Efficacy of topical latanoprost in the treatment of eyelid vitiligo: A randomized,double‐blind clinical trial study

Numerous studies have demonstrated that the pigmentation of iris and around the eyelid is a common side effect of latanoprost, a prostaglandin F2alpha analogue used in the treatment of glaucoma. Hence, the authors decided to study the effectiveness of topical latanoprost on vitiligo patches around the eyelid. In this randomized, double‐blind, clinical trial study, 31 patients with vitiligo vulgaris and focal vitiligo involving the eyelids were evaluated. Patients were randomly divided into two groups. First group received topical latanoprost gel twice daily for 12 weeks, whereas the second group received placebo with the same protocol. To evaluate severity of the disease the VIDA rating system was used. Serial photos of the patches were taken to compare and evaluate the repigmentation percentage of the patches. The patients in both groups had almost similar VIDA score (p > .05). First group showed improved pigmentation, whereas participants in the second group did not show any improvement in the pigmentation. The group treated with latanoprost showed significant reduction in the symptoms of the disease, whereas those treated with placebo did not show any alteration (p > .05). No significant complications were observed in either groups. Latanoprost proved effective in treating vitiligo disease involving eyelids.     

Nonavalent human papillomavirus vaccination as alternative treatment for genital warts

Genital warts caused by the human papillomavirus (HPV) are the most common sexually transmitted disease and have a negative impact on quality of life. Of the more than 200 different types of HPV, low‐risk types 6 and 11 are mainly responsible for the development of condyloma acuminata. Despite a large arsenal of local therapies such as numerous topical agents, CO₂ laser ablation, and surgical removal, genital warts tend to be recalcitrant. HPV vaccination is mainly used as a preventive strategy to prevent genital warts, cervical cancer, and other anogenital cancers. However, in a few cases, HPV vaccination has been shown to be a good treatment alternative for patients with recalcitrant skin warts. Here we report five cases of recalcitrant genital warts that responded well to treatment with the nonavalent HPV vaccine. HPV vaccines could be beneficial as a noninvasive treatment alternative for recalcitrant genital warts.     

Bioinspired pressure-sensitive adhesive: evaluation of the effect of dopamine methacrylamide comonomer as a general property modifier using molecular dynamics simulation

The use of catechol-containing comonomers as a general property enhancer to achieve unique properties has received particular attention for designing bioinspired polymeric materials. In this study, molecular dynamics simulation was used to investigate the role of dopamine methacrylamide (DMA) and N-phenethyl methacrylamide (PMA) comonomers in chain conformation and their effects on the mechanical properties and adhesion of poly(n-butyl acrylate-co-acrylic acid) copolymer. Addition of 4% by weight of DMA comonomer in the terpolymer structure reduces the gyration radius of the poly(n-butyl acrylate-co-acrylic acid) copolymer. This reduction is due to the formation of intramolecular hydrogen bond interactions. A further increase in the DMA up to 12.2% by weight increases the radius of gyration by 5%. The effect of PMA on the gyration radius of the poly(n-butyl acrylate-co-acrylic acid) copolymer is more extensive, compared to DMA. While DMA enhances both van der Waals and electrostatic components of the cohesive energy density through increasing π–π interactions and hydrogen bond formations, PMA only improves the van der Waals component. Assessment of mechanical properties revealed that the addition of DMA comonomer resulted in a transition from brittle to tough behavior in poly(n-butyl acrylate-co-acrylic acid) pressure-sensitive adhesive. Ductility index improvement by DMA is higher than that by PMA. DMA comonomers accumulate on the silica surface resulting in the terpolymer chains approaching the dry silica surface from the hydroxyl groups of the catechol. Accumulation of DMA only enhances the cohesive energy and does not improve the adhesive energy.

The use of catechol-containing comonomers as a general property enhancer to achieve unique properties has received particular attention for designing bioinspired polymeric materials.     

Ivermectin as an adjunct treatment for hospitalized adult COVID-19 patients: A randomized multi-center clinical trial

Objective: To evaluate different doses of ivermectin in adult patients with mild COVID-19 and to evaluate the effect of ivermectin on mortality and clinical consequences.Methods: A randomized, double-blind, placebo-controlled, multicenter clinical trial was performed at five hospitals. A total of 180 mild hospitalized patients with COVID-19 confirmed by PCR or chest image tests were enrolled and allocated to six arms including hydroxychloroquine 200 mg twice per day, placebo plus hydroxychloroquine 200 mg twice per day, single dose ivermectin(200 μg/kg), three low interval doses of ivermectin(200, 200, 200 μg/kg), single dose ivermectin(400 μg/kg), and three high interval doses of ivermectin(400, 200, 200 μg/kg). The primary endpoint of this trial was all-cause of mortality or clinical recovery. The radiographic findings, hospitalization and low O_2 saturation duration, and hematological variables of blood samples were analyzed. Results: A total of 16.7%(5/30) and 20.0%(6/30) patients died in arms treated with hydroxychloroquine 200 mg twice per day and placebo plus hydroxychloroquine 200 mg twice per day, respectively, and a reduction in mortality rate in patients receiving ivermectin treatment to 0%, 10%, 0% and 3.3% for arms 1-4 were observed. Risk of mortality was also decreased about 15% in the ivermectin treated arms. Conclusions: Ivermectin as an adjunct reduces the rate of mortality, time of low O_2 saturation, and duration of hospitalization in adult COVID-19 patients. The improvement of other clinical parametersshows that ivermectin, with a wide margin of safety, had a high therapeutic effect on COVID-19.     

Nanoconfinement of microvilli alters gene expression and boosts T cell activation

T cells sense and respond to their local environment at the nanoscale by forming small actin-rich protrusions, called microvilli, which play critical roles in signaling and antigen recognition, particularly at the interface with the antigen presenting cells. However, the mechanism by which microvilli contribute to cell signaling and activation is largely unknown. Here, we present a tunable engineered system that promotes microvilli formation and T cell signaling via physical stimuli. We discovered that nanoporous surfaces favored microvilli formation and markedly altered gene expression in T cells and promoted their activation. Mechanistically, confinement of microvilli inside of nanopores leads to size-dependent sorting of membrane-anchored proteins, specifically segregating CD45 phosphatases and T cell receptors (TCR) from the tip of the protrusions when microvilli are confined in 200-nm pores but not in 400-nm pores. Consequently, formation of TCR nanoclustered hotspots within 200-nm pores allows sustained and augmented signaling that prompts T cell activation even in the absence of TCR agonists. The synergistic combination of mechanical and biochemical signals on porous surfaces presents a straightforward strategy to investigate the role of microvilli in T cell signaling as well as to boost T cell activation and expansion for application in the growing field of adoptive immunotherapy.

Microvilli are small actin-rich protrusions that are used by cells to explore and respond to their local environment, and they are used by immune system cells to sense the surface features of pathogens and antigen presenting cells (1–3). Besides their exploratory role in maximizing surface contact to detect cognate antigens (4), microvilli can regulate T cell signaling by forming areas with high membrane curvature (5). Formation of high membrane curvature is thought to be sensed by triggering biological processes, such as the assembly of signaling microclusters. Formation of high membrane curvatures (200 to 1,000 nm in diameter) supports antigen recognition in T cells, through amplified and sustained signaling at the tip of the protrusions (1, 6). Recent studies suggest that sporadic nonspecific T cell receptor (TCR) phosphorylation can occur at the tip of microvilli, where CD45 is sterically excluded through the formation of “tight contacts” (7, 8). However, the underlying mechanism and the biological processes triggered by microvilli formation in the process of T cell activation remain largely unknown.Understanding signaling processes induced by microvilli formation is important both from a physiological and technological point of view. This becomes obvious in Whiskott–Aldrich Syndrome and Leukemia, where disrupted formation of microvilli leads to compromised function of various immune cells (9). Importantly, microvilli formation can be regulated by common anticancer drugs such as cytokines, chemokines, or cytoskeletal inhibitors, potentially impairing T cells in being able to efficiently recognize their cognate antigens, thus limiting the efficiency of the therapy (10, 11). Beside chemical signals, the physical environment of the cell can also regulate microvilli formation, particularly at the nanoscale (12). The consequences of T cell microvilli regulation by nanomaterial implants is largely unexplored, which is particularly significant considering the rise of nanotechnology-based immunotherapy approaches and a large pipeline of associated treatments in clinical trials (13, 14). From an engineering perspective, one may exploit the possibility of engineering T cell functions by regulating microvilli formation ex vivo, which can have an impact in the growing field of adoptive T cell therapy.Despite the importance of microvilli as a structural unit of the cell and their role in T cell signaling, there is a limited amount of studies that investigated microvilli function in T cell activation (4, 5, 9). This is mainly due to the fact that microvilli are nanoscale projections from the cell membrane displaying high dynamics of formation and retraction, therefore difficult to investigate by standard optical microscopy (4, 15, 16). While electron microscopy enables their visualization, their dynamic behavior still remains largely unresolved (1). The fast and transient nature of microvilli protrusions makes it challenging to detect downstream signaling events. Using lattice light-sheet microscopy and real-time tracing of dynamic microvilli on two-dimensional (2D) surfaces, the lifetime of the microvilli protrusions is estimated to be roughly 1 min (16).To investigate how microvilli interact with nanoscale surface features, we studied the natural behavior of T cells in exploring their environment when in contact with engineered nanoporous materials. Surprisingly, microvilli formation was triggered by presenting a physical cue. The dimensions of the T cell projections are defined by the pore size, and it matches the dimensions of membrane protrusions used by T cells to explore antigen presenting cells. Particularly, confinement of the microvilli into pores with 200 nm in diameter markedly alters cell signaling cascades and subsequent gene expression, even enabling physical activation of T cells without TCR engagement. We explain this phenomenon by nanoconfinement enforced spatiotemporal segregation of the CD45 phosphatase from the TCR. Physically separated from the inhibitory function of CD45, TCR downstream signaling is enhanced even in the absence of specific TCR agonistic stimuli. Scientifically, this discovery that size-matched nanopores promote microvilli formation provides a platform to study microvilli formation processes and their role in T cell activation. Technologically, this opens unforeseen opportunities to boost T cell activation and expansion ex vivo by inducing microvilli formation with specific dimensions, which has potential applications in cell-based immunotherapies.     

Novel variants underlying autosomal recessive neurodevelopmental disorders with intellectual disability in Iranian consanguineous families

BackgroundIntellectual disability (ID) is a heterogeneous group of neurodevelopmental disorders that is characterized by significant impairment in intellectual and adaptive functioning with onset during the developmental period. Whole‐exome sequencing (WES)‐based studies in the consanguineous families with individuals affected with ID have shown a high burden of relevant variants. So far, over 700 genes have been reported in syndromic and non‐syndromic ID. However, genetic causes in more than 50% of ID patients still remain unclear.MethodsWhole‐exome sequencing was applied for investigation of various variants of ID, then Sanger sequencing and in silico analysis in ten patients from five Iranian consanguineous families diagnosed with autosomal recessive neurodevelopmental disorders, intellectual disability, performed for confirming the causative mutation within the probands. The most patients presented moderate‐to‐severe intellectual disability, developmental delay, seizure, speech problem, high level of lactate, and onset before 10 years.ResultsFiltering the data identified by WES, two novel homozygous missense variants in FBXO31 and TIMM50 genes and one previously reported mutation in the CEP290 gene in the probands were found. Sanger sequencing confirmed the homozygote variant''s presence of TIMM50 and FBXO31 genes in six patients and two affected siblings in their respective families. Our computational results predicted that the variants are located in the conserved regions across different species and have the impacts on the protein stability.ConclusionHence, we provide evidence for the pathogenicity of two novel variants in the patients which will expand our knowledge about potential mutation involved in the heterogeneous disease.     

The Effect of Eco-Friendly Inhibitors on the Corrosion Properties of Concrete Reinforcement in Harsh Environments

In the present research, the synergistic effect of Arabic and guar gum inhibitors on the corrosion efficiency of concrete reinforcement was investigated. Thus, eight types of Arabic and guar gum combinations with 100, 250, 500, 750, and 1000 ppm were added to the steel reinforcement for 1, 7, 28, 48, and 72 days. The corrosion behavior of the samples was investigated by the electrochemical impedance (EIS) test. Water transmissibility, electrical resistivity, and compressive strength of concrete were also studied. The results showed that adding inhibitors generally increased the compressive strength of concrete. It was also found that water transmissibility was reduced by the addition of inhibitors. The electrical resistivity of the samples increased slightly with increasing time up to 72 days. EIS and Tafel results have demonstrated that Arabic and guar gums are effective inhibitors for reinforced concrete structures. Furthermore, scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) utilized to analyze the samples indicated that inhibitor grain size was enhanced by enhancing the concentration of the inhibitor combination, showing that the guar and Arabic inhibitor combinations were properly absorbed on the reinforcement surface. Results showed that a sample with 250 ppm Arabic gum and 250 ppm guar gum having a properly distributed inhibitor combination on the reinforcement surface creates a desirable cathode current.     

NiII NPs entrapped within a matrix of l-glutamic acid cross-linked chitosan supported on magnetic carboxylic acid-functionalized multi-walled carbon nanotube: a new and efficient multi-task catalytic system for the green one-pot synthesis of diverse heterocyclic frameworks

In the present study, a new l-glutamic acid cross-linked chitosan supported on magnetic carboxylic acid-functionalized multi-walled carbon nanotube (Fe₃O₄/f-MWCNT-CS-Glu) nanocomposite was prepared through a convenient one-pot multi-component sequential strategy. Then, nickel^II nanoparticles (Ni^II NPs) were entrapped within a matrix of the mentioned nanocomposite. Afterward, the structure of the as-prepared Fe₃O₄/f-MWCNT-CS-Glu/Ni^II nanosystem was elucidated by various techniques, including FT-IR, PXRD, SEM, TEM, SEM-based EDX and elemental mapping, ICP-OES, TGA/DTA, and VSM. In the next part of this research, the catalytic applications of the mentioned nickel^II-containing magnetic nanocomposite were assessed upon green one-pot synthesis of diverse heterocyclic frameworks, including bis-coumarins (3a–n), 2-aryl(or heteroaryl)-2,3-dihydroquinazolin-4(1H)-ones (5a–r), 9-aryl-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2H)-diones (7a–n), and 2-amino-4-aryl-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitriles (9a–n). The good-to-excellent yields of the desired products, satisfactory reaction rates, use of water solvent or solvent-free reaction medium, acceptable turnover numbers (TONs) and turnover frequencies (TOFs), along with comfortable recoverability and satisfying reusability of the as-prepared nanocatalyst for at least eight successive runs, and also easy work-up and purification procedures are some of the advantages of the current synthetic protocols.

In this research work, an Fe₃O₄/f-MWCNT-CS-Glu/Ni^II hybrid nanocomposite was synthesized, characterized, and used as a new and efficient multi-task catalytic system for the green one-pot synthesis of diverse heterocyclic frameworks.     

A comparison between SARS-CoV-1 and SARS-CoV2: an update on current COVID-19 vaccines

Since the outbreak of the novel coronavirus disease 2019 (COVID-19) in Wuhan, China, many health care systems have been heavily engaged in treating and preventing the disease, and the year 2020 may be called as “historic COVID-19 vaccine breakthrough”. Due to the COVID-19 pandemic, many companies have initiated investigations on developing an efficient and safe vaccine against the virus. From Moderna and Pfizer in the United States to PastocoVac in Pasteur Institute of Iran and the University of Oxford in the United Kingdom, different candidates have been introduced to the market. COVID-19 vaccine research has been facilitated based on genome and structural information, bioinformatics predictions, epitope mapping, and data obtained from the previous developments of severe acute respiratory syndrome coronavirus (SARS-CoV or SARS-CoV-1) and middle east respiratory syndrome coronavirus (MERS-CoV) vaccine candidates. SARS-CoV genome sequence is highly homologous to the one in COVID-19 and both viruses use the same receptor, angiotensin-converting enzyme 2 (ACE2). Moreover, the immune system responds to these viruses, partially in the same way. Considering the on-going COVID-19 pandemic and previous attempts to manufacture SARS-CoV vaccines, this paper is going to discuss clinical cases as well as vaccine challenges, including those related to infrastructures, transportation, possible adverse reactions, utilized delivery systems (e.g., nanotechnology and electroporation) and probable vaccine-induced mutations.Graphical abstract      

Microstructure,Fractography, and Mechanical Properties of Hardox 500 Steel TIG-Welded Joints by Using Different Filler Weld Wires

This paper deals with the effects of three low-carbon steel filler metals consisting of ferritic and austenitic phases on the weld joints of the tungsten inert gas (TIG) welding of Hardox 500 steel. The correlation between the microstructure and mechanical properties of the weld joints was investigated. For this purpose, macro and microstructure were examined, and then microhardness, tensile, impact, and fracture toughness tests were carried out to analyze the mechanical properties of joints. The results of optical microscopy (OM) images showed that the weld zones (WZ) of all three welds were composed of different ferritic morphologies, including allotriomorphic ferrite, Widmanstätten ferrite, and acicular ferrite, whereas the morphology of the heat-affected zone (HAZ) showed the various microstructures containing mostly ferrite and pearlite phases. Further, based on mechanical tests, the second filler with ferritic microstructure represented better elongation, yield strength, ultimate tensile strength, impact toughness, and fracture toughness due to having a higher amount of acicular ferrite phase compared to the weld joints concerning the other fillers consisting of austenitic and ferritic-austenitic. However, scanning electron microscopy (SEM) images on the fracture surfaces of the tensile test showed a ductile-type fracture with a large number of deep and shallow voids while on the fracture surfaces resulting from the Charpy impact tests and both ductile and cleavage modes of fracture took place, indicating the initiation and propagation of cracks, respectively. The presence of acicular ferrite as a soft phase that impedes the dislocation pile-up brings about the ductile mode of fracture while inclusions may cause stress concentration, thus producing cleavage surfaces.