Myeloid neoplasms are clonal disorders that arise via acquisition of genetic mutations leading to excessive proliferation and defective differentiation. Mutational profiling is vital as it has implications for diagnosis, prognosis, and therapeutic decision-making. Next-generation sequencing (NGS) has become a mainstay in the evaluation of myeloid malignancies, as it enables efficient characterization of multiple genetic changes. Herein, the analytical validation of the 37-gene Archer VariantPlex Core Myeloid panel is reported, using 58 DNA specimens with 87 single-nucleotide variants and 23 insertions/deletions. The panel achieved good depth of coverage, 100% analytical sensitivity and specificity for single-nucleotide variants and insertions/deletions ≤21 bp, and 100% reproducibility, with a reportable limit of detection determined as 5%. The Archer NGS panel can accurately and reproducibly detect variants of clinical significance in myeloid neoplasms. A retrospective analysis of 535 clinical specimens tested with the Archer NGS panel showed a frequency and pattern of mutations across myeloid malignancies that were similar to other published studies. A review of the diagnostic classification of patients with acute myeloid leukemia and myelodysplastic syndrome using the World Health Organization 2017/2022 and International Consensus Classification 2022 guidelines, in addition to European LeukemiaNet 2017/2022 risk stratification of patients with acute myeloid leukemia, was also performed to assess the utility of the molecular information provided by the Archer NGS panel.

The mesocorticolimbic (MCL) system is crucial in developing risky health behaviors which lead to cardiovascular diseases (CVDs) and type 2 diabetes (T2D). Although there is some knowledge of the MCL system genes linked to CVDs and T2D, a comprehensive list is lacking, underscoring the significance of this review. This systematic review followed PRISMA guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. The PubMed and Web of Science databases were searched intensively for articles related to the MCL system, single nucleotide variants (SNVs, formerly single nucleotide polymorphisms, SNPs), CVDs, T2D, and associated risk factors. Included studies had to involve a genotype with at least one MCL system gene (with an identified SNV) for all participants and the analysis of its link to CVDs, T2D, or associated risk factors. The quality assessment of the included studies was performed using the Q-Genie tool. The VEP and DAVID tools were used to annotate and interpret genetic variants and identify enriched pathways and gene ontology terms associated with the gene list. The review identified 77 articles that met the inclusion criteria. These articles provided information on 174 SNVs related to the MCL system that were linked to CVDs, T2D, or associated risk factors. The COMT gene was found to be significantly related to hypertension, dyslipidemia, insulin resistance, obesity, and drug abuse, with rs4680 being the most commonly reported variant. This systematic review found a strong association between the MCL system and the risk of developing CVDs and T2D, suggesting that identifying genetic variations related to this system could help with disease prevention and treatment strategies.

Glycosyltransferases (GTs) catalyze the transfer of active monosaccharide donors to carbohydrates to create a wide range of oligosaccharide structures. GTs display strong regioselectivity and stereoselectivity in producing glycosidic bonds, making them extremely valuable in the in vitro synthesis of oligosaccharides. The synthesis of oligosaccharides by GTs often gives high yields; however, the enzyme activity may experience product inhibition. Additionally, the higher cost of nucleotide sugars limits the usage of GTs for oligosaccharide synthesis. In this review, we comprehensively discussed the structure and mechanism of GTs based on recent literature and the CAZY website data. To provide innovative ideas for the functional studies of GTs, we summarized several remarkable characteristics of GTs, including folding, substrate specificity, regioselectivity, donor sugar nucleotides, catalytic reversibility, and differences between GTs and GHs. In particular, we highlighted the recent advancements in multi-enzyme cascade reactions and co-immobilization of GTs, focusing on overcoming problems with product inhibition and cost issues. Finally, we presented various types of GT that have been successfully used for oligosaccharide synthesis. We concluded that there is still an opportunity for improvement in enzymatically produced oligosaccharide yield, and future research should focus on improving the yield and reducing the production cost.

Recent years have seen a lot of interest in transition metal carbides/carbonitrides (MXenes), Which is one of newly proliferating two-dimensional (2D) materials.The advantages and applications of synthesizing MXenes-based biosensing systems are interesting. There is an urgent requirement for synthesis of MXenes. Through foliation, physical adsorption, and interface modification,it has been proposed that many biological disorders are related to genetic mutation. Majority of mutations were discovered to be nucleotide mismatches. Consequently, accurate -nucleotide mismatched discrimination is crucial for both diagnosing and treating diseases. To differentiate between such a sensitivealterations in the DNA duplex, several detection methods, particularly Electrochemical-luminescence (ECL) ones, have really been investigated.Mn+1XnTx is common name for MXenes, a novel family of two-dimensional (2D) transition metal carbides, nitrides, and carbonitrides, where T stands for interface termination units (i.e. = O, OH, and/or F). These electronic characteristics of MXenes may be changed between conductive to semiconducting due to abundant organometallic chemistry.Solid-state ECL sensors predicated on MXene would provide the facile nucleotide detection and convenience for usage with minimal training, mobility and possibly minimal cost.This study emphasizes upcoming requirements and possibilities in this area while describing the accomplishments achieved in the usage and employing of MXenes in the research and development of facile biomarkerdetection and their significance in designing electrochemical sensors. Opportunities are addressed for creating 2D MXene materials sensors and devices with incorporated biomolecule sensing. MXenes Carry out this process sensors, address the advantages of using MXenes and their variants as detecting materials for gathering different types of data, and attempt to clarify the design principles and operation of related MXene-based sensors, such as nucleotide detection, Single nucleotide detectors, Cancer theranostics, Biosensing capabilities, Gliotoxin detection, SARS-COV-2 nucleocapsid detection, electrochemical sensors, visual sensors, and humidity sensors. Finally, we examine the major issues and prospects for MXene-based materials used in various sensing applications.

Chronic unresolving inflammation is emerging as a key underlying pathological feature of many if not most diseases ranging from autoimmune conditions to cardiometabolic and neurological disorders. Dysregulated immune and inflammasome activation is thought to be the central driver of unresolving inflammation, which in some ways provides a unified theory of disease pathology and progression. Inflammasomes are a group of large cytosolic protein complexes that, in response to infection- or stress-associated stimuli, oligomerize and assemble to generate a platform for driving inflammation. This occurs through proteolytic activation of caspase-1-mediated inflammatory responses, including cleavage and secretion of the proinflammatory cytokines interleukin (IL)-1β and IL-18, and initiation of pyroptosis, an inflammatory form of cell death. Several inflammasomes have been characterized. The most well-studied is the nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome, so named because the NLRP3 protein in the complex, which is primarily present in immune and inflammatory cells following activation by inflammatory stimuli, belongs to the family of nucleotide-binding and oligomerization domain (Nod) receptor proteins. Several NLRP3 inflammasome inhibitors are in development, all with multi-indication activity. This review discusses the current status, known mechanisms of action, and disease-modifying therapeutic potential of RRx-001, a direct NLRP3 inflammasome inhibitor under investigation in several late-stage anticancer clinical trials, including a phase 3 trial for the treatment of third-line and beyond small cell lung cancer (SCLC), an indication with no treatment, in which RRx-001 is combined with reintroduced chemotherapy from the first line, carboplatin/cisplatin and etoposide (ClinicalTrials.gov Identifier: NCT03699956). Studies from multiple independent groups have now confirmed that RRx-001 is safe and well tolerated in humans. Additionally, emerging evidence in preclinical animal models suggests that RRx-001 could be effective in a wide range of diseases where immune and inflammasome activation drives disease pathology.

The alphabet of building blocks for RNA molecules is much larger than the standard four nucleotides. The diversity is achieved by the post-transcriptional biochemical modification of these nucleotides into distinct chemical entities that are structurally and functionally different from their unmodified counterparts. Some of these modifications are constituent and critical for RNA functions, while others serve as dynamic markings to regulate the fate of specific RNA molecules. Together, these modifications form the epitranscriptome, an essential layer of cellular biochemistry. As of the time of writing this review, more than 300 distinct RNA modifications from all three life domains have been identified. However, only a few of the most well-established modifications are included in most reviews on this topic. To provide a complete overview of the current state of research on the epitranscriptome, we analyzed the extent of the available information for all known RNA modifications. We selected 25 modifications to describe in detail. Summarizing our findings, we describe the current status of research on most RNA modifications and identify further developments in this field.

UNASSIGNED: Next-generation sequencing methods have been developed and proposed to investigate any query in genomics or clinical activity involving DNA. Technical advancement in these sequencing methods has enhanced sequencing volume to several billion nucleotides within a very short time and low cost. During the last few years, the usage of the latest DNA sequencing platforms in a large number of research projects helped to improve the sequencing methods and technologies, thus enabling a wide variety of research/review publications and applications of sequencing technologies.
UNASSIGNED: The proposed study is aimed at highlighting the most fast and accurate NGS instruments developed by various companies by comparing output per hour, quality of the reads, maximum read length, reads per run, and their applications in various domains. This will help research institutions and biological/clinical laboratories to choose the sequencing instrument best suited to their environment. The end users will have a general overview about the history of the sequencing technologies, latest developments, and improvements made in the sequencing technologies till now.
UNASSIGNED: The proposed study, based on previous studies and manufacturers\' descriptions, highlighted that in terms of output per hour, Nanopore PromethION outperformed all sequencers. BGI was on the second position, and Illumina was on the third position.
UNASSIGNED: The proposed study investigated various sequencing instruments and highlighted that, overall, Nanopore PromethION is the fastest sequencing approach. BGI and Nanopore can beat Illumina, which is currently the most popular sequencing company. With respect to quality, Ion Torrent NGS instruments are on the top of the list, Illumina is on the second position, and BGI DNB is on the third position. Secondly, memory- and time-saving algorithms and databases need to be developed to analyze data produced by the 3rd- and 4th-generation sequencing methods. This study will help people to adopt the best suited sequencing platform for their research work, clinical or diagnostic activities.

Genetic kidney disease comprises a diverse group of disorders. These can roughly be divided in the phenotype groups congenital anomalies of the kidney and urinary tract, ciliopathies, glomerulopathies, stone disorders, tubulointerstitial kidney disease, and tubulopathies. Many etiologies can lead to chronic kidney disease that can progress to end-stage kidney disease. Despite each individual disease being rare, together these genetic disorders account for a large proportion of kidney disease cases. With the introduction of massively parallel sequencing, genetic testing has become more accessible, but a comprehensive analysis of the diagnostic yield is lacking. This review gives an overview of the diagnostic yield of genetic testing across and within the full range of kidney disease phenotypes through a systematic literature search that resulted in 115 included articles. Patient, test, and cohort characteristics that can influence the diagnostic yield are highlighted. Detection of copy number variations and their contribution to the diagnostic yield is described for all phenotype groups. Also, the impact of a genetic diagnosis for a patient and family members, which can be diagnostic, therapeutic, and prognostic, is shown through the included articles. This review will allow clinicians to estimate an a priori probability of finding a genetic cause for the kidney disease in their patients.

BACKGROUND: Quantitative polymerase chain reaction (qPCR) is a molecular method used in laboratories for detection and quantification of DNA nucleotides. Standard curves and reference values are usually combined into the PCR amplification process to calculate initial amount of target DNA molecule in a testing sample. This study is a retrospective review to examine the performance of standard curves in a qPCR-based assay for the screening of a genetic disorder in laboratories.
METHODS: Three different scenarios were designed to replay the historical data generated from over 3,000 qPCR assays to evaluate how omission of standard curves would affect the overall screening results.
RESULTS: The outcomes of all the scenarios concluded that including standard curves in qPCR assays had decreased the screening specificity and accuracy, resulting in more false positives and additional retests. This was particularly true in case the initial DNA molecules were at relatively low copy numbers.
CONCLUSIONS: It strongly suggests that the implantation of qPCR assays in diagnostic procedures should be frequently retested and reviewed. More importantly, the strategies of retrospective review and scenario analysis presented here will provide a good framework for assay validation and periodic quality assurance in laboratory.

Nucleotidases contribute to the regulation of inflammation, coagulation, and cardiovascular activity. Exercise promotes biological adaptations, but its effects on nucleotidase activities and expression are unclear. The objective of this study was to review systematically the effects of exercise on nucleotidase functionality in healthy and unhealthy subjects. The MEDLINE, EMBASE, Cochrane Library, and Web of Science databases were searched to identify, randomized clinical trials, non-randomized clinical trials, uncontrolled clinical trials, quasi-experimental, pre-, and post-interventional studies that evaluated the effects of exercise on nucleotidases in humans, and was not limited by language and date. Two independent reviewers performed the study selection, data extraction, and assessment of risk of bias. Of the 203 articles identified, 12 were included in this review. Eight studies reported that acute exercise, in healthy and unhealthy subjects, elevated the activities or expression of nucleotidases. Four studies evaluated the effects of chronic training on nucleotidase activities in the platelets and lymphocytes of patients with metabolic syndrome, chronic kidney disease, and hypertension and found a decrease in nucleotidase activities in these conditions. Acute and chronic exercise was able to modify the blood plasma and serum levels of nucleotides and nucleosides. Our results suggest that short- and long-term exercise modulate nucleotidase functionality. As such, purinergic signaling may represent a novel molecular adaptation in inflammatory, thrombotic, and vascular responses to exercise.