Background:DNA methylation markers have been proposed as molecular triage tools for detecting cervical precancer and cancer, particularly among HPV-positive women. However, diagnostic performance varies across markers, assays, specimens, and clinical settings. This study aimed to evaluate the marker-specific diagnostic accuracy of DNA methylation markers and methylation panels for detecting CIN2+ and CIN3+ in cervical cancer screening, triage, and related diagnostic contexts. Methods:This systematic review and diagnostic test accuracy meta-analysis was reported according to PRISMA-DTA 10. Marker-specific analyses were performed separately by endpoint to avoid double counting. Pooled sensitivity, specificity, diagnostic odds ratio, clinical utility estimates, risk of bias, publication bias, and certainty of evidence were assessed using diagnostic test accuracy methods, QUADAS-2 11, Deeks' test 14, and GRADE-DTA 12,13. Results:The broad main diagnostic meta-analysis included 74 eligible studies 15-88, contributing 260 diagnostic test accuracy comparisons across 130 marker-endpoint-sample analyses. A strict sensitivity dataset included 164 comparisons from 51 studies. Seven marker analyses were available for CIN2+ and seven for CIN3+. Diagnostic performance varied by marker and endpoint. For CIN2+, S5 EPB41L3 plus HPV16/18/31/33 methylation showed the highest sensitivity but lower specificity, whereas PAX1, JAM3, SOX1, PAX1/JAM3, and Six-gene/GynTect showed higher specificity. For CIN3+, S5 showed the highest sensitivity, while PAX1/JAM3, JAM3, SOX1, PAX1, and Six-gene/GynTect had more balanced performance. Deeks' test did not show strong evidence of publication bias for most analyses, although borderline findings were observed in selected marker-endpoint analyses. GRADE-DTA certainty was low or very low across marker-endpoint analyses. Conclusions:DNA methylation markers showed heterogeneous diagnostic accuracy for detecting CIN2+ and CIN3+. Some markers demonstrated potentially useful sensitivity- or specificity-oriented profiles, but certainty of evidence was low or very low. Further standardized prospective validation is required before routine clinical implementation.

An affordable, precise detection of mutations is critical for guiding targeted cancer therapies and improving patient outcomes. Epidermal growth factor receptor (EGFR), a protein on the surface of cells that regulates growth and division, is frequently mutated in non-small cell lung cancer (NSCLC). Early identification of these mutations enables clinicians to select the most effective tyrosine kinase inhibitors, thereby enhancing treatment response and survival rates. Recent studies have focused on developing CRISPR-based detection strategies incorporating nanomaterials to achieve more accurate results. In this study, we present a CRISPR-based "turn-on" detection platform that leverages the cleavage of a novel enhanced bimetallic DNA nanocluster to measure EGFR exon 19 deletion in non-small cell lung cancer (NSCLC). The system is innovatively designed using guide RNAs (gRNAs) rationally derived from the normal EGFR gene, enabling the determination of exon 19 deletion through CRISPR-Cas activation in samples containing the normal and mutant. Upon recognition of the normal EGFR gene, the Cas12a enzyme induces cleavage of the Spermiform-designed Ag/Au DNA nanocluster and fluorescence quenching. At the same time, fluorescence signal retention depends on mutation frequency, with higher mutation frequencies resulting in greater or "turn-on" fluorescence signals. This approach achieves a detection limit (LOD) of approximately 0.35 nM, which is capable of detecting about 1.5% mutation, offering a cost-effective, label-free diagnostic tool and a promising strategy for future detection of deletion-related subtypes in PCR products by targeting normal sequences. The integration of bimetallic nanocluster-based reporters with CRISPR precision provides an emerging platform for next-generation molecular diagnostics targeting EGFR and other clinically relevant mutations.

Purpose:Bladder cancer is a prevalent malignancy, with high recurrence rates for non-muscle invasive cases and significant progression risks. Traditional diagnostic methods, such as cystoscopy and urine cytology, are limited by their invasiveness and low sensitivity for detecting low-grade tumors, respectively. Advances in non-invasive diagnostics focus on biomarkers such as cfDNA and DNA methylation, offering promising tools for early detection. Patients and Methods:This study investigated methylation and expression changes in POU4F2, HOXA9, RBM46, and TSGA10 genes in bladder cancer. A total of 22 patients and 30 controls were enrolled, with urine and plasma samples collected for analysis. cfDNA and total RNA were extracted using commercial kits. Methylation was assessed via MSRE-PCR, and gene expression was evaluated with Real-Time PCR. Statistical analysis was performed using GraphPad Prism software, with an unpaired t-test and ANOVA to compare the differences between the cancer and control groups. A p-value of less than 0.05 was considered statistically significant. Results:Urine cfDNA from bladder cancer patients showed significantly higher promoter methylation of POU4F2, HOXA9, RBM46, and TSGA10 compared with controls (approximately 2.2-, 9.0-, 3.6- and 6.1-fold increases; all p < 0.0001), with smaller but still significant differences in plasma (p = 0.0005-0.0278). ROC analysis of urine methylation yielded AUCs of 0.97 for POU4F2, 0.95 for HOXA9, 0.88 for RBM46 and 0.98 for TSGA10 (sensitivities 95-100%, specificities 80-100%; all p < 0.0001). A PCA-derived composite methylation score further improved discrimination (AUC = 0.993, 95% CI 0.974-1.000; sensitivity 100%, specificity 95%; p < 0.001). Consistently, gene expression analysis in urine showed significant downregulation of POU4F2 and HOXA9 (≈7- and 9-fold decreases; p = 0.0099 and p = 0.025) and upregulation of RBM46 and TSGA10 (≈2.5- and 2.3-fold increases; p = 0.0037 and p = 0.0114) in patients versus controls. Conclusion:The results indicate that these methylation and expression profiles can be used as non-invasive biomarkers for the early diagnosis of bladder cancer. The use of these methods provides both greater sensitivity and accuracy than traditional methods and can pave the way for the development of more effective screening tests.

TSGA10 has recently been highlighted as an important factor in spermatogenesis with critical roles during sperm maturation. Although up-regulation of TSGA10 expression in early stages and its down-regulation in advanced stages of some cancers has already been demonstrated, the regulatory mechanism governing its expression has not yet been elucidated. RHOXF1 transcription factor is known to be a cancer/testis antigen with vital roles in spermatogenesis. Besides, both RHOXF1 and TSGA10 are cancer/testis antigens that are involved in the carcinogenic processes. Given that RHOXF1 is a transcription factor; and both RHOXF1 and TSGA10 are highly expressed in round spermatids during the transition of meiotic to post-meiotic stages of spermatogenesis, we aimed to investigate RHOXF1 knockdown effect on the expression levels of TSGA10. RHOXF1 shRNA vector was prepared and transient transfected into MCF7 cells that exhibit high expression of RHOXF1 and TSGA10. The efficiency of transfection was assessed by real-time PCR for evaluation of RHOXF1 knock down. TSGA10 expression was also measured. Untransfected cells and cells transfected with empty vector as well as scrambled vector were used as control. Our data showed that shRNA-mediated knockdown of RHOXF1 expression led to decreased expression levels of TSGA10. We found the positive co-expression of RHOXF1 and TSGA10 in all normal tissues as well as in variety of cancer tissues, with the highest positive co-expression in pancreas, breast, and kidney cancers. Therefore, TSGA10 expression might be regulated by RHOXF1 transcription factor. Future studies are needed to elaborate whether this regulatory role is exerted directly or indirectly. The results of this study might broaden understanding of transcriptional regulation in cancer biology and facilitate novel strategies to overcome the effects of oncogenic transcription factors on their targets.

Background To accurately diagnose cervical cancer, high-quality genetic material (DNA and RNA) from clinical samples is crucial. Current preservation methods often have limitations, including poor RNA stability and safety concerns. This study aimed to develop an optimized ethanol-based fixative to preserve DNA and RNA in cervical samples under ambient conditions. Methods HeLa cells were fixed in ethanol-based fixatives containing polyhydric compounds (Sorbitol and polyethylene glycol [PEG]) and chelating agents. We used a central composite design (CCD) approach to evaluate the effects of pH, Sorbitol concentration, and PEG concentration on nucleic acid preservation. DNA and RNA quality were assessed using agarose gel electrophoresis, PCR, and real-time PCR. Cellular morphology was evaluated using Papanicolaou-stained slides. HPV genotyping of clinical samples was conducted using real-time PCR. Results The optimized fixative, developed in this study consisted of 40% ethanol, 4.3% Sorbitol, 1.2% PEG 8000, with a pH of 5.6. This new formula significantly improved DNA and RNA preservation compared to the commercial solution, PreservCyt. DNA showed high integrity and was successfully amplified in PCR test targeting HPV-18 oncogenes. RNA quality was confirmed through clear 28S and 18S rRNA bands and lower threshold cycle (Ct) values in qRT-PCR. HPV genotyping and morphological analysis revealed excellent preservation, enabling both molecular and cytological evaluations. Conclusion The new ethanol-based fixative represents a promising cost-effective and environmentally friendly solution for preserving nucleic acids and cellular morphology in cervical samples. Its good performance under ambient conditions suggests it may serve as an option for Human Papillomavirus (HPV) testing and cervical cancer prevention, particularly in places with limited resources.

Genome editing tools have provided researchers and clinicians with an invaluable opportunity to understand and treat various disorders. These tools can potentially be used to precisely, efficiently, and safely treat disorders with genetic components. Among these disorders, are different malignancies. CRISPR/Cas9 has evolved to be the method of choice for most genome editing applications since it is much easier to work with. It can modify the aberrant sequence of oncogenes and tumor suppressor genes. It can also be used to design and optimize oncolytic viruses and immunotherapies with great accuracy. In the field of cancer research, it can be used to detect possible drug targets, mechanisms of drug resistance, and design cancer models such as cell lines, organoids, and even whole animals. However, the widespread application of this therapy has been limited because of its possible off-target activity and difficulties associated with its delivery to a specific site. Different approaches have been implemented to compensate for these shortcomings which are discussed in detail in this paper. With the incredible pace of progression in the field of biochemistry and data science, it will not be long before we witness the widespread application of CRISPR/Cas9 in the field of cancer therapeutics and research. Finally, a list of clinical trials applying CRISPR/Cas9 has been provided in the final section of this paper.

Background and Objectives: Probiotics are effective in improving inflammatory bowel disease (IBD). This study assessed the effect of mesalazine and two candidate probiotics on the improvement of acetic acid (AA)-induced colitis model. Materials and Methods: Lactobacillus plantarum MS1and Lactobacillus delbrueckii YN1 were used for IBD model in rat. Twenty-five male Wistar rats weighing 250 ± 50 grams were used in 5 classified groups: Control (CO); Colitis (CL); Colitis, Probiotic (CLP); Colitis, Mesalazine (CLM); Colitis, Probiotic, Mesalazine (CLPM) and the treatment period was 3 weeks. The rats were treated with mesalazine 30 mg/kg and probiotic 109 CFU/ml after induction of colitis. Histopathological and immunological analyses were performed to evaluate the effects of probiotic bacteria on IBD. Results: The results showed that the probiotic bacteria reduced inflammation (P<0.05), extent (P<0.01), crypt abscesses (P<0.01), edema (P<0.05), inflammatory cell infiltration (P<0.5), and increased mucosa (P<0.001) in rats. Mesalazine administration in animals with colitis did not have a significant effect. Administration of probiotics in both CLP and CLPM groups reduced extent, crypt abscesses, edema, and inflammatory cell infiltration and showed an important role in the down-regulation of consolidation of pro-inflammatory factors (TNFα, IL-6, and IL-17), as well as up-regulation of anti-inflammatory factors such as IL-10. Conclusion: Lactobacillus plantarum MS1 and Lactobacillus delbrueckii YN1 have shown significant potential in alleviating AA-induced colitis symptoms. Their administration leads to a marked reduction in pro-inflammatory cytokines such as TNF-α, IL-17, and IL-6, while enhancing IL-10 levels, indicating their promise as therapeutic candidates for inflammatory bowel disease (IBD).

The global public health is still at risk due to the COVID-19 pandemic, which was caused by SARS-CoV-2. Disease severity varies among patients and is influenced by mutations in the viral genome, particularly within the spike protein's receptor-binding domain (RBD). This study aimed to investigate the association between RBD mutations and disease severity and to shed light on the fundamental molecular mechanisms. Nasopharyngeal and oropharyngeal samples were obtained from 70 COVID-19 patients in Iran, including 35 mild and 35 deceased cases. The RBD region of the spike protein gene underwent amplification through reverse transcription-polymerase chain reaction (RT-PCR) and was subsequently sequenced using Sanger sequencing. The impact of RBD mutations on binding affinity to human ACE2 (hACE2) was assessed by molecular docking analyses. Sequence analysis identified seven nonsynonymous mutations within the RBD region. The N501Y mutation, which was the most prevalent, showed a significant correlation with disease severity. Molecular docking revealed that the N501Y substitution enhanced binding affinity to hACE2 by increasing hydrophobic interactions and altering the interaction patterns of neighboring residues. This study demonstrates that the N501Y mutation has an independent association with increased severity of COVID-19, likely due to its effect on strengthening the RBD-hACE2 interaction. Further studies involving larger cohorts and diverse populations are necessary to confirm these results and to explore their potential implications for disease management and therapeutic strategies.

Recurrent miscarriage (RM) or recurrent pregnancy loss (RPL) is a complex situation, characterized by two, three, or more pregnancy losses. The normal progression of pregnancy relies heavily on the proper functioning of the PROZ and ARNT genes, and their partial or complete deficiencies will result in early pregnancy loss and also recurrent pregnancy losses. Present study aims to find PROZ and ARNT novel mutations as causes of RPL; and involves two couples that had a consanguineous marriage and were referred with three recurring miscarriages. Pathological tests were requested for the fetus, and high-resolution Giemsa banding karyotypes were requested for the couple to determine the cause. Abortion samples were also used for array CGH and whole-exome sequencing to analyze mutations. Confirming the mutation involved conducting Sanger sequencing, which is noteworthy. Based on the results, our first proband has a novel likely pathogenic homozygous mutation NM_003891:c.349T > C (p.Y117H) in the PROZ gene located on 13q34 as a novel mutation of the PROZ gene, and our second proband has a novel likely pathogenic homozygous mutation NM_001286035:exon16:c.1353-2A > G in the ARNT gene, located on 1q21.3. Sanger sequencing confirmed homozygosity of these two mutations in the probands and heterozygosity of these loci in their parents, suggesting them as likely pathogenic mutations and an autosomal recessive inheritance pattern in RPL. Novel likely pathogenic homozygous mutation NM_003891:c.349T > C (p.Y117H) in PROZ gene, and novel likely pathogenic homozygous mutation in ARNT gene may be related to RPL.

Copy number variation in the SMN1 gene is the main cause of Spinal Muscular Atrophy (SMA). We assessed the carrier frequency of SMA, which is the second most common genetic disease, in the Iranian population. This paper demonstrates the largest population including unrelated subjects and also provides an evaluation with variant analysis of SMN1 in cis. To acquire inclusive molecular data about the carrier frequency of SMA and the frequency of SMN1 polymorphisms g.27134T>G (c.*3+80T>G) among Iranian population, we analyzed data from 2157 individuals referred to the Pars-Genome and Genome-Nilou laboratories for SMA carrier detection between 2018 and 2024. A total of 2003 unrelated non-consanguineous healthy individuals were selected from 2157 individuals underwent MLPA using kit P460 or P021. We also assessed available whole exome sequencing (WES) data of another cohort of patients for the presence of the c.*3+80T>G variant in the SMN1. The results indicated that 3.5 % (n = 70) were carriers of the disease, possessing only one copy of the SMN1 gene. Totally, 89 % (n = 1783) of all participants exhibited two copies of SMN1. Among 526 cases underwent assessment by P460 kit and 2211 cases underwent WES, c.*3+80T>G variant was detected in 28 (1 %) cases. This data can be used in the genetic counseling, carrier screening, and prenatal diagnosis of SMA in Iran.

Background This study investigated the functional and translational role of long non-coding RNAs (lncRNAs), specifically MIR22HG, LNCTAM34A, and TP53TG1, in breast cancer (BC). Methods The expression of the lncRNAs was measured using RT-qPCR. Knockdown experiments using siRNA were conducted in breast cancer cell lines (MDA-MB-231, MDA-MB-453, and MCF-7) to assess the functional impact of silencing these lncRNAs. Cell proliferation, colony formation, invasion, migration, and apoptosis assays were performed to evaluate phenotypic changes. Results The expression of MIR22HG, LNCTAM34A, and TP53TG1 was significantly decreased in tumor tissues compared to NATs (p < 0.05). Lower expression of these lncRNAs correlated with advanced TNM stage and grade groups (p < 0.05). MIR22HG was overexpressed in the BC cell lines MDA-MB-231 and MCF-7, while LNCTAM34A and TP53TG1 were upregulated in MDA-MB-453 and MCF-7 BC cell lines. Silencing these lncRNAs led to a significant increase in cell proliferation, colony formation, invasion, and migration (p < 0.001). Additionally, apoptosis was significantly decreased in cells with silenced lncRNAs (p < 0.05). Knockdown of MIR22HG, LNCTAM34A, and TP53TG1 in BC cells resulted in increased cell proliferation and colony formation. Silencing of these lncRNAs significantly increased cell migration and invasion. The silencing of MIR22HG, LNCTAM34A, and TP53TG1 decreased apoptosis in BC cells. Conclusion Study demonstrates that MIR22HG, LNCTAM34A, and TP53TG1 function as tumor suppressors in breast cancer. Downregulation of these lncRNAs promotes tumor progression by enhancing cell proliferation, invasion, and migration, while inhibiting apoptosis.

Polyploidy, a conserved mechanism involved in normal development and tissue homeostasis, plays a paradoxical role in cancer by facilitating both tumor progression and therapeutic vulnerability. Although polyploidization may confer survival advantages to cancer cells, its controlled induction could represent an effective anticancer strategy. Aurora B kinase, a critical regulator of mitosis, plays a pivotal role in ensuring chromosomal integrity and preventing polyploidy. However, its role in chromosome ploidy and telomere length maintenance in breast cancer remains insufficiently explored. In this study, we identified a significant association between Aurora B overexpression and poor prognosis exclusively in patients with HER2-amplified breast cancer. Treatment with AZD1152-HQPA, a selective Aurora B kinase inhibitor, significantly reduced cell viability and colony-forming potential, with a pronounced effect on HER2-amplified breast cancer cell lines. Importantly, we found that Aurora B inhibition is sufficient to induce polyploidy/multinucleation (8 N and 16 N), cellular enlargement, and mitotic catastrophe. Furthermore, we observed telomere shortening, downregulation of the human telomerase reverse transcriptase (hTERT) and TERRA (telomeric repeat-containing RNA), and a concomitant increase in ROS production following Aurora B inhibition and polyploidization. Mechanistically, we investigated the protein-protein interaction between Aurora B kinase and upstream regulators of hTERT. Collectively, this study elucidates a novel anticancer mechanism associated with Aurora B inhibition, revealing that AZD1152-HQPA not only impairs mitotic fidelity and promotes polyploidization but also compromises the telomere/telomerase maintenance system. These findings highlight the therapeutic potential of Aurora B inhibitors in targeting telomere-associated vulnerabilities in polyploid cancer cells.

Cellular senescence is understood to be a biological process that is defined as irreversible growth arrest and was originally recognized as a tumor-suppressive mechanism that prevents further propagation of damaged cells. More recently, cellular senescence has been shown to have a dual role in prevention and tumor promotion. Senescent cells carry a senescence-associated secretory phenotype (SASP), which is altered by secretory factors including pro-inflammatory cytokines, chemokines, and other proteases, leading to the alteration of the tissue microenvironment. Though senescence would eventually halt the growth of cancerous potential cells, SASP contributes to the tumor environment by promoting inflammation, matrix remodeling, and tumor cell invasion. The paradox of tumor prevention/promotion is particularly relevant to the bone niche tumor microenvironment, where longer-lasting, chronic inflammation promotes tumor formation. Insights into a mechanistic understanding of cellular senescence and SASP provide the basis for targeted therapies, such as senolytics, which aim to eliminate senescent cells, or SASP inhibitors, which would eliminate the tumor-promoting effects of senescence. These therapeutic interventions offer significant clinical implications for treating cancer and healthy aging.

The intrinsic nature of CRISPR-Cas in conferring immunity to bacteria and archaea has been repurposed to combat pathogenic agents in mammalian and plant cells. In this regard, CRISPR-Cas13 systems have proved their remarkable potential for single-strand RNA viruses targeting. Here, different types of Cas13 orthologs were applied to knockdown foot-and-mouth disease virus (FMDV), a highly contagious disease of a wide variety of species with genetically diverse strains and is widely geographically distributed. Using programmable CRISPR RNAs capable of targeting conserved regions of the viral genome, all Cas13s from CRISPR system type VI (subtype A/B/D) could comprehensively target and repress different serotypes of FMDV virus. This approach has the potential to destroy all strains of a virus as targets the ultra-conserved regions of genome. We experimentally compared the silencing efficiency of CRISPR and RNAi by designing the most effective short hairpin RNAs according to our developed scoring system and observed comparable results. This study showed successful usage of various Cas13 enzymes for suppression of FMDV, which provides a flexible strategy to battle with other animal infectious RNA viruses, an underdeveloped field in the biotechnology scope.

Background: Accurate detection of the BRAF V600E (1799T > A) mutation status can significantly contribute to selecting an optimal therapeutic strategy for diverse cancer types. CRISPR-based diagnostic platforms exhibit simple programming, cost-effectiveness, high sensitivity, and high specificity in detecting target sequences. The goal of this study is to develop a simple BRAF V600E mutation detection method. Methods: We combined the CRISPR/Cas12a system with recombinase polymerase amplification (RPA). Subsequently, several parameters related to CRISPR/Cas12a reaction efficiency were evaluated. Then, we conducted a comparative analysis of three distinct approaches toward identifying BRAF V600E mutations in the clinical samples. Results: Our data suggest that CRISPR/Cas detection is considerably responsive to variations in buffer conditions. Magnesium acetate (MgOAc) demonstrated superior performance compared to all other examined additive salts. It was observed using 150 nM guide RNA (gRNA) in an optimized reaction buffer containing 14 mM MgOAc, coupled with a reduction in the volumes of PCR and RPA products to 1 mu L and 3 mu L, respectively, resulted in an enhanced sensitivity. Detection time was decreased to 75 min with a 2% limit of detection (LOD), as evidenced by the results obtained from the blue light illuminator. The CRISPR/Cas12a assay confirmed the real-time PCR results in 31 of 32 clinical samples to identify the BRAF V600E mutation status, while Sanger sequencing detected BRAF V600E mutations with lower sensitivity. Conclusion: We propose a potential diagnostic approach that is facile, fast, and affordable with high fidelity. This method can detect BRAF V600E mutation with a 2% LOD without the need for a thermocycler.

Harnessing the power of the immune system to target cancer cells is one of the most appealing approaches for cancer therapy. Among these immunotherapies, messenger ribonucleic acid (mRNA) cancer vaccines are worthy of consideration, as they have demonstrated promising results in clinical trials. These vaccines have proven to be safe and well-tolerated. They can be easily mass-produced in a relatively short time and induce a systemic immune response effective against both the primary tumor and metastases. Transcripts encoding immunomodulatory molecules can also be incorporated into the mRNA, enhancing its efficacy. On the other hand, there are some challenges associated with their application, including mRNA instability, insufficient uptake by immune cells, and intrinsic immunogenicity, which can block mRNA translation. Many innovations have been suggested to overcome these obstacles, including structural modification (such as 5’ cap modification), optimizing delivery vehicles (especially dendritic cells (DCs) and nanoparticles), and using antigens that can enhance immunogenicity by circumventing tolerance mechanisms. A popular approach is to combine mRNA cancer vaccines with traditional and novel cancer treatments like chemotherapy, radiotherapy, and immune checkpoint blockade (ICB). They are most efficacious when combined with other therapies like ICBs. There is still a long way to go before these vaccines enter the standard of care for cancer patients, but with the incredible pace of development in this field, their clinical application will soon be witnessed. This review highlights the recent advances and challenges of mRNA cancer vaccines. Finally, some of the most prominent clinical applications of these vaccines will be reviewed.

Introduction: IQ motif-containing GTPase-activating protein3 (IQGAP3) contributes to the progression of bladder urothelial carcinoma (BLCA), but its mechanisms are not systematically specified. Due to the oncogenic potential of IQGAP3, the current in-silico study intended to elucidate IQGAP3's role in BLCA progression. Materials and Methods: Many bioinformatics tools, including UALCAN, Kaplan–Meier plotter, TNMplot, cBioPortal, GeneMania, Enrichr, TIMER2, muTarget, and UCSC Xena, were applied in the current study. Results: The IQGAP3 level was more pronouncedly raised in BLCA tissues than in normal bladder tissues, and its increased expression was related to the advanced stage and higher grade. Enhanced IQGAP3 expression could result from its genetic alteration. Moreover, the mutation in P53 and RB1 genes was robustly associated with increased IQGAP3 expression. Besides, IQGAP3 correlative genes were dominantly involved in the cell cycle. On the other hand, IQGAP3 upregulation influenced immune checkpoint levels in the tumor microenvironment. Conclusion: The in-silico findings suggested that IQGAP3 overexpression could be a crucial biomarker in BLCA.

Neurofibromatosis type 1 (NF1) is a genetic disorder caused by mutations in the NF1 gene. This disorder shows nearly complete penetrance and high phenotypic variability. We used the whole-exome sequencing technique to identify mutations in 32 NF1 cases from 22 Iranian families. A total of 31 variants, including 30 point mutations and one large deletion, were detected. In eight cases, variants were inherited, while they were sporadic in the remaining. Seven novel variants, including c.5576 T > G, c.6658_6659insC, c.2322dupT, c.92_93insAA, c.4360C > T, c.3814C > T, and c.4565_4566delinsC, were identified. The current study is the largest in terms of the sample size of Iranian NF1 cases with identified mutations. The results can broaden the spectrum of NF1 mutations and facilitate the process of genetic counseling in the affected families.

Abstract In this study, we sought to reduce the released CO2 into the atmosphere from bacterial growth by reducing formic acid conversion into CO2. Since E. coli is the biotechnological workhorse and its higher growth rate is desirable, another goal was to monitor the bacterial biomass after the metabolic engineering. The conversion of formic acid to CO2 is a crucial reaction. Therefore, we compared the growth of control strains, alongside two strains in which two different genes coding two formate dehydrogenase (FDH) subunits were deleted. The knockout bacteria grew better than the controls. Thiobacillus FDH (TsFDH) transformation increased the growth of both knockouts of E.coli compared with the controls and the knockouts strain without TsFDH. Through a transcriptomics-level analysis of the strain knockout genes, the genes negatively correlated with the target genes were shown to belong to tRNA-related pathways. Observing higher cell biomass for the knockout and transformed strains indicates possible underlying mechanisms leading to reduced carbon leakage and increased carbon assimilation, which need more detailed investigations. Gene expression correlations and pathway analysis outcomes suggested possible over-expression of the genes involved in tRNA processing and charging pathways.