Endoscopic Repair of Internal Carotid Artery Injury with a Lateral Tongue Muscle Patch Graft: Novel Technique and Literature Review.

Objectives Iatrogenic injury to the internal carotid artery (ICA) is one of the most catastrophic complications of endoscopic sinus and skull base surgery. Previous research has shown that packing with a crushed muscle graft at the injury site can be an effective management technique to control bleeding and prevent the need for ICA sacrifice. Here, we describe a novel and readily available repair donor site-an autologous lateral tongue muscle patch. Design Three representative cases of a successful repair of ICA injuries using a lateral tongue muscle patch are included in this study. The graft measured approximately 2 × 3 cm and was taken from the lateral intrinsic tongue musculature. We describe the harvest of the graft, its advantages, and the details of operative repair. Results The lateral tongue provides a large and readily accessible source of muscle within the surgical field that can be quickly harvested during an endoscopic procedure. For the first case, an expanding parasellar ICA pseudoaneurysm was managed with a tongue muscle patch and nasal packing. In the second case, a cavernous ICA injury was sustained during craniopharyngioma resection. Case three involved an ICA injury during endonasal debridement of invasive fungal rhinosinusitis. None of the patients required embolization or neurovascular stenting. Postoperative angiograms and serial computed tomography angiograms showed complete resolution of the pseudoaneurysm, and the patients continued to do well at least 1 year after repair. Conclusion Lateral tongue muscle graft is an effective and efficient method to manage ICA injuries during endoscopic endonasal surgery. Advantages include the speed of harvest, donor site being readily accessible in the surgical field, and low donor site morbidity. It should be added to the repertoire of possible donor sites for addressing catastrophic sinonasal bleeding.

Genetic dependencies associated with transcription factor activities in human cancer cell lines.

Transcription factors (TFs) are important mediators of aberrant transcriptional programs in cancer cells. In this study, we focus on TF activity (TFa) as a biomarker for cell-line-selective anti-proliferative effects, in that high TFa predicts sensitivity to loss of function of a given gene (i.e., genetic dependencies [GDs]). Our linear-regression-based framework identifies 3,047 pan-cancer and 3,952 cancer-type-specific candidate TFa-GD associations from cell line data, which are then cross-examined for impact on survival in patient cohorts. One of the most prominent biomarkers is TEAD1 activity, whose associations with its predicted GDs are validated through experimental evidence as proof of concept. Overall, these TFa-GD associations represent an attractive resource for identifying innovative, biomarker-driven hypotheses for drug discovery programs in oncology.

Postoperative Cosmetic Scores and Revision Rates After Nasal Mohs Reconstructive Surgery.

OBJECTIVE: Few studies have examined the impact of preoperative and surgical factors on the change in cosmetic survey scores after nasal Mohs reconstruction using a subset of the 10-item Standardized Cosmesis and Health Nasal Outcomes Survey-Cosmesis (SCHNOS-C). We aim to determine preoperative and surgical factors that impact cosmetic outcomes following Mohs nasal reconstruction. STUDY DESIGN: Retrospective analysis. SETTING: Nasal Mohs reconstruction patients at a tertiary medical center. METHODS: All patients receiving Mohs reconstruction of any nasal subunit at a tertiary medical center were analyzed. Variables collected included demographic and Mohs defect/reconstruction characteristics. Primary outcomes were changes in cosmetic (SCHNOS-C) scores and revision rates. Multivariable analysis was used to identify independent predictors of cosmetic scores/revision. RESULTS: We included 296 patients for analysis. On multivariable logistic regression, factors contributing to better final cosmetic scores were receiving a skin/composite graft (odds ratio [OR]: 0.22, 95% confidence interval: 0.06-0.68, P = .014) compared to a local flaps. Women were more likely to have worsening cosmetic scores (OR: 2.27, 1.06-4.99, P = .037). Only initial cosmetic scores independently predicted receiving any revision (OR: 1.11, 1.03-1.20, P = .006). CONCLUSION: Average SCHNOS-C scores after nasal reconstruction of Mohs defects are low. Only worse patient reported SCHNOS-C scores predicted revision. It is important to understand preoperative and surgical factors that affect cosmetic outcomes to optimize patient counseling and reconstructive planning. Patient perception is a key factor in predicting revisions.

Explorative Discovery of Gene Signatures and Clinotypes in Glioblastoma Cancer Through GeneTerrain Knowledge Map Representation.

This study introduces the GeneTerrain Knowledge Map Representation (GTKM), a novel method for visualizing gene expression data in cancer research. GTKM leverages protein-protein interactions to graphically display differentially expressed genes (DEGs) on a 2-dimensional contour plot, offering a more nuanced understanding of gene interactions and expression patterns compared to traditional heatmap methods. The research demonstrates GTKM's utility through four case studies on glioblastoma (GBM) datasets, focusing on survival analysis, subtype identification, IDH1 mutation analysis, and drug sensitivities of different tumor cell lines. Additionally, a prototype website has been developed to showcase these findings, indicating the method's adaptability for various cancer types. The study reveals that GTKM effectively identifies gene patterns associated with different clinical outcomes in GBM, and its profiles enable the identification of sub-gene signature patterns crucial for predicting survival. The methodology promises significant advancements in precision medicine, providing a powerful tool for understanding complex gene interactions and identifying potential therapeutic targets in cancer treatment.

A case report of successful primary percutaneous coronary intervention to an occluded anomalous left main coronary artery arising from the right coronary sinus.

Background: Anomalous aortic origin of a coronary artery from the opposite sinus is a rare congenital abnormality that may be encountered during primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). Case summary: A 65-year-old man presented with chest pain and signs of heart failure. Electrocardiogram demonstrated atrial fibrillation with ST elevation in the high lateral leads, and he was taken emergently to the cardiac catheterization laboratory for primary PCI. Coronary angiography identified the culprit to be an occluded anomalous left main coronary artery (LMCA) arising from the right coronary cusp, and primary PCI was successfully performed in the LMCA and the left anterior descending artery (LAD). Computed tomography angiography confirmed a benign retroaortic course of the anomalous LMCA with no additional high-risk features, as well as a new left atrial appendage thrombus. He subsequently developed deep venous thrombosis, acute pulmonary embolism, and acute kidney injury secondary to renal artery embolism with associated infarction. Workup for patent foramen ovale and thrombophilia were negative, and he was discharged in a stable condition. At 2-month follow-up, he was asymptomatic with no evidence of myocardial ischaemia on stress cardiac magnetic resonance imaging. Discussion: We present the first reported case of an occluded anomalous LMCA arising from the right coronary sinus in a patient presenting with STEMI. Rapid recognition of this congenital anomaly and selection of an appropriate guide catheter were keys to achieving timely reperfusion and a good outcome in this case.

Comparative Outcomes for Microvascular Free Flap Monitoring Outside the Intensive Care Unit.

OBJECTIVE: There is a trend towards nonintensive care unit (ICU) or specialty ward management of select patients. Here, we examine postoperative outcomes for patients transferred to a general ward following microvascular free flap (FF) reconstruction of the head and neck. STUDY DESIGN: Retrospective quality control study. SETTING: Single tertiary care center. METHODS: Consecutive patients who underwent FF of the head and neck before and after a change in protocol from immediate postoperative monitoring in the ICU ("Pre-protocol") to the general ward setting ("Post-protocol"). Outcomes included overall length of stay (LOS), ICU LOS, FF compromise, and postoperative complications. RESULTS: A total of 150 patients were included, 70 in the pre-protocol group and 80 in the post-protocol group. There were no significant differences in age, sex, comorbidities, tumor stage, or type of FF. Mean LOS decreased from 8.18 to 7.68 days (P = .4), and mean ICU LOS decreased significantly from 5.2 to 1.7 days (P < .01). There were no significant differences in postoperative or airway-related complications (P = .6) or FF failure rate (2.9% vs 2.6%, P > .9). There was a non-significant increase in ancillary consults in the post-protocol group (45% vs 33%, P = .13) and a significant increase in rapid response team calls, a nurse-driven safety net for abnormal vitals or mental status (19% vs 3%, P = .003). CONCLUSION: We show the successful implementation of a protocol shifting care of FF patients from the ICU to a general ward postoperatively, suggesting management on the floor with less frequent flap monitoring is safe and conserves ICU beds. Additional teaching and familiarity with these patients may over time reduce the rapid response calls.

Redesigning the kinetics of lysozyme amyloid aggregation by cephalosporin molecules.

In lysozyme amyloidosis, fibrillar aggregates of lysozyme are associated with severe renal, hepatic, and gastrointestinal manifestations, with no definite therapy. Current drugs are now being tested in amyloidosis clinical trials as aggregation inhibitors to mitigate disease progression. The tetracycline group among antimicrobials in use is in phase II of clinical trials, whereas some macrolides and cephalosporins have shown neuroprotection. In the present study, two cephalosporins, ceftazidime (CZD) and cefotaxime (CXM), and a glycopeptide, vancomycin (VNC), are evaluated for inhibition of amyloid aggregation of hen egg white lysozyme (HEWL) under two conditions (i) 4 M guanidine hydrochloride (GuHCl) at pH 6.5 and 37° C, (ii) At pH 1.5 and 65 °C. Fluorescence quench titration and molecular docking methods report that CZD, CXM, and VNC interact more strongly with the partially folded intermediates (PFI) in comparison to the protein's natural state (N). However, only CZD and CXM proficiently inhibit the aggregation. Transmission electron microscopy, tinctorial assessments, and aggregation kinetics all support oligomer-level inhibition. Transition structures in CZD-HEWL and CXM-HEWL aggregation are shown by circular dichroism (CD). On the other hand, kinetic variables and soluble fraction assays point to a localized association of monomers. Intrinsic fluorescence (IF),1-Anilino 8-naphthalene sulphonic acid, and CD demonstrate structural and conformational modifications redesigning the PFI. GuHCl-induced unfolding and differential scanning fluorimetry suggested that the PFI monomers bound to CZD and CXM exhibited partial stability. Our results present two mechanisms that function in both solution conditions, creating a novel avenue for the screening of putative inhibitors for drug repurposing. We extend our proposed mechanisms in the designing of physical inhibitors of amyloid aggregation considering shorter time frames and foolproof methods.Communicated by Ramaswamy H. Sarma.

Drug repurposing has overcome failures in drug discovery and has reduced the overall time and cost of drug discovery and development.We examined the effect of screened antibiotics, ceftazidime (CZD), cefotaxime (CXM), and vancomycin (VNC) on lysozyme aggregation under two solution conditions.These antibiotics inhibit/modulate the aggregation reactions by strongly interacting with aggregation-prone intermediate and modulation of conformation and stability.Our study puts forward with caution two cephalosporins for aggregation inhibition studies.

Decoding Altered Consciousness: An Artery of Percheron Stroke.

The artery of Percheron (AOP) is a unique variant of the thalamic and midbrain perforating arteries. It originates from the P1 branch of the posterior cerebral artery (PCA) and supplies the bilateral paramedian thalami (BPT) along with variable contributions to the rostral midbrain. Four infarction patterns have been identified as a result of an AOP stroke, each associated with varying prognostic outcomes. We present an 89-year-old female with an AOP infarction and discuss the associated symptoms, implicated anatomy, and prognosis.

Green synthesis of chitosan-encapsulated CuO nanocomposites for efficient degradation of cephalosporin antibiotics in contaminated water.

The synthesis and characterization of chitosan encapsulated copper oxide nanocomposites (CuNPs) using plant extracts for the photocatalytic degradation of second-generation antibiotics, cefixime and cefuroxime, were investigated. The study revealed that the presence of diverse chemical components in the plant extract significantly influenced the size of the CuNPs, with transmission electron microscopy (TEM) showing spherical shapes and sizes ranging from 11-35 nm. The encapsulation process was confirmed by an increase in size for certain samples, indicating successful encapsulation. X-ray photoelectron spectroscopy (XPS) analysis further elucidated the chemical makeup, confirming the valency state of Cu2+ and the presence of Cu-O bonding, with no contaminants detected. Photocatalytic activity assessments demonstrated that the copper oxide nanocomposites exhibited significant degradation capabilities against both antibiotics under UV light irradiation, with encapsulated nanocomposites (EnCu30) showing up to 96.18% degradation of cefuroxime within 60 min. The study highlighted the influence of chitosan encapsulation on enhancing photocatalytic performance, attributed to its high adsorption capability. Recycling studies confirmed the sustainability of the Cu nanocomposites, maintaining over 89% degradation rate after five consecutive cycles. This research underscores the potential of green-synthesized CuNPs as efficient, stable photocatalysts for the degradation of harmful antibiotics, contributing to environmental sustainability and public health protection.

Morphometric Evaluation of Sutural Patterns at the Pterion and Asterion in Dry Indian Skulls: Surgical Relevance.

INTRODUCTION: The pterion and asterion serve as crucial landmarks on the skull, representing the antero-lateral and postero-lateral fontanelles in neonates, respectively. In clinical practice, these points play a pivotal role in guiding the understanding of deeper structures and their relationships to the head's surface. The thin calvarium at these junctures is susceptible to fractures, and the underlying vessels are prone to tear, often leading to extradural hematoma formation, necessitating burr hole surgery for evacuation. MATERIAL AND METHODS: The study involved 40 human dry skulls in Indians (n= 27 male (10.8%), n= 13 female (5.2%)) of unknown age, evaluating morphometric characteristics of 80 pterions and asterions. Measurements were conducted using a digital caliper (SKADIOO±0.2mm/0.01") in millimeters on both sides of each skull. The investigation also included an examination of sutural patterns in Pterion and asterion. RESULTS: Three types of sutural patterns were identified in the pterion, the most common being the sphenoparietal variety (75% on the right, 70% on the left), followed by the epipteric variety, which was the second most common (11.3% on the right, 12.5% on the left), and then the frontotemporal type (1.3% on the right, 2.5% on the left). Two sutural patterns were observed in the asterion: type 1 (presence of sutural bone) in 17.9% of skulls and type 2 (absence of sutural bone) in 82.1%. CONCLUSION: The differences in pterion and asterion positions across various populations explored in previous studies motivated us to conduct this research in the Indian population. Our findings revealed that among Indians, the predominant pterion type is predominantly sphenoparietal, whereas type 2 is the most prevalent in asterion. Understanding the clinical significance of the pterion and asterion is crucial for healthcare professionals to ensure precise and safe surgical procedures, particularly for the effective treatment of head trauma patients.

Calcifying Aponeurotic Fibroma of Leg Masquerading as Hemangioma in an Adolescent Male along with Review of Literature.

Calcifying aponeurotic fibroma (CAF) is a rare soft tissue tumor which falls under the WHO category of benign fibroblastic and myofibroblastic tumors. It typically occurs on the distal extremities (hands and foot) of children and adolescents. Other less common sites include wrists, ankles, trunk and rarely legs and arms. These tumors present as a painless soft tissue mass, arising in the subcutis, and are usually connected to tendons or aponeuroses. Computed tomography (CT) and magnetic resonance imaging (MRI) are the radiological investigations of choice; however, histopathology remains the diagnostic modality of choice for the diagnosis of CAF. We present a rare case of a 17-year-old boy who presented with a gradually progressive mass lesion on the leg which was later diagnosed as calcifying aponeurotic fibroma on histopathology.

An improved mouse model of sepsis based on intraperitoneal injections of the enriched culture of cecum slurry.

AIM: Sepsis is a life-threatening clinical syndrome comprising multiorgan dysfunctions caused by a disproportionate body immune response. There are several animal sepsis models which are based on cecum ligation, cecal puncture, and cecum slurry injection. The major limitation of all current sepsis models is the high variability owing to the variable degree of ligation, puncture and inconsistent microbial composition used for sepsis initiation. The primary objective of this work is to demonstrate the feasibility of a standardized method for sepsis development. MATERIALS AND METHODS: The cecal slurry bacterial culture was developed and preserved in glycerol stocks. Antibiotics aztreonam and vancomycin were used for generating several defined, enriched cecal slurry bacterial cultures. Mice survival was assessed until 48 hrs post injection, and the tissue samples were collected after 10 hrs from sepsis initiation. KEY FINDINGS: The results indicate that increasing polymicrobial load resulted in lower survival rates and was associated with the higher number of infiltrating immune cells and necrosis. H&E (haematoxylin & eosin) staining & serum markers revealed that septic mice exhibited increased inflammation and significant damage to the liver and kidneys. The defined Gram-negative and Gram-positive specific cecal slurry bacterial cultures were developed and their efficiency in inducing sepsis was characterized. SIGNIFICANCE: Enriched cecal slurry bacterial cultures can be stored in glycerol stocks at -80 °C. This has an ethical advantage of avoiding unnecessary animal euthanasia for each experiment and provides a standardization capability of sepsis development.

Developments in conducting polymer-, metal oxide-, and carbon nanotube-based composite electrode materials for supercapacitors: a review.

Supercapacitors are the latest development in the field of energy storage devices (ESDs). A lot of research has been done in the last few decades to increase the performance of supercapacitors. The electrodes of supercapacitors are modified by composite materials based on conducting polymers, metal oxide nanoparticles, metal-organic frameworks, covalent organic frameworks, MXenes, chalcogenides, carbon nanotubes (CNTs), etc. In comparison to rechargeable batteries, supercapacitors have advantages such as quick charging and high power density. This review is focused on the progress in the development of electrode materials for supercapacitors using composite materials based on conducting polymers, graphene, metal oxide nanoparticles/nanofibres, and CNTs. Moreover, we investigated different types of ESDs as well as their electrochemical energy storage mechanisms and kinetic aspects. We have also discussed the classification of different types of SCs; advantages and drawbacks of SCs and other ESDs; and the use of nanofibres, carbon, CNTs, graphene, metal oxide-nanofibres, and conducting polymers as electrode materials for SCs. Furthermore, modifications in the development of different types of SCs such as pseudo-capacitors, hybrid capacitors, and electrical double-layer capacitors are discussed in detail; both electrolyte-based and electrolyte-free supercapacitors are taken into consideration. This review will help in designing and fabricating high-performance supercapacitors with high energy density and power output, which will act as an alternative to Li-ion batteries in the future.

An NLP-based technique to extract meaningful features from drug SMILES.

NLP is a well-established field in ML for developing language models that capture the sequence of words in a sentence. Similarly, drug molecule structures can also be represented as sequences using the SMILES notation. However, unlike natural language texts, special characters in drug SMILES have specific meanings and cannot be ignored. We introduce a novel NLP-based method that extracts interpretable sequences and essential features from drug SMILES notation using N-grams. Our method compares these features to Morgan fingerprint bit-vectors using UMAP-based embedding, and we validate its effectiveness through two personalized drug screening (PSD) case studies. Our NLP-based features are sparse and, when combined with gene expressions and disease phenotype features, produce better ML models for PSD. This approach provides a new way to analyze drug molecule structures represented as SMILES notation, which can help accelerate drug discovery efforts. We have also made our method accessible through a Python library.

Adaptor molecules mediate negative regulation of macrophage inflammatory pathways: a closer look.

Macrophages play a central role in initiating, maintaining, and terminating inflammation. For that, macrophages respond to various external stimuli in changing environments through signaling pathways that are tightly regulated and interconnected. This process involves, among others, autoregulatory loops that activate and deactivate macrophages through various cytokines, stimulants, and other chemical mediators. Adaptor proteins play an indispensable role in facilitating various inflammatory signals. These proteins are dynamic and flexible modulators of immune cell signaling and act as molecular bridges between cell surface receptors and intracellular effector molecules. They are involved in regulating physiological inflammation and also contribute significantly to the development of chronic inflammatory processes. This is at least partly due to their involvement in the activation and deactivation of macrophages, leading to changes in the macrophages' activation/phenotype. This review provides a comprehensive overview of the 20 adaptor molecules and proteins that act as negative regulators of inflammation in macrophages and effectively suppress inflammatory signaling pathways. We emphasize the functional role of adaptors in signal transduction in macrophages and their influence on the phenotypic transition of macrophages from pro-inflammatory M1-like states to anti-inflammatory M2-like phenotypes. This endeavor mainly aims at highlighting and orchestrating the intricate dynamics of adaptor molecules by elucidating the associated key roles along with respective domains and opening avenues for therapeutic and investigative purposes in clinical practice.

Identification and characterization of repurposed small molecule inhibitors of Mycobacterium tuberculosis caseinolytic protease B (ClpB) as anti-mycobacterials.

Mycobacterium tuberculosis (Mtb) caseinolytic protease B (ClpB) is a chaperone possessing a unique ability to resolubilize the aggregated proteins in vivo. ClpB has been shown to be important for the survival of Mtb within the host. Thus, it appears to be a promising target to develop new therapeutic molecules against tuberculosis. In this study, we have screened FDA approved compounds in silico to identify inhibitors against Mtb ClpB. In our screen, several compounds interacted with ClpB. The top four compounds, namely framycetin, gentamicin, ribostamycin and tobramycin showing the highest binding energy were selected for further investigation. MD simulations and tryptophan-based quenching of ClpB-drug complexes established that the selected inhibitors stably interacted with the target protein. The inhibitor and protein complexes were found to be stabilized by hydrogen bonding, and hydrophobic interactions. Although, the compounds did not affect the ATPase activity of ClpB significantly, the protein resolubilization activity of ClpB was remarkably reduced in their presence. All four compounds potently inhibited the growth of Mtb H37Ra. The antimycobacterial activity of the compounds appears to be due the inhibition of functional ClpB oligomer formation, in turn affecting its chaperonic activity.

Safe and sustainable food packaging: Argemone albiflora mediated green synthesized silver-carrageenan nanocomposite films.

Silver-Carrageenan (Ag/Carr) nanocomposite film for food packing application by the green method using Argemone albiflora leaf extract has been developed in this study. Different plant parts of Argemone albiflora (blue stem prickly poppy) are used all over the world for the treatment of microbial infections, jaundice, skin diseases etc. GC-MS analysis was used to examine the phytochemical found in the Argemone albiflora leaf extract which reduces the metal ions to nanoscale. The biopolymer employed in the synthesis of nanocomposite film was carrageenan, a natural carbohydrate (polysaccharide) extracted from edible red seaweeds. We developed a food packing that is biodegradable, eco-friendly, economical and free from harmful chemicals. These films possess better UV barrier and mechanical and antimicrobial properties with 1 mM AgNO3 solution. The presence of silver nanoparticles in the carrageenan matrix was evident from FESEM. The mechanical properties were analysed by a Universal testing machine (UTM) and different properties like water vapour permeability (WVP), moisture content (MC) and total soluble matter (TSM) important for food packing applications were also analysed. The antimicrobial properties of the synthesized film samples were studied against E. coli and S. aureus pathogenic bacteria. These films were employed for the storage of cottage cheese (dairy product) and strawberries (fruit). This packing increased the shelf life of the packed food effectively. Ag/Carr films are biodegradable within four weeks.

Role of Vena Cava Filter in the Prophylaxis and Treatment of Venous Thromboembolism in Injured Adult Patients: A Systematic Review, Meta-Analysis, and Practice Management Guideline from the Eastern Association for the Surgery of Trauma [RETRACTED].

BACKGROUND: Injured patients are at an increased risk of developing deep vein thrombosis (DVT) and pulmonary embolism (PE). Inferior vena cava (IVC) filters have been used in injured patients to prevent venous thromboembolism (VTE), but current evidence-based guidelines are lacking. METHODS: Questions regarding IVC filter use in injured patients with clearly defined Population(s), Intervention(s), Comparison(s), and appropriately selected Outcomes (PICO) were formulated. The study sought to understand the evidence behind use of ultra short term IVC filters and use of IVC filters in injured patients with and without known VTE who are unable to receive therapeutic anticoagulation and chemoprophylaxis, respectively. A literature search and review was conducted, followed by meta-analysis. The quality of evidence was assessed per Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. RESULTS: There were twenty-one studies that were analyzed. Three studies were randomized controlled trials (RCTs), three were observational studies, and fifteen studies were retrospective studies. In injured patients without known acute VTE who cannot receive chemoprophylaxis, we recommend against placement of an IVC filter due to associated higher rate of mortality, DVT, PE, and length of stay. The quality of evidence was assessed to be low. In injured patients with known DVT who cannot receive chemoprophylaxis we conditionally recommend against placement of an IVC filter. The quality of evidence was assessed to be very low. No recommendations can be made with respect to placement of ultra short term IVC filters based upon available data. CONCLUSION: IVC filters should not be placed routinely for prophylaxis in injured adult patients without known VTE who cannot receive chemoprophylaxis. The taskforce conditionally recommends against the placement of IVC filter in injured adult patients with known DVT who cannot receive chemoprophylaxis. LEVEL OF EVIDENCE: Guideline; Systematic review/meta-analysis, level IV.

Loss of flavin-containing monooxygenase 3 modulates dioxin-like polychlorinated biphenyl 126-induced oxidative stress and hepatotoxicity.

Dioxin-like pollutants (DLPs), such as polychlorinated biphenyl 126 (PCB 126), are synthetic chemicals classified as persistent organic pollutants. They accumulate in adipose tissue and have been linked to cardiometabolic disorders, including fatty liver disease. The toxicity of these compounds is associated with activation of the aryl hydrocarbon receptor (Ahr), leading to the induction of phase I metabolizing enzyme cytochrome P4501a1 (Cyp1a1) and the subsequent production of reactive oxygen species (ROS). Recent research has shown that DLPs can also induce the xenobiotic detoxification enzyme flavin-containing monooxygenase 3 (FMO3), which plays a role in metabolic homeostasis. We hypothesized whether genetic deletion of Fmo3 could protect mice, particularly in the liver, where Fmo3 is most inducible, against PCB 126 toxicity. To test this hypothesis, male C57BL/6 wild-type (WT) mice and Fmo3 knockout (Fmo3 KO) mice were exposed to PCB 126 or vehicle (safflower oil) during a 12-week study, at weeks 2 and 4. Various analyses were performed, including hepatic histology, RNA-sequencing, and quantitation of PCB 126 and F2-isoprostane concentrations. The results showed that PCB 126 exposure caused macro and microvesicular fat deposition in WT mice, but this macrovesicular fatty change was absent in Fmo3 KO mice. Moreover, at the pathway level, the hepatic oxidative stress response was significantly different between the two genotypes, with the induction of specific genes observed only in WT mice. Notably, the most abundant F2-isoprostane, 8-iso-15-keto PGE2, increased in WT mice in response to PCB 126 exposure. The study's findings also demonstrated that hepatic tissue concentrations of PCB 126 were higher in WT mice compared to Fmo3 KO mice. In summary, the absence of FMO3 in mice led to a distinctive response to dioxin-like pollutant exposure in the liver, likely due to alterations in lipid metabolism and storage, underscoring the complex interplay of genetic factors in the response to environmental toxins.

Real-time study of spatio-temporal dynamics (4D) of physiological activities in alive biological specimens with different FOVs and resolutions simultaneously.

This article reports the development of a microscopy imaging system that gives feasibility for studying spatio-temporal dynamics of physiological activities of alive biological specimens (over entire volume not only for a particular section, i.e., in 4D). The imaging technology facilitates to obtain two image frames of a section of the larger specimen ([Formula: see text]) with different FOVs at different resolutions or magnifications simultaneously in real-time (in addition to recovery of 3D (volume) information). Again, this imaging system addresses the longstanding challenges of housing multiple light sources (6 at the maximum till date) in microscopy (in general) and light sheet fluorescence microscopy (LSFM) (in particular), by using a tuneable pulsed laser source (with an operating wavelength in the range [Formula: see text]-670 nm) in contrast to the conventional CW laser source being adopted for inducing photo-excitation of tagged fluorophores. In the present study, we employ four wavelengths ([Formula: see text] 488 nm, 585 nm, 590 nm, and 594 nm). Our study also demonstrates quantitative characterization of spatio-temporal dynamics (velocity-both amplitude and direction) of organelles (mitochondria) and their mutual correlationships. Mitochondria close to the nucleus (or in clustered cells) are observed to possess a lower degree of freedom in comparison to that at the cellular periphery (or isolated cells). In addition, the study demonstrates real-time observation and recording of the development and growth of all tracheal branches during the entire period ([Formula: see text] min) of embryonic development (Drosophila). The experimental results-with experiments being conducted in various and diversified biological specimens (Drosophila melanogaster, mouse embryo, and HeLa cells)-demonstrate that the study is of great scientific impact both from the aspects of technology and biological sciences.