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Resistance to genotoxic therapies and tumor recurrence are hallmarks of glioblastoma (GBM), an aggressive brain tumor. In this study, we investigated functional drivers of post-treatment recurrent GBM through integrative genomic analyses, genome-wide genetic perturbation screens in patient-derived GBM models and independent lines of validation. Specific genetic dependencies were found consistent across recurrent tumor models, accompanied by increased mutational burden and differential transcript and protein expression compared to its primary GBM predecessor. Our observations suggest a multi-layered genetic response to drive tumor recurrence and implicate PTP4A2(protein tyrosine phosphatase 4A2) as a modulator of self-renewal, proliferation and tumorigenicity in recurrent GBM. Genetic perturbation or small-molecule inhibition of PTP4A2 acts through a dephosphorylation axis with roundabout guidance receptor 1 (ROBO1) and its downstream molecular players, exploiting a functional dependency on ROBO signaling. Because a pan-PTP4A inhibitor was limited by poor penetrance across the blood–brain barrier in vivo, we engineered a second-generation chimeric antigen receptor (CAR) T cell therapy against ROBO1, a cell surface receptor enriched across recurrent GBM specimens. A single dose of ROBO1-targeted CAR T cells doubled median survival in cell-line-derived xenograft (CDX) models of recurrent GBM. Moreover, in CDX models of adult lung-to-brain metastases and pediatric relapsed medulloblastoma, ROBO1 CAR T cells eradicated tumors in 50–100% of mice. Our study identifies a promising multi-targetable PTP4A–ROBO1 signaling axis that drives tumorigenicity in recurrent GBM, with potential in other malignant brain tumors.

According to the nonlocal theory, the dynamic instability and vibration of functionally graded (FG) porous sandwich nanobeams resting on a visco-elastic foundation under axial harmonic load are studied. In this paper the Timoshenko and nonlocal continuum theory are employed to take shear deformation, rotational bending and small-scale effects into account. The governing equations of motion are extracted using the nonlinear Von-Karman, and Hamilton approaches. Then, to turn the partial differential equations (PDEs) into ordinary differential equations (ODEs) in the case of equations of motion, the method of Galerkin is employed, followed by the use of the multiple time scale method to solve the resulting equations. According to the results of this study, it can be claimed that the porosity ratio is more effective than porosity distribution and nonlocal parameters on the amplitude response and dynamic instability regions. Moreover, to examine thermal increments, foundation characteristics, slenderness, and thickness ratios, the bifurcation diagrams are drawn and discussed. It is found that foundation and geometric characteristics are of the highest significance in the nonlinear response of the Timoshenko nanobeams. The main intention of this study is to present a holistic idea about the porous materials used in sandwich structures which can be used in many composite structures in aircraft and automobiles.

•This study showed that some mutations are stabilized over time.•Novel mutations reveal the importance of monitoring the virus genome.

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Background: The regeneration of the muscles of the rotator cuff represents a grand challenge in musculoskeletal regenerative engineering. Several types of matrices have been proposed for skeletal muscle regeneration. However, biomimetic matrices to promote muscle regeneration and mimic native muscle tissue have not been successfully engineered. Besides topographical cues, an electrical stimulus may serve as a critical cue to improve interactions between materials and cells in scenarios fostering muscle regeneration. In this in vitro study, we engineered a novel stimulus-responsive conductive nanocomposite matrix and studied its ability to regulate muscle cell adhesion, proliferation, and differentiation. Electroconductive nanocomposite matrices demonstrated tunable conductivity and biocompatibility. Under the optimum concentration of conductive material, the matrices facilitated muscle cell adhesion, proliferation, and differentiation. Importantly, aligned conductive fibrous matrices were effective in promoting myoblast differentiation by upregulation of myogenic markers. The results demonstrated a promising potential of aligned conductive fibrous matrices for skeletal muscle regenerative engineering. Lay Summary: Around 40% of the human body mass consists of skeletal muscle. Musculoskeletal disorders such as muscle atrophy and fatty infiltration after rotator cuff injury lead to disability and pain and increase the rate of retear after rotator cuff surgery. The study showed the potential of novel engineered matrix to regenerate skeletal muscle by utilizing conductive material and nanofiber-based matrices. The incorporation of conductive material and aligned nanofibers as electrical and topographical cues significantly impacted cell viability and differentiation to support muscle regeneration. Future Work: The study demonstrated that electroconductive nanocomposite matrix can favorably modulate myoblast proliferation and differentiation. Future study will investigate the in vivo efficacy of the engineered matrix using a rat rotator cuff tear model to understand the ability of the engineered matrix in reducing the fatty infiltration.

Electronic metadevice is a new concept in which microscopic manipulation of radiofrequency fields results in extraordinary device properties. This approach can lead to a new generation of semiconductor devices that outperform their classical counterparts in terms of speed and energy efficiency. To fully unlock their potentials and to be able to design a variety of functionalities based on this new concept, a fundamental understanding of their operation principle is crucial. Using Maxwell’s equations under electrostatic assumptions, here we present a concrete theory of electronic metadevices which reveals the origin of their superior performance compared to classic devices. We show how deep-subwavelength field manipulation driven by a stripe array of metals formed on top of a heterostructure, can modify macroscopic device properties. By establishing this theoretical framework, our work lays the foundation for future implementations of electronic metadevices, opening up avenues for ultrafast electronics, including 5G and 6G telecommunications.

AbstractSARS-CoV-2 put a heavy financial burden on the healthcare system, with millions of laboratory-confirmed cases and deaths worldwide in the last 2 years. During the seventh wave of this pandemic, the continuously evolving nature of SARS-CoV-2 resulted in the emergence of new variants that harbor different mutations. Mutations are associated with changes in the virus behavior, including increased transmissibility, increased virulence, and evasion of neutralizing antibodies. Currently, we need detailed and comprehensive genomic information on all SARS-CoV-2 variants. One of the key points in this study was the genome survey of mutation profiles across variants as a genomic data source, to determine the efficiency of RT-qPCR assays. We also used the source to calculate the binding affinity changes of neutralizing antibodies–mutant receptor binding domain (RBD) complexes and determine vaccine efficacy. Our result revealed that the number of nucleotide mismatches is variable in the WHO-recommended primer-probe sets. Mismatches located at the 3′ ends of the oligonucleotide, may lead to false-negative results. Only the primer-probe sets designed by the Ministry of Public Health of Thailand were exclusive and cannot detect the omicron variant reliably. Binding affinity changes showed that E484K was more deleterious than other mutations and decreased stability between the mutant RBD protein and neutralizing antibodies. The Omicrons show the highest change in binding affinity which may lead to immune escape and increase transmissibility. Additionally, the 7D6 monoclonal antibody in the 7eam complex could neutralize all variants of SARS-CoV-2. We strongly recommend creating and improving a matrix accuracy by processing a large number of SARS-CoV-2 sequences to update RT-qPCR assays and identified immunogenic residues among conserved RBD. Also, a detail computational analysis is needed to investigate distinctive amino acid substitution patterns which may be foundational in the vaccines. Finally, designing in-vitro studies can help confirm the present study and manage COVID-19 patients.Communicated by Ramaswamy H. Sarma

Type II diabetes is one of the metabolic diseases that leads to the main complications for human health. Food-derived bioactive peptides were shown to have substantial potential for use in diabetes management. This study assessed how the activity of lactic acid bacteria (LAB) isolated from Iranian dairy products improved milk's antioxidant and antidiabetic properties with an insight into the activity of produced peptides. The inhibition of 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) was used to measure the antioxidant activity, and the inhibition of α-amylase and α-glucosidase enzymes was used to investigate the antidiabetic properties. The results of antioxidant activity showed that the milk fermented by L. delbrueckiiPTCC 1900 (59.43%, IC50= 0.2 mg protein) and L. paracaseissp. paracaseiPTCC 1945 (85.93%, IC50= 0.01 mg protein) had the highest DPPH and ABTS free radical scavenging at 48 h, respectively. The highest α-amylase and α-glucosidase inhibitory activities were observed, respectively, in milk fermented by L. helveticusPTCC 1930 (35%, IC50= 0.28 mg protein) and L. paracaseissp. paracaseiPTCC 1945 (50%, IC50= 0.03 mg protein) strains after 48 h. In addition, peptide fractions with a lower molecular weight demonstrated the highest proteolysis, antidiabetic, and antioxidant properties (p< 0.05). These results showed bioactive peptides derived from microbial fermentation can play an important role in creating the appropriate antidiabetic and antioxidant properties. Additionally, the results showed that the antidiabetic and antioxidant properties depended on the type of strain. Besides, the findings revealed a significant possibility for selected LAB strains to produce fermented milk as a nutraceutical or functional food.

This systematic review and meta-analysis focused on the effectiveness of biomaterials integrated with specific microRNAs (miRNAs) for bone fracture repair treatment. We conducted a comprehensive search of the PubMed, Web of Science, and Scopus databases, identifying 42 relevant papers up to March 2022. Hydrogel-based scaffolds were the most commonly used, incorporating miRNAs like miR-26a, miR-21, and miR-222, with miR-26a being the most prevalent. The meta-analysis revealed significant benefits of incorporating miRNAs into scaffolds for bone repair, particularly in hydrogel scaffolds. However, some controversies were observed among studies, presenting challenges in selecting appropriate miRNAs for this purpose. The study concludes that incorporating specific miRNAs into bone biomaterials enhances bone regeneration, but further trials comparing different biomaterials and miRNAs are necessary to validate their potential applications for bone tissue regeneration.

This paper is a new view to earlier research about the impact of state ownership on the internationalization of EMNEs. Although there are publications on Chinese MNEs about state ownership’s effects on their international expansion, there are still many opportunities to study EMNEs from other developing countries, especially to link the advantages to disadvantages of state ownership (How does state ownership involvement affect EMNEs internationalization?). We found ambiguity in whether state ownership benefits or harms EMNEs’ internationalization. The new discussion would be more informative if we found the scope conditions and factors involved in generating a positive or negative result. Adopting and adapting the institutional theory (coercive part) creates a clearer insight into SOEMNE internationalization, and finally, for this, proposes new statements as the result of the paper could be tested in the future.

This paper is a new view to earlier research about the impact of state ownership on the internationalization of EMNEs. Although there are publications on Chinese MNEs about state ownership’s effects on their international expansion, there are still many opportunities to study EMNEs from other developing countries, especially to link the advantages to disadvantages of state ownership (How does state ownership involvement affect EMNEs internationalization?). We found ambiguity in whether state ownership benefits or harms EMNEs’ internationalization. The new discussion would be more informative if we found the scope conditions and factors involved in generating a positive or negative result. Adopting and adapting the institutional theory (coercive part) creates a clearer insight into SOEMNE internationalization, and finally, for this, proposes new statements as the result of the paper could be tested in the future.

ABSTRACTIntroductionMesenchymal stromal cell (MSC)-based therapy has generated great hope for the treatment of various diseases such as myocardial infarction and stroke. Unfortunately, MSC-based therapy faces major hurdles in its translation to clinical practice. To address these issues, preconditioning and genetic modification strategies have been developed. Through preconditioning, MSCs are cultured under sub-lethal conditions of environmental stresses or treated with specific drugs, biomolecules, and growth factors. Genetic modification is a procedure in which specific genetic sequences are transferred into the MSCs via viral vectors or CRISP/Cas9 in order to alter the expression of distinctive genes.Areas coveredIn this article, a comprehensive review on preconditioning and gene modification inducers, mechanisms of action, and their impacts were discussed. In addition, clinical trials that used preconditioned and genetic modified MSCs are debated.Expert opinionNumerous preclinical investigations have demonstrated that preconditioning and genetic modifications considerably enhance MSC’s therapeutic capacity through improving their survival rate, antioxidant activity, growth factor secretion, immunomodulation, homing efficiency, and angiogenesis. For MSC preconditioning and genetic modification to achieve clinical translation, remarkable outcomes in clinical trials are of pivotal importance.

The liver and cardiovascular system disorders are not common in COVID-19 patients, but the patients suffering from these complications are exposed to a higher rate of mortality and disease progression. Hepatic injuries can drive to increased levels of liver enzymes, including ALT, AST, and LDH. Abundant levels of AST, LDH, and CPK can be indicators of cardiac injuries. The current study comparise 366 individuals who are divided into COVID-19 patients and healthy individuals groups, in which we have examined hepatic and cardiac function parameters. Moreover, the clinical characteristics of the participants, ethnicities, and their difference with studied parameters were assessed. The results showed Fars individuals are more susceptible to the disease progression, including liver and heart damage. COVID-19 infection is associated with aging, which indicates that the mean age of the case group is ten years older than the control group (P< 0.001). The blood sugar in the case group (140.50) was higher than in the control group (131.66), although there was no difference between the infection and BS (P= 0.505). Similarly, the increased- mean of the ALT level in the case group (102.369) compared with the control group (68.324) resulted in no significant difference (P= 0.318). Other parameters, including CPK, LDH, and AST showed an increase in the control group values compared to the case group; however, the differences were not significant (P= 0.264, P= 0.795, P= 0.417). Considering the involvement of cardiac and hepatic organs by SARS-CoV-2, paying particular attention to the disorders of these organs through assessing the hepatic and cardiac function parameters can enhance the patient's recovery and survival. However, in this study, we not observed significant differences, except for the Fars people. There is need for further assessment of this issue.

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The evolution of electronics has largely relied on downscaling to meet the continuous needs for faster and highly integrated devices1. As the channel length is reduced, however, classic electronic devices face fundamental issues that hinder exploiting materials to their full potential and, ultimately, further miniaturization2. For example, the carrier injection through tunnelling junctions dominates the channel resistance3, whereas the high parasitic capacitances drastically limit the maximum operating frequency4. In addition, these ultra-scaled devices can only hold a few volts due to the extremely high electric fields, which limits their maximum delivered power5,6. Here we challenge such traditional limitations and propose the concept of electronic metadevices, in which the microscopic manipulation of radiofrequency fields results in extraordinary electronic properties. The devices operate on the basis of electrostatic control of collective electromagnetic interactions at deep subwavelength scales, as an alternative to controlling the flow of electrons in traditional devices, such as diodes and transistors. This enables a new class of electronic devices with cutoff frequency figure-of-merit well beyond ten terahertz, record high conductance values, extremely high breakdown voltages and picosecond switching speeds. This work sets the stage for the next generation of ultrafast semiconductor devices and presents a new paradigm that potentially bridges the gap between electronics and optics.

Neuraminidase inhibitors are the only FDA-approved class of antiviral agents against influenza Bviruses. Resistance to these drugs has been reported from different parts of the world; however, there seems to be not enough information about this issue in Iran. We aimed to study the genetic evolution of these viruses as well as the presence of possible mutations concerning drug resistance in northern Iran. RNA was extracted from naso- and oropharyngeal swabs and amplified by one-step RT-PCR for detection and sequencing of the neuraminidase gene. All the data were edited and assembled utilizing BioEdit DNASequence Alignment Editor Software, and the phylogenetic tree was constructed via MEGA software version 10. Finally, resistance-associated mutations and B-cell epitopes substitutions were assessed by comparing our sequences with the counterparts in the reference strains. Comparing our sequences with reference strains revealed that the analyzed isolates of influenza Bpertained to the B-Yamagata lineage, had a few B-cell epitopes alterations, and contained no particular mutations concerning resistance against neuraminidase inhibitors, such as oseltamivir. Our findings suggest that all the strains circulating in northern Iran and hopefully other parts of the country can be considered sensitive to this class of drugs. Although it is promising, we strongly recommend additional investigations to evaluate the impact of such drug-resistant mutations in other regions, which in turn will assist the public health agencies in taking immediate and effective therapeutic measures into account when needed.

In recent years, plant-derived bioactive compounds have been developed as antiviral agents. Plants synthesize a variety of compounds, especially peptides, which possess antimicrobial activity. Current studies have shown that some antimicrobial peptides have antiviral activity against a wide range of human DNA and RNA viruses and play an effective role in the treatment of human viral diseases. These peptides act through different mechanisms. They can integrate into the envelope of the target virus or cell membrane of the host, resulting in an unstable membrane. For instance, some peptides prevent the attachment of viral spike proteins to host cells. On the other hand, some peptides may alter the cellular pathways, including DNA replication or protein synthesis, leading to the suppression of viral infection. However, the antiviral activity of peptides can be affected by their chemical and structural properties. In several studies, the properties of antimicrobial (antiviral) peptides were altered by minor modifications, but these changes require tools to predict. Recently, computational approaches have been introduced to analyze the effects of structural modifications on the physicochemical properties, mechanism of action, stability, and activity of peptides. In this mini-review, we will describe the design and function of antiviral peptides derived from plants.

•A dual-continuum model is developed for CO2-circulated geothermal harvest.•Response surface models are developed for global sensitivity analysis.•Fracture permeability dominates the system performance.•The system is sensitive to Da and Lm, but insensitive to Lf.•The coupled impact of Da and Lm on T decline is non-monotonic.

Patients with brain metastases (BM) face a 90% mortality rate within one year of diagnosis and the current standard of care is palliative. Targeting BM-initiating cells (BMICs) is a feasible strategy to treat BM, but druggable targets are limited. Here, we apply Connectivity Map analysis to lung-, breast-, and melanoma-pre-metastatic BMIC gene expression signatures and identify inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme in the de novoGTP synthesis pathway, as a target for BM. We show that pharmacological and genetic perturbation of IMPDH attenuates BMIC proliferation in vitroand the formation of BM in vivo.Metabolomic analyses and CRISPR knockout studies confirm that de novoGTP synthesis is a potent metabolic vulnerability in BM. Overall, our work employs a phenotype-guided therapeutic strategy to uncover IMPDH as a relevant target for attenuating BM outgrowth, which may provide an alternative treatment strategy for patients who are otherwise limited to palliation.

Cheshmeh Kileh and Shiroud in southern Caspian Sea have very important as habitats for the migration and reproduction of valuable fishery species. According to the agricultural industry in the north of Iran, products such as kiwi fruits, citrus fruits, rice and greenhouse products are the dominant products in this area. EC and pH are one of the important parameters in agricultural sciences. Therefore, conducting comprehensive studies to determine factors affecting the chemical composition of water and sediment along the rivers can help to identify pollutants and controlling factors of water chemistry and the sustainable development of the region. Sampling sites were determined based on the geogenic and anthropogenic effects, and samples were collected in September 2021. Hydrogeochemical diagrams, irrigation, industrial and HMs indices were drawn or calculated. The results showed that one sample in Sehazar sub-river is under the influence of gypsum lithology in the Karaj Formation located upstream of Maran heights. In Cheshmeh Kileh Catchment, one sample had a higher amount of bicarbonate, sodium, potassium and HMs ions than other samples due to the infiltration of landfill waste water. Diagrams for Shiroud Catchment showed that in the estuary, the phenomenon of saltwater intrusion has occurred due to excessive sand and gravel harvesting. Therefore, the corrosion rate in this station is high, and for the construction of metal and reinforced concrete structures, caution and further investigations should be used to prevent damages. It is also suggested that EC and pH values are always controlled in agricultural activities.

An eight-week feeding trial was conducted to elucidate the effects of rainbow trout by-products protein hydrolysates (FPH, 92 % peptides <1 kDa, ∼78.1 % crude protein, ∼2.7 % lipid) on growth and some selected physiological responses in sobaity (Sparidentex hasta) (1.7 ± 0.0 g) and Arabian yellowfin (Acanthopagrus arabicus)(0.9 ± 0.0 g) seabream. Fish meal in a basal diet (∼58 % crude protein, ∼12 % lipid) was replaced with FPH at four levels, including 0 (control), 1 % (FPH1), 2.5 % (FPH2.5), and 5 % (FPH5). Each experimental diet was offered thrice daily to fish in triplicate. At the end of the feeding trial, S. hastafed with FPH diets showed positive linear and quadratic trends in growth performance, and those fed with FPH5 had the highest final weight (FBW; 9.8 ± 0.4) and better feed conversion ratio (FCR; 0.9 ± 0.0). Regarding A. arabicusit showed positive quadratic trend and fish fed FPH2.5 diet had the highest FBW (6.2 ± 0.3), and better FCR (1.2 ± 0.0) value. Trypsin and alkaline phosphatase (ALP) activities showed both positive linear and quadratic trends in S. hasta. In A. arabicus, both linear and quadratic trends were observed in the activities of trypsin and total proteases (P = 0.001), while positive quadratic trends in pepsin and ALP activities were noticed. Lysozyme activity significantly increased by supplementing the diet with FPH and showed both linear and quadratic trends in S. hasta, but it did not change in A. arabicus. Total antioxidant capacity (TAC) in A. arabicusincreased and showed both linear and quadratic responses. The catalase and glutathione peroxidase activities in both species increased significantly in response to dietary FPH. This study showed that FPH effects in diet were species-specific and its supplementation levels at 2.5 and 5 % could be recommended in A. arabicusand S. hastajuveniles, respectively.

Cardiovascular magnetic resonance (CMR) imaging is an important tool for evaluating the severity of aortic stenosis (AS), co-existing aortic disease, and concurrent myocardial abnormalities. Acquiring this additional information requires protocol adaptations and additional scanner time, but is not necessary for the majority of patients who do not have AS. We observed that the relative signal intensity of blood in the ascending aorta on a balanced steady state free precession (bSSFP) 3-chamber cine was often reduced in those with significant aortic stenosis. We investigated whether this effect could be quantified and used to predict AS severity in comparison to existing gold-standard measurements.

ABSTRACTPurposeTo compare the accuracy of anterior segment optical coherence tomography (AS-OCT) and ultrasound biomicroscopy (UBM) in localizing rectus muscle insertions.MethodsThe study was performed on 27 patients (39 rectus muscles) who required primary or secondary surgery. Using caliper function in the AS-OCT and UBM software, the distance from the insertion site to the anterior chamber angle was measured. The actual muscle insertion distance from limbus was considered as the measured distance plus 1 mm. The measurements by UBM and AS-OCT were compared with intraoperative measurements and with each other.ResultsAS-OCT and UBM were performed on 13 medial rectus, 24 lateral rectus, and 2 superior rectus muscles. Ninety two percent of UBM measurements (36 muscles) were within 1 mm, one was within 1–1.5 mm, and 2 were within 1.5–2 mm of surgery measurements. Eighty five percent of AS-OCT measurements (33 muscles) were within 1 mm, 5 were within 1–1.5 mm, and one was within 1.5–2 mm of surgery measurements. In all cases, the mean absolute error of the UBM (0.54 ± 0.44) and AS-OCT (0.51 ± 0.36) showed no significant difference (p = .76).ConclusionAS-OCT and UBM can be used interchangeably to localize rectus muscle insertions and showed good agreement with intraoperative measurements.

There are reports regarding the effects of intracellular Ca2+and synthesis and release of endocannabinoids. The secretion of endocannabinoids depends on the L-type calcium channel. The present study evaluated the involvement of the cannabinoid CB1 receptors in the effect of L-type calcium channel blocker verapamil on passive avoidance learning (PAL) in adult male rats. In this study, we examined the effects of an acute administration of the cannabinoid CB1 receptors antagonist/inverse agonist AM251 following a chronic administration of the Ca2+channel blocker verapamil on PAL. Male Wistar rats were administered verapamil (10, 25 and 50 mg/kg) or saline intraperitoneally (i.p) daily for 13 days (n= 10/group). After this treatment period, a learning test (acquisition) was performed, and a retrieval test was performed the following day. The results indicated that chronic systemic administration of verapamil (in a dose-dependent manner) impaired memory acquisition and retrieval. Pre-training acute administration of a selective CB1 antagonist/inverse agonist, AM251 (5 mg/kg, i.p.) did not change memory acquisition and retrieval. Co-administration of the verapamil and AM251 significantly reversed verapamil-induced amnesia, suggesting a functional interaction between AM251 and verapamil. The results indicated the interactive effects of cannabinoid CB1 receptors and L-type calcium channel in passive avoidance learning and AM251 can counter the effects of verapamil on memory.

PurposeTo evaluate the superficial vascular density of the optic nerve head in different stages of pseudoexfoliation disease using optical coherence tomography angiography (OCTA).MethodsIn this cross-sectional study, 57 normal eyes, 41 eyes with pseudoexfoliation syndrome (PXS), 82 eyes with pseudoexfoliation glaucoma (PXG) and 27 non-glaucomatous fellow eyes of PXG (NL-PXG) that had OCTA were included. Circumpapillary RNFL (cpRNFL) thickness and circumpapillary capillary density (cpCD) were compared among the groups after adjusting for confounders using linear-mixed model.ResultsPXG eyes had thinner global RNFL and lower cpCD (74.2±14.3 µm and 36.7±10.0%) than control (103.3±8.6 µm and 52.5±2.3%), PXS (96.8±8.8 µm and 51.5±2.3%), and NL-PXG eyes (96.3±11.1 µm and 50.1±3.9%) (p<0.001). After adjustment for age, gender and signal strength index, global cpRNFL thickness was comparable among control, PXS and NL-PXG. NL-PXG had the lowest cpCD (p=0.045) and sectoral cpCD compared to PXS and control eyes. Although cpCD was comparable between control and PXS (p=0.425) eyes, sectoral differences (p=0.009 and 0.004, for inferonasal and temporal-inferior cpCD, respectively) were detectable between the two groups. AUROC for differentiating NL-PXG eyes from normal were better for cpCD (0.78) compared to cpRNLF (0.69).ConclusionsOCTA can detect reduced capillary density before significant changes in cpRNFL in fellow eyes of PXG patients. This can enable earlier detection of glaucomatous loss in pseudoexfoliation disease and enhance management of the disease.

AbstractToday, Alzheimer’s disease (AD) is one of the most important neurodegenerative disorders that affected millions of people worldwide. Hundreds of academic investigations highlighted the potential roles of natural metabolites in the cornerstone of AD prevention. Nevertheless, alkaloids are only metabolites that successfully showed promising clinical therapeutic effects on the prevention of AD. In this regard, other plant metabolites such as flavonoids are also considered as promising substances in the improvement of AD complications. The lack of data on molecular mode of action of flavonoids inside brain tissues, and their potential to transport across the blood-brain barrier, a physical hindrance between bloodstream and brain tissues, limited the large-scale application of these compounds for AD therapy programs. Herein, a coupled docking and quantum study was applied to determine the binding mode of flavonoids and three protein kinases involved in the pathogenesis of AD. The results suggested that all docked metabolites showed considerable binding affinity to interact with target receptors, but some compounds possessed higher binding energy values. Because docking simulation cannot entirely reveal the potential roles of ligand substructures in the interaction with target residues, quantum chemical analyses (QCAs) were performed to cover this drawback. Accordingly, QCAs determined that distribution of molecular orbitals have a pivotal function in the determination of the type of reaction between ligands and receptors; therefore, using such quantum chemical descriptors may correct the results of virtual docking outcomes to highlight promising backbones for further developments.Communicated by Ramaswamy H. Sarma

Abstract: Recently, genetic engineering by various strategies to stimulate gene expression in a specific and controllable mode is a speedily growing therapeutic approach. Genetic modification of human stem or progenitor cells, such as Embryonic Stem Cells (ESCs), Neural Progenitor Cells (NPCs), Mesenchymal Stem/Stromal Cells (MSCs), and Hematopoietic Stem Cells (HSCs) for direct delivery of specific therapeutic molecules or genes has been evidenced as an opportune plan in the context of regenerative medicine due to their supported viability, proliferative features, and metabolic qualities. On the other hand, a large number of studies have investigated the efficacy of modified stem cells in cancer therapy using cells from various sources, disparate transfection means for gene delivery, different transfected yields, and wide variability of tumor models. Accordingly, cell-based gene therapy holds substantial aptitude for the treatment of human malignancy as it could relieve signs or even cure cancer succeeding expression of therapeutic or suicide transgene products; however, there exist inconsistent results in this regard. Herein, we deliver a brief overview of stem cell potential to use in cancer therapy and regenerative medicine and importantly discuss stem cells based gene delivery competencies to stimulate tissue repair and replacement in concomitant with their potential to use as an anti-cancer therapeutic strategy, focusing on the last two decades in vivo studies.

Abstract: The rotator cuff is a musculotendon unit responsible for movement in the shoulder. Rotator cuff tears represent a significant number of musculoskeletal injuries in the adult population. In addition, there is a high incidence of retear rates due to various complications within the complex anatomical structure and the lack of proper healing. Current clinical strategies for rotator cuff augmentation include surgical intervention with autograft tissue grafts and beneficial impacts have been shown, but challenges still exist because of limited supply. For decades, nanomaterials have been engineered for the repair of various tissue and organ systems. This review article provides a thorough summary of the role nanomaterials, stem cells, and biological agents has played in rotator cuff repair to date and offers input on next generation approaches for regenerating this tissue. Lay Summary: The rotator cuff is a group of muscles and tendons that allow movement of the shoulder. Rotator cuff injuries occur often in athletes and in people that frequently perform overhead motion. The risk of injury also increases with age. Currently, implants from one part of the body to another are used to surgically repair the rotator cuff, but problems still rise because of limited supply in patients. To overcome this challenge and other concerns, nanomaterials have been used to help renew damaged tissues and organs. In this review article, we describe the role of nanomaterials, stem cells, and biological agents in rotator cuff repair and provide insight on strategies for successful rotator cuff regeneration.

This study proposes a model for the kinetics and hydrodynamics of gypsum scale deposition on surfaces of anhydrite, calcite, dolomite, and sandstone rocks while interacting with the brines of 3000 and 6000 mg/L [Ca2+] at 363 K and 1 atm. To do so, this study utilizes the surface energy characteristics of an interacting scale–brine–rock system as well as the geochemical interactions between brine–brine and brine–rock. The results showed that the deposition flux decreases steeply over time, followed by asymptotic propensity as time elapses. A higher degree of salinity in terms of [Ca2+] increases the deposition flux as much as 2.9-fold for the flowing velocity of 10–6m/s and 2.4-fold for a velocity of 10–5m/s. Moreover, higher flow velocity would lead to more deposition on sandstone followed by carbonate and anhydrite rocks: ∼2.6-fold for the salinity of 3000 mg/L and 2.2-fold for 6000 mg/L [Ca2+].

Background:Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is currently the most important etiological agent of acute respiratory distress syndrome (ARDS) with millions of infections and deaths in the last 2 years worldwide. Several reasons and parameters are responsible for the difficult management of coronavirus disease-2019 (COVID-19) patients; the first is virus behavioral factors such as high transmission rate, and the different molecular and cellular mechanisms of pathogenesis remain a matter of controversy, which is another factor. Summary:In the present review, we attempted to explain about features of SARS-COV-2, particularly focusing on the various aspects of pathogenesis and treatment strategies. Key Messages:We note evidence for the understanding of the precise molecular and cellular mechanisms of SARS-CoV-2 pathogenesis, which can help design the appropriate drug or vaccine. Additionally, and importantly, we reported the updated issues associated with the history and development of treatment strategies such as, drugs, vaccines, and other medications that have been approved or under consideration in clinics and markets worldwide.