Molecular Level Research Articles

Application of transgenic mice to the molecular pathogenesis of cataract

One of the most prevalent disorders that cause blindness worldwide is cataract, and its essence is the visual disorder caused by the opacity of the lens. The significant degree of variation in cataracts and the fact that a variety of factors can impact a patient’s lens transparency make it especially crucial to investigate the pathogenesis of cataracts at the molecular level. It has been found that more than 60 genes are linked to the formation of cataracts, and the construction of a transgenic mouse model of cataract similar to the selection of human lens clouding due to a variety of causes has become an important means of studying the pathogenesis of cataract. Therefore, the research on the application of transgenic mice to the molecular pathogenesis of cataracts will be the main topic of this review of the literature.

The Potential Use of Targeted Proteomics and Metabolomics for the Identification and Monitoring of Diabetic Kidney Disease

Diabetic kidney disease (DKD) is a prevalent microvascular complication of diabetes mellitus and is associated with a significantly worse prognosis compared to diabetic patients without kidney involvement, other microvascular complications, or non-diabetic chronic kidney disease, due to its higher risk of cardiovascular events, faster progression to end-stage kidney disease, and increased mortality. In clinical practice, diagnosis is based on estimated glomerular filtration rate (eGFR) and albuminuria. However, given the limitations of these diagnostic markers, novel biomarkers must be identified. Omics is a new field of study involving the comprehensive analysis of various types of biological data at the molecular level. In different fields, they have shown promising results in (early) detection of diseases, personalized medicine, therapeutic monitoring, and understanding pathogenesis. DKD is primarily utilized in scientific research and has not yet been implemented in routine clinical practice. The aim of this review is to provide an overview of currently available data on targeted omics. After an extensive literature search, 25 different (panels of) omics were withheld and analyzed. Both serum/plasma and urine proteomics and metabolomics have been described with varying degrees of evidence. For all omics, there is still a relative paucity of data from large, prospective, longitudinal cohorts, presumably because of the heterogeneity of DKD and the lack of patient selection in studies, the complexity of omics technologies, and various practical and ethical considerations (e.g., limited accessibility, cost, and privacy concerns).

Theoretical Investigation into Polymorphic Transformation between β-HMX and δ-HMX by Finite Temperature String

Polymorphic transformation is important in chemical industries, in particular, in those involving explosive molecular crystals. However, due to simulating challenges in the rare event method and collective variables, understanding the transformation mechanism of molecular crystals with a complex structure at the molecular level is poor. In this work, with the constructed order parameters (OPs) and K-means clustering algorithm, the potential of mean force (PMF) along the minimum free-energy path connecting β-HMX and δ-HMX was calculated by the finite temperature string method in the collective variables (SMCV), the free-energy profile and nucleation kinetics were obtained by Markovian milestoning with Voronoi tessellations, and the temperature effect on nucleation was also clarified. The barriers of transformation were affected by the finite-size effects. The configuration with the lower potential barrier in the PMF corresponded to the critical nucleus. The time and free-energy barrier of the polymorphic transformation were reduced as the temperature increased, which was explained by the pre-exponential factor and nucleation rate. Thus, the polymorphic transformation of HMX could be controlled by the temperatures, as is consistent with previous experimental results. Finally, the HMX polymorph dependency of the impact sensitivity was discussed. This work provides an effective way to reveal the polymorphic transformation of the molecular crystal with a cyclic molecular structure, and further to prepare the desired explosive by controlling the transformation temperature.

Structural characterization of wild edible Pleurotuscollected from Punjab, India

Oyster mushroom (Pleurotus spp.) belongs to the class Basidiomycetes, family Agaricaceae, commonly known as ‘dhingri’ in India and proliferates naturally on dead, decay wooden logs or trunks of deciduous or coniferous woods in tropical and temperate forests. Although Pleurotus mushrooms are commercially important mushrooms but wild Pleurotus still require public recognition. Hence, the present study aimed to conduct a field survey for collection of Pleurotus mushrooms from wild regions of of Punjab Two wild Pleurotus were collected and domesticated at Mushroom Research Complex, Punjab Agricultural University, Ludhiana, Punjab which were further analyzed at molecular and biochemical levels. These mushrooms were identified at species level through ITS (Internal transcribed spacer region) based method (18S ribosomal RNA gene, internal transcribed spacer, 5.8S ribosomal RNA gene, complete sequence; and 28S ribosomal RNA gene) was carried out. The gene bank accessioned Pleurotus sapidus as MK 281339 and Pleurotus floridanus as MK 281340. Hyphae of Pleurotus sapidus was observed to be packed tightly to a greater extent as compared to Pleurotus floridanus according to the ultra-structure recorded by scanning electron microscope. Both species of Pleurotus share two different proteins of same molecular weight 24.81 KDa and 28.43 KDa. Collecting and identifying wild species is crucial to preserve the wild fruits and fathom out the benefits of wild edible Pleurotus spp.

Gene expression profiling of Cacopsylla pyricola (Hemiptera: Psyllidae) infected with Ca. Phytoplasma pyri (Acholeplasmatales: Acholeplasmataceae) reveals candidate effectors and mechanisms of infection.

Phytoplasmas can negatively or positively alter vector host fitness. "Candidatus Phytoplasma pyri," is the causal agent of pear decline in commercial pear (Pyrus communis L.; Rosales: Rosaceae) and peach yellow leafroll in peach [Prunus persica (L.); Rosaceae]. This plant pathogen is transmitted by several species of pear psyllids (Cacopsylla spp. Hemiptera: Psyllidae). We sought to explore the relationship between the pear decline phytoplasma and its US vector, Cacopsylla pyricola (Förster), at the molecular genetic level through transcriptomic analysis using RNA-sequencing methodology. We also focused on phytoplasma and insect effectors, which are secreted proteins that can modulate interactions within a pathosystem. In this study, we identified 30 differentially expressed genes, 14 candidate insect effector genes, and 8 Ca. Phytoplasma pyri candidate effectors. Two strains of Ca. Phytoplasma pyri were identified based on immunodominant membrane protein sequence analysis from C. pyricola collected in the Pacific Northwest agricultural region. Here, we present a first genetic look at the pear decline pathosystem and report gene candidates for further exploration of infection mechanisms and potential tools for integrated pest management.

Dibenzothiophene S, S-Dioxide-Containing Dipolar Molecules As Efficient Hole-Transport Materials for p-i-n Perovskite Solar Cells.

Organic-inorganic hybrid perovskite solar cells (OIH-PSCs) have developed rapidly in the past decade, and the commercialization of OIH-PSCs demands low-cost hole-transport materials (HTMs) with high performance and stability. The present study synthesized two organic HTMs containing dibenzothiophene S-dioxide as the acceptor unit and triphenylamine as the donor (denoted by TPAF-SO2 and TPA-SO2). In TPAF-SO2, the methoxy group and adjacent fluorine atom were introduced to decrease the highest occupied molecular orbital energy level. In TPA-SO2, the methyl sulfide group is the end group that can passivate the lead ion. TPAF-SO2 and TPA-SO2 exhibit hole-transport mobilities as high as 1.12 × 10-3 and 2.31 × 10-3 cm2 v-1 s-1, respectively, and strongly passivate Pb vacancies. Compared with TPAF-SO2, TPA-SO2 is more suitable for the growth of perovskite crystals. The perovskite grown on the latter has a lower trap density and higher carrier mobility; thus, both the nonradiative recombination and the charge-transport loss are decreased. The OIH-PSC based on TPA-SO2 as the HTM achieved a power conversion efficiency (PCE) as high as 22.08%, whereas the device based on TPAF-SO2 achieved a PCE of only 18.42%. In addition, the unencapsulated device based on TPA-SO2 can maintain 85% of the initial PCE after being stored in N2 for 1200 h, whereas the device based on TPAF-SO2 decayed rapidly to zero in 800 h under the same conditions.

Molecularly and Structurally Designed Polyimide Nanofiber Radiative Cooling Films for Spacecraft Thermal Management

AbstractRadiative cooling films (RCFs) are crucial for spacecraft thermal management, but their optical performance is currently limited by their structures and intrinsic high absorption at short wavelengths. In this study, a novel RCF using electrospun polyimide nanofibers optimized at both the molecular and microscale levels is developed. The newly designed polyimide molecules significantly decrease visible and ultraviolet (UV) light absorption while maintaining excellent thermal radiation properties in the infrared spectrum. By optimizing the diameter and orientation of the nanofibers using Monte Carlo simulations, the resulting film achieves a solar reflectivity of 99.6% and a mid‐infrared emissivity of 0.93. Its physical structures and optical properties remain stable under exposure to UV light, atomic oxygen, and extreme temperature changes. Further vacuum radiative cooling tests reveal that the thermal equilibrium temperature of this film is approximately 28 °C lower than that of Kapton‐based RCFs currently used in spacecraft. These results provide a new approach for creating efficient thermal management materials for space applications, with potential for broader use in architecture, electronic devices, and outdoor equipment.

Generating Protein Structures for Pathway Discovery Using Deep Learning.

Resolving the intricate details of biological phenomena at the molecular level is fundamentally limited by both length- and time scales that can be probed experimentally. Molecular dynamics (MD) simulations at various scales are powerful tools frequently employed to offer valuable biological insights beyond experimental resolution. However, while it is relatively simple to observe long-lived, stable configurations of, for example, proteins, at the required spatial resolution, simulating the more interesting rare transitions between such states often takes orders of magnitude longer than what is feasible even on the largest supercomputers available today. One common aspect of this challenge is pathway discovery, where the start and end states of a scientific phenomenon are known or can be approximated, but the mechanistic details in between are unknown. Here, we propose a representation-learning-based solution that uses interpolation and extrapolation in an abstract representation space to synthesize potential transition states, which are automatically validated using MD simulations. The new simulations of the synthesized transition states are subsequently incorporated into the representation learning, leading to an iterative framework for targeted path sampling. Our approach is demonstrated by recovering the transition of a RAS-RAF protein domain (CRD) from membrane-free to interacting with the membrane using coarse-grain MD simulations.

Molecular detection of Coxiella burnetii in blood and hard tick-infested Egyptian camels and the possibility of coinfections

Coxiella burnetii, a bacterium that causes Q fever. It can infect mammals and has a global geographical distribution, but data on its occurrence in Egyptian dromedaries and the associated ticks are limited. Therefore, this study aims to detect C. burnetii in the blood of infested camels and associated ticks collected from Egypt by using molecular techniques and to examine the possibility of coinfections with C. burnetii. A total of 133 blood samples and 1260 hard ticks infesting these camels were collected from Egyptian slaughterhouses. Nested PCR and sequencing were used based on the IS1111 gene for molecular detection of C. burnetii. The identification of tick species at the molecular level was performed using the COX1 gene. C. burnetii was detected in Hyalomma (H) dromedarii, H. anatolicum, H. marginatum, Amblyomma (Am) lipidium, and Am. cohaerens with an overall prevalence rate of 1.3% (16/1260), while in the camel blood samples, it was 15.8% (21/133). Out of C. burnetii-positive ticks, there were double infections by Borrelia species and C. burnetii in H. dromedarii and Am. lipidium and triple infections at one Am. cohaerens tick (C. burnetii, Borrelia spp., and Babesia microti). In addition, two positive camel blood samples were found to carry C. burnetii with Borrelia spp. Our research findings indicate the presence of Coxiella burnetii among camels and their associated ticks in Egypt and emphasize the potential of having coinfection. To prevent the transmission of this infection to other animal species or humans, appropriate control measures should be implemented.

The conserved genetic program of male germ cells uncovers ancient regulators of human spermatogenesis.

Male germ cells share a common origin across animal species, therefore they likely retain a conserved genetic program that defines their cellular identity. However, the unique evolutionary dynamics of male germ cells coupled with their widespread leaky transcription pose significant obstacles to the identification of the core spermatogenic program. Through network analysis of the spermatocyte transcriptome of vertebrate and invertebrate species, we describe the conserved evolutionary origin of metazoan male germ cells at the molecular level. We estimate the average functional requirement of a metazoan male germ cell to correspond to the expression of approximately 10,000 protein-coding genes, a third of which defines a genetic scaffold of deeply conserved genes that has been retained throughout evolution. Such scaffold contains a set of 79 functional associations between 104 gene expression regulators that represent a core component of the conserved genetic program of metazoan spermatogenesis. By genetically interfering with the acquisition and maintenance of male germ cell identity, we uncover 161 previously unknown spermatogenesis genes and three new potential genetic causes of human infertility. These findings emphasize the importance of evolutionary history on human reproductive disease and establish a cross-species analytical pipeline that can be repurposed to other cell types and pathologies.

Compressive stresses in cancer: characterization and implications for tumour progression and treatment.

Beyond their many well-established biological aberrations, solid tumours create an abnormal physical microenvironment that fuels cancer progression and confers treatment resistance. Mechanical forces impact tumours across a range of biological sizes and timescales, from rapid events at the molecular level involved in their sensing and transmission, to slower and larger-scale events, including clonal selection, epigenetic changes, cell invasion, metastasis and immune response. Owing to challenges with studying these dynamic stimuli in biological systems, the mechanistic understanding of the effects and pathways triggered by abnormally elevated mechanical forces remains elusive, despite clear correlations with cancer pathophysiology, aggressiveness and therapeutic resistance. In this Review, we examine the emerging and diverse roles of physical forces in solid tumours and provide a comprehensive framework for understanding solid stress mechanobiology. We first review the physiological importance of mechanical forces, especially compressive stresses, and discuss their defining characteristics, biological context and relative magnitudes. We then explain how abnormal compressive stresses emerge in tumours and describe the experimental challenges in investigating these mechanically induced processes. Finally, we discuss the clinical translation of mechanotherapeuticsthat alleviate solid stresses and their potential to synergize with chemotherapy, radiotherapy and immunotherapies.

Long non-coding RNA MALAT1 triggers ferroptosis via interaction with FUS to enhance ACSF2 mRNA stabilization in septic acute kidney injury.

Septic acute kidney injury (AKI) is a fatal disease in the intensive care unit, with ferroptosis playing a crucial role in its pathogenesis. Long non-coding RNA (LncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been implicated in septic-induced AKI inflammation and apoptosis. However, its regulatory role in ferroptosis and underlying mechanisms remain unclear. In vivo and in vitro models of septic AKI were established using cecal ligation and puncture (CLP) and lipopolysaccharide (LPS) challenge, respectively. Serum levels of creatinine (Cr), blood urea nitrogen (BUN), kidney injury molecule-1 (Kim-1), neutrophil gelatinase-associated lipocalin (NGAL), and inflammatory cytokine in kidney tissues were determined by ELISA kits. Histopathological alterations and apoptosis were evaluated by HE staining and TUNEL. Ferroptosis was accessed by measuring MDA, GSH, Fe2+, total and lipid ROS levels, and mitochondrial ultrastructure changes. Target molecular levels were determined using RT-qPCR, Western blotting, and immunofluorescence. Interactions among MALAT1, acyl-CoA synthetase family member 2 (ACSF2) and FUS RNA binding protein (FUS) were validated by RIP and RNA-pull down. MALAT1 level was significantly elevated in both in vivo and in vitro septic AKI models, of which knockdown impeded ferroptosis to alleviate septic AKI. Mechanistically, high MALAT1 expression increased ACSF2 mRNA stability via interaction with FUS. Rescue experiments showed that ACSF2 overexpression partially reversed the ferroptosis inhibition mediated by MALAT1 silencing. MALAT1 induces ferroptosis and exacerbates septic AKI by stabilizing ACSF2 mRNA with the assistance of FUS. These findings provide theoretical evidence for MALAT1 as a potential therapeutic target for septic AKI.

Machine Learning-Aided 3D Dynamic SERS Strategy for Physiological Mapping: Biotoxicity of Environmentally Dimensional Aged Nanoplastics and Corresponding Protein Corona Complexes.

Nanoplastics (NPs) are emerging pollutants that undergo inevitable aging in the environment, raising concerns about human exposure and health hazards. Research on the cytotoxicity of various polymer types of NPs, aged nanoplastics (aNPs), and their interactions with proteins (aNPs-protein corona) is still nascent. Traditional cytotoxicity detection methods often rely on end point assays with restricted temporal resolution and analysis of single or multiple biomarkers. Here, we propose a novel approach integrating the 3D dynamic SERS strategy (DSS) with machine learning to rapidly analyze the cell fate and death modes induced by NPs, aNPs, and aNPs-protein corona complexes at the molecular level. PS, PVC, PMMA, and PC products from the water environment were used to prepare the corresponding NPs, and the impact of UV irradiation on their physicochemical properties was examined. DSS systematically maps the molecular changes in the cellular secretome caused by these NPs. Machine learning effectively extracts information from complex spectra, differentiating between biological samples. Results show prolonged UV exposure increases cell sensitivity to ferroptosis and cytotoxicity in various aNPs, while the protein corona on aNPs significantly mitigates toxicity associated with surface oxygen-containing functional groups, resulting in a reduced similarity to ferroptosis signatures. 3D DSS with machine learning technique analyzes the overall metabolite profile at the molecular level rather than individual biomarkers. This study is the first attempt to compare the biotoxicity of diverse polymer NPs, aNPs, and aNPs-protein coronas at cellular and molecular levels in human hepatocytes, enhancing our understanding of the complex biological impacts of NPs.

Non-nutritive Sweetener Aspartame Disrupts Circadian Behavior and Causes Memory Impairment in Mice.

As a non-nutritive sweetener, aspartame is widely used in everyday life. However, its safety is highly controversial, especially its effects on neurobehavior. We evaluated the effects of chronic daily oral administration of aspartame-containing drinking water (at doses equivalent to 7-28% of the FDA-recommended human DIV) on memory and rhythm behaviors in mice and further investigated changes at the molecular level in the brains. Our results demonstrated that mice exposed to aspartame exhibited memory impairment. Disorders of hippocampal neurotransmitter metabolism and pathological damage may be responsible for the aspartame-induced memory impairment via inhibition of the BDNF/TrkB pathway. Furthermore, our findings suggested that disturbed clock gene expression in the hypothalamus after aspartame exposure led to altered rest-activity behavior, and this disruption of the circadian rhythm may exacerbate memory impairment. This study highlights the negative neurobehavioral effects of aspartame and provides valuable insights into its rational and safe use.

Molecularly Modified Electrodes for Efficient Triboelectric Nanogenerators

The integration of organic molecules into monolayers on triboelectric layers and electrodes has significantly improved the performance of triboelectric nanogenerators (TENGs) in recent years. By modifying surfaces at the molecular level, one can enhance durability, power density, and cost‐efficiency, leading to flexible, lightweight, and more efficient devices. A simple chemistry of organic monolayer formation allows a precise control over orientation, coverage, consistency, and functionality. These monolayers boost surface charge density and output voltage while influencing surface polarization and dipole interactions. This review focuses on recent advances in chemical modification of electrodes for controlling surface charge density and altering surface dipoles, emphasizing the significance of organic monolayers. A new concept of Schottky‐based TENGs is also introduced that explores chemically modified sliding surfaces. Furthermore, the importance of flexoelectricity and its contribution to triboelectricity is discussed. By addressing current challenges and outlining future directions, this review underscores the crucial role of surface chemistry in advancing TENGs.

Purple Butter Clam (Saxidomus Purpurata) as a Potential Functional Food Source for Obesity Treatment.

Saxidomus purpurata extract (SPE) is a highly consumable seafood worldwide with known health-related benefits. However, there are no reports of its' anti-obesity effect. This study explores the potential of SPE for anti-obesity effects by modulating adipogenesis and lipolysis. SPE reduced intracellular lipid and triglyceride accumulation while increasing free glycerol release in adipocytes. SPE inhibited lipogenesis protein expressions and increased the phosphorylation of hormone-sensitive lipase and Adenosine monophosphate-activated protein kinase (AMPK) to promote lipolysis. In addition, SPE suppressed adipogenesis by downregulating protein expression of key adipogenic markers, peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein 1 (SREBP1) via Wnt/β-catenin signaling. SPE augmented the heme oxygenase-1 (HO-1) expression. Thus, pharmacological intervention with Zinc protoporphyrin (ZnPP-HO-1 antagonist) was employed to validate the HO-1 role. The presence of ZnPP increased the lipid accumulation and reduced the free glycerol release. At the molecular level, adipogenic transcription factors (PPARγ, C/EBPα, and SREBP1) expressions were restored in the presence of ZnPP. GC-MS analysis revealed that SPE was comprised of several fatty acids, contributing to its anti-obesity activity. SPE is an effective nutraceutical that can be used to reduce the progression of obesity. HO-1 expression during adipogenesis might be the mechanism of action for the anti-obesity effect of SPE.

Assessing the role of bacterial innate and adaptive immunity as barriers to conjugative plasmids.

Plasmids are ubiquitous mobile genetic elements, that can be either costly or beneficial for their bacterial host. In response to constant viral threat, bacteria have evolved various immune systems, such as the prevalent restriction modification (RM) (innate immunity) and CRISPR-Cas systems (adaptive immunity). At the molecular level, both systems also target plasmids, but the consequences of these interactions for plasmid spread are unclear. Using a modeling approach, we show that RM and CRISPR-Cas are effective as barriers against the spread of costly plasmids, but not against beneficial ones. Consequently, bacteria can profit from the selective advantages that beneficial plasmids confer even in the presence of bacterial immunity. While plasmids that are costly for bacteria may persist in the bacterial population for a certain period, RM and CRISPR-Cas can eventually drive them to extinction. Finally, we demonstrate that the selection pressure imposed by bacterial immunity on costly plasmids can be circumvented through a diversity of escape mechanisms and highlight how plasmid carriage might be common despite bacterial immunity. In summary, the population-level outcome of interactions between plasmids and defense systems in a bacterial population is closely tied to plasmid cost: Beneficial plasmids can persist at high prevalence in bacterial populations despite defense systems, while costly plasmids may face extinction.

A Study on the Morphology and Molecular Biology of Tropical Strawberries

The studies on the morpho-molecular characteristics of different strawberry genotypes were conducted at Bangabandhu Sheikh Mujibur Rahman Agricultural University (BSMRAU), Gazipur, Bangladesh. BARI Strawberry 1, BARI Strawberry 2, BARI Strawberry 3, FA 005, and Festival were used for this experiment. This study was undertaken to assess five tropical strawberry genotypes at morphological and molecular level. BARI Strawberry 2 was recognised as the preeminent genotype among five strawberry cultivars based on fruit production per plant (594.73 grammes), yield per hectare (19.39 tonnes), and fruit count per plant (32.42). The SSR technique was utilised to assess genetic variation and connections among five strawberry cultivars. Initially, ten primers were evaluated, and finally, three primers—EMFv104, ARSFL-10, and ARSFL-15—were selected for analysis. ARSFL-10 produced the fewest polymorphic alleles (3), while the markers EMFv104 and ARSFL-15 generated the most polymorphism alleles (4). The allele frequency for each location ranged from 0.4 (EMFv104) to 0.6 (ARSFL-10). The PIC values ranged from 0.672 on EMFv104 to 0.4992 on ARSFL-10. EMFv104 and ARSFL-15 demonstrated gene diversity scores of 0.72, whereas ARSFL-10 achieved a value of 0.56. The genotypes demonstrating the minimal genetic dissimilarity were BARI Strawberry 1 and Festival, with a value of 0.16667. Primer EMFv104 and ARSFL-15 are regarded as the most efficacious SSR markers for strawberry genotypes.

ESR Essentials: staging and restaging with FDG-PET/CT in oncology-practice recommendations by the European Society for Hybrid, Molecular and Translational Imaging.

Positron emission tomography (PET) stands as the paramount clinical molecular imaging modality, especially in oncology. Unlike conventional anatomical-morphological imaging methods such as computed tomography (CT) and magnetic resonance imaging (MRI), PET provides detailed visualizations of internal activity at the molecular and cellular levels. 18-fluorine-fluorodeoxyglucose ([18F]FDG)-PET combined with contrast-enhanced CT (ceCT) significantly improves the detection of various cancers. Appropriate patient selection is crucial, and physicians should carefully assess the appropriateness of [18F]FDG-PET/CT based on specific clinical criteria and evidence. Due to its high diagnostic accuracy, [18F]FDG-PET/CT is indispensable for evaluating the extent of disease, staging, and restaging known malignancies, and assessing the response to therapy. PET/CT imaging offers significant advantages in patient management, particularly by identifying occult metastases that might otherwise go undetected. This can help prevent unnecessary surgeries, allowing many patients to be redirected to systemic chemotherapy instead. However, it is important to note that the gold standard for surgical planning remains CT and/or MRI, depending on the body region. These imaging modalities, with or without associated angiography, provide superior contrast and spatial resolution, essential for detailed surgical preparation and planning. [18F]FDG-PET/CT has a central role in the precise and early diagnosis of cancer, contributing significantly to personalized treatment plans. However, it has limitations, including non-tumor-specific uptake and the potential to inaccurately capture the metabolic activity of certain tumor types due to low uptake in some well-differentiated tumor cell lines. Therefore, it should be utilized in clinical scenarios where it offers crucial diagnostic insights not readily available with other imaging modalities. KEY POINTS: Use [18F]FDG-PET/CT selectively based on clinical appropriateness criteria and existing evidence to optimize resource utilization and minimize patient exposure. Employ [18F]FDG-PET/CT in treatment planning and monitoring, particularly for assessing chemotherapy or radiotherapy response in FDG-avid lymphoma and solid tumors. When available, [18F]FDG-PET/CT can be integrated with other diagnostic tools, such as MRI, to enhance overall diagnostic accuracy.

Leveraging Multi-Omics Approaches and Advanced Technologies to Unravel the Molecular Complexities, Modifiers, and Precision Medicine Strategies for Hemoglobin H Disease.

Hemoglobin H (HbH) disease, a form of alpha-thalassemia, poses significant clinical challenges due to its complex molecular underpinnings. It is characterized by reduced synthesis of the alpha-globin chain. The integration of multi-omics and precision medicine holds immense potential to comprehensively understand and capture interactions at the molecular and genetic levels. This review integrates current multi-omics approaches and advanced technologies in HbH research. Furthermore, it delves into detailed pathophysiology and possible therapeutics in the upcoming future. We explore the role of genomics, transcriptomics, proteomics, and metabolomics studies, alongside bioinformatics tools and gene-editing technologies like CRISPR/Cas9, to identify genetic modifiers, decipher molecular pathways, and discover therapeutic targets. Recent advancements are unveiling novel genetic and epigenetic modifiers impacting HbH disease severity, paving the way for personalized precision medicine interventions. The significance of multi-omics research in unraveling the complexities of rare diseases like HbH is underscored, highlighting its potential to revolutionize clinical practice through precision medicine approaches. This paradigm shift can pave the way for a deeper understanding of HbH complexities and improved disease management.