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Lung transplant recipients (LTRs) are at increased risk of morbidity and mortality from coronavirus disease 2019 (COVID-19); however, the disease course has changed as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants have mutated. We compared COVID-19-related clinical outcomes in LTRs at different stages of the pandemic. We also identified risk factors for developing severe COVID-19 independent of the dominant SARS-CoV-2 variant. This single-center, retrospective cohort study of LTRs with COVID-19 used Cox regression analyses and bootstrapping to identify factors affecting COVID-19 severity. Between March 2020 and August 2022, 195 LTRs were diagnosed with COVID-19, almost half (89 [45.6%]) during the Omicron period. A total of 113 (58.5%) LTRs were hospitalized and 47 (24.1%) died. Age >65 years increased the risk of hospitalization and death. Although infection with the Omicron variant was associated with a lower risk of hospitalization, the median length of hospital stay (10 days, [interquartile range, 5-19]) was similar between the variants. Intensive care unit (ICU) admission and death were more common with the Delta variant but comparable between the original, Alpha, and Omicron variants. Remdesivir and molnupiravir reduced the risk of hospitalization, and monoclonal antibody therapy reduced the risk of ICU admission, intubation, and death. Vaccination and pre-exposure prophylaxis (PrEP) with tixagevimab-cilgavimab did not significantly reduce COVID-19-related ICU admission, intubation, or mortality among LTRs. LTRs with COVID-19 continue to have high hospitalization rates and prolonged hospital stays, despite the reduced virulence of the Omicron variant. More effective PrEP and therapeutic interventions for COVID-19 among vulnerable patient groups are needed. [ABSTRACT FROM AUTHOR]

Background: In the general population, prior infection with SARS‐CoV‐2 reduces the risk of severe COVID‐19; however, studies in lung transplant recipients (LTRs) are lacking. We sought to describe the clinical course of COVID‐19 recurrence and compare outcomes between the first and second episodes of COVID‐19 in LTRs. Methods: We conducted a retrospective, single‐center cohort study of LTRs with COVID‐19 between January 1, 2022, and September 30, 2022, during the Omicron wave. We compared the clinical course of a second episode of COVID‐19 to that of the patients' own first episode and to that of LTRs who developed a first episode during the study period. Results: During the study period, we identified 24 LTRs with COVID‐19 recurrence and another 75 LTRs with a first episode of COVID‐19. LTRs who survived the initial episode of COVID‐19 had a similar disease course with recurrence, with a trend toward reduced hospitalization (10 (41.6%) vs. 4 (16.7%), p =.114). Furthermore, compared to LTRs with a primary infection during the Omicron wave, those with a reinfection had a non‐statistically significant trend toward reduced hospitalizations (aOR.391, 95% CI [.115–1.321], p =.131), shorter lengths‐of‐stay (median, 4 vs. 9 days, p =.181), and reduced intensive care unit admissions, intubations, and COVID‐19–related mortality. Conclusions: LTRs who survive the first episode of COVID‐19 are likely to have a similar clinical course with recurrent episodes. Although recurrent COVID‐19 may be milder, larger, well‐powered studies are needed to confirm this observation. Ongoing precautions are warranted. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a growing health concern projected to cross over a million cases worldwide by 2025. HCC presents a significant burden of disease in Middle East and North African (MENA) countries due to a high prevalence of risk factors such as hepatitis C and B infections and rising incidence of non‐alcoholic steatohepatitis and non‐alcoholic fatty liver disease. In August 2022, an advisory meeting consisting of experts from 5 MENA countries was convened in an attempt to provide consensus recommendations on HCC screening, early diagnosis, current treatment modalities and unmet medical needs in the region. Data were collected from a pre‐meeting survey questionnaire and responses analysed and presented during the advisory meeting. This review summarizes the evidence discussed at the meeting and provides expert recommendations on the management of HCC. The 2022 update of Barcelona clinic liver cancer (BCLC) staging and treatment strategy and its implementation in the MENA region was extensively discussed. A key consensus of the expert panel was that multidisciplinary care is crucial to effective patient management that results in better clinical outcomes and overall survival of the patient. The panel recommended the use of predictive and early response biomarkers to guide clinicians in arriving at more effective therapeutic decisions. The experts also emphasized the role of robust screening/surveillance systems, population‐based registries, effective referral pathways and standardization of guidelines to ensure the successful management of HCC in the region. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Lung Transplantation in the United States for COVID-19 Related Lung Disease During the Pandemic." The author has identified errors in the title and some values in the results section, figures, and captions. The corrected title is "Lung Transplantation in the United States for COVID-19 Related Lung Disease During the Pandemic." The correction also includes revised sentences and values in the results section. The figures and captions have been corrected as well. The original article has been updated to reflect these corrections. [Extracted from the article]

A series of novel macroacyclic Schiff base ligands and their Cu (II) complexes were synthesised via reacting dicarbonyls of varying chain lengths with S-methyl dithiocarbazate (SMDTC) and S-benzyl dithiocarbazate (SBDTC) followed by coordination with Cu (II) ions. X-ray crystal structures were obtained for compound 4, an SBDTC-diacetyl analogue, and Cu7, an SMDTC-hexanedione Cu (II) complex. Anticancer evaluation of the compounds showed that Cu1, an SMDTC-glyoxal complex, demonstrated the highest cytotoxic activity against MCF-7 and MDA-MB-231 breast cancer cells with IC50 values of 1.7 µM and 1.4 µM, respectively. There was no clear pattern observed between the effect of chain length and cytotoxic activity; however, SMDTC-derived analogues were more active than SBDTC-derived analogues against MDA-MB-231 cells. The antibacterial assay showed that K. rhizophila was the most susceptible bacteria to the compounds, followed by S. aureus. Compound 4 and the SMDTC-derived analogues 3, 5, Cu7 and Cu9 possessed the highest antibacterial activity. These active analogues were further assessed, whereby 3 possessed the highest antibacterial activity with an MIC of <24.4 µg/mL against K. rhizophila and S. aureus. Further antibacterial studies showed that at least compounds 4 and 5 were bactericidal. Thus, Cu1 and 3 were the most promising anticancer and antibacterial agents, respectively. [ABSTRACT FROM AUTHOR]

Wind Tunnel measurements are conducted using scaled down models of aerospace as well as automotive systems. These models are attached to supporting struts. The forces on the support system are taken into account to obtain the corrected aerodynamic data. Most of the struts used in testing are cylindrical in shape with a pitch rod for the alpha mechanism. These model attachments introduce additional forces and moments due to their size and frontal area. A diamond shaped strut is one of the proposed solutions with other benefits of reduced contribution towards the lift due to its tapered profile. This paper describes the effect of support interference due to the two different strut types. First, the entire cylindrical strut was shrouded by a streamlined metal fairing and its influence on the actual force and moments were measured through a series of blow downs in the IIUM low speed wind tunnel at different velocities and side slip angles. Later, the tests were conducted for the diamond shaped strut with a pitch rod mounted on the turntable at a certain distance from the central diamond shaped strut. Lastly the cylindrical strut was installed without the fairing. In comparison with the cylindrical strut (with or without fairing), the diamond shaped strut was found to have smaller lift. The developed databank for different struts will be beneficial for the future design of experiments in wind tunnels of similar dimensions. Such support systems not only contribute towards drag but also to the lift as well as side force. [ABSTRACT FROM AUTHOR]

Purpose Realistic data bank of aerodynamic and stability derivatives is still missing for hybrid buoyant aerial vehicles. Such vehicles take-off and land similar to an aircraft with their partial weight balanced by the aerostatic lift. The purpose of this paper is to use wind tunnel testing for a better understanding of the aerodynamic and static stability behavior of such vehicles.Design/methodology/approach The effect of wing on the aerodynamic and static stability characteristics of a clean configuration hybrid buoyant is analyzed. The free stream velocity is 20 m/s, and ranges of angle of attack and side slip angle are from −8° to 12° and ±16°, respectively. Data are corrected to account for the effect of strut interference and zero load condition. The maximum blockage of the model with respect to the cross-section area of the test section is about 2.7 per cent.Findings A hybrid model manufactured by using wood and metal is an optimum solution with less number of parts. The vehicle is statically, longitudinally and directionally stable. Wings designed to fulfill the partial requirement of lift contribute significantly to counter the huge moment generated by the voluminous hull for centre of gravity location ahead of the leading edge of the wing.Research limitations/implications There are number of manufacturing constraints for scaling down a model of a hybrid buoyant aerial vehicle configuration. Specially, the thickness of the wing limits the testing envelop of angle of attack and free stream velocity.Practical implications The data presented here are a preliminary guide for further work on larger size models. The data may also be used to build and perform flight tests on small full-scale instrumented models and to obtain flight dynamics data.Originality/value The estimated aerodynamic and stability derivatives and slopes can be utilized in future for multidisciplinary design. [ABSTRACT FROM AUTHOR]

Plants contain a wide variety of bioactive compounds, which have attracted the interest of researchers in finding novel sources of natural medicine. In the following paper, we aim to evaluate the antibacterial potential of extract fractions associated with Parkia speciosa pods and beans against human pathogenic bacteria. Antimicrobial activity was determined with disc diffusion and broth microdilution assays against eight skin colonising microorganisms including Staphylococcus aureus , Staphylococcus epidermidis , Salmonella enterica , Escherichia coli , Pseudomonas aeruginosa , Klebsiella pneumonia followed by further fractionation of the pods ethyl acetate fraction by column chromatography along with preparative thin-layer chromatography. Quantification of bacterial death mechanism was elucidated by the measurement of hole size in cell wall that has been induced by extract constituents via field-emission scanning electron microscopy (FESEM). Four fractions showed significant antimicrobial activity against the six microorganisms tested (p < 0.01), with inhibition zones ranging from 35.67 to 17.00 mm, and minimum inhibitory concentration ranging from 6.25 to 50.00 mg/ml in which the pods ethyl acetate fraction was the most effective. The methanol fraction isolated from the pods ethyl acetate fraction was much more effective with a four-fold increase from 6.25 to 1.25 mg/ml against S. epidermidis. The disintegration of S. aureus was due to chronic cell wall alterations with pore creation, invaginations and morphological disorganisation. Autolysis in bacterial cells via the expression of peptidoglycan-disrupting lysozyme or bacterial murein hydrolase was postulated. A significantly large pore with a mean diameter of 293.7 nm was detected in the cell wall of S. aureus. P. speciosa fraction could be a potential novel source for the development of a natural antibacterial agent. • Four fractions of Parkia speciosa showed significant antimicrobial activity against the six microorganisms tested. • Pods ethyl acetate fraction was the most effective. • The methanol fraction isolated from the pods ethyl acetate fraction was much more effective with a four-fold increase from 6.25 to 1.25 mg/ml against S. epidermidis. • The disintegration of S. aureus was due to chronic cell wall alterations with pore creation, invaginations and morphological disorganisation. • Autolysis in bacterial cells via the expression of peptidoglycan-disrupting lysozyme or bacterial murein hydrolase was postulated. [ABSTRACT FROM AUTHOR]

Background. Persistent orthostatic hypotension (OH) is a lesser-known complication of lung transplantation (LTx). In this retrospective case series, we describe the clinical manifestations, complications, and treatment of persistent OH in 13 LTx recipients. Methods. We identified LTx recipients who underwent transplantation between March 1, 2018, and March 31, 2020, with persistent symptomatic OH and retrospectively queried the records for clinical information. Results. Thirteen patients were included in the analysis, 9 (69%) had underlying pulmonary fibrosis, and 12 (92%) were male. The median age, height, and body mass index at LTx were 68 years, 70 inches, and 27 kg/m2, respectively. Six (46%) patients were deceased at the time of chart abstraction with a median (IQR) posttransplant survival of 12.6 months (6, 21); the 7 remaining living patients were a median of 19.6 months (18, 32) posttransplant. Signs and symptoms of OH developed a median of 60 (7, 75) days after transplant. Patients were treated with pharmacological agents and underwent extensive physical therapy. Most patients required inpatient rehabilitation (n = 10, 77%), and patients commonly developed comorbid conditions including weight loss, renal insufficiency with eGFR <50 (n = 13, 100%), gastroparesis (n = 7, 54%), and tachycardia-bradycardia syndrome (n = 2, 15%). Falls were common (n = 10, 77%). The incidence of OH in LTx recipients at our center during the study period was 5.6% (13/234). Conclusions. Persistent OH is a lesser-known complication of LTx that impacts posttransplant rehabilitation and may lead to comorbidities and shortened survival. In addition, most LTx recipients with OH at our center were tall, thin men with underlying pulmonary fibrosis, which may offer an opportunity to instate pretransplant OH screening of at-risk patients. [ABSTRACT FROM AUTHOR]

The landscape of chronic liver disease in Egypt has drastically changed over the past few decades. The prevalence of metabolic-associated fatty liver disease (MAFLD) has risen to alarming levels. Despite the magnitude of the problem, no regional guidelines have been developed to tackle this disease. This document provides the clinical practice guidelines of the key Egyptian opinion leaders on MAFLD screening, diagnosis, and management, and covers various aspects in the management of MAFLD. The document considers our local situations and the burden of clinical management for the healthcare sector and is proposed for daily clinical practical use. Particular reference to special groups was done whenever necessary. [ABSTRACT FROM AUTHOR]

An accurate numerical method is developed for computing inviscid flows containing discontinuities. The method is based on flux vector splitting (FVS) and a third-order accurate upwind-biased compact finite-difference scheme. Two different flux splitting techniques, namely, the kinetic flux vector splitting (KFVS) and van Leer's flux splitting, are used to solve one-dimensional gas dynamics test problems. The idea of total variation diminishing (TVD) is employed to suppress spurious numerical oscillations. The stability and high-order accuracy of the scheme are shown. [ABSTRACT FROM AUTHOR]

Background and Aim: Direct acting antiviral agents (DAAs) are highly effective and safe treatment in patients with chronic hepatitis C infection (CHC). The aim of this study is to evaluate outcomes of direct acting antiviral drugs for treatment of HCV infection in patients with decompensated liver cirrhosis. Materials and methods: This study included 115 HCV decompensated cirrhotic patients who were treated according to the Egyptian National Treatment Program for Hepatitis C Virus. The patients were divided into 3 groups; Group I, included 70 patients received sofosbuvir and daclatasvir for 24 weeks, Group II, included 18 patients received sofosbuvir, daclatasvir and ribavirin for 12 weeks and control group, included 27 patients refused antiviral therapy. Results: The sustained virologic response (SVR) in the present study was 91% (89.3% in group I and 92.3% in group II) with non-significant difference between both groups. Compared to untreated control group and to baseline parameters, both treated groups showed significant improvement as regarding, liver function, INR, creatinine, Child-Turcott-Pugh score and MELD score12 weeks post-treatment. There was a statistically significant decrease in variceal bleeding, ascites and hepatic encephalopathy in treated group compared to control group with no statistically significant difference recorded between the three studied groups regarding hepatocellular carcinoma, hepatorenal syndrome, spontaneous bacterial peritonitis and pleural effusion. Conclusions: Treatment of decompensated HCV cirrhotic patients with DAAs had SVR about 91%. SVR is associated with improvement in liver function and a significant reduction cirrhotic related complications. [ABSTRACT FROM AUTHOR]

Background: Research has revealed that asymptomatic and pre-symptomatic infections are important contributors to the transmission of SARS-CoV-2 in populations. In Egypt, the true prevalence of infections is veiled due to the low number of screening tests. The aim of this study was to determine the SARS-CoV-2 PCR positivity rate as well the seroprevalence of the SARS-CoV-2 antibodies before the ultimate development of a second wave of the epidemic in Cairo, Egypt. Methods: Our study was carried out between May 5 and the end of October 2020. It included all patients requiring admission to Ain Shams University hospitals. An interview questionnaire was used to collect demographic and clinical data. Laboratory tests for all participants included RT-PCR and total antibody assay for SARS-CoV-2. Results: A total of 4,313 subjects were enrolled in our study, with females representing 56% of the sample. Adults and middle-aged individuals represented around 60% of the study sample. The positivity rate of SARS-CoV-2 PCR was 3.84% (95% CI 3.29–4.48), and the SARS-CoV-2 antibody seroprevalence was 29.82% (95% CI: 28.16–31.51). Males showed a higher risk for getting the COVID-19 infection, while middle-age group had significantly higher antibody seroprevalence rates. Conclusion: SARS-CoV-2 infection imposes a high burden on the community as detected by high seroprevalence rates. [ABSTRACT FROM AUTHOR]

Background: Smoking negatively impacts COVID-19 severity and adverse outcomes. Evidence on whether smoking is associated with SARS-Co-V2 infection and having a positive test is scarce, particularly from low-and middle-income countries, where most of the world's billion smokers live. The inconsistency in relevant findings calls for study designs and analyses to account for possible confounders including background characteristics and pre-existing co-morbidities, to disentangle the specific effect of smoking. In healthcare workers (HCWs) the frequency of exposure to COVID-19 cases adds another layer of risk that was not factored in previous studies. We examined the association of HCWs' tobacco/nicotine use (never, former, and current use) with having a positive SARS-Co-V2 test result and symptoms suggestive of infection, accounting for demographics, exposures, and co-morbidities.Methods: A prospective cohort study of 4040 healthcare workers with baseline and follow-up screening took place during April-June 2020 in 12 healthcare facilities in Cairo, Egypt. Data on demographics, tobacco/nicotine use (manufactured or roll-your-own cigarettes, waterpipe tobacco, and electronic devices), co-morbidities, symptoms, exposures, and SARS-Co-V2 investigations were analyzed. Multinomial and multivariable logistic regression analyses were performed.Results: Overall, 270/4040 (6.7, 95%CI: 5.9-7.5) had positive SARS-CoV-2 tests, 479 (11.9%) were current and 79 (2.0%) were former tobacco/nicotine users. The proportion of positive tests was 7.0% (243/3482, 95%CI: 6.1-7.8) among never, 5.1% (4/79, 95%CI: 0.1-10.0) among former, and 4.8% (23/479, 95%CI: 2.9-6.7) among current users. HCWs' SARS-CoV-2 test results did not vary significantly by single/multiple or daily/non-daily tobacco/nicotine use. Compared to never users, former users were more likely to self-report a pre-existing medical condition (ORadjusted1.87, 95%CI: 1.05-3.33, p = 0.033), and to experience symptoms suggestive of COVID-19 (ORadjusted1.76, 95%CI: 1.07-2.90, p = 0.027). After adjustment, former (ORadjusted0.45, 95%CI: 0.11-1.89, p = 0.273) and current (ORadjusted0.65, 95%CI: 0.38-1.09, p = 0.101) tobacco/nicotine use was not associated with HCWs' SARS-CoV-2 positive test results.Conclusions: This is the first report on this association from low- and middle-income countries with high tobacco/nicotine use prevalence. In this HCW cohort, having a positive SARS-CoV-2 test was not associated with tobacco/nicotine use after accounting for demographics, exposures, and co-morbidities. Additional population-based studies could use such preliminary evidence to investigate this controversial association. [ABSTRACT FROM AUTHOR]

Exosomes isolated from plasma of lung transplant recipients (LTxRs) with bronchiolitis obliterans syndrome (BOS) contain human leukocyte antigens and lung self-antigens (SAgs), K-alpha 1 tubulin (Kα1T) and collagen type V (Col-V). The aim was to determine the use of circulating exosomes with lung SAgs as a biomarker for BOS. Circulating exosomes were isolated retrospectively from plasma from LTxRs at diagnosis of BOS and at 6 and 12 months before the diagnosis (n = 41) and from stable time-matched controls (n = 30) at 2 transplant centers by ultracentrifugation. Exosomes were validated using Nanosight, and lung SAgs (Kα1T and Col-V) were detected by immunoblot and semiquantitated using ImageJ software. Circulating exosomes from BOS and stable LTxRs demonstrated 61- to 181-nm vesicles with markers Alix and CD9. Exosomes from LTxRs with BOS (n = 21) showed increased levels of lung SAgs compared with stable (n = 10). A validation study using 2 separate cohorts of LTxRs with BOS and stable time-matched controls from 2 centers also demonstrated significantly increased lung SAgs–containing exosomes at 6 and 12 months before BOS. Circulating exosomes isolated from LTxRs with BOS demonstrated increased levels of lung SAgs (Kα1T and Col-V) 12 months before the diagnosis (100% specificity and 90% sensitivity), indicating that circulating exosomes with lung SAgs can be used as a non-invasive biomarker for identifying LTxRs at risk for BOS. [ABSTRACT FROM AUTHOR]

Respiratory viral infections can increase the risk of chronic lung allograft dysfunction after lung transplantation, but the mechanisms are unknown. In this study, we determined whether symptomatic respiratory viral infections after lung transplantation induce circulating exosomes that contain lung-associated self-antigens and assessed whether these exosomes activate immune responses to self-antigens. Serum samples were collected from lung transplant recipients with symptomatic lower- and upper-tract respiratory viral infections and from non-symptomatic stable recipients. Exosomes were isolated via ultracentrifugation; purity was determined using sucrose cushion; and presence of lung self-antigens, 20S proteasome, and viral antigens for rhinovirus, coronavirus, and respiratory syncytial virus were determined using immunoblot. Mice were immunized with circulating exosomes from each group and resulting differential immune responses and lung histology were analyzed. Exosomes containing self-antigens, 20S proteasome, and viral antigens were detected at significantly higher levels (p < 0.05) in serum of recipients with symptomatic respiratory viral infections (n = 35) as compared with stable controls (n = 32). Mice immunized with exosomes from recipients with respiratory viral infections developed immune responses to self-antigens, fibrosis, small airway occlusion, and significant cellular infiltration; mice immunized with exosomes from controls did not (p < 0.05). Circulating exosomes isolated from lung transplant recipients diagnosed with respiratory viral infections contained lung self-antigens, viral antigens, and 20S proteasome and elicited immune responses to lung self-antigens that resulted in development of chronic lung allograft dysfunction in immunized mice. [ABSTRACT FROM AUTHOR]

Lung transplant recipients (LTxRs) with acute or chronic rejection release circulating exosomes that mostly originate from donor lung tissue and express mismatched human leucocyte antigens (HLA) and lung-associated self-antigens (SAgs), Collagen-V and K alpha 1 Tubulin. During lung transplant (LTx), donor lungs often undergo injuries that increase the antigenicity of the transplanted organ. 30% of LTxRs also have pre-transplant antibodies (Abs) to HLA and lung SAgs, which may induce conditions that increase the risk of chronic lung allograft dysfunction (CLAD). Post-transplant, some recipients experience de novo development of Abs to mismatched donor HLA (donor-specific antibody [DSA]) and Abs to lung SAgs, which have been implicated in CLAD pathogenesis. Because most LTxRs who develop DSA also develop Abs to SAgs, some have suggested a synergistic relationship between alloimmunity and autoimmunity in CLAD immunopathogenesis. These processes likely occur from stress-induced exosome release. Exosomes carry allo-antigens, lung SAgs, several micro RNAs, proteasome, co-stimulatory molecules, and pro-inflammatory transcription factors—resulting in efficient antigen presentation by direct, semidirect, and indirect pathways, leading to immune responses to both allo-antigens and lung-associated SAgs. This review summarizes recent findings on the role of exosomes, and processes triggering immune responses to allo-antigens and lung SAgs that ultimately culminate in CLAD. [ABSTRACT FROM AUTHOR]

This paper presents novel wind tunnel test results on the aerodynamics of a symmetric thin porous airfoil and a porous rectangular half wing using a symmetric thin airfoil as its cross section, obtained by a six-component force balance. The variation of lift coefficient, drag coefficient, pitching moment, lift versus drag, the gradient of lift, and location of the aerodynamic center with respect to the angle of attack are presented as a function of the porosity. The data, where possible, are compared with the analytical results. The trend of the experimental results behaves in the same manner as the analytical solution. The measured drag coefficients of the airfoil and wing are also presented. The applicability of the standard equation relating the lift coefficient of a non-porous wing with that of a non-porous airfoil to the case of porous wings is verified by applying the equation to porous wings and validating the results using experimental data. Lift slope decreases as the porosity increases. The drag decreases at a low value of porosity and then increases as porosity increases. The standard equation for obtaining the lift coefficient of a wing from the lift coefficient of an airfoil is applicable and valid for porous wings and airfoils. [ABSTRACT FROM AUTHOR]

[Display omitted] Pancreatic cancer is one of the deadliest types of malignancies. A new intervention aiming to combat pancreatic cancer is targeting its extra-ordinary ability to tolerate nutrition starvation, a phenomenon known as "Austerity". As a part of a research program aiming to develop a new-generation of anticancer agents, known as "anti-austerity agents", guggulsterone derivatives (GSDs) were identified as unique anti-austerity agents in terms of potency and selectivity. These agents are able to exert preferential cytotoxic activity only under nutrient-deprived conditions with little or no toxicity under normal conditions. In the present study, a library of 14 GSDs was synthesized and screened against PANC-1 human pancreatic cells. Among tested compounds, GSD-11 showed the most potent activity with PC 50 a value of 0.72 μM. It also inhibited pancreatic cancer cell migration and colony formation in a concentration-dependent manner. A mechanistic study revealed that this compound can inhibit the activation of the Akt/mTOR signaling pathway. Therefore, GSD-11 could be a promising lead compound for the anticancer drug discovery against pancreatic cancer. [ABSTRACT FROM AUTHOR]

Two higher-order compact finite difference approaches, the Hermitian and the Lax-Wendroff are examined by applying them to the viscous Burgers' equation. The difference equations obtained by the two methods were integrated in time through the third-order Strong-Stability-Preserving Runge-Kutta scheme. Absolute errors are computed by using an exact solution. The results are also compared with a second order central difference scheme. The Hermitian approach is far easier to implement. On uniform grids the Lax-Wendroff scheme produces smaller errors during the initial stages, but both methods are equally good for larger durations of integration. The convergence rate of the Hermitian scheme is slightly higher than the Lax-Wendroff scheme although both are of fourth order. Both schemes are unstable beyond a certain step size in time and space. When numerical boundary conditions are imposed, second-order conditions produce the best results whereas linear extrapolation proved to be the worst. It was also observed that large domains were required to implement the numerical boundary conditions properly. There was no detrimental effect on the accuracy of the results obtained through either of the two schemes when the size of the domain was greatly increased. Both schemes showed remarkable improvement in accuracy when clustered grids were employed. However much smaller time steps are required for stable solutions. [ABSTRACT FROM AUTHOR]

Chronic lung transplant rejection occurs in over 50% of lung transplant recipients and mechanism of chronic rejection is unknown. Evaluation of potential mechanism of exosomes from lung transplant recipients diagnosed with respiratory viral infection (RVI) in inducing chronic lung allograft dysfunction (CLAD). Exosomes were isolated from lung transplant recipients followed by DNA and RNA isolation from exosomes. Cell signaling mechanisms were studied by co-culturing exosomes with human epithelial cells. Mice were immunized with exosomes and lung homogenates were studied for immune signaling proteins. Exosomes from lung transplant recipients with RVI carry nucleic acids which are capable of inducing innate immune signaling, endoplasmic reticulum stress, and epithelial mesenchymal transition. Therefore, we propose that RVI can lead to induction of exosomes that initiate the process leading to CLAD in mice models. These novel findings identified the molecular mechanisms by which RVI increases the risk of CLAD. • Exosomes isolated from respiratory viral infection patients carry viral sequences. • Exosomes can induce DNA/RNA, stress and epithelial to mesenchymal signaling pathways in airway epithelial cells. • Mice immunized with exosomes, induce lesions in lungs with development of antibodies to collagen V and Kα1Tubulin. [ABSTRACT FROM AUTHOR]

[Display omitted] An ethanolic extract of Derris scandens flowers showed potent preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrient-deprived condition, with a PC 50 value of 0.7 μg/mL. Phytochemical investigation of this active extract led to the isolation of four prenylated isoflavones (1 – 4) including a new compound named 4′- O -methylgrynullarin (1). The structure elucidation of the new compound was achieved by HRFABMS and NMR spectroscopic analysis. The isolated compounds exhibited potent anti-austerity activity against four different human pancreatic cancer cell lines under nutrient-deprived conditions. The new compound 4′- O -methylgrynullarin (1) was also found to inhibit PANC-1 cell migration and colony formation under nutrient-rich condition. Mechanistically, compound 1 inhibited key survival proteins in the Akt/mTOR signaling pathway. Therefore, 4′- O -methylgrynullarin (1) can be considered as a potential lead compound for the anticancer drug development based on the anti-austerity strategy. [ABSTRACT FROM AUTHOR]

A methanolic extract of the rhizomes of Boesenbergia rotunda showed potent preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrient deficiency conditions with a PC 50 value of 6.6 μg/mL. Bioactivity-guided phytochemical investigation of the rhizomes of B. rotunda led to the isolation of nine undescribed dimeric metabolites, panduratins Q–Y. Their structures were elucidated based on NMR, MS, and ECD spectroscopic data interpretation. Panduratins Q–S and U–W exhibited potent cytotoxicity towards PANC-1 cell line with the PC 50 values ranging from 0.8 to 6.3 μM. Panduratin W, which possessed a cyclohexenylchalcone-linked flavanone skeleton, showed the most cytotoxicity with a PC 50 value of 0.8 μM under nutrient-deprived medium. Image 1 • Chemical structures of nine undescribed dimeric metabolites were elucidated. • Preferential cytotoxicity against PANC-1 cells of all isolated compounds were tested. • Panduratin W showed the most preferential cytotoxicity against PANC-1 cells. [ABSTRACT FROM AUTHOR]