Therapeutic potential of CRISPR/CAS9 genome modification in T cell-based immunotherapy of cancer.

Today, genome editing technologies like zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats (CRISPR) are being used in clinical trials and the treatment of diseases like acquired immunodeficiency syndrome (AIDS) and cancer. CRISPR stands out as one of the most advanced tools for genome editing due to its simplicity and cost-effectiveness. It can selectively modify specific locations in the genome, offering new possibilities for treating human diseases. The CRISPR system uses ribonucleic acid-deoxyribonucleic acid (RNA-DNA) recognition to combat infections, regulate gene expression, and treat cancer. Chimeric antigen receptor (CAR) T-cell therapy, which uses T lymphocytes to eliminate cancer cells, can be improved by combining it with CRISPR technology. However, there are challenges in using CAR-T cells, including a lack of quantity and quality, exhaustion, neurotoxicity, cytokine release syndrome (CRS), B cell aplasia, tumor lysis syndrome, and anaphylaxis. Preclinical studies on CRISPR-edited CAR-T cells show promising results and targeting detrimental regulatory genes can enhance cancer treatment in the future.

CRISPR-Cas9 technology: As an efficient genome modification tool in the cancer diagnosis and treatment.

Cancer is the second most common cause of death globally and is a major public health concern. Managing this disease is difficult due to its multiple stages and numerous genetic and epigenetic changes. Traditional cancer diagnosis and treatment methods have limitations, making it crucial to develop new modalities to combat the increasing burden of cancer. The clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system has transformed genetic engineering due to its simplicity, specificity, low cytotoxicity, and cost-effectiveness. It has been proposed as an effective technology to enhance cancer diagnosis and treatment strategies. This article presents the most recent discoveries regarding the structure, mechanism, and delivery methods of the highly powerful genome editing tool, CRISPR-Cas9. In terms of diagnosis, the article examines the role of CRISPR-Cas9 in detecting microRNAs and DNA methylation, and discusses two popular gene detection techniques that utilize the CRISPR-Cas system: DNA endonuclease-targeted CRISPR trans reporter and specific high sensitivity enzymatic reporter unlocking. Regarding treatment, the article explores several genes that have been identified and modified by CRISPR-Cas9 for effective tumorigenesis of common cancers such as breast, lung, and colorectal cancer. The present review also addresses the challenges and ethical issues associated with using CRISPR-Cas9 as a diagnostic and therapeutic tool. Despite some limitations, CRISPR-Cas9-based cancer diagnosis has the potential to become the next generation of cancer diagnostic tools, and the continuous progress of CRISPR-Cas9 can greatly aid in cancer treatment.

The association between quality of life and diabetes: the Bushehr Elderly Health Program.

BACKGROUND AND OBJECTIVE: Considering the importance of diabetes and its increased prevalence with aging, this study aimed to evaluate the association between diabetes status and quality of life (QOL) and the determining factors in individuals over 60. METHODS: Two thousand three hundred seventy-five individuals including 819 (34.5%) with diabetes, aged 69.4 ± 6.4, from Bushehr Elderly Health Program (BEHP) were enrolled. We categorized the participants as non-diabetic, controlled diabetic, and poorly controlled diabetic. The QOL was assessed using the SF-12 questionnaire. The physical (PCS) and mental (MCS) component summaries of QOL were estimated. We compared the SF-12 domains and components between the categories using ANOVA. Further, the association of diabetes status with PCS and MCS was assessed after adjustment for possible confounders including age, sex, depression, cognitive impairment, physical activity, and other relevant factors using linear regression analysis. RESULTS: Individuals with diabetes had lower PCS (40.9 ± 8.8 vs. 42.7 ± 8.6, p-value < 0.001), and MCS scores (45.0 ± 10.2 vs. 46.4 ± 9.4, p-value < 0.001) compared to participants without diabetes. No significant differences were observed in PCS or MCS scores between controlled or poorly controlled individuals with diabetes. Diabetes status was associated with PCS and MCS scores in univariable analysis. Regarding physical component of QOL, after adjusting for other confounders, poorly controlled diabetes was significantly associated with PCS [beta: -1.27 (-2.02, -0.52)]; some other determinants include depression [-7.66 (-8.51, -6.80)], male sex [3.90 (3.24,4.57)], and good physical activity [1.87 (1.17,2.57)]. As for the mental component, controlled diabetes was significantly associated with MCS [-1.17 (-2.13, -0.22)]; other contributing factors include depression [-14.35 (-15.34, -13.37)], male sex [1.97 (1.20,2.73)], good physical activity [-1.55 (-2.35, -0.75)], and smoking [-1.42 (-2.24, -0.59)]. BMI had an inverse association with PCS [-0.19 (-0.26, -0.13)] and a direct association with MCS [0.14 (0.07,0.21)]. CONCLUSION: Individuals with diabetes exhibited reduced QOL scores. Upon adjusting for other variables, it was found that uncontrolled diabetes correlated with decreased PCS scores, whereas controlled diabetes was linked to lower MCS scores. Factors such as depression and being female were identified as contributors to diminished QOL in both physical and mental aspects. These results have the potential to guide healthcare decision-making, facilitating the creation of tailored interventions aimed at improving the QOL for individuals with diabetes, with a specific focus on women and depression.

Engineering Heat Transport Across Epitaxial Lattice-Mismatched van der Waals Heterointerfaces.

Artificially engineered 2D materials offer unique physical properties for thermal management, surpassing naturally occurring materials. Here, using van der Waals epitaxy, we demonstrate the ability to engineer extremely insulating thermal metamaterials based on atomically thin lattice-mismatched Bi2Se3/MoSe2 superlattices and graphene/PdSe2 heterostructures with exceptional thermal resistances (70-202 m2 K/GW) and ultralow cross-plane thermal conductivities (0.012-0.07 W/mK) at room temperature, comparable to those of amorphous materials. Experimental data obtained using frequency-domain thermoreflectance and low-frequency Raman spectroscopy, supported by tight-binding phonon calculations, reveal the impact of lattice mismatch, phonon-interface scattering, size effects, temperature, and interface thermal resistance on cross-plane heat dissipation, uncovering different thermal transport regimes and the dominant role of long-wavelength phonons. Our findings provide essential insights into emerging synthesis and thermal characterization methods and valuable guidance for the development of large-area heteroepitaxial van der Waals films of dissimilar materials with tailored thermal transport characteristics.

Surveying haemoperfusion impact on COVID-19 from machine learning using Shapley values.

BACKGROUND: Haemoperfusion (HP) is an innovative extracorporeal therapy that utilizes special cartridges to filter the blood, effectively removing pro-inflammatory cytokines, toxins, and pathogens in COVID-19 patients. This retrospective cohort study aimed to assess the clinical benefits of HP for severe COVID-19 cases using Shapley values for machine learning models. METHODS: The research involved 578 inpatients (≥ 20 years old) admitted to Baqiyatallah hospital (Tehran, Iran). The control group (359 patients) received standard treatment, including high doses of corticosteroids (a single 500 mg methylprednisolone pulse, followed by 250 mg for 2 days), categorized as regimen (I). On the other hand, the HP group (219 patients) received regimen II, consisting of the same corticosteroid treatment (regimen I) along with haemoperfusion using Cytosorb H300. The frequency of haemoperfusion sessions varied based on the type of lung involvement determined by chest CT scans. In addition, the value function v defines the Shapley value of the i th feature for the query point x , where the input matrix features represent individual characteristics, drugs, and history and clinical conditions of the patient. RESULTS: Our data showed a favorable clinical response in the HP group compared to the control group. Notably, one-to-three sessions of HP using the CytoSorb® 300 cartridge led to reduced ventilation requirements and mortality rates in severe COVID-19 patients. Shapley values were calculated to evaluate the contribution of haemoperfusion among other factors, such as side effects, medications, and individual characteristics, to COVID-19 patient outcomes. In addition, there is a significant difference between the two groups among the treatments and medications used remdesivir, adalimumab, tocilizumab, favipiravir, Interferon beta-1a, enoxaparin prophylaxis, enoxaparin full dose, heparin prophylaxis, and heparin full dose (P < 0.05). It seems that haemoperfusion has a positive impact on the reduction of inflammation markers and renal functional such as ferritin and creatinine, respectively, as well as D-dimer and WBC levels in the HP group were significantly lower than the control group. CONCLUSION: The findings indicated that haemoperfusion played a crucial role in predicting patient survival, making it a significant feature in classifying patients' prognoses.

Effect of multifactorial free and liposome-coated of bay laurel (Laurus nobilis) and rosemary (Salvia rosmarinus) extracts on the behavior of Listeria monocytogenes and Vibrio parahaemolyticus in silver carp (Hypophthalmichthys molitrix) stored at 4 °C.

In this study, the effect of bay laurel (Laurus nobilis) (LE) and rosemary (Salvia rosmarinus) (RE) extracts, in two free forms and loaded with liposome, on the behavior of Listeria monocytogenes and Vibrio parahaemolyticus in silver carp (Hypophthalmichthys molitrix) minced, were examined. After extraction, the extracts were evaluated for phenolic, flavonoid, and antibacterial compounds (determination of MIC and MBC). The treatments studied included control treatment, treatments containing 1 and 1.5% of free extracts, and treatments containing 1 and 1.5% of liposome-coated extracts of LE and RE which were examined at times of 0, 4, 8, and 12 days with 3 replications. The findings indicated that the amount of flavonoid and phenolic compounds and the results of antibacterial tests (MIC and MBC tests) in RE extract were more favorable than LE extract. The aqueous extract of rosemary had higher levels of phenolic (344.66 mg gallic acid/g extract) and flavonoid (245.33 mg Catechin/g extract) compounds compared to the bay laurel extract (257.66 mg gallic acid/g extract) and (151.26 mg Catechin/g extract) respectively. The results of the behavior of L. monocytogenes and V. parahaemolyticus in fish showed that with increasing the storage time at 4 °C, these parameters increased, but in the treatment containing the coated forms of LE and RE extracts (concentration 1.5%), changes were significantly slower than other treatments. According to the obtained results, it can be concluded that in general, adding extracts of bay laurel and rosemary in a concentration of 1.5% reduces the proliferation of bacteria that cause food poisoning.

Comprehensive study of moiré deflectometry based on diffraction order filtering of fringes.

This paper presents a detailed investigation of the theory of moiré deflectometry through a comprehensive analysis of the higher-order diffraction of moiré fringes. We demonstrate the possibility of achieving always-high-resolution moiré fringes regardless of Ronchi grating positions and Talbot distance by filtering out the even diffraction orders of moiré fringes. Our theoretical studies lead to a comprehensive formulation of this technique, revealing the high potential of moiré deflectometry towards more precise measurement.

Genetically engineered E. coli invade epithelial cells and transfer their genetic cargo into the cells: an approach to a gene delivery system.

PURPOSE: Despite advances in gene therapy, the lack of safe and efficient gene delivery systems limited the clinical effectiveness of gene therapy. Due to the inherent potential of bacteria, they can be considered as a good option for the gene transfer system. This study aimed to create a genetically engineered bacterium capable of entering epithelial cells and transferring its genetic cargo to the cell's cytoplasm, eventually expressing the gene of interest in the cell. METHODS: The invasin (inv) gene from Yersinia pseudotuberculosis and the listeriolysin (hlyA) gene from Listeria monocytogenes were isolated by PCR assay and inserted into a pACYCDuet-1 vector. The recombinant plasmid was then transformed into E. coli strain BL21. Subsequently, pEGFP-C1 plasmids containing a CMV promoter were transformed into the engineered bacteria. Finally, the engineered bacteria containing the reporter genes were incubated with the HeLa and LNCaP cell lines. Fluorescence microscopy, flow cytometry, and TEM were used to monitor bacterial entry into the cells and gene expression. We used native E. coli strain BL21 as a control. RESULTS: A fluorescence microscope showed that, in contrast to the control group, the manipulated E. coli were able to penetrate the cells and transport the plasmid pEGFP-C1 to the target cells. Flow cytometry also showed fluorescence intensity of 54.7% in HeLa cells and 71% in LNCaP cells, respectively. In addition, electron micrographs revealed the presence of bacteria in the cell endosomes and in the cytoplasm of the cells. CONCLUSION: This study shows that genetically engineered E. coli can enter cells, transport cargo into cells, and induce gene expression in the target cell. In addition, flow cytometry shows that the gene transfer efficiency was sufficient for protein expression.

Assessment of Risk Factors and Clinical Outcomes in Hospitalized COVID-19 Patients with Candida spp. Co-infections: Species Distribution and Antifungal Susceptibility Patterns of Isolates.

INTRODUCTION: Fungal co-infections are considered an important complication in hospitalized patients with SARS-CoV-2 that can be attributed to disease aggravation, increased mortality, and poor outcomes. This study was conducted to determine the species distribution and antifungal susceptibility patterns of Candida isolates from hospitalized COVID-19 patients in Shiraz, Iran, in addition to associated risk factors and outcomes of co-infections with Candida species. MATERIALS AND METHODS: In this single-center study, a total of 106 hospitalized COVID-19 patients were evaluated for clinical characteristics and outcomes. Species identification was performed by ITS1-5.8S-ITS2 gene sequencing. Antifungal susceptibility testing to fluconazole, itraconazole, voriconazole, posaconazole, caspofungin, amphotericin B, and nystatin was determined according to the M27-A3/S4 CLSI protocol. RESULTS: Candida species were recovered from 48% (51/106) of hospitalized COVID-19 patients. Statistical analysis showed that patients who had heart failure, bacterial co-infection, and were receiving empirical antifungal therapy had a higher risk of developing Candida co-infection. In total, 71 Candida isolates were recovered, of which C. albicans (69%) was the most prevalent isolate. The majority of the Candida isolates were susceptible to all classes of tested antifungal drugs. DISCUSSION: Our results elucidate a high rate of Candida co-infections among hospitalized COVID-19 patients. Comorbidities such as heart failure, HTN, COPD, bacterial infections as well as therapeutic interventions including catheterization, mechanical ventilation, and ICU admission increased the risk of Candida spp. isolation from the bloodstream, respiratory tract and urine samples, which led to a higher in-hospital mortality rate. Additionally, obtained data clarified that empirical antifungal therapy was not as successful as anticipated.

Anchoring ZnO on spinel cobalt ferrite for highly synergic sono-photo-catalytic, surfactant-assisted PAH degradation from soil washing solutions.

In this study, the photocatalytic activity of ZnO was effectively improved via its combination with spinel cobalt ferrite (SCF) nanoparticles. The catalytic performance of ZnO@SCF (ZSCF) was investigated in coupling with UV irradiation and ultrasound (US), as a heterogeneous sono-photocatalytic process, for the decontamination of phenanthrene (PHE) from contaminated soil. Soil washing tests were conducted in a batch environment, after extraction assisted by using Tween 80. Several characterization techniques such as XRD, FESEM-EDS, BET, TEM, UV-vis DRS, PL and VSM were utilized to determine the features of the as-prepared catalysts. ZSCF showed an excellent catalytic activity toward degradation of PHE in the presence of US and UV with a significant synergic effect. It was found that more than 93% of PHE (35 mg/L) and 87.5% of TOC could be eliminated by the integrated ZSCF/US/UV system under optimum operational conditions (pH: 8.0, ZSCF: 1.5 g/L, UV power: 6.0 W and US power: 70 W) within 90 min of reaction. After five times of use, ZSCF illustrated good reusability in the decontamination of PHE (87%) and TOC (79%). Quenching tests revealed the contribution of h+, HO• and e- species during PHE degradation over ZSCF/UV/US and an S-scheme photocatalytic mechanisms was proposed for the possible charge transfer routes under the ZSCF system. This study provides the important role of SCF in enhancing the ZnO photocatalytic activity due to its high performance, easy recovery and excellent durability, which it make an efficient and promising catalyst in environmental clean-up applications.

Spinel cobalt ferrite-based porous activated carbon in conjunction with UV light irradiation for boosting peroxymonosulfate oxidation of bisphenol A.

Developing heterogeneous catalysts with high performance for peroxymonosulfate (PMS) activation to decontaminate organic pollutants from wastewater is of prominent importance. In this study, spinel cobalt ferrite (CoFe2O4) materials were coated on the surface of powdered activated carbon (CoFe2O4@PAC) via the facile co-precipitation method. The high specific surface area of PAC was beneficial for the adsorption of both bisphenol A (BP-A) and PMS molecules. The CoFe2O4@PAC-mediated PMS activation process under UV light could effectively eliminate 99.4% of the BP-A within 60 min of reaction. A significant synergy effect was attained between CoFe2O4 and PAC towards PMS activation and subsequent elimination of BP-A. Comparative tests demonstrated that the heterogeneous CoFe2O4@PAC catalyst had a better degradation performance in comparison with its components and homogeneous catalysts (Fe, Co, and, Fe + Co ions). The formed by-products and intermediates during BP-A decontamination were evaluated using LC/MS analysis, and then a possible degradation pathway was proposed. Moreover, the prepared catalyst exhibited excellent performance in recyclability with slight leaching amounts of Co and Fe ions. A TOC conversion of 38% was obtained after five consecutive reaction cycles. It can be concluded that the PMS photo-activation process via the CoFe2O4@PAC catalyst can be utilized as an effective and promising method for the degradation of organic contaminants from polluted-water resources.

The functional impact of home-based self-rehabilitation following arthroscopic meniscus root repair.

BACKGROUND: Corona virus infectious pandemic makes outdoors rehabilitation a potential hazard. Patient education to perform simple home-based exercises seems to be an interesting and sometimes a mandatory option. This study provides a comparison between the conventional and home-based virtual rehabilitation after surgical repair of medial meniscus root tears. METHODS: In this prospective study, all patients who underwent medial meniscus posterior root repair with a modified trans-tibial pull-out technique from March 2019 to March 2021 were evaluated. Those who underwent surgery after December 2019 were trained to perform self-rehabilitation. The rest had undergone outdoors specialized rehabilitation according to a unified protocol and these were used as a historical control group. All patients were followed up for a minimum of 2 year after surgery. Final Lysholm scores were utilized to compare functional outcomes after considering the effect of age, body mass index and time from surgery by multivariate linear regression analysis. RESULTS: Forty-three consecutive patients with medial meniscal root tears were studied. Thirty-nine (90.7%) were women and 4 (9.3%) were men. The mean age of participants was 53.2 ± 8.1 years. The total Lysholm knee score, and all its items were significantly improved in both groups at a two-year follow-up (p < 0.05), except the "Using cane or crutches" item (p = 0.065). Nevertheless, the final Lysholm knee score improvement was higher in patients who performed outdoors specialized rehabilitation and in patients with shorter time-to-surgery. CONCLUSION: Regardless of age and gender, home-based rehabilitation after meniscal root repair with the modified trans-tibial pull-out technique improved the patients' function at a two-year follow-up. Nonetheless, this effect was still significantly lower than that of the outdoors specialized rehabilitation. Future work is required to clarify basic protocols for home-based tele-rehabilitation programs and determine clinical, radiological and functional results. LEVEL OF EVIDENCE: Level IV, therapeutic, historically controlled study.

Schemes for Single Electron Transistor Based on Double Quantum Dot Islands Utilizing a Graphene Nanoscroll, Carbon Nanotube and Fullerene.

The single electron transistor (SET) is a nanoscale switching device with a simple equivalent circuit. It can work very fast as it is based on the tunneling of single electrons. Its nanostructure contains a quantum dot island whose material impacts on the device operation. Carbon allotropes such as fullerene (C60), carbon nanotubes (CNTs) and graphene nanoscrolls (GNSs) can be utilized as the quantum dot island in SETs. In this study, multiple quantum dot islands such as GNS-CNT and GNS-C60 are utilized in SET devices. The currents of two counterpart devices are modeled and analyzed. The impacts of important parameters such as temperature and applied gate voltage on the current of two SETs are investigated using proposed mathematical models. Moreover, the impacts of CNT length, fullerene diameter, GNS length, and GNS spiral length and number of turns on the SET's current are explored. Additionally, the Coulomb blockade ranges (CB) of the two SETs are compared. The results reveal that the GNS-CNT SET has a lower Coulomb blockade range and a higher current than the GNS-C60 SET. Their charge stability diagrams indicate that the GNS-CNT SET has smaller Coulomb diamond areas, zero-current regions, and zero-conductance regions than the GNS-C60 SET.

Energy, Exergy, Exergoeconomic and Emergy-Based Exergoeconomic (Emergoeconomic) Analyses of a Biomass Combustion Waste Heat Recovery Organic Rankine Cycle.

In recent decades, there has been an increasing trend toward the technical development of efficient energy system assessment tools owing to the growing energy demand and subsequent greenhouse gas emissions. Accordingly, in this paper, a comprehensive emergy-based exergoeconomic (emergoeconomic) method has been developed to study the biomass combustion waste heat recovery organic Rankine cycle (BCWHR-ORC), taking into account thermodynamics, economics, and sustainability aspects. To this end, the system was formulated in Engineering Equation Solver (EES) software, and then the exergy, exergoeconomic, and emergoeconomic analyses were conducted accordingly. The exergy analysis results revealed that the evaporator unit with 55.05 kilowatts and the turbine with 89.57% had the highest exergy destruction rate and exergy efficiency, respectively. Based on the exergoeconomic analysis, the cost per exergy unit (c), and the cost rate (C˙) of the output power of the system were calculated to be 24.13 USD/GJ and 14.19 USD/h, respectively. Next, by applying the emergoeconomic approach, the monetary emergy content of the system components and the flows were calculated to evaluate the system's sustainability. Accordingly, the turbine was found to have the highest monetary emergy rate of capital investment, equal to 5.43×1012 sej/h, and an output power monetary emergy of 4.77×104 sej/J. Finally, a sensitivity analysis was performed to investigate the system's overall performance characteristics from an exergoeconomic perspective, regarding the changes in the transformation coefficients (specific monetary emergy).

Resistance to tetracyclines among clinical isolates of Mycoplasma hominis and Ureaplasma species: a systematic review and meta-analysis.

BACKGROUND: Resistance to tetracyclines, the first-line treatment for urogenital infections caused by Mycoplasma hominis and Ureaplasma species, is increasing worldwide. The aim of the present study was to determine the global status of resistance to this class of antibiotics. METHODS: Electronic databases were searched using keywords including 'Mycoplasma', 'Mycoplasma hominis', 'M. hominis', 'Ureaplasma', 'Ureaplasma urealyticum', 'Ureaplasma parvum', 'U. urealyticum', 'U. parvum', 'Ureaplasma species', 'resistance', 'antibiotic resistance', 'antibiotic susceptibility', 'antimicrobial resistance', 'antimicrobial susceptibility', 'tetracycline', 'doxycycline' and 'minocycline'. Finally, after some exclusions, 37 studies from different countries were included in the study and meta-analysis was performed on the data collected. RESULTS: The midrange resistance rates for M. hominis and U. urealyticum/parvum to tetracycline, doxycycline and minocycline were 50.0%, 9.0% and 16.7% and 43.3%, 28.6% and 9.0%, respectively. A high level of heterogeneity was observed in all studies (I2 > 50%, P value < 0.05), except those representing doxycycline resistance in M. hominis isolates (I2 = 39.1%, P  = 0.02). No evidence of publication bias was observed in the studies and neither Egger's test nor Begg's test showed significant publication bias. CONCLUSIONS: The results of the present study show that the overall resistance to tetracyclines is relatively high and prevalent among M. hominis and Ureaplasma species throughout the world. This highlights the importance of and necessity for regional and local antibiotic susceptibility testing before treatment choice as well as development of newer generations of tetracyclines to prevent antibiotic misuse, emergence and spread of resistant strains and, finally, the failure of treatment.

Exposure to waterpipe smoke and blood heavy metal concentrations.

Waterpipe (WP) smoking is a global phenomenon, with the most consumers in Middle East countries and China. Heavy metals exposure related to WP smoking has been associated with many adverse health effects. However, the association of lifestyle factors and smoking habits with blood heavy metals concentration in WP smokers is unclear yet. Therefore, we aimed to investigate the relationship of lifestyle factors (i.e., diet and physical activity) and smoking habits (i.e., duration of the use of WP and times of smoking WP per week) with blood concentrations of lead (Pb) and cadmium (Cd). This cross-sectional study was based on 86 WP smokers in Khalkhal, Iran (2018). Graphite furnace atomic absorption spectrometry (GFAAS) was used to measure heavy metals. The median (interquartile range (IQR)) of Pb and Cd concentrations were 39 (24) and 1.3 (1.2) µg/L. The blood Pb and Cd levels were significantly higher in participants with lower education level (P-value = 0.049 and 0.041, respectively). An IQR increase in physical activity per week was associated with -0.12 µg/L (95% confidence interval (CI): -0.23, -0.01, P-value = 0.04) decrease in Pb concentration. An increase in the times of consuming fruit per week was negatively associated with the concentration of Cd. Overall, our findings suggested that physical activity and healthy diet have been associated with lower blood heavy metal concentrations in WP smokers; however, further studies are needed to confirm these findings.

Genetic diversity of healthcare-associated methicillin-resistant Staphylococcus aureus isolates from Southern Iran.

Staphylococcus aureus is a common pathogen causing hospital infections. The increasing rate of healthcare-associated infections caused by methicillin-resistant Staphylococcus aureus (MRSA) in developing countries has led to many public health problems. This study aimed to investigate the molecular epidemiology as well as the antibiotic resistance pattern of clinical isolates of MRSA from Southern Iran. A total of 135 S. aureus isolates were collected from the patients referred to three hospitals in South Iran. The phenotypic and genotypic diagnosis of MRSA isolates was performed by disk diffusion and PCR methods, respectively. The antibiotic resistance pattern for MRSA isolates was performed using Kirby-Bauer method. The molecular epidemiology of isolates was performed by MLST, Spa typing and SCCmec typing. From 135 S. aureus isolates, 50 (37%) MRSA strains were detected from which two different sequence types including ST239 and ST605 were identified. SCCmec type III was the most common profile (50%) and t030 was the predominant spa type (48%) among the strains. The MRSA isolates had the highest resistance to penicillin (100%), tetracycline (88%), levofloxacin (86%), ciprofloxacin (84%), erythromycin (82%), gentamicin (80%), and clindamycin (78%). The results of this study show that the most common genetic type among the MRSA isolates was ST239-SCCmec III/t030. The rapid and timely detection of MRSA and the administration of appropriate antibiotics according to the published antibiotic resistance patterns are essential. Furthermore, the continuous and nationwide MRSA surveillance studies are necessary to investigate clonal distribution and spreading of MRSA from community to hospitals.

In vitro bioaccessibility, phase partitioning, and health risk of potentially toxic elements in dust of an iron mining and industrial complex.

Dust emitted from mining, ore processing, and tailing dumps have direct effects on miners who work close to these operations. The Gol-E-Gohar (GEG) mining and industrial company is one of the most important iron concentrate producers in the Middle East. The objective of the present study was to estimate the distribution, fractionation, and oral bioaccessibility of potentially toxic elements (PTEs) in dust generated by the GEG mining and industrial company. Total PTE content including Al, As, Cd, Co, Cr, Cu, Fe, Hg, Mn, Mo, Ni, Pb, V, and Zn was quantified for suspended particulate matter (PM) in PM2.5, PM10, and total suspended particulate matter (TSP). As, Cd, Co, Cu, Fe, Ni, and Pb were quantified in fallout dust samples for oral bioaccessibility using in vitro Unified BARGE (UBM) Method and modified BCR fractionation analysis. Enrichment factors (EF) were calculated for the studied elements in PM; Cu, Fe, and As were found to be extremely enriched. Oral bioaccessibility of selected PTEs in fallout dust samples ranged from 0.35% to 41.55% and 0.06-37.58% in the gastric and intestinal phases, respectively. Regression modeling revealed that the bioaccessibilities of the PTEs could mostly be explained by total concentrations in dust particles. Average daily intake (ADI) calculations revealed that the intake of PTEs did not exceed the tolerable daily intake (TDI) values and as such was not considered a significant risk to workers. Additionally, the hazard quotients (HQ) and carcinogenic risk (CR) values were lower than the acceptable level. This study can provide further risk assessment and management of PTE pollution in occupational environments.

Randomized double-blind clinical trial examining the Ellagic acid effects on glycemic status, insulin resistance, antioxidant, and inflammatory factors in patients with type 2 diabetes.

Oxidative stress can worsen glycemic status. Considering the antioxidant properties of Ellagic acid (EA), this study was designed to evaluate the effect of EA on glycemic indices, lipid profile, oxidative stress, and inflammation status in type 2 diabetic patients. Overall, 44 patients were recruited and were randomly allocated consumed 180 mg of EA per day (n = 22) or placebo (n = 22) for 8 weeks. The blood sugar (BS), insulin, insulin resistance (IR), hemoglobin A1c (HbA1 c), total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), total antioxidant capacity (TAC), malondialdehyde (MDA), the activity of glutathione peroxidase (GPx) and superoxide dismutase (SOD), C-reactive protein (CRP), TNF-α and interleukin 6 (IL-6) were measured at the beginning and end of the study. At the end of the study, the mean of BS, insulin, IR, HbA1 c, TC, TG, LDL, MDA, CRP, TNF-α, and IL-6 were significantly decreased in the intervention group (p < .05). Also, the mean of TAC (+0.8 ± 0.01) and activity of GPx (+10.26 ± 0.22) and SOD enzymes (+459.6 ± 9.76) significantly increased in the intervention group (p < .05). EA supplementation can be helpful as a diet supplement in patients with type 2 diabetes through improvement in chronic adverse effects.

The interaction of phages and bacteria: the co-evolutionary arms race.

Since the dawn of life, bacteria and phages are locked in a constant battle and both are perpetually changing their tactics to overcome each other. Bacteria use various strategies to overcome the invading phages, including adsorption inhibition, restriction-modification (R/E) systems, CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated proteins) systems, abortive infection (Abi), etc. To counteract, phages employ intelligent tactics for the nullification of bacterial defense systems, such as accessing host receptors, evading R/E systems, and anti-CRISPR proteins. Intense knowledge about the details of these defense pathways is the basis for their broad utilities in various fields of research from microbiology to biotechnology. Hence, in this review, we discuss some strategies used by bacteria to inhibit phage infections as well as phage tactics to circumvent bacterial defense systems. In addition, the application of these strategies will be described as a lesson learned from bacteria and phage combats. The ecological factors that affect the evolution of bacterial immune systems is the other issue represented in this review.