translocation. Hence, the study demonstrates the remarkable role of silicon in supporting growth and inducing arsenic tolerance by increasing antioxidant activities and endogenous hormones in date palm. The outcomes of our study can be employed in further studies to better understand arsenic tolerance and decode mechanism.
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Hypertension is one of the major issues worldwide and one of the main factors involved in heart and kidney failure. Angiotensinogen and renin are key components of the renin-angiotensin-aldosterone system, which plays an indispensable role in hypertension. The aim of this study was to find out the non-synonymous mutations and structure-based mutation-function correlation in the renin-AGT complex and reveal the most deleterious mutations to accelerated hypertension. In the current study, we employed computational modeling and molecular simulation approaches to demonstrate the impact of specific mutations in the REN-AGT interface in hypertension. Computational algorithms, that is, PhD-SNP, PolyPhen-1, MAPP, Sorting Intolerant from Tolerant, Screening of non-acceptable polymorphism, PredictSNP, PolyPhen-2, and Protein Analysis Through Evolutionary Relationships predicted 20 mutations as deleterious in AGT while only five mutations were confirmed as deleterious in the renin protein. Investigation of the bonding analysis revealed that two mutations S107L and V193F in renin altered the hydrogen-bonding paradigm at the interface site. Furthermore, exploration of structural-dynamic behaviors demonstrated by that these mutations also increases the structural stability to regulate the expression of disease pathway. The flexibility index of each residues and structural compactness analysis further validated the findings by portraying the difference in the dynamic behavior in contrast to the wild type. Binding energy calculations based on molecular mechanics/generalized Born surface area methods were used which further established the binding differences between the wild type, S107L, and V193F mutant variants. The total binding energy for wild type, S107L, and V193F was reported to be -27.79, -47.72, and -38.25, respectively. In conclusion, these two mutations increase the binding free energy alongside the docking score to enhance the binding between renin and AGT to overexpress this pathway in a hypertension disease condition. Patients with these mutations may be screened for potential therapeutic intervention.