This paper is develops an effective method based on two-dimensional Chelyshkov polynomials (2DCPs) to provied an approximate solution of a class of nonlinear two-dimensional Volterra Integral equations of the first kind. This problem is transformed to a nonlinear two-dimensional Volterra Integral equations of the second kind. The method transforms the integral equation to a system of nonlinear algebraic equations by means of collocation points. Finally, some numerical examples are given to clarify the efficiencey of the presented method.

There are criminal cases that no frequently used evidence, for example, DNAs from the criminal, is available. Such cases usually are unresolvable. With the advent of DNA metabarcoding, evidences are mined from environmental DNA and such cases become resolvable. This study reports how a criminal suspect was determined by environmental plant DNA metabarcoding technology. A girl was killed in a rural wet area in China without a witness or video record. Pants with dried mud was found from one of her boyfriend's house. The mud was removed from the pants and 11 more mud or soil samples surrounding murder scene were collected. DNA was extracted from the soil. Chloroplast rbcL gene fragments were amplified and sequenced on a next generation sequencing platform. Of the 2980 ZOTUs in total from the 12 samples, 1495 ZOTUs were identified to species, genera or families based on the existing public database. The feast analysis based on either taxa or taxa plus abundance data demonstrated that the mud on the suspect's pants was from the criminal scene. The suspect finally made a clean breast of his crime. This case implies that plant DNA in the environment soil is a new source of evidence in determination of suspects using DNA metabarcoding technology and has high potentials of extensive applications in criminal cases.

The coronavirus diseases 2019 (COVID-19) pneumonia may cause cystic features of lung parenchyma which can resolve or progress to larger blebs. Spontaneous pneumothorax (SP) was reported as a complication of COVID-19 with an incidence of 1% in hospitalized patients, in 3% of patients hospitalized with pneumonia, in 6% mechanically ventilated patients and in 1% of decased patients. Pneumothorax was more likely in patients with neutrophilia, severe lung injury and a prolonged clinical course. We present 11 cases of SP managed with chest tube thoracostomy (CTT) or high dose oxygen therapy. Isolated SP was detected in all cases. Eight cases were male and three cases were female. There were bilateral ground-glass opacities or pulmonary infiltrates in the parenchyma of the ten cases. We detected neutrophilia, lymphopenia and increased CRP, Ferritin, LDH, D-Dimer, IL-6 levels in almost all cases. CTT was sufficient to treat pneumothorax in our nine of case. In two cases, pneumothorax healed with high dose oxygen therapy. Favipiravir and antibiotic treatment were given to different ten patients. In our institution, all patients with COVID-19 infection were placed on prophylactic or therapeutic anticoagulation, unless contraindicated. The treatments of patients diagnosed with secondary spontaneous pneumothorax during the pandemic period and those diagnosed with secondary spontaneous pneumothorax in the previous three years were compared with the durations of tube thoracostomy performed in both groups. The increased number of cases of pneumothorax suggests that pneumothorax may be a complication of covid-19 infection. During medical treatment of covid-19, pneumothorax may be the only reason for hospitalization. Although tube thoracostomy is a sufficient treatment option in most cases, clinicians should be aware of the difficulties that may arise in diagnosis and treatment.

Background and purpose: To investigate the effect of hIgDFc-Ig (DG), a new biological agent that competitively binds to IgD receptors, on collagen-induced arthritis and its potential mechanism in regulating B cell antigen-receptor signaling pathway. Experimental approach: DBA1 mice were used to establish collagen-induced arthritis model, three doses of DG were administered by intraperitoneal injection. Clinical assessment of CIA, histopathological examination, flow cytometry, western blotting, immunofluorescence staining, protein chips and other methods were used to evaluate the therapeutic effects. The effects of DG on Daudi cells and IgαIgβ KO Ramos cells stimulated by IgD were also evaluated. Key results: We found that DG has a significant therapeutic effect on CIA mice. DG relieved the clinical assessment of CIA mice and improved the pathology of joints and spleen. In addition, DG can also regulate B cell subsets in the PBMC and spleen of CIA mice, and decrease the level of immunoglobulins. DG can inhibit the BCR signaling activation stimulated by IgD and effect the expression of transcription factors in vitro. In Ramos cells, Igβ or IgαIgβ knockout may reverse the activation of BCR signal pathway under the stimulation of IgD. Conclusion and Implications: DG may play a therapeutic role in CIA mice by regulating BCR-Lyn-Syk-NF-κB signaling pathway, and may be a new promising biological agent for rheumatoid arthritis.

Letter to the editor

COVID-19 outbreak is the recently reported worldwide pandemic threat. As part of our interventions with molecular simulation approaches, we report the inhibitory effect of thirty compounds reported from the sacred plant Aerva lanata and compare their activity with the one of the present medication, hydroxy chloroquine, on the main protease (PDB:6YB7) of SARS-CoV-2. Our studies pointed out the effectiveness of the plant with twenty seven compounds having potential activity against the main protease compared to the reference HCQ. The robustness of some of the phytochemicals such as ervoside, which is only present in Aerva lanata computed to have very high anticoronavirus activity. The results are indicative of potential natural antivirus source, which subsidizes in thwarting the invasion of coronavirus into the human body. Many phytochemicals which are computed to be effective towards SARS-CoV-2 in this study are used as drugs for various other diseases. Perhaps these compounds could be attractive for the management of COVID-19, but clinical trials must be performed in order to validate this observation.

Background: Intramedullary fixation is the preferred treatment for AO type 31A2.2-3.3 intertrochanteric fractures. However, the planting position of the spiral blade into the femoral head is controversial, and relative biomechanical studies are sparse. This article aims to investigate the influence of different position of spiral blade on fixation of intertrochanteric fracture. Methods: A three-dimensional (3D) finite element model of a femoral intertrochanteric fracture with proximal femoral nail antirotation (PFNA) fixation was developed in which the collum femoris was divided into three parts based on the length of the spiral blades. Subsequently, we measured the displacement and stress both the intertrochanteric fracture model and the spiral blade in nine fixation modalities. Results: When the spiral blade was placed in the middle position of the femoral neck, the displacement was the lowest (2.68 mm) and the stress was the least (180.77 Mpa), followed by the lower position of femoral neck, while the displacement and the stress of the upper position of the femoral neck were the largest. The stress decreased stepwise from the tip of the spiral blade to the distal end of the intramedullary nail. Conclusion: The upper spiral blade position produced the largest displacement of the finite element model. A medium-length spiral blade located in the middle of the femoral neck can achieve a stable fixation, and reduce the cutting effect on the femoral head, which is recommended for the treatment of intertrochanteric fractures.

At the beginning of the Coronavirus disease (COVID-19) pandemic due to the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), scientists primarily have focused on diagnostic tests. At the 9th month of the pandemic, discussions are being continued on preventive and therapeutic drugs. Meanwhile, vaccine development strategies like “operation warp speed” gave their early results in developed countries. Nowadays, these vaccines are at the forefront of the world health agenda. Numerous social media posts, conspiracy theories, and some health professional’s statements that raise vaccination hesitancy are the equipment of anti-vaxxers propaganda. On the other hand, declarations like ballyhoo of nationalism with the claims of scientific quacksalvers have intertwined, and that has been led to the loss of trust in the scientific community to the vaccine. We have to admit that this propaganda has affected millions of people in an unwanted direction. Scientific declarations have to rely on researches that have accurate and reliable statistical methods supported with basic biological knowledge. Scientific research results should be disclosed transparently and its methods must have reproducibility to provide replicability. Here, we scrutinize the biological features of the respiratory transmitted and successfully prevented measles virus (MV) and variola virus (smallpox virus) and their vaccines to compare them with the SARS-COV-2 virus and vaccine. Next, we will discuss the statistical details of measuring the effectiveness of an improved vaccine.

Introduction Etiological diagnosis of fever in sickle cell disease (SCD) children is often challenging. Objective: to analyze the pattern of inflammatory biomarkers in SCD febrile children and controls, in order to determine predictors of severe bacterial infection (SBI). Methods Prospective, case-control study of febrile and steady-state SCD children carried out during 3 years. Clinical characteristics and laboratory parameters, including 10 serum proinflammatory cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17a, IFN-γ and TNF-α) and comparisons among study subgroups were analyzed. Results A total of 137 patients (78 cases and 59 controls) were included in the study; 78.5% males, median age 4.1 (1.7-7.5) years. Four cases were diagnosed with SBI, 41 viral infection (VI) and 33 no proven infection (NPI). IL-6 was significantly higher in patients with SBI than in patients with VI or NPI (163 vs 0.7 vs 0.7 pg/ml, p < 0.001), and undetectable in all controls. The rest of the cytokines analyzed did not show any significant difference. The optimal cut-off value of IL-6 for the diagnosis of SBI was 125 pg/mL, with high PPV and NPV (PPV of 100% for a prevalence of 5, 10 and 15% and NPV of 98.7%, 97.3% and 95.8% for those prevalences, respectively). Conclusion We found that IL-6 (optimal cut-off value of 125 pg/ml) was a very good marker for SBI in this cohort of febrile SCD children, with high PPV and NPV. Therefore, IL-6 may be useful, alone or combined with other biomarkers, to guide the management of these patients.

Background: Venous thromboembolism (VTE) is a disease that could endanger maternal health, especially its serious complications. Although several previous studies have examined many risk factors of VTE in pregnancy and postpartum, we still lack studies that use quantitative methods to evaluate the strength, quality, and consistency of existing evidence. Objectives: to summarize risk factors for VTE in pregnancy and postpartum. Search Strategy: The search was conducted in PubMed、EMBASE, web of science、MEDLINE. Selection Criteria: Study reporting risk factors for VTE in pregnancy and postpartum. Data Collection and Analysis: Review Manager (RevMan, version 5.3) was used for meta-analysis, and the outcome of the analysis was presented as odds ratio (OR). Main Results: We included 24 studies (7 case-control studies, 2 nested case-control studies and 15 cohort studies) and 14 of them were used for the meta-analysis. There were 59 risk factors with positive evidence in all studies and we selected 13 risk factors for the meta-analysis. The three most significant risk factors in the meta-analysis were Factor V Leiden (FVL) (OR = 9.95, 95% CI: 5.93–16.70), Placenta previa (OR = 8.74, 95% CI: 3.40–22.50), and cardiac disease (OR = 7.77, 95% CI: 5.31–11.38). Conclusions: The number of risk factors for VTE during pregnancy and postpartum is very huge. Our study showed that the main risk factors are advanced age, overweight, cesarean section, multiple pregnancy, placenta previa, FVL, F2 20210A and cardiac disease.

Antimicrobial resistance is a serious problem to solve especially in developing countries like India. Antibiotic use in India increased several times since 2005. Many studies in India have reported inappropriate and overuse of antibiotics which could be one of the possible reasons for increased antibiotic resistance in country. This is an important and urgent issue that mandate strict regulations regarding rational use of antibiotics. World Health Organization (WHO) has done major revision in essential medicines list which classify antibiotics in three categories (access, watch and reserve) to ensure the availability and correct use of antibiotics. Several countries started antimicrobial stewardship programme to promote appropriate use of antibiotics, reduce antibiotic resistance as well as financial burden. Indian government implemented national action plan on antibiotic resistance in 2017 with the aim of prompting rational use of antibiotics but it is still in its formative stage as all stewardship components are yet to be implemented. This review emphasizes on the importance and the need for implementing WHO’s AWaRe classification and antimicrobial stewardship to promote rational antibiotic use in country.

Abstract: Objective To investigate the efficacy and prognosis of obesity in the treatment of children with capillary bronchitis. Methods: A retrospective analysis of the clinical data of 200 children with capillary bronchitis hospitalized in our hospital from January 2015 to January 2016 was performed. Results: After nebulization treatment, the total effective rate was significantly higher in the normal weight group than in the obese group (93.3% vs 65.5％, p＜0.005, x2=19.77). And the significantly effective rate was higher in the normal weight group than in the obese group (53.3% vs 36％, p=0.008, x2=5.76). The children in the normal weight group had a significantly shorter duration of coughing, wheezing and croup than those in the obese group, and the difference was statistically significant (p<0.05). In the normal weight group, the proportions of recurrent wheezing episodes and confirmed asthma were significantly lower than those in the obese group, among which the proportions of wheezing episodes >1, wheezing episodes >3 and confirmed asthma were significantly different (p<0.05). The results of univariate and logistic regression analyses showed that obesity may be a risk factor for the development of asthma in children with capillary bronchitis. Conclusion Obesity has a negative impact on the treatment and prognosis of children with capillary bronchitis and significantly increases the chance of developing asthma in the future, suggesting a new direction for the future treatment of capillary bronchitis that deserves attention.

Background: Snake biting are a substantially neglected health problem in rural areas of Pakistan. There is a need for producing larger and better quality anti-snake venom to decrease mortality associated with snakebite cases. Objectives: The current study aimed to evaluate the efficacy of a novel strategy to produce antivenom against the venom of two common krait species found in Sindh, Pakistan Methods: This was an animal-based research conducted at Dow University of Health Sciences, Karachi, Sindh, Pakistan. All experimental subjects were categorized equally into two groups with unique numerals for identification purposes. i.e. Group A for Bungarus sindanus and Group B for Bungarus caeruleus. Each group consisted of 6 horses. One horse in each group acted as a control. Before initiating the immunization process, baseline serums were collected from the subject’s jugular veins and stored as baseline controls. Post immunization serums were weekly collected from the horses and stored. Enzyme-linked immunosorbent assay (ELISA) was used to estimate immunoglobulin of the subjects by adding a fixed amount of venom antigen with coating buffer pH of 9.5 to 10 ng, 100 ng, and 1000 ng. Incubated overnight at 37° C temperature in the incubator. Results: The results showed that the two species of the krait family did not show significant neutralizing antibodies against each other. The novel oral adjuvant formulation of snake venoms is safe and easy to administer which will be useful for commercial ASV production of potent antibodies at a significantly reduced cost and without any significant adverse effects on equine health. Conclusions: The current study presents an effective novel approach for the production of anti-snake venom for Bungarus sindanus and Bungarus caeruleus.

Introduction: part of the effectiveness of follow-ups of patients with HIV in antiretroviral therapy is done through the quantification of CD4 + lymphocytes, hence the correct establishment of these values is an issue of interest in the clinical setting. Objective: to establish predictive mathematical relationships between CD4+ cell counts in ranges >500, [200,500], <200, between 200 and >500 and <200 up to 500 cells/μL3 with the absolute leukocyte count of patient samples over time in the context of the theory of probability. Methods: Through an inductive process carried out in 11 patient samples, mathematical patterns that forecast in time the correspondence between absolute leukocyte counts and CD4+ counts that can occur in five ranges of clinical interest. Then, a confirmation was done with 139 patients in a blind study obtaining the probability values for each range as well as sensitivity and specificity. Results: The five dynamics predicted achieved probabilities that varied between 0.96 and 1, with a global probability of 0.99 with sensitivity and specificity values of 99%. Conclusions: a self-organized mathematical temporal order that allows to forecast the values of CD4+ cells in relation to leukocyte counts in ranges of clinical interests was found, which could be useful to develop surveillance programs of HIV-infected patients in low-income countries, improving their survival rates.

Avian leukosis virus subgroup J (ALV-J) is the most prevalent subgroup in chickens and exhibits increasing pathogenicity and stronger horizontal and vertical transmission ability in different kinds of chicken. Although vertical transmission of ALV-J from hens infected through artificial insemination with ALV-J infected semen was reported before by the detection of swabs and serum, there was no further research on the trasmission pattern of ALVs in the roosters. In the present study, the introduction of Hy-line brown roosters infected with ALV-J significantly increased the p27 positive rate of ALV in a indigenous flock detected by virus isolation. Sequence analysis and IFA showed that it is classified into ALV-J subgroup, locating in a new branch compared with the domestic and foreign referential sequences. Meanwhile, the gp85 gene of the ALV-J isolated in the hens and its albumens had a homology of 94.1-99.7% with that in the roosters, which means that the strain is quite likely transmitted to the hens and their offspring through insemination of the roosters. Moreover, Semens are directly detected by ELISA method is not completely accurate. There are four ALV-J infection status in plasma and semen of rooster (V+S+, V-S+, V+S-, V-S-), so the eradication of ALV in rooster requires simultaneous virus isolation of semen and plasma. Therefore, we speculate that the reason why there are still some sporadic findings of ALV-J in laying hens is probably due to the incomplete eradication process of roosters.

A predictive understanding of ecological processes requires identifying the factors that explain variation in the organismal traits that drive these processes. Integrating evolutionary history and ecology has been shown to be essential to understand variation in traits that determine species interactions in community ecology. However, the extent to which these factors determine traits relevant for ecosystem dynamics (and thus ecosystem ecology) is poorly understood. Nutrient cycling is essential for reef ecosystem dynamics, and consumers are critical drivers of this process. We use a dataset of nine consumer “chemical traits” (e.g., body nutrient content and nutrient excretion rates) associated with nutrient cycling, collected from 1,572 individual coral reef fish (178 species spanning 41 families) in two biogeographic regions, the Caribbean and Polynesia, to quantify the relative importance of phylogenetic history and ecological context as a driver of chemical trait variation on coral reefs. We find: (1) phylogenetic history is a better predictor of variation in all chemical traits, overwhelming the influence of ecological factors, (2) phylogenetic conservatism in chemical traits is greater in the Caribbean than Polynesia, where our data suggests that ecological forces may have a greater influence on chemical trait variation, and (3) differences in chemical traits between regions can be explained by differences in nutrient limitation associated with our study locations. Our study provides multiple lines of evidence that phylogenetic conservatism is a critical determinant of contemporary nutrient dynamics on coral reefs. More broadly our findings highlight the utility of evolutionary history to improve prediction in ecosystem ecology.

The impacts of human-driven environmental changes on the stability of natural grasslands have been assessed by comparing differences between manipulative warming and grazing plots and reference plots. However, little is known about whether or how ambient climate regulates the effects of manipulative treatments. A 36-year observational dataset shows that there is a nonlinear response of community stability to ambient climate. Manipulative warming and grazing decrease community stability with experiment duration through an increase in legume coverage and/or decrease in species asynchrony, due to exceeding the threshold of background annual mean air temperature with decreasing background annual mean air temperature through time during the 10-year experiment period. Moreover, the temperature sensitivity of community stability is more sensitive under the ambient treatment than under the manipulative treatments. Therefore, our study emphasizes the importance of the context dependency of the response of community stability to human-driven environmental changes.

Thrombotic complications of SARS-CoV-2 have been increasingly recognized as an important component of COVID-19 in adults; however, they have been less evident in children. We report a case of a teenager with positive SARS‐CoV‐2 RT–PCR and underlying prothrombotic risk factors, including aromatase inhibitor therapy, who developed deep vein thrombosis resulting in pulmonary embolism. Laboratory tests revealed deranged coagulation parameters (high D-dimers and Factor VIII and low antithrombin). The patient required intensive care and was managed with anticoagulants, dexamethasone and antithrombin concentrate. Clinical condition and hemostatic profile gradually improved. A review of the available literature for similar cases is presented.

Rationale, aims and objectives The study aimed to investigate the rate of the potential cytochrome P450 (CYP450)-mediated drug-drug interactions (DDIs) between selective serotonin reuptake inhibitors (SSRI) and other drugs, and identify the most common CYP450-interacted SSRI-drug combinations in real-life clinical practice. Methods This is a retrospective analysis of SSRI prescribing data from the Akdeniz University Hospital database, a tertiary hospital database in Turkey. Prescriptions which were included an SSRI had been selected (from January 2014 to December 2018). Lexicomp® Online™ was used to identify potential CYP450-mediated DDIs. Results A total of 7.5% of SSRI prescriptions were at risk of potential CYP450-mediated DDIs; 74.4% (n = 67) of the pDDIs were identified as category D modification of treatment should be considered. Antipsychotics were involved in 71.8% category D potential DDIs and 83.6% category C potential DDIs. The medications most frequently identified in combination with SSRIs were risperidone (31.7%) and aripiprazole (31.6%). Finally, CYP2D6 and CYP3A4 were the two most commonly affected CYP450 isozymes. Conclusions Prescribing antipsychotic-SSRI pairs interacting via CYP450 may increase serum concentrations of antipsychotics. Using DDI alert software while writing electronic prescriptions during clinical practice may reduce the frequency of ADRs.

Rationale, aims and objective: Eosinophilia is rare, but one of the important reasons to refer patients to pneumonological centers. Determining its etiology has practical implications for therapeutic intervention and disease prognosis. The study aimed to determine the role of peripheral eosinophilia in the diagnosis of lung disorders. Methods: The prospective study included 46 consecutive patients diagnosed with peripheral eosinophilia with coexisting respiratory symptoms and/or radiologically detected lung lesions. All patients underwent standard diagnostic procedures, including a detailed clinical history review, physical examination, routine laboratory tests with basal cardiological examinations, and serological tests to detect parasites and allergies. Other procedures carried out depended on the symptoms of each patient. Results: Severe eosinophilia (≥5,000 cells/μL) was associated with extrapulmonary involvement and constitutional symptoms. Skin, heart, and pleural diseases were more frequent in these patients than in patients with mild or moderate eosinophilia (p=0.010, p=0.040, and p=0.007, respectively), and only these patients showed signs of kidney disease (p=0.006). Vasculitis was significantly more frequent in the severe eosinophilia group (p=0.048) than in the other two groups. In patients with moderate eosinophilia (1,500-5,000 cells/μL), extrapulmonary symptoms were less common, although signs of cardiac involvement were confirmed in 44% of subjects. In this group, vasculitis was the most commonly observed disease (42% of cases). Mild eosinophilia (<1,500 cells/μL) was mainly associated with airway disease. In this group, vasculitis and interstitial lung diseases were identified, but most were not typically connected with eosinophilia. Conclusion: Identification of peripheral eosinophilia essentially determines diagnostic procedures in patients with lung disorders and can be a useful indicator of disease etiology.

Letter to the Editor, BJOG

SARS coronavirus 2 (SARS-CoV-2) in the viral spike (S) encoding a SARS-COV-2 SPIKE D614G mutation protein predominate over time in locales revealing the dynamic aspects of its key viral processes where it is found, implying that this change enhances viral transmission. It has also been observed that retroviruses infected ACE2-expressing cells pseudotyped with SG614 that is presently affecting a growing number of countries markedly more efficiently than those with SD614. The availability of newer powerful computational resources, molecular modeling techniques, and cheminformatics quality data have made it feasible to generate reliable algebraic calculations to design new chemical entities, merging chemicals, fragmentizing natural products, and a lot of other substances fuelling further development and growth of this AI-quantum based drug design field to balance the trade-off between the structural complexity and the quality of such biophysics predictions that cannot be obtained by any other method. In this paper, we strongly combine topology geometric methods targeting at the atomistic level the protein apparatus of the SARS-COV-2 virus that are simple in machine learning anti-viral characteristics, to propose computer-aided rational drug design strategies efficient in computing docking usage, and powerful enough to achieve very high accuracy levels for this in-silico effort for the generation of the AI-Quantum designed molecule the RoccustyrnaTM small molecule, a multi-targeting druggable scaffold 2‐({[fluoro({[(2E)‐5‐oxabicyclo [2.1.0]pentan‐2‐ylidene]cyano‐lambda6‐sulfanyl}) methyl]phosphorylidene} amino)-4,6‐dihydro‐1H‐purin‐6‐onetargeting the COVID-19-SARS-COV-2 SPIKE D614G mutation using Chern-Simons Topology Euclidean Geometric in a Lindenbaum-Tarski generated QSAR automating modeling and Artificial Intelligence-Driven Predictive Neural Networks.

It is thought that all of the rich content in the present-day Universe based on an array of recent observations developed through gravitational amplification of primeval density fluctuations generated in the very early phase of cosmic evolution. In this paper, we strongly combine machine learning characteristics to achieve very high accuracy levels for the in-silico generation of the RoccuffirnaTM small molecule, a ligand targeted the SARS-COV-2 virus main protease (M pro ) using Quantum Kerr-(A)dS and Myers–Perry black microBlackHole-Inspired Gravitational for both Euclidean and Lorentzian signatures in Practice. We provide also an extensive toolbox of methods for performing quantum schrodinger inspired docking algorithms, teleportation and other information-theoretic tasks in MathCast programming language, and compared these algorithms by means of mean percentile free energy ranking, in a new recall-based evaluation metric for the in-silico design of the Novel Series of the RoccuffirnTMQMMMCoRoNNARRFr anti-(nCoV-19) ligands. In this paper we in-silico designed new drug leads that target the COVID-19 virus main protease (M pro ). M pro, a key CoV enzyme, which plays a pivotal role in mediating viral replication and transcription, and discuss various general results including Galilean transformation to a rigid QMMM heuristic horizon topology, and near-horizon fragmentation symmetry ranging from supergravity theories to Lorentzian signatures in order to enhance the Roccuffirna’s gravity to trap the SARS-COV-2 viruses in practice.

Background and Purpose: The dual inhibition of thioredoxin reductase (TrxR) and glutathione reductase (GSHR) has emerged as a promising approach for the treatment of cancer and for promoting the defense mechanism by the immune system. In a previous report, we described a modular and novel strategy for the synthesis of a small molecule library. Here, we aim to discover a novel benzopyrane derivative that possesses a multitarget anticancer mechanism of action. Experimental Approach: The anticancer effect of SIMR1281 was evaluated in vitro to determine its effect on GSHR, TrxR, mitochondrial metabolism, DNA damage, cell cycle progression, and induction of apoptois. In addition, SIMR1281 was evaluated in vivo for its safety and in xenograft mice model. Key Results: SIMR1281 strongly inhibits GSHR while moderately inhibits TrxR. It inhibits cell proliferation of various cancers and mediates the induction of DNA damage machinery. SIMR1281, perturbs cell cycle, inactivates Ras/ERK and PI3K/Akt pathways. Furthermore, SIMR1281 induces apoptosis and strongly attenuates cell survival machinery. SIMR1281 significantly reduces tumor volume in a xenograft model while maintaining a high in vivo safety profile. Conclusion and Implications: Our findings demonestrate that SIMR1281 possesses a promising multitarget anticancer activity in vitro and in vivo against multiple types of cancers while maintaining a high in vivo safety profile. This unique activity of SIMR1281 represents an innovative strategy for the treatment of various types of cancers and places this compound in a privileged position as a potential clinical drug candidate.