Estimation of microtubule-generated forces using a DNA origami nanospring.

Microtubules are dynamic cytoskeletal filaments that can generate forces when polymerizing and depolymerizing. Proteins that follow growing or shortening microtubule ends and couple forces to cargo movement are important for a wide range of cellular processes. Quantifying these forces and the composition of protein complexes at dynamic microtubule ends is challenging and requires sophisticated instrumentation. Here, we present an experimental approach to estimate microtubule-generated forces through the extension of a fluorescent spring-shaped DNA origami molecule. Optical readout of the spring extension enables recording of force production simultaneously with single-molecule fluorescence of proteins getting recruited to the site of force generation. DNA nanosprings enable multiplexing of force measurements and only require a fluorescence microscope and basic laboratory equipment. We validate the performance of DNA nanosprings against results obtained using optical trapping. Finally, we demonstrate the use of the nanospring to study proteins that couple microtubule growth and shortening to force generation.

Recent Progress in MOF-Aerogel Fabrication and Applications.

Recent advancements in metal-organic frameworks (MOFs) underscore their significant potential in chemical and materials research, owing to their remarkable properties and diverse structures. Despite challenges like intrinsic brittleness, powdered crystalline nature, and limited stability impeding direct applications, MOF-based aerogels have shown superior performance in various areas, particularly in water treatment and contaminant removal. This review highlights the latest progress in MOF-based aerogels, with a focus on hybrid systems incorporating materials like graphene, carbon nanotube, silica, and cellulose in MOF aerogels, which enhance their functional properties. The manifold advantages of MOF-based aerogels in energy storage, adsorption, and catalysis are discussed, with an emphasizing on their improved stability, processability, and ease of handling. This review aims to unlock the potential of MOF-based aerogels and their real-world applications. Aerogels are expected to reshape the technological landscape of MOFs through enhanced stability, adaptability, and efficiency.

Clinical and genomic evaluations of a persistent fatal SARS-CoV-2 infection in a goods syndrome patient: a case report.

The coronavirus disease of 2019 (COVID-19) resulted from an infection by severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) which is the main cause of acute respiratory distress syndrome (ARDS) in global population from 2019 on. It may contribute to higher rate of death among the patients with immunodeficiency based on recent reports. In addition, Good syndrome (GS) as a result of thymoma removal might cause in some long-lasting microbial infections. We described clinical aspects and viral mutations on a case of GS suffering from COVID-19. A 46-year-old man with fever, common respiratory disease symptoms and positive COVID-19 polymerase chain reaction (PCR) test, with the history of thymoma removal surgery was admitted to Masih Daneshvari Hospital, Tehran, Iran. Lung radiographs and oxygen saturation measurement disclosed considerable implication resulted in application of several anti-microbial medication. The delta variant (B.1.617.2 (21 J Clade)) was the strain isolated from the patient by sequencing methods done by the COVID-19 National Reference Laboratory (CNRL), Pasteur Institute of Iran, while the dominant strain circulated mostly among population was Omicron (B.1.1.529) at the time of sampling. Unfortunately, the patient had passed away a month later by sudden respiratory failure progressed in refractory septic shock. Despite the fact that opportunistic infections may lead the GS patients to a major health problematic condition, unusual persistent of infections such as non-dominant variant of SARS-Cov-2 could be observed through the disease timeline. Therefore, a fully screening of thymoma plus intra-host evolution monitoring of SARS-CoV-2 is highly recommended in immunocompromised patients.

Bonding states of gold/silver plasmonic nanostructures and sulfur-containing active biological ingredients in biomedical applications: a review.

As one of the most instrumental components in the architecture of advanced nanomedicines, plasmonic nanostructures (mainly gold and silver nanomaterials) have been paid a lot of attention. This type of nanomaterial can absorb light photons with a specific wavelength and generate heat or excited electrons through surface resonance, which is a unique physical property. In innovative biomaterials, a significant number of theranostic (therapeutic and diagnostic) materials are produced through the conjugation of thiol-containing ingredients with gold and silver nanoparticles (Au and Ag NPs). Hence, it is essential to investigate Au/Ag-S interfaces precisely and determine the exact bonding states in the active nanobiomaterials. This study intends to provide useful insights into the interactions between Au/Ag NPs and thiol groups that exist in the structure of biomaterials. In this regard, the modeling of Au/Ag-S bonding in active biological ingredients is precisely reviewed. Then, the physiological stability of Au/Ag-based plasmonic nanobioconjugates in real physiological environments (pharmacokinetics) is discussed. Recent experimental validation and achievements of plasmonic theranostics and radiolabelled nanomaterials based on Au/Ag-S conjugation are also profoundly reviewed. This study will also help researchers working on biosensors in which plasmonic devices deal with the thiol-containing biomaterials (e.g., antibodies) inside blood serum and living cells.

Remediation of Safranin-O and Acid Fuchsin by Using Ti3C2 MXene /rGo-Cu2O Nanocomposite: Preparation, Characterization, Isotherm, Kinetics and Thermodynamic Studies.

In recent years, MXene has become one of the most intriguing two-dimensional layered (2Dl) materials extensively explored for various applications. In this study, a Ti3C2 MXene/rGo-Cu2O Nanocomposite (TGCNCs) was developed to eliminate Safranin-O effectively (SO) and Acid Fuchsin (AF) as cationic dyes from the aquatic environment. Multistep was involved in the preparation of the adsorbent system, including the Preparation of Ti3C2, after that, GO synthesis by the Humer method, followed by rGO production, then added CuSO4 to obtain a final Nanocomposite (NCs) called "TGCNCs". The structure of TGCNCs can be varied in several ways, including FTIR, SEM, TGA, Zeta, EDX, XRD, and BET, to affirm the efficacious preparation of TGCNCs. A novel adsorbent system was developed to remove SO and AF, both cationic dyes. Various adsorption conditions have been optimized through batch adsorption tests, including the pH of the solution (4-12), the effect of dosage (0.003-0.03 g), the impact of the contact time (5-30 min), and the effect of beginning dye concentration (25-250 mg/L). Accordingly, the TGCNCs exhibited excellent fitting for Freundlich isotherm mode, resulting in maximum AF and SO adsorption capacities of 909.09 and 769.23 mg.g-1. This research on adsorption kinetics suggests that a pseudo-second-order (PSO) model would fit well with the experimental data ( = 0.998 and = 0.990). It is evident from the thermodynamic parameters that adsorption is an endothermic process that is spontaneous and favourable. During the adsorption of SO and AF onto NCs, it is hypothesized that these molecules interact intramolecularly through stacking interactions, H-bond interactions, electrostatic interactions, and entrapment within the polymeric Poros structure nanocomposite. Regeneration studies lasting up to five cycles were the most effective for both organic dyes under study.

A Modified Hybrid Brain-Computer Interface Speller Based on Steady-State Visual Evoked Potentials and Electromyogram.

BACKGROUND: To enhance the information transfer rate (ITR) of a steady-state visual evoked potential (SSVEP)-based speller, more characters with flickering symbols should be used. Increasing the number of symbols might reduce the classification accuracy. A hybrid brain-computer interface (BCI) improves the overall performance of a BCI system by taking advantage of two or more control signals. In a simultaneous hybrid BCI, various modalities work with each other simultaneously, which enhances the ITR. METHODS: In our proposed speller, simultaneous combination of electromyogram (EMG) and SSVEP was applied to increase the ITR. To achieve 36 characters, only nine stimulus symbols were used. Each symbol allowed the selection of four characters based on four states of muscle activity. The SSVEP detected which symbol the subject was focusing on and the EMG determined the target character out of the four characters dedicated to that symbol. The frequency rate for character encoding was applied in the EMG modality and latency was considered in the SSVEP modality. Online experiments were carried out on 10 healthy subjects. RESULTS: The average ITR of this hybrid system was 96.1 bit/min with an accuracy of 91.2%. The speller speed was 20.9 char/min. Different subjects had various latency values. We used an average latency of 0.2 s across all subjects. Evaluation of each modality showed that the SSVEP classification accuracy varied for different subjects, ranging from 80% to 100%, while the EMG classification accuracy was approximately 100% for all subjects. CONCLUSIONS: Our proposed hybrid BCI speller showed improved system speed compared with state-of-the-art systems based on SSVEP or SSVEP-EMG, and can provide a user-friendly, practical system for speller applications.

Applications of hollow nanostructures in water treatment considering organic, inorganic, and bacterial pollutants.

One of the major issues of modern society is water contamination with different organic, inorganic, and contaminants bacteria. Finding cost-effective and efficient materials and methods for water treatment and environment remediation is among the scientists' most important considerations. Hollow-structured nanomaterials, including hollow fiber membranes, hollow spheres, hollow nanoboxes, etc., have shown an exciting capability for wastewater refinement approaches, including membrane technology, adsorption, and photocatalytic procedure due to their extremely high specific surface area, high porosity, unique morphology, and low density. Diverse hollow nanostructures could potentially eliminate organic contaminants, including dyes, antibiotics, oil/water emulsions, pesticides, and other phenolic compounds, inorganic pollutants, such as heavy metal ions, salts, phosphate, bromate, and other ions, and bacteria contaminations. Here, a comprehensive overview of hollow nanostructures' fabrication and modification, water contaminant classification, and recent studies in the water treatment field using hollow-structured nanomaterials with a comparative attitude have been provided, indicating the privilege abd detriments of this class of nanomaterials. Eventually, the future outlook of employing hollow nanomaterials in water refinery systems and the upcoming challenges arising in scaling up are also propounded.

Recent advances in non-small cell lung cancer targeted therapy; an update review.

Lung cancer continues to be the leading cause of cancer-related death worldwide. In the last decade, significant advancements in the diagnosis and treatment of lung cancer, particularly NSCLC, have been achieved with the help of molecular translational research. Among the hopeful breakthroughs in therapeutic approaches, advances in targeted therapy have brought the most successful outcomes in NSCLC treatment. In targeted therapy, antagonists target the specific genes, proteins, or the microenvironment of tumors supporting cancer growth and survival. Indeed, cancer can be managed by blocking the target genes related to tumor cell progression without causing noticeable damage to normal cells. Currently, efforts have been focused on improving the targeted therapy aspects regarding the encouraging outcomes in cancer treatment and the quality of life of patients. Treatment with targeted therapy for NSCLC is changing rapidly due to the pace of scientific research. Accordingly, this updated study aimed to discuss the tumor target antigens comprehensively and targeted therapy-related agents in NSCLC. The current study also summarized the available clinical trial studies for NSCLC patients.

Current status of skin cancers with a focus on immunology and immunotherapy.

Skin cancer is one of the most widespread cancers, with a significant global health effect. UV-induced DNA damage in skin cells triggers them to grow and proliferate out of control, resulting in cancer development. Two common types of skin cancer include melanoma skin cancer (MSC) and non-melanoma skin cancer (NMSC). Melanoma is the most lethal form of skin cancer, and NMSC includes basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and other forms. The incidence of skin cancer is increasing in part owing to a demographic shift toward an aging population, which is more prone to NMSC, imposing a considerable financial strain on public health services. The introduction of immunostimulatory approaches for cancer cell eradication has led to significant improvements in skin cancer treatment. Over the last three decades, monoclonal antibodies have been used as powerful human therapeutics besides scientific tools, and along with the development of monoclonal antibody production and design procedures from chimeric to humanized and then fully human monoclonal antibodies more than 6 monoclonal antibodies have been approved by the food and drug administration (FDA) and have been successful in skin cancer treatment. In this review, we will discuss the epidemiology, immunology, and therapeutic approaches of different types of skin cancer.

Epidemiological surveillance of respiratory viral infections in SARS-CoV-2-negative samples during COVID-19 pandemic in Iran.

BACKGROUND: To improve the patient care, public health surveillance, and infection control, it is crucial to identify the presence and frequency of the common respiratory infections in individuals with COVID-19 symptoms but tested negative for SARS-CoV-2. This study aimed to shed light on this during the COVID-19 pandemic in Iran. METHODS: In this cross-sectional study, a total of 1,002 patients with acute respiratory infection who had negative SARS-CoV-2 test results and referred to Valfajr Health Center, the National Collaborating Laboratory of Influenza and COVID-19 National Reference Laboratory at Pasteur Institute of Iran were recruited between January 2020 and January 2022. Nasopharyngeal and oropharyngeal swab samples were collected to detect 17 common respiratory viruses via TaqMan one-step real-time multiplex PCR. Demographic and clinical data of the participants were obtained from their electronic medical records. RESULTS: In total, 218 samples (21.8%) were tested positive for at least one respiratory virus infection. Most of the common investigated respiratory viruses belonged to the years 2020 and 2022. The number of investigated patients in 2021 was few, which highlights the impact of health measures following the COVID-19 pandemic in Iran. Influenza A was the most common virus (5.8%), while adenovirus had the lowest prevalence (0.1%). Although the rate of respiratory virus infection was higher in men (24%) compared to women (19.3%), this difference was not statistically significant (P = 0.069). The prevalence of respiratory viruses had an inverse association with increasing age, with the highest rate (55.6%) observed in the age group below 2 years and the lowest rate (12.7%) in those above 65 years. CONCLUSION: Our findings underscore the significance of adopting a comprehensive approach to respiratory infections detection and management. These results can be employed for the development of syndromic surveillance systems and implementation of the effective infection control measures. Furthermore, the results contribute to better understanding of the dynamics of respiratory viruses, both during pandemic periods and in non-pandemic contexts.

Advances in immune checkpoint-based immunotherapies for multiple sclerosis: rationale and practice.

Beyond the encouraging results and broad clinical applicability of immune checkpoint (ICP) inhibitors in cancer therapy, ICP-based immunotherapies in the context of autoimmune disease, particularly multiple sclerosis (MS), have garnered considerable attention and hold great potential for developing effective therapeutic strategies. Given the well-established immunoregulatory role of ICPs in maintaining a balance between stimulatory and inhibitory signaling pathways to promote immune tolerance to self-antigens, a dysregulated expression pattern of ICPs has been observed in a significant proportion of patients with MS and its animal model called experimental autoimmune encephalomyelitis (EAE), which is associated with autoreactivity towards myelin and neurodegeneration. Consequently, there is a rationale for developing immunotherapeutic strategies to induce inhibitory ICPs while suppressing stimulatory ICPs, including engineering immune cells to overexpress ligands for inhibitory ICP receptors, such as program death-1 (PD-1), or designing fusion proteins, namely abatacept, to bind and inhibit the co-stimulatory pathways involved in overactivated T-cell mediated autoimmunity, and other strategies that will be discussed in-depth in the current review. Video Abstract.

Comparison of a Multiplex Real-Time PCR Technique with Oxford Nanopore Technologies Next-Generation Sequencing for Identification of SARS-CoV-2 Variants of Concern.

INTRODUCTION: The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and their potential to endangering the global health has increased the demand for a fast-tracking method in comparison to the next-generation sequencing (NGS) as a gold standard assay, particularly in developing countries. This study was designed to evaluate the performance of a commercial multiplex real-time PCR technique (GA SARS-CoV-2 OneStep RT-PCR Kit, Iran) for identification of SARS-CoV-2 variants of concern (VOCs) compared to the Oxford Nanopore NGS assay. METHODS: A total of 238 SARS-CoV-2-positive respiratory samples from different waves of COVID-19 in Iran were randomly selected in this study. To determine the SARS-CoV-2 VOC, the samples were analyzed via the commercial triple target assay, GA SARS-CoV-2 OneStep RT-PCR Kit, and NGS as well. RESULTS: The results revealed good concordance between GA SARS-CoV-2 OneStep RT-PCR Kit and NGS for identification of SARS-CoV-2 VOCs. GA SARS-CoV-2 OneStep RT-PCR Kit identified Wuhan, Alpha, and Delta variants with 100% relative sensitivity and specificity. Regarding Omicron subvariants of BA.1, BA.2, and BA.4/5, the relative sensitivity of 100%, 100%, and 81.5% and the relative specificity of 95.3%, 93.5%, and 100% were observed. CONCLUSION: Overall, GA SARS-CoV-2 OneStep RT-PCR Kit can be used as a rapid and cost-effective alternative to NGS for identification of SARS-CoV-2 VOCs.

Vancomycin-Loaded Fe3O4/MOF-199 Core/Shell Cargo Encapsulated by Guanidylated-ß-Cyclodextrine: An Effective Antimicrobial Nanotherapeutic.

This study describes an efficient antimicrobial drug delivery system composed of iron oxide magnetic nanoparticles (Fe3O4 NPs) coated by an MOF-199 network. Then, the prepared vancomycin (VAN)-loaded carrier was fully packed in a lattice of beta-cyclodextrin (BCD). For cell adhesion, beta-cyclodextrin has been functionalized with guanidine (Gn) groups within in situ synthetic processes. Afterward, drug loading efficiency and the release patterns were investigated through precise analytical methods. Confocal microscopy has shown that the prepared cargo (formulated as [VAN@Fe3O4/MOF-199]BCD-Gn) could be attached to the Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) bacterial cells in a higher rate than the individual VAN. The presented system considerably increased the antibacterial effects of the VAN with a lower dosage of drug. The cellular experiments such as the zone of inhibition and optical density (OD600) have confirmed the enhanced antibacterial effect of the designed cargo. In addition, the MIC/MBC (minimum inhibitory and bactericidal concentrations) values have been estimated for the prepared cargo compared to the individual VAN, revealing high antimicrobial potency of the VAN@Fe3O4/MOF-199]BCD-Gn cargo.

Magnetic biosensors for identification of SARS-CoV-2, Influenza, HIV, and Ebola viruses: a review.

Infectious diseases such as novel coronavirus (SARS-CoV-2), Influenza, HIV, Ebola, etc kill many people around the world every year (SARS-CoV-2 in 2019, Ebola in 2013, HIV in 1980, Influenza in 1918). For example, SARS-CoV-2 has plagued higher than 317 000 000 people around the world from December 2019 to January 13, 2022. Some infectious diseases do not yet have not a proper vaccine, drug, therapeutic, and/or detection method, which makes rapid identification and definitive treatments the main challenges. Different device techniques have been used to detect infectious diseases. However, in recent years, magnetic materials have emerged as active sensors/biosensors for detecting viral, bacterial, and plasmids agents. In this review, the recent applications of magnetic materials in biosensors for infectious viruses detection have been discussed. Also, this work addresses the future trends and perspectives of magnetic biosensors.

Molecular diagnosis, phylogenetic analysis, and antifungal susceptibility profiles of Candida species isolated from neutropenic oncological patients.

BACKGROUND: Neutropenia is the most important cause of life-threatening invasive fungal infections (IFIs). Here, we studied the frequency and antifungal susceptibility profiles of Candida species that colonized or caused infections among neutropenic patients with solid or hematological malignancies. METHODS: A total of 362 clinical samples were collected from 138 patients. After initial isolation using a mix of mycological methods, isolates were screened using chromogenic culture media. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was applied for molecular identification. Positive or suspected cases were confirmed using the reference method of sequencing. Antifungal susceptibility testing for voriconazole and caspofungin was carried out using the microbroth dilution method. An in-silico assay was applied for phylogenetic analysis. RESULTS: Thirty-four Candida strains were isolated. C. albicans (47.06%) and C. glabrata (29.41%) were the most frequent strains. Antifungal treatment reduced the chance of Candida colonization by almost 76% in neutropenic patients (OR: 1.759; 95% CI: 1.349 to 2.390; p value: 0.000). An unusual and non-resistant strain, C. lambica, was reported from the bloodstream of a 56-year-old man with hematologic malignancy (HM). Eight isolates were non-susceptible, and one isolate was resistant to voriconazole. Also, four isolates were non-susceptible to caspofungin. CONCLUSION: We can conclude that there is a cause-and-effect relationship between neutropenia, HM background, and Candida species separated from neutropenic patients, which can lead to possible infections. Further and repetitive studies are recommended using different molecular methods for better prediction and management of fungal infections in neutropenic patients.

In situ preparation of MOF-199 into the carrageenan-grafted-polyacrylamide@Fe3O4 matrix for enhanced adsorption of levofloxacin and cefixime antibiotics from water.

In this research study, a novel method, an in-situ growth approach, to incorporate metal-organic framework (MOF) into carrageenan-grafted- polyacrylamide-Fe3O4 substrate was introduced. Carrageenan-grafted-polyacrylamide-Fe3O4/MOF nanocomposite (kC-g-PAAm@Fe3O4-MOF-199) was fabricated utilizing three stages. In this way, the polyacrylamide (PAAm) was grafted onto the carrageenan (kC) backbone via free radical polymerization in the presence of methylene bisacrylamide (MBA) as cross-linker and Fe3O4 magnetic nanoparticles. Next, the kC-g-PAAm@Fe3O4 was modified by MOF-199 via an in-situ solvothermal approach. Several analyses such as Fourier transform infrared spectroscopy (FT-IR), X-Ray diffraction (XRD), field emission scanning electron microscopy (FESEM), energy-Dispersive X-ray Spectroscopy (EDX), thermogravimetric analysis (TGA), vibrating sample magnetometer (VSM), Brunauer-Emmett-Teller (BET) demonstrated the successful synthesis of kC-g-PAAm@Fe3O4-MOF-199 magnetic hydrogel nanocomposite. The XRD pattern of magnetic hydrogel nanocomposite illustrated characteristic peaks of Fe3O4, neat kC, and MOF-199 with enhanced crystallinity in comparison with kC-g-PAAm@Fe3O4. TGA showed it has a char yield of 24 wt% at 800 °C. VSM confirmed its superparamagnetic behavior (with Ms of 8.04 emu g-1), and the BET surface area of kC-g-PAAm@Fe3O4-MOF-199 was measured at 64.864 m2 g-1, which was higher than that of kC-g-PAAm@Fe3O4 due to the highly porous MOF-199 incorporation with a BET surface area of 905.12 m2 g-1). The adsorption effectiveness of kC-g-PAAm@Fe3O4-MOF-199 for eliminating cephalosporin and quinolones antibiotics, i.e., Cefixime (CFX) and Levofloxacin (LEV) from the aquatic area was considered. Several experimental setups were used to evaluate the efficacy of adsorption, such as solution pH, amount of adsorbent, contact duration, and initial concentration. The maximum adsorption capacity (Qmax) of the prepared magnetic hydrogel nanocomposite was found to be 2000 and 1666.667 mg-1 for LEV and CFX using employing 0.0025 g of adsorbent. The Freundlich isotherm model well described the experimental adsorption data with R2CFX = 0.9986, and R2LEV = 0.9939. And the adsorption kinetic data were successfully represented by the pseudo-second-order model with R2LEV = 0.9949 and R2CFX = 0.9906. Hydrogen bonding, π-π interaction, diffusion, and entrapment in the hydrogel network all contributed to the successful adsorption of both antibiotics onto the kC-g-PAAm@Fe3O4-MOF-199 adsorbent. Other notable physicochemical properties include the three-dimensional structure and availability of the reactive adsorption sites. Moreover, the adsorption/desorption efficacy of magnetic hydrogel nanocomposites was not significantly diminished after four cycles of recovery.

Antibacterial and antibiofilm effects of green synthesized selenium nanoparticles on clinical Klebsiella pneumoniae isolates.

Nanotechnology covers many disciplines, including the biological sciences. In this study, selenium nanoparticles (Se-NPs) were synthesized using Artemisia annua extract and investigated against clinical strains of klebsiella pneumoniae (K. pneumoniae) for their anti-biofilm effects. In this experimental study, from May 1998 to September 1998, 50 clinical samples of blood, urine, and sputum were collected, and K. pneumoniae strains were isolated using microbiological methods. Subsequently, the antibacterial effects of Se-NPs at concentrations of 12-25-50-100/5-6/3-25/125 µg/mL were studied. Finally, biofilm-producing strains were isolated, and the expression of mrkA biofilm gene was studied in real-time strains treated with Se-NPs using real-time polymerase chain reaction (PCR). Out of 50 clinical samples, 20 strains of K. pneumoniae were isolated. Minimum inhibitory concentration (MIC) results of Se-NPs showed that Se-NPs were capable of significant cell killing. Real-time PCR results also showed that mrkA gene expression was significantly reduced in strains treated with Se-NPs. According to this study, Se-NPs could reduce bacterial growth and biofilm formation, therefore, could be considered a candidate drug in the medical application for infections caused by K. pneumoniae.

CAR-T cell combination therapy: the next revolution in cancer treatment.

In recent decades, the advent of immune-based therapies, most notably Chimeric antigen receptor (CAR)-T cell therapy has revolutionized cancer treatment. The promising results of numerous studies indicate that CAR-T cell therapy has had a remarkable ability and successful performance in treating blood cancers. However, the heterogeneity and immunosuppressive tumor microenvironment (TME) of solid tumors have challenged the effectiveness of these anti-tumor fighters by creating various barriers. Despite the promising results of this therapeutic approach, including tumor degradation and patient improvement, there are some concerns about the efficacy and safety of the widespread use of this treatment in the clinic. Complex and suppressing tumor microenvironment, tumor antigen heterogeneity, the difficulty of cell trafficking, CAR-T cell exhaustion, and reduced cytotoxicity in the tumor site limit the applicability of CAR-T cell therapy and highlights the requiring to improve the performance of this treatment. With this in mind, in the last decade, many efforts have been made to use other treatments for cancer in combination with tuberculosis to increase the effectiveness of CAR-T cell therapy, especially in solid tumors. The combination therapy results have promising consequences for tumor regression and better cancer control compared to single therapies. Therefore, this study aimed to comprehensively discuss different cancer treatment methods in combination with CAR-T cell therapy and their therapeutic outcomes, which can be a helpful perspective for improving cancer treatment in the near future.

Oxytocin Prevents the Development of 3-NP-Induced Anxiety and Depression in Male and Female Rats: Possible Interaction of OXTR and mGluR2.

Huntington disease (HD) is a progressive neurological disorder with dominant motor symptoms. It also has psychiatric manifestations, like anxiety and depression, that can emerge themselves before motor symptoms and impose a major burden on patients. Oxytocin (OXT) is a newly emerged treatment for disorders like autism and schizophrenia and recently is using to alleviate depression and anxiety. In the current study, we investigated the behavioral and molecular effects of OXT on the development of anxiety and depression in 3-nitropropionic acid (3-NP)-induced model of HD. Anxiety- and depression-like behaviors as well as the levels of oxytocin receptor (OXTR), metabotropic glutamate receptor (mGluR) 2, mGluR5, and glutathione (GSH) were measured in striatum, hippocampus, prefrontal cortex, and amygdala. Also, we questioned if sex had any modulatory effect. We found that 3-NP increased anxiety and depression compared to controls. It also reduced the levels of OXTR and mGluR2, increased mGluR5, and reduced GSH in studied brain regions. Pretreatment with OXT before the injection of 3-NP ameliorated anxiety and depression. Additionally, it protected the brain from developing low levels of OXTR, mGluR2, and GSH and high levels of mGluR5 in studied regions. The protective effects of OXT were similar between male and female animals. These data suggest that OXTR, mGluR2, mGluR5, and GSH may contribute to psychiatric manifestations of HD. In addition, pretreatment with OXT could prevent the mood changes in male and female rats.

Cefixime-Containing Silica Nanoseeds Coated by a Hybrid PVA-Gold Network with a Cys-Arg Dipeptide Conjugation: Enhanced Antimicrobial and Drug Release Properties.

Therapeutic nano-bioconjugates (TNBCs) as an advanced class of drug delivery systems have attracted much attention due to more efficacy than the individual medications. Hence, in this study, a novel anti-infection TNBC system is designed based on highly porous silica nanoparticles, gold nanoparticles (AuNPs), and hybridized polyvinyl alcohol (PVA) for the efficient delivery of cefixime (CFM). Furthermore, a conjugation of cysteine-arginine (CR) dipeptide is made onto the surfaces for the enhancement of cell adhesion. Concisely, the AuNPs incorporated inside the PVA network play the key role in the controlled release process triggered by localized surface plasmon resonance (LSPR) heating. The drug content of the CFM-containing cargo (named as CFM@SiO2/PVA/Au-CR) and related release profile have been precisely studied by the confirmed analytical methods. Eventually, confocal microscopy on the stained cells has revealed that the TNBC particles are capable of entering the Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) bacterial cells better than the individual CFM. Also, optical density experiments (OD600) have corroborated that the prepared CFM@SiO2/PVA/Au-CR TNBC includes a high antimicrobial effect on K. pneumoniae and E. coli cells with (93.0 ± 1.5) % and (86.8 ± 1.0) % success rates, respectively, whereas the same dosage of the individual CFM has shown a lower effect on the cell growth rate. Also, estimation of minimum inhibitory/bactericidal concentrations (MIC/MBC) confirmed the enhanced antibacterial property of the CFM through the presented delivery method. Overall, this product is suggested to be clinically administrated instead of the individual CFM due to its high efficacy and containing lower dosage of the antibiotic drug.