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Abstract Background The aim of the study was to determine the facial divergence and lip position combinations that are most and least preferred, and to investigate whether age or gender has an impact on these preferences. Methods The current investigation was carried out on a sample of 1077 individuals who were not experts in the field (253 men and 824 females). The research employed black silhouette photographs of profiles featuring different lip locations and profile divergences. The recruitment of participants was conducted in order to assess the attractiveness of the profiles, employing a Likert scale. The various positions of the lips and variations in facial profiles were thoroughly categorized. Results were analyzed using the Chi-square test. Results The findings of the research demonstrated that aesthetic perceptions displayed diversity when considering different lip locations and profile divergences. It was shown that neutral lip positions were predominantly favored, accounting for approximately 40.2% of the total frequencies in the anterior diverging group. It is noteworthy to highlight the aesthetically pleasing features exhibited by those with the most prominent lip position, occurring at a frequency of 10.9% in straight-diverging group. In the posterior divergent group, the most protruded lip position, showed very attractive aesthetics with frequency (7.1%). Gender, age, region, and level of education had significant influence on aesthetic perception. Conclusions The variety of aesthetic preferences is influenced by the location of the lips and the divergence of the facial profile, resulting in different outcomes within the categories of anterior, straight, and posterior divergence. Clinicians are advised to customize the treatment regimen in order to correspond with the unique desires and preferences of the patient.

Abstract Everyone is talking about coronavirus from the last couple of months due to its exponential spread throughout the globe. Lives have become paralyzed, and as many as 180 countries have been so far affected with 928,287 (14 September 2020) deaths within a couple of months. Ironically, 29,185,779 are still active cases. Having seen such a drastic situation, a relatively simple epidemiological SIR model with Caputo derivative is suggested unlike more sophisticated models being proposed nowadays in the current literature. The major aim of the present research study is to look for possibilities and extents to which the SIR model fits the real data for the cases chosen from 1 April to 15 March 2020, Pakistan. To further analyze qualitative behavior of the Caputo SIR model, uniqueness conditions under the Banach contraction principle are discussed and stability analysis with basic reproduction number is investigated using Ulam–Hyers and its generalized version. The best parameters have been obtained via the nonlinear least-squares curve fitting technique. The infectious compartment of the Caputo SIR model fits the real data better than the classical version of the SIR model (Brauer et al. in Mathematical Models in Epidemiology 2019). Average absolute relative error under the Caputo operator is about 48% smaller than the one obtained in the classical case ( ν = 1 $\nu =1$ ). Time series and 3D contour plots offer social distancing to be the most effective measure to control the epidemic.

Zulkifal Malik,1,2 Muzaffar Abbas,2 Lina Tariq Al Kury,3 Fawad Ali Shah,1 Mahboob Alam,2 Arif-ullah Khan,1 Humaira Nadeem,1 Saad Alghamdi,4 Muhammad Umar Khayam Sahibzada,5 Shupeng Li6 1Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan; 2Faculty of Pharmacy, Capital University of Science and Technology, Islamabad, Pakistan; 3College of Natural and Health Sciences, Zayed University, Abu Dhabi, United Arab Emirates; 4Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Mecca, Saudi Arabia; 5Department of Pharmacy, Sarhad University of Science and Information Technology, Peshawar, KPK, Pakistan; 6State Key Laboratory of Oncogenomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Peking University, Shenzhen, People’s Republic of ChinaCorrespondence: Muzaffar AbbasFaculty of Pharmacy, Capital University of Science and Technology, Islamabad Expressway, Kahuta Road, Zone-V, Islamabad, PakistanTel +92-51-111555666Fax +92-51-4486705Email Muzaffar.abbas@cust.edu.pkShupeng LiState Key Laboratory of Oncogenomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Shenzhen, 518055, People’s Republic of ChinaEmail lisp@pku.edu.cnBackground: Peripheral inflammation leads to the development of persistent thermal hyperalgesia and mechanical allodynia associated with increased expression of interleukin-1β (IL-1β) in the spinal cord. The aim of the present study was to investigate the effects of thiazolidine derivatives, 1b ([2-(2-hydroxyphenyl)-1,3-thiazolidin-4-yl](morpholin-4-yl)methanone) and 1d (2-hydroxy-4-{[2-(2-hydroxyphenyl)-1,3-thiazolidine-4-carbonyl]amino}benzoic acid), on thermal hyperalgesia, mechanical allodynia and on IL-1β expression during carrageenan-induced inflammation in the spinal cord in mice. Inflammatory pain was induced by injecting 1% carrageenan into the right hind paw of the mice.Methods: The animals were administered thiazolidine derivatives, 1b and 1d (1 mg/kg, 3 mg/kg, or 10 mg/kg), intraperitoneally 30 minutes before carrageenan administration. The animals’ behavior was evaluated by measuring thermal hyperalgesia, mechanical allodynia, and motor coordination. The IL-1β expression was measured by enzyme-linked immunosorbent assay. Acute and sub-acute toxicity studies were conducted to evaluate the toxicity profile of compounds.Results: Treatment with the thiazolidine derivative, 1b and 1d, attenuated carrageenan-induced thermal hyperalgesia and mechanical allodynia at doses of 1 mg/kg, 3 mg/kg, and 10 mg/kg. No motor coordination deficits were observed in animals. The compounds also reduced IL-1β expression in the spinal cord of mice. Acute and sub-acute toxicity studies revealed that both compounds were safe.Conclusion: The compounds exhibit promising activity against inflammatory pain due to their ability to produce anti-hyperalgesic and anti-allodynic effects and to inhibit IL-1β expression in the spinal cord.Keywords: inflammatory pain, IL-1β, thiazolidine derivatives, mechanical allodynia, thermal hyperalgesia

Abstract Piriformospora indica, a root endophytic fungus, augments plant nutrition and productivity as well as protects plants against pathogens and abiotic stresses. High salinity is a major problem faced by plants as well as by microbes. Until now, the precise mechanism of salt stress tolerance in P. indica has remained elusive. In this study, the transcriptomes of control and salt-treated (0.5 M NaCl) P. indica were sequenced via the RNA-seq approach. A total of 30,567 transcripts and 15,410 unigenes for P. indica were obtained from 7.3 Gb clean reads. Overall 661 differentially expressed genes (DEGs) between control and treated samples were retrieved. Gene ontology (GO) and EuKaryotic Orthologous Groups (KOG) enrichments revealed that DEGs were specifically involved in metabolic and molecular processes, such as “response to salt stress”, “oxidoreductase activity”, “ADP binding”, “translation, ribosomal structure and biogenesis”, “cytoskeleton”, and others. The unigenes involved in “cell wall integrity”, “sterol biosynthesis”, and “oxidative stress” such as Rho-type GTPase, hydroxymethylglutaryl-CoA synthase, and thioredoxin peroxidase were up-regulated in P. indica subjected to salt stress. The salt-responsive DEGs have shown that they might have a potential role in salt stress regulation. Our study on the salt-responsive DEGs established a foundation for the elucidation of molecular mechanisms related to P. indica stress adaptation and a future reference for comparative functional genomics studies of biotechnologically important fungal species.

RNA interference (RNAi) has been exploited by scientists worldwide to make a significant contribution in the arena of sustainable agriculture and integrated pest management. These strategies are of an imperative need to guarantee food security for the teeming millions globally. The already established deleterious effects of chemical pesticides on human and livestock health have led researchers to exploit RNAi as a potential agri-biotechnology tool to solve the burning issue of agricultural wastage caused by pests and pathogens. On the other hand, CRISPR/Cas9, the latest genome-editing tool, also has a notable potential in this domain of biotic stress resistance, and a constant endeavor by various laboratories is in progress for making pathogen-resistant plants using this technique. Considerable outcry regarding the ill effects of genetically modified (GM) crops on the environment paved the way for the research of RNAi-induced double-stranded RNAs (dsRNA) and their application to biotic stresses. Here, we mainly focus on the application of RNAi technology to improve disease resistance in plants and its relevance in today’s CRISPR-dominated world in terms of exogenous application of dsRNAs. We also focused on the ongoing research, public awareness, and subsequent commercialization of dsRNA-based biocontrol products.

Plants’ stress response machinery is characterized by an intricate network of signaling cascades that receive and transmit environmental cues and ultimately trigger transcriptional reprogramming. The family of epigenetic regulators that are the key players in the stress-induced signaling cascade comprise of chromatin remodelers, histone modifiers, DNA modifiers and regulatory non-coding RNAs. Changes in the histone modification and DNA methylation lead to major alterations in the expression level and pattern of stress-responsive genes to adjust with abiotic stress conditions namely heat, cold, drought and salinity. The spotlight of this review falls primarily on the chromatin restructuring under severe abiotic stresses, crosstalk between epigenetic regulators along with a brief discussion on stress priming in plants.

Modern diets containing high quantities of salt and cholesterol have exhibited to cause a considerable effect on our health. Such diets, when consumed in the long term, have also shown to be a precursor to several disorders such as the metabolic disorder and consequently, various other diseases, including cognitive deficits. In the present study, we used a high salt and cholesterol diet (HSCD) to induce cognitive impairment in rats and also investigated the pharmacological action of tannins enriched fractions of Emblica officinalis (EOT) – a fruit that has been traditionally used for the treatment of numerous disorders for centuries. Significant alterations in MDA, GSH, TBARS, GPx, mitochondrial ATP, and mitochondrial membrane potential levels were observed in rats fed HSCD, which indicated presence of oxidative stress. Moreover, classic signs of cognitive impairment and deficits in spatial learning and memory were observed in the neurobehavioral tests. E. officinalis tannins exhibited good affinity to Nrf2 receptors in in silico studies, significantly reversed the changes in the aforementioned biomarkers of oxidative stress which were altered in the model group, as well as improved the performance of rats in Morris water maze task. Our results also reflected that EOT supplementation significantly increased the expression of Nrf2 in the CA1 region of hippocampus and cortex. Additionally, TUNEL assay indicated that EOT supplementation led to reversal of DNA fragmentation and apoptosis caused by HSCD. Immunohistochemical analysis and western blot further revealed a surge in the nuclear location of Nrf2. Through our study, we have demonstrated that cognitive impairment can be caused in rats via HSCD as a result of the oxidative stress induced by the same. Additionally, we have investigated a novel mechanism of action for EOT (which strongly suggests to be via the Nrf2–ARE pathway) and demonstrated that it has the potential to be used in the treatment of cognitive impairment.

Dengue virus is a pathogen of global concern and has a huge impact on public health system in low- and middle-income countries. The capsid protein of dengue virus is least conserved among related flavivirus and there is very limited information on the role of cytosolic proteins that interact with dengue virus capsid. We identified DEAD (Asp-Glu-Ala-Asp) Box Helicase 3, an X-Linked (DDX3X), cytosolic ATP-dependent RNA helicase as a dengue virus capsid-interacting protein. We show that the N-terminal region of capsid is important for interaction with DDX3X, while the N-terminal domain of DDX3X seems to be involved in interaction with dengue capsid. DDX3X was down-regulated in dengue virus infected cells at later stages of infection. Our results show that DDX3X is an antiviral protein as suppression of DDX3X expression by siRNA led to an increase in viral titers and overexpression of DDX3X led to inhibition of viral replication. Knock-down of DDX3X did not affect induction of type I interferon response upon infection suggesting that the effect of DDX3X knock-down is independent of the interferon-dependent pathways that DDX3X modulates under normal conditions. Thus, our study identifies DDX3X as a dengue virus capsid interacting protein and indicates a potential link between the antiviral functions of DDX3X and dengue capsid at later stages of dengue infection.

Natalya Iorio, Zubair Malik, Ron Schey Section of Gastroenterology, Department of Medicine, Temple University Hospital, Philadelphia, PA, USA Abstract: Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder characterized by recurrent abdominal pain and abnormal bowel patterns. Alteration in gut flora, visceral hypersensitivity, and abnormal bowel motility are among numerous factors in the complex pathophysiology of IBS. Antibiotics have been used adjunctively to treat IBS for many years but are associated with various systemic side effects. Rifaximin is a nonabsorbable, broad-spectrum antimicrobial that inhibits bacterial RNA synthesis by binding the β-subunit of microbial RNA polymerase. It targets the gastrointestinal tract and works by reducing the quantity of gas-producing bacteria and altering the predominant species of bacteria present. In vivo animal studies suggest additional beneficial mechanisms of rifaximin, including reducing mucosal inflammation and visceral hypersensitivity. Clinical studies have demonstrated that rifaximin improves symptoms associated with IBS, such as bloating, flatulence, stool consistency, and abdominal pain, and has a side-effect profile similar to placebo. Although additional investigation into optimal dosing, treatment duration, and potential resistance is required, rifaximin presents as a safe and beneficial addition to the current management options for IBS. Keywords: irritable bowel syndrome, rifaximin, small intestinal bacterial overgrowth, mucosal inflammation

Abstract Background Exploration of immunomodulatory antileishmanials of plant origin is now being strongly recommended to overcome the immune suppression evident during visceral leishmaniasis (VL) and high cost and toxicity associated with conventional chemotherapeutics. In accordance, we assessed the in vitro and in vivo antileishmanial and immunomodulatory potential of ethanolic fractions of Azadirachta indica leaves (ALE) and seeds (ASE). Methods A. indica fractions were prepared by sequential extraction of the powdered plant parts in hexane, ethanol and water. Erythrosin B staining was employed to appraise the anti-promastigote potential of ALE and ASE. Cytostatic or cytocidal mode of action was ascertained and alterations in parasite morphology were depicted under oil immersion light microscopy. Study of apoptotic correlates was performed to deduce the mechanism of induced cell death and anti-amastigote potential was assessed in Leishmania parasitized RAW 264.7 macrophages. In vivo antileishmanial effectiveness was evaluated in L. donovani infected BALB/c mice, accompanied by investigation of immunomodulatory potential of ALE and ASE. Adverse toxicity of the bioactive fractions against RAW macrophages was studied by MTT assay. In vivo side effects on the liver and kidney functions were also determined. Plant secondary metabolites present in ALE and ASE were analysed by Gas chromatography–mass spectrometry (GC-MS). Results ALE and ASE (500 μg ml−1) exhibited leishmanicidal activity in a time- and dose-dependent manner (IC50 34 and 77.66 μg ml−1, respectively) with alterations in promastigote morphology and induction of apoptosis. ALE and ASE exerted appreciable anti-amastigote potency (IC50 17.66 and 24.66 μg ml−1, respectively) that was coupled with profound in vivo therapeutic efficacy (87.76% and 85.54% protection in liver and 85.55% and 83.62% in spleen, respectively). ALE exhibited minimal toxicity with selectivity index of 26.10 whereas ASE was observed to be non-toxic. The bioactive fractions revealed no hepato- and nephro-toxicity. ALE and ASE potentiated Th1-biased cell-mediated immunity along with upregulation of INF-γ, TNF-α and IL-2 and decline in IL-4 and IL-10 levels. GC-MS analysis revealed several compounds that may have contributed to the observed antileishmanial effect. Conclusion Dual antileishmanial and immunostimulatory efficacy exhibited by the bioactive fractions merits their use alone or as adjunct therapy for VL.

Short-chain fatty acids (SCFAs), such as butyric acid, have a broad range of applications in chemical and fuel industries. Worldwide demand of sustainable fuels and chemicals has encouraged researchers for microbial synthesis of SCFAs. In this study we compared three thioesterases, i.e., TesAT from Anaerococcus tetradius, TesBF from Bryantella formatexigens and TesBT from Bacteroides thetaiotaomicron, for production of SCFAs in Escherichia coli utilizing native fatty acid synthesis (FASII) pathway and modulated the genetic and bioprocess parameters to improve its yield and productivity. E. coli strain expressing tesBT gene yielded maximum butyric acid titer at 1.46 g L-1, followed by tesBF at 0.85 g L-1 and tesAT at 0.12 g L-1. The titer of butyric acid varied significantly depending upon the plasmid copy number and strain genotype. The modulation of genetic factors that are known to influence long chain fatty acid production, such as deletion of the fadD and fadE that initiates the fatty acid degradation cycle and overexpression of fadR that is a global transcriptional activator of fatty acid biosynthesis and repressor of degradation cycle, did not improve the butyric acid titer significantly. Use of chemical inhibitor cerulenin, which restricts the fatty acid elongation cycle, increased the butyric acid titer by 1.7-fold in case of TesBF, while it had adverse impact in case of TesBT. In vitro enzyme assay indicated that cerulenin also inhibited short chain specific thioesterase, though inhibitory concentration varied according to the type of thioesterase used. Further process optimization followed by fed-batch cultivation under phosphorous limited condition led to production of 14.3 g L-1 butyric acid and 17.5 g L-1 total free fatty acid at 28% of theoretical yield. This study expands our understanding of SCFAs production in E. coli through FASII pathway and highlights role of genetic and process optimization to enhance the desired product.

A diallel analysis of wheat (Triticum aestivum L. em. Thell) parents (n = 11) and their F1 (n = 55) and F2 (n = 55) offspring was carried out for the following four traits: grain filling duration (GFD), GFD for growing degree days (GDD), 1000 seed weight and seed yield per plant. Analysis of variance for general combining ability (GCA) and specific combining ability (SCA) displayed significant F1 and F2 general and specific combining ability effects for the four traits studied. For all the traits the GCA effects were relatively more important than the SCA effects, indicating that additive genetic effects were predominant. Crosses displaying high SCA effects for grain filling duration, seed weight and yield were observed to be derived from parents having various types of GCA effects (high x high, high x low, low x low and medium x low). The single seed descent method can be applied to exploit additive gene effects whereas dominance gene effects could be valuable in hybrid wheat breeding programs. Among the parents, genotypes from the International Maize and Wheat Improvement Center (Centro Internacional de Mejoramiento de Maíz y Trigo, CIMMYT) as well as South Asia were found to be superior general combiners for grain filling duration. Likewise, crosses involving diverse parents from CIMMYT and South Asia showed significant SCA effects for grain filling duration and other traits.

Cotton leaf curl Burewala virus (CLCuBuV), belonging to the genus Begomovirus, possesses single-stranded monopartite DNA genome. The bidirectional promoters representing Rep and coat protein (CP) genes of CLCuBuV were characterized and their efficacy was assayed. Rep and CP promoters of CLCuBuV and 35S promoter of Cauliflower mosaic virus (CaMV) were fused with β-glucuronidase (GUS) and green fluorescent protein (GFP) reporter genes. GUS activity in individual plant cells driven by Rep, CP and 35S promoters was estimated using real-time PCR and fluorometric GUS assay. Histochemical staining of GUS in transformed tobacco (Nicotiana tabacum cv. Xanthi) leaves showed highest expression driven by Rep promoter followed by 35S promoter and CP promoter. The expression level of GUS driven by Rep promoter in transformed tobacco plants was shown to be two to four-fold higher than that of 35S promoter, while the expression by CP promoter was slightly lower. Further, the expression of GFP was monitored in agroinfiltrated leaves of N. benthamiana, N. tabacum and cotton (Gossypium hirsutum) plants using confocal laser scanning microscopy. Rep promoter showed strong consistent transient expression in tobacco and cotton leaves as compared to 35S promoter. The strong constitutive CLCuBuV Rep promoter developed in this study could be very useful for high level expression of transgenes in a wide variety of plant cells.

Volumetric laser endomicroscopy (VLE) uses optical coherence tomography (OCT) for real-time, microscopic cross-sectional imaging. A US-based multi-center registry was constructed to prospectively collect data on patients undergoing upper endoscopy during which a VLE scan was performed. The objective of this registry was to determine usage patterns of VLE in clinical practice and to estimate quantitative and qualitative performance metrics as they are applied to Barrett's esophagus (BE) management. All procedures utilized the NvisionVLE Imaging System (NinePoint Medical, Bedford, MA) which was used by investigators to identify the tissue types present, along with focal areas of concern. Following the VLE procedure, investigators were asked to answer six key questions regarding how VLE impacted each case. Statistical analyses including neoplasia diagnostic yield improvement using VLE was performed. One thousand patients were enrolled across 18 US trial sites from August 2014 through April 2016. In patients with previously diagnosed or suspected BE (894/1000), investigators used VLE and identified areas of concern not seen on white light endoscopy (WLE) in 59% of the procedures. VLE imaging also guided tissue acquisition and treatment in 71% and 54% of procedures, respectively. VLE as an adjunct modality improved the neoplasia diagnostic yield by 55% beyond the standard of care practice. In patients with no prior history of therapy, and without visual findings from other technologies, VLE-guided tissue acquisition increased neoplasia detection over random biopsies by 700%. Registry investigators reported that VLE improved the BE management process when used as an adjunct tissue acquisition and treatment guidance tool. The ability of VLE to image large segments of the esophagus with microscopic cross-sectional detail may provide additional benefits including higher yield biopsies and more efficient tissue acquisition. Clinicaltrials.gov NCT02215291.