Impact of Inspiratory Muscle Training and Positive Expiratory Pressure on Lung Function and Extubation Success of ICU Patients: a Randomized Controlled Trial.

Introduction: Preparing patients for extubation from mechanical ventilation (MV) necessitates focused respiratory muscle strengthening. This study aimed to evaluate the effect of threshold inspiratory muscle training (IMT) and positive expiratory pressure (PEP) exercises on outcomes of patients who underwent MV in intensive care unit (ICU). Methods: This randomized controlled trial was conducted in 2023 at the ICUs of Imam Reza Hospital, Mashhad, Iran. Participants were allocated to either intervention or control group (each comprising 35 patients) through block randomization. The intervention group received standard daily chest physiotherapy as well as targeted inspiratory and expiratory muscle strengthening exercises using the threshold IMT/PEP device, administered twice daily over one week. The control group received standard daily chest physiotherapy alone. Finally, the outcomes (lung compliance, duration of intubation, extubation success rate, and diaphragmatic metrics) of the two groups were compared. Results: 70 patients with the mean age of 56.10 ± 14.15 (range: 28.00-85.00) years were randomly divided into two groups (50% male). Significant improvements were observed in the intervention group regarding pulmonary compliance values (35.62 ± 4.43 vs. 30.85 ± 6.93; p= 0.001), peak expiratory flow (PEF) (55.20 ± 10.23 vs. 47.80 ± 11.26; p = 0.002), and maximum inspiratory pressure (MIP) (33.40 ± 4.25 vs. 30.08 ± 6.08; p = 0.01) compared to the control group. Diaphragm inspiratory thickness (0.29 ± 0.03 vs. 0.26 ± 0.04; p = 0.001), diaphragm expiratory thickness (0.22 ± 0.03 vs. 0.20 ± 0.04; p = 0.006) and motion (1.61 ± .29 vs. 1.48 ± .21; p = 0.04) also exhibited significant differences between the two groups. Extubation success rate was higher in the intervention group (68.60% vs. 40%; p = 0.01). The duration of mechanical ventilation was 15.14±7.07 days in the intervention group and 17.34±7.87 days in the control group (p = 0.20). The mean extubation time was 7.00 ± 1.88 days for the intervention group and 9.00 ± 2.00 days for the control (p < 0.001). Conclusion: Threshold IMT/PEP device exercises effectively enhance respiratory muscle strength, diaphragm thickness, and reduce ventilator dependency. These findings support their potential for inclusion in rehabilitation programs for ICU patients.

Association of new onset seizure and COVID-19 vaccines and long-term follow-up: A systematic review and meta-analysis.

OBJECTIVE: Seizures have been reported as an adverse event of the COVID-19 vaccine. However, there is no solid evidence of increased seizure occurrence compared to the general population. This study was undertaken to investigate seizure occurrence among COVID-19 vaccine recipients compared to unvaccinated controls. METHODS: A systematic search was made of PubMed, Web of Science, Scopus, and Cochrane Library up to April 9, 2024. Studies reporting seizure occurrence following COVID-19 vaccination were included. This study is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework and was conducted using random- and common-effect models. The risk of bias in the studies was evaluated by the Newcastle-Ottawa Scale. The outcome of interest was new onset seizure incidence proportion compared among (1) COVID-19 vaccine recipients, (2) unvaccinated cohorts, and (3) various types of COVID-19 vaccines. RESULTS: Forty studies were included, of which seven entered the meta-analysis. Results of the pooled analysis of the new onset seizure incidence (21- or 28-day period after vaccination) in 13 016 024 vaccine recipients and 13 013 262 unvaccinated individuals by pooling the cohort studies did not show any statistically significant difference between the two groups (odds ratio [OR] = .48, 95% confidence interval [CI] = .19-1.20, p = .12, I2 = 95%, τ2 = .7145). Pooling four studies accounting for 19 769 004 mRNA versus 47 494 631 viral vector vaccine doses demonstrated no significant difference in terms of new onset seizure incidence between the groups (OR = 1.18, 95% CI = .78-1.78, p = .44, I2 = 0%, τ2 = .004). SIGNIFICANCE: This systematic review and meta-analysis shows no statistically significant difference in the risk of new onset seizure incidence between COVID-19 vaccinated individuals and unvaccinated individuals.

SIRPα engagement regulates ILC2 effector function and alleviates airway hyperreactivity via modulating energy metabolism.

Group-2 innate lymphoid cells (ILC2) are part of a growing family of innate lymphocytes known for their crucial role in both the development and exacerbation of allergic asthma. The activation and function of ILC2s are regulated by various activating and inhibitory molecules, with their balance determining the severity of allergic responses. In this study, we aim to elucidate the critical role of the suppressor molecule signal regulatory protein alpha (SIRPα), which interacts with CD47, in controlling ILC2-mediated airway hyperreactivity (AHR). Our data indicate that activated ILC2s upregulate the expression of SIRPα, and the interaction between SIRPα and CD47 effectively suppresses both ILC2 proliferation and effector function. To evaluate the function of SIRPα in ILC2-mediated AHR, we combined multiple approaches including genetically modified mouse models and adoptive transfer experiments in murine models of allergen-induced AHR. Our findings suggest that the absence of SIRPα leads to the overactivation of ILC2s. Conversely, engagement of SIRPα with CD47 reduces ILC2 cytokine production and effectively regulates ILC2-dependent AHR. Furthermore, the SIRPα-CD47 axis modulates mitochondrial metabolism through the JAK/STAT and ERK/MAPK signaling pathways, thereby regulating NF-κB activity and the production of type 2 cytokines. Additionally, our studies have revealed that SIRPα is inducible and expressed on human ILC2s, and administration of human CD47-Fc effectively suppresses the effector function and cytokine production. Moreover, administering human CD47-Fc to humanized ILC2 mice effectively alleviates AHR and lung inflammation. These findings highlight the promising therapeutic potential of targeting the SIRPα-CD47 axis in the treatment of ILC2-dependent allergic asthma.

CB2 stimulation of adipose resident ILC2s orchestrates immune balance and ameliorates type 2 diabetes mellitus.

Development of type 2 diabetes mellitus (T2DM) is associated with low-grade chronic type 2 inflammation and disturbance of glucose homeostasis. Group 2 innate lymphoid cells (ILC2s) play a critical role in maintaining adipose homeostasis via the production of type 2 cytokines. Here, we demonstrate that CB2, a G-protein-coupled receptor (GPCR) and member of the endocannabinoid system, is expressed on both visceral adipose tissue (VAT)-derived murine and human ILC2s. Moreover, we utilize a combination of ex vivo and in vivo approaches to explore the functional and therapeutic impacts of CB2 engagement on VAT ILC2s in a T2DM model. Our results show that CB2 stimulation of ILC2s protects against insulin-resistance onset, ameliorates glucose tolerance, and reverses established insulin resistance. Our mechanistic studies reveal that the therapeutic effects of CB2 are mediated through activation of the AKT, ERK1/2, and CREB pathways on ILC2s. The results reveal that the CB2 agonist can serve as a candidate for the prevention and treatment of T2DM.

Sperm epigenetics and male infertility: unraveling the molecular puzzle.

BACKGROUND: The prevalence of infertility among couples is estimated to range from 8 to 12%. A paradigm shift has occurred in understanding of infertility, challenging the notion that it predominantly affects women. It is now acknowledged that a significant proportion, if not the majority, of infertility cases can be attributed to male-related factors. Various elements contribute to male reproductive impairments, including aberrant sperm production caused by pituitary malfunction, testicular malignancies, aplastic germ cells, varicocele, and environmental factors. MAIN BODY: The epigenetic profile of mammalian sperm is distinctive and specialized. Various epigenetic factors regulate genes across different levels in sperm, thereby affecting its function. Changes in sperm epigenetics, potentially influenced by factors such as environmental exposures, could contribute to the development of male infertility. CONCLUSION: In conclusion, this review investigates the latest studies pertaining to the mechanisms of epigenetic changes that occur in sperm cells and their association with male reproductive issues.

A prediction of the CRNDE role by modulating NF-κB pathway in inflammatory bowel disease (IBD).

Long non-coding RNAs (lncRNAs) regulate multiple pathways and cellular mechanisms. Recent research has emphasized their involvement in the pathogenesis of complex diseases, such as Inflammatory Bowel Disease (IBD) which is characterized by chronic inflammation of the intestines. The two most common types of IBD are ulcerative colitis and Crohn's disease. CRNDE lncRNA was initially detected in colorectal cancer (CRC) and found to be involved in the tumorigenesis pathways. Further studies revealed the role of CRNDE in activating inflammation and promoting the release of inflammatory cytokines. This study utilizes the RNA-seq data analysis and bioinformatics tools to clarify the role of CRNDE in the IBD pathogenesis and confirms its expression in inflamed HT-29 and Caco-2 cell lines and also colonic and blood samples of UC patients and controls ex vivo. Based on our results, CRNDE was significantly upregulated in IBD samples compared to controls in RNA-seq data analysis and Real-time PCR of inflamed HT-29 cell line and colonic biopsies from UC patients. Additionally, predicted that its expression is positively correlated with the pro-inflammatory cytokines production. CRNDE interactions was investigated with several inflammation-related miRNAs and regulatory proteins computationally. Thus, CRNDE upregulation in the colon of IBD patients could be involved in IBD pathogenesis by promoting inflammatory pathways and targeting anti-inflammatory miRNAs.

Iron controls the development of airway hyperreactivity by regulating ILC2 metabolism and effector function.

Group 2 innate lymphoid cells (ILC2s) rapidly induce a type 2 inflammation in the lungs in response to allergens. Here, we focused on the role of iron, a critical nutritional trace element, on ILC2 function and asthma pathogenesis. We found that transferrin receptor 1 (TfR1) is rapidly up-regulated and functional during ILC2 activation in the lungs, and blocking transferrin uptake reduces ILC2 expansion and activation. Iron deprivation reprogrammed ILC2 metabolism, inducing a HIF-1α-driven up-regulation of glycolysis and inhibition of oxidative mitochondrial activity. Consequently, we observed that in vivo iron chelation or induction of hypoferremia reduced the development of airway hyperreactivity in experimental models of ILC2-driven allergic asthma. Human circulating ILC2s rapidly induced TfR1 during activation, whereas inhibition of iron uptake or iron deprivation reduced effector functions. Last, we found a negative relationship between circulating ILC2 TfR1 expression and airway function in cohorts of patients with asthma. Collectively, our studies define cellular iron as a critical regulator of ILC2 function.

CTNS Mutations Causing Autosomal Recessive Cystinosis in a Subset of Iranian Population: Report of Two New Variants.

Background: Nephropathic cystinosis (NC) is an uncommon autosomal recessive disease with abnormality in lysosomal storage that appearances in patients with mutations in the CTNS gene encoding a lysosomal transporter cystinosin. Disrupted function of this transporter is followed by accumulation of cysteine crystals in cells of many various organs. This study aimed to investigate the mutations of the CTNS gene in 20 Iranian patients suffering from NC. Materials and Methods: Twenty Iranian cystinosis patients referring to Imam Hossein Hospital of Isfahan were employed in this case-series study. After extraction of genomic DNA, the promoter and entire coding regions of CTNS were analysed using sanger sequencing in all patients. Gap-Polymerase Chain Reaction was used to detect 57 kb deletion in the CTNS gene. In silico study was performed to analyse variants. Results: The large deletion was not seen in any NC patients. Molecular analysis which conducted to screen the CTNS gene of patients, identified eight different mutations, including two new mutations, c.971_972insC and c.956_956delA, which have not been reported before, and c.681G>A mutation, which was identified as a frequently founded mutation in the Middle East and was observed in 35% of patients. In this study, five other mutations including c.1015G>A, c.922G>A, c.323_323delA, c.433C>T, and c.18_21delGACT were also observed, which have been reported in previous studies. Conclusion: The mutational spectrum in the Iranian patients is the same as previously reported mutations except that two new mutations were found. The present findings will present suggestions for regular molecular diagnosis of cystinosis in Iran.

Piezo1 channels restrain ILC2s and regulate the development of airway hyperreactivity.

Mechanosensitive ion channels sense force and pressure in immune cells to drive the inflammatory response in highly mechanical organs. Here, we report that Piezo1 channels repress group 2 innate lymphoid cell (ILC2)-driven type 2 inflammation in the lungs. Piezo1 is induced on lung ILC2s upon activation, as genetic ablation of Piezo1 in ILC2s increases their function and exacerbates the development of airway hyperreactivity (AHR). Conversely, Piezo1 agonist Yoda1 reduces ILC2-driven lung inflammation. Mechanistically, Yoda1 inhibits ILC2 cytokine secretion and proliferation in a KLF2-dependent manner, as we found that Piezo1 engagement reduces ILC2 oxidative metabolism. Consequently, in vivo Yoda1 treatment reduces the development of AHR in experimental models of ILC2-driven allergic asthma. Human-circulating ILC2s express and induce Piezo1 upon activation, as Yoda1 treatment of humanized mice reduces human ILC2-driven AHR. Our studies define Piezo1 as a critical regulator of ILC2s, and we propose the potential of Piezo1 activation as a novel therapeutic approach for the treatment of ILC2-driven allergic asthma.

Determination of the radioanatomical factors related to the position of facial nerve in accessing jugular foramen and carotid artery in temporal bone.

Introduction: Preservation of the facial nerve is of great importance in temporal bone surgeries. We intend to investigate the measurements of the radioanatomical factors related to the position of the facial nerve in accessing jugular foramen and internal carotid artery (ICA) in temporal bone of patients who were candidates for temporal high resolution computed tomography (HRCT) scan. Methods: In this correlation cross-sectional study, samples were selected from patients referred to Amir Alam Hospital who were previously candidates for temporal HRCT. Radioanatomic factors were evaluated in three axial, coronal and sagittal views. Analyzes were performed using descriptive statistics, correlation analysis and factor analysis. Results: A total of 173 samples were investigated. The most reliable radioanatomical factor based on coefficient of variation (CV) was the distance of the 7th nerve to the temporomandibular joint (TMJ) in the inferior to the cochlea in the sagittal view (variable name S2) (CV = 8.1%) and then the distance from the 7th nerve to the TMJ in the inferior section of the cochlea in the axial view (variable name AI3) (CV = 8.4%). Based on correlation analysis and then confirmatory factor analysis, three common latent factors were identified (overall R2 = 0.999). Conclusion: The results of this study can be used for two purposes. First, the direct use of the estimated measures in surgical operations, and the second is more advanced modeling to choose the approach in the surgical operation and how to implement that approach. For the first aim, the two factors AI3 and S2 were the most reliable radioanatomical factors in different people. For the second aim, the three-dimensional understanding of the obtained measurements and the further identification of the anatomical nature of the latent factors can help in choosing the approach in surgery.

Vertical triband flag sign for differential diagnosis of Rathke's cleft cyst.

Background: The Rathke cleft cyst (RCC) is a type of cystic growth that is benign, circular, and well-defined with an incidence rate of 4 %. This study aims to identify a useful diagnostic imaging sign that can aid in the differentiation of RCC from other cystic lesions. Methods: We retrospectively analyzed the records of 42 symptomatic RCC patients who were referred to our facility between 2016 and 2023. The data for the study were obtained from our electronic database. All magnetic resonance imaging (MRI) studies were performed using a 1.5-T superconducting magnetic scanner. All patients underwent endonasal transsphenoidal surgical resection. All MRIs were reviewed and evaluated by a neurosurgeon and a neuroradiologist. Results: There were 8 (19 %) males and 34 (81 %) females with a mean age of 37.2-years. Our study identified a distinct imaging characteristic in 38 of the cases, which we have named the "vertical triband flag sign", due to the growth of the cyst developing a specific appearance. The flag sign was mostly observed only in the T1-images (71.5 %), while in four cases the sign was spotted only in T2-images, and in four cases it appeared in both T1 and T2. In 4 cases, the flag sign was not observed in which further investigations revealed that these cases were suprasellar or small sellar RCCs. The dot sign, which is a characteristic finding in RCCs was only observed in one of our cases. Conclusion: Early diagnosis of RCCs may be facilitated by utilizing the vertical triband flag sign.

Keratinocyte Exosomes for Topical Delivery of Tofacitinib in Treatment of Psoriasis: an In Vitro/ In Vivo Study in Animal Model of Psoriasis.

INTRODUCTION: Exosomes are extracellular vesicles in the range of 40-150 nm released from the cell membrane. Exosomes secreted by keratinocytes can communicate with other keratinocytes and immune cells with specific biomarkers at their surface, which may be effective on inflammation of psoriasis and its pathogenesis. OBJECTIVE: The present study aimed to formulate and study effectiveness of an exosomal delivery system of tofacitinib (TFC). METHODS: TFC was loaded by different methods in exosomes and then characterized for particle size, zeta potential, drug loading efficiency, and release efficiency. By comparing these parameters, the probe sonication method was chosen to load TFC into exosomes. The MTT assay was used to compare the cytotoxicity of the free drug with the TFC-loaded exosomes (TFC-Exo), and Real-time PCR was used to determine the expression levels of several genes involved in psoriasis expressed in the A-431 keratinocyte and their suppression after treatment. Animal model of psoriasis was induced in BALB/c mice by imiquimod and the efficacy of free TFC, and TFC-Exo were studies on macroscopic appearance and histopathological symptoms. RESULTS: Exosomes encapsulating TFC showed lower cytotoxicity in MTT assay, higher suppression the expression of TNF-a, IL-23, IL-6, and IL-15 genes in real-time PCR and better therapeutic effect on animal models compered to free TFC. CONCLUSIONS: This method of drug delivery for TFC may be effective on enhancing its therapeutic effects and reduction its side effects favorably in chronic administration.

Blocking CD226 regulates type 2 innate lymphoid cell effector function and alleviates airway hyperreactivity.

BACKGROUND: Type 2 innate lymphoid cells (ILC2s) play a pivotal role in type 2 asthma. CD226 is a costimulatory molecule involved in various inflammatory diseases. OBJECTIVE: We aimed to investigate CD226 expression and function within human and mouse ILC2s, and to assess the impact of targeting CD226 on ILC2-mediated airway hyperreactivity (AHR). METHODS: We administered IL-33 intranasally to wild-type mice, followed by treatment with anti-CD226 antibody or isotype control. Pulmonary ILC2s were sorted for ex vivo analyses through RNA sequencing and flow cytometry. Next, we evaluated the effects of CD226 on AHR and lung inflammation in wild-type and Rag2-/- mice. Additionally, we compared peripheral ILC2s from healthy donors and asthmatic patients to ascertain the role of CD226 in human ILC2s. RESULTS: Our findings demonstrated an inducible expression of CD226 in activated ILC2s, enhancing their cytokine secretion and effector functions. Mechanistically, CD226 alters intracellular metabolism and enhances PI3K/AKT and MAPK signal pathways. Blocking CD226 ameliorates ILC2-dependent AHR in IL-33 and Alternaria alternata-induced models. Interestingly, CD226 is expressed and inducible in human ILC2s, and its blocking reduces cytokine production. Finally, we showed that peripheral ILC2s in asthmatic patients exhibited elevated CD226 expression compared to healthy controls. CONCLUSION: Our findings underscore the potential of CD226 as a novel therapeutic target in ILC2s, presenting a promising avenue for ameliorating AHR and allergic asthma.

Predictors of MACE following PPCI in patients with a prior history of CABG.

BACKGROUND: Evidence suggests patients undergoing Primary Percutaneous Coronary Intervention (PPCI) who have a prior history of Coronary Artery Bypass Grafting (CABG) are more likely to experience adverse cardiac events compared to patients without prior CABG. We aimed to study risk factors of one-year Major Adverse Cardiovascular Events (MACE) in patients undergoing PPCI with a prior history of CABG. METHODS: Patients with a history of CABG undergoing PPCI on Saphenous Vein Graft (SVG) were contacted one year after PPCI. One-year follow-up sought MACE, death, and cardiovascular hospitalisation. RESULTS: A total of 69 patients were included in this study of which 66 were followed-up. Within the one-year follow-up, 6 (8.7%) patients were hospitalised due to cardiovascular causes, and 20 (29%) developed MACE. Patients with prior PCI had a significantly higher one-year MACE rate compared to others. Among patients undergoing pre-dilation, patients who experienced MACE had a significantly higher pre-dilation diameter. Moreover, patients experiencing MACE had a significantly lower Ejection Fraction (EF). According to logistic regression models, prior PCI, pre-dilation, and EF were predictors of one-year MACE. Furthermore, The EF was an independent predictor of one-year MACE. CONCLUSION: Higher pre-dilation diameter might be associated with a higher one-year MACE rate in patients undergoing PPCI on SVG with a prior history of CABG. Additionally, EF was an independent predictor of one-year MACE.

Expression of Matrix Metalloproteinases in Human Cystic Echinococcosis.

BACKGROUND: Cystic echinococcosis (CE) is a zoonotic disease caused by the Echinococcus granulosus senso lato (E. granulosus s.l.) larval stages. Parasitederived products have been shown to regulate host matrix metalloproteinases (MMPs), contributing to CE pathogenesis and progressive liver fibrosis in intermediate hosts. The current study aimed to investigate the potential role of MMP1, 7, 8, and 13 in E. granulosus s.l-induced liver fibrosis. METHODS: Thirty CE patients with active, transitional, or inactive hydatid cysts were enrolled in this study to determine the inductive effects of E. granulosus on the expression of MMP-1, MMP-7, MMP-8, and MMP-13 in healthy liver tissue and fibrotic liver tissue using qRT-PCR. RESULTS: According to the WHO-IWGE classification, patients with functional cysts (CE1 and CE2) had the highest percentage (46.6%). MMP-1, MMP-7, MMP-8, and MMP-13 expression levels were significantly higher in fibrotic liver than in normal liver tissue. MMP-13 and MMP-1 had the highest and lowest expression levels among MMPs. Compared to the normal group, the fold change for MMP-13 in the fibrotic group was greater than 12 and had the highest AUC value (AUC= 0.8283). CONCLUSION: Our findings suggest that E. granulosus-derived products might be involved in regulating host MMPs. Thus, MMPs may be considered potential biomarkers for predicting CE prognosis. Because of the non-normal distribution of our patients' CE types, further research, particularly on circulation MMPs, is needed to confirm the potential role of MMPs in CE pathogenesis and to follow up on CE patients.

Differential Gene Expressions of CALM1, PSMD6, and AK124742 Long Noncoding RNA in Cumulus Cells from Polycystic Ovary Syndrome Patients versus Normal Control Women.

Background: One of the well-known causes of subfertility is polycystic ovary syndrome (PCOS). Genetic components play a critical role in the etiology of PCOS. The recognition of differentially expressed genes in PCOS patients might provide a better understanding of the pathophysiology of this syndrome and paves the way for novel therapeutics. Gene expression profiles in cumulus cells (CCs) could be used as biological criteria for embryo competence and their analysis might lead to important molecular information about embryo quality. CALM1, PSMD6, and AK124742 are three well-known genes associated with embryo development. Therefore, the objective of this study was to compare the expression of CALM1, PSMD6, and AK124742 genes in the CCs of infertile PCOS patients with their expression in the CCs of the donor fertile group. Materials and Methods: CCs were collected from the follicular fluid of 33 patients with PCOS as the experimental group and 33 cumulus donor women who were referred to the infertility center for egg donation as the control group. CCs were frozen until genetic testing. The expression of CALM1, PSMD6, and AK124742 genes was detected by real-time polymerase chain reaction. Results: CALM1 and AK124742 gene expressions significantly increased (CALM1 P = 0.003) (AK124742 P = 0.000) and PSMD6 expression significantly decreased (P = 0.002) in the PCOS group compared to the cumulus donor (control) group. Conclusion: Therefore, our research findings suggest that the potential impact of Polycystic Ovary Syndrome (PCOS) on fertility could be attributed to modifications in the expression levels of genes that affect the reproductive.

Time-series bioinformatics analysis of SARS-CoV-infected cells to identify the biological processes associated with severe acute respiratory syndrome.

BACKGROUND: The COVID-19 pandemic, caused by the new virus of the coronavirus family, SARS-CoV-2, could lead to acute respiratory syndrome. The molecular mechanisms related to this disorder are still debatable. METHODS: In this study to understand the pathogenicity mechanism of SARS-CoV-2, using the bioinformatics approaches, we investigated the expression of involved genes, their regulatory, and main signaling pathways during the time on days 1, 2, 3, and 4 of SARS-CoV infected cells. RESULTS: Here, our investigation shows the complex changes in gene expression on days 2 and 3 post-infection. The functional analysis showed that especially related to immune response, response to other organisms, and defense response. IL6-AS1 is the predicted long non-coding RNA and is a key regulator during infection. In this study, for the first time has been reported the role of IL6-AS1. Also, the correlation of differential expression genes with the level of immune infiltration was shown in the relationship of Natural killer cells and T cell CD 4+ with DE genes. CONCLUSION: In the current study, identification of the altered expression pattern of genes in SARS-CoV-infected cells in time course also can help identify and link the molecular mechanisms and explore the holistic view of infection of SARS-CoV-2.

Diagnostic yield of prenatal exome sequencing in the genetic screening of fetuses with brain anomalies detected by MRI and ultrasonography: A systematic review and meta-analysis.

BACKGROUND: Brain anomalies (BAs) have been the focus of research, as they have a high impact on fetal health but therapeutic and diagnostic approaches are limited. OBJECTIVES: In this study, the application and efficiency of exome sequencing (ES) in detecting different cases of BAs in fetuses were evaluated and compared with chromosomal microarray analysis (CMA). SEARCH STRATEGY: To conduct this study, three databases including PubMed, Web of Science and Embase were utilised with the keywords 'prenatal', 'diagnoses', 'brain anomalies' and 'exome sequencing'. SELECTION CRITERIA: Studies were included based on the STARD checklist, for which the ES and CMA diagnostic yields were calculated. DATA COLLECTION AND ANALYSIS: Meta-analysis was performed on the included studies using a random-effects model and subgroup analysis to define the risk difference between them. MAIN RESULTS: We included 11 studies representing 779 fetuses that implemented ES along with imaging techniques. The pooled ES diagnostic yield in fetuses with BAs detected through magnetic resonance imaging (MRI) and ultrasonography was 26.53%, compared with 3.46% for CMA. The risk difference between ES and CMA for complex BAs was 0.36 [95% confidence interval (CI) 0.24-0.47], which was higher than for single BAs (0.22; 95% CI 0.18-0.25]. CONCLUSIONS: ES is a useful method with a significantly higher diagnostic yield than CMA for genetic assessment of fetuses with complex BAs detected by imaging techniques. Moreover, ES could be applied to suspected fetuses with related family histories to predict congenital diseases with high efficiency.

Anchor Loss Reduction in Micro-Electro Mechanical Systems Flexural Beam Resonators Using Trench Hole Array Reflectors.

The quality factor of microelectromechanical resonators is a crucial performance metric and has thus been the subject of numerous studies aimed at maximizing its value by minimizing the anchor loss. This work presents a study on the effect of elastic wave reflectors on the quality factor of MEMS clamped-clamped flexural beam resonators. The elastic wave reflectors are a series of holes created by trenches in the silicon substrate of the resonators. In this regard, four different shapes of arrayed holes are considered, i.e., two sizes of squares and two half circles with different directions are positioned in proximity to the anchors. The impact of these shapes on the quality factor is examined through both numerical simulations and experimental analysis. A 2D in-plane wave propagation model with a low-reflecting fixed boundary condition was used in the numerical simulation to predict the behavior, and the MEMS resonator prototypes were fabricated using a commercially available micro-fabrication process to validate the findings. Notably, the research identifies that half-circle-shaped holes with their curved sides facing the anchors yield the most promising results. With these reflectors, the quality factor of the resonator is increased by a factor of 1.70× in air or 1.72× in vacuum.

Catalase-gold nanoaggregates manipulate the tumor microenvironment and enhance the effect of low-dose radiation therapy by reducing hypoxia.

Radiotherapy as a standard method for cancer treatment faces tumor recurrence and antitumoral unresponsiveness. Suppressive tumor microenvironment (TME) and hypoxia are significant challenges affecting efficacy of radiotherapy. Herein, a versatile method is introduced for the preparation of pH-sensitive catalase-gold cross-linked nanoaggregate (Au@CAT) having acceptable stability and selective activity in tumor microenvironment. Combining Au@CAT with low-dose radiotherapy enhanced radiotherapy effects via polarizing protumoral immune cells to the antitumoral landscape. This therapeutic approach also attenuated hypoxia, confirmed by downregulating hypoxia hallmarks, such as hypoxia-inducible factor α-subunits (HIF-α), vascular endothelial growth factor (VEGF), and EGF. Catalase stability against protease digestion was improved significantly in Au@CAT compared to the free catalase. Moreover, minimal toxicity of Au@CAT on normal cells and increased reactive oxygen species (ROS) were confirmed in vitro compared with radiotherapy. Using the nanoaggregates combined with radiotherapy led to a significant reduction of immunosuppressive infiltrating cells such as myeloid-derived suppressor cells (MDSCs) and regulatory T cells (T-regs) compared to the other groups. While, this combined therapy could significantly increase the frequency of CD8+ cells as well as M1 to M2 macrophages (MQs) ratio. The combination therapy also reduced the tumor size and increased survival rate in mice models of colorectal cancer (CRC). Our results indicate that this innovative nanocomposite could be an excellent system for catalase delivery, manipulating the TME and providing a potential therapeutic strategy for treating CRC.