Tissue Types Research Articles

Evolution of the ocular immune system.

The evolution of the ocular immune system should be viewed within the context of the evolution of the immune system, and indeed organisms, as a whole. Since the earliest time, the most primitive responses of single cell organisms involved molecules such as anti-microbial peptides and behaviours such as phagocytosis. Innate immunity took shape ~2.5 billion years ago while adaptive immunity and antigen specificity appeared with vertebrate evolution ~ 500 million years ago. The invention of the microscope and the germ theory of disease precipitated debate on cellular versus humoral immunity, resolved by the discovery of B and T cells. Most recently, our understanding of the microbiome and consideration of the host existing symbiotically with trillions of microbial genes (the holobiont), suggests that the immune system is a sensor of homoeostasis rather than simply a responder to pathogens. Each tissue type in multicellular organisms, such as vertebrates, has a customised response to immune challenge, with powerful reactions most evident in barrier tissues such as the skin and gut mucosa, while the eye and brain occupy the opposite extreme where responses are attenuated. The experimental background which historically led to the concept of immune privilege is discussed in this review; however, we propose that the ocular immune response should not be viewed as unique but simply an example of how the tissues variably respond in nature, more or less to the same challenge (or danger).

The Performance of a New Nanosecond Pulsed Field Ablation Surgical Clamp in Ablation of Cardiac Tissue: A Chronic Porcine Model.

The purpose of this chronic porcine model is to demonstrate safety and efficacy of a new nanosecond pulsed field ablation (nsPFA) parallel clamp in ablating different cardiac tissue. The Pulse Biosciences nsPFA CellFX Clamp System was tested on 6 pigs. Ablations were performed in all four heart chambers by delivering a sequence of very short duration high amplitude electrical pulses taking 1.25 seconds per application independent of tissue thickness or type. Testing for electrical exit block was performed at the time of surgery and at study termination. At 35 days, animals were euthanized and anonymized histopathology was performed to assess lesion width, depth and transmurality. Lesion pattern and general safety was compared to 6 animals in which a bipolar radiofrequency clamp was used (AtriCure Synergy Isolator System). There were no device-related serious adverse events in the nsPFA group. There was one early device related mortality at day 24 in the RFA group from perforation of one of the ventricular ablation sites. There were also two intracardiac thrombotic events with one systemic thromboembolic event in the radiofrequency group. Exit block was confirmed in all animals from both groups for the pulmonary veins and the posterior wall. Histological findings were consistent and demonstrated mature scar formation in all nsPFA ablation specimens, while a 7.1% rate of incomplete histopathological scar maturation was present in the RFA group. In this chronic porcine model, a single 1.25 second application independent of tissue thickness with the CellFX Parallel Clamp System demonstrated promising safety and efficacy profile. All lesions produced by this technology resulted in persistent exit block around pulmonary veins and the posterior atrial wall consistent with a reliable, contiguous and transmural ablation without injury to adjacent organs.

Genome-Wide Identification and Expression Analysis of Pseudo-Response Regulators (PRRs) in the Tea Plant Camellia sinensis (L.) O. Kuntze

The circadian clock plays a vital role in facilitating plant adaptation to rhythmically changing environmental factors. Pseudo-response regulators (PRRs) are key components regulating the plant circadian clock and have been extensively characterized in model plants. However, the PRRs in the tea plant have not been comprehensively studied. In this study, seven CsPRRs were cloned from the tea plant. Domain, phylogenetic evolution, gene structure, motifs, and cis-acting element analysis revealed their sequence characters and suggested that the first subgroup members, CsPRR1a, 1b, 5a, 5b, 7, and 37, may be responsible for circadian rhythm regulation and abiotic stress responses, while the second subgroup member, CsPRR2, may be involved in development and chloroplast function regulation. Most CsPRRs showed relatively higher expression in flowers, implying their potential roles in photoperiod-regulated flower induction. Moreover, rhythmic expression of CsPRR7, 5b, 5a, 37, 1b, and 1a was observed under long-day conditions in a sequential manner. Additionally, CsPRRs were differently induced/inhibited by cold, heat, and drought stresses in tissue-specific and photoperiod-related manners. A stronger cold induction of CsPRRs was observed under long-day conditions than under short-day conditions. And, among the two tested tissues, changes in the expression of CsPRRs caused by various stresses were more obvious in young shoots. Studies using a floriferous cultivar (FDDB) and an oliganthous cultivar (PYTZ) implied that CsPRRs also played crucial roles in tea-plant flower induction. This study presents the first comprehensive analysis of CsPRRs in the tea plant, providing vital information for further elucidation of CsPRR functions. It also suggests that tissue type and photoperiod conditions should be taken into consideration when conducting gene function studies in the tea plant.

Genome-wide DNA methylation analysis reveals a unique methylation pattern for pleural mesothelioma compared to healthy pleura and other lung diseases

BackgroundPleural mesothelioma (PM) is a rare and aggressive cancer type, typically diagnosed at advanced stages. Distinguishing PM from other lung diseases is often challenging. There is an urgent need for biomarkers that can enable early detection. Interest in the field of epigenetics has increased, particularly in the context of tumour development and biomarker discovery. This study aims to identify specific changes in DNA methylation from healthy pleural tissue to PM and to compare these methylation patterns with those found in other lung diseases.ResultsEPIC methylation array data (850 K) were generated for 11 PM and 29 healthy pleura in-house collected samples. This is the first time such a large dataset of healthy pleura samples has been generated. Additional EPIC methylation array data (850 K) for pleural mesothelioma and other lung-related diseases were downloaded from public databases. We conducted pairwise differential methylation analyses across all tissue types, which facilitated the identification of significantly differentially methylated CpG sites. Extensive differential methylation between PM and healthy pleura was observed, identifying 81,968 differentially methylated CpG sites across all genomic regions. Among these, five CpG sites located within four genes (MIR21, RNF39, SPEN and C1orf101) exhibited the most significant and pronounced methylation differences between PM and healthy pleura. Moreover, our analysis delineated distinct methylation patterns specific to PM subtypes. Finally, the methylation profiles of PM were distinctly different from those of other lung cancers, enabling accurate differentiation.ConclusionsDNA methylation analyses provide a robust method for distinguishing PM from healthy pleural tissues, and specific methylation patterns exist within PM subtypes. These methylation differences underscore their importance in understanding disease progression and may serve as viable biomarkers or therapeutic targets. Moreover, differential methylation patterns between PM and other lung cancers highlights its diagnostic potential. These findings necessitate further translational studies to explore their clinical applications.

Using artificial intelligence to prioritize pathology samples: report of a test drive.

The digital transformation of pathology, through automation and computational tools, addresses current challenges in the field. This study evaluates Paige Pan Cancer, a novel artificial intelligence tool based on the Virchow foundation model, designed to flag invasive cancer in haematoxylin and eosin-stained slides from 16 primary tissue types. Using 62 cases from the Ipatimup Pathology Laboratory, we found the tool had a sensitivity of 93.3% and specificity of 87.5% in biopsies, and 94.7% sensitivity and 75.0% specificity in resections. Overall accuracy was 90.3%. Despite some misclassifications, Paige Pan Cancer demonstrates high sensitivity as a multi-organ screening tool in clinical practice.

Possible phylogenetic relationships of Gymnarrhena (Gymnarrheneae, Gymnarrhenoideae, Asteraceae) based on comparative carpology

The amphicarpic annual Gymnarrhena micrantha (Asteraceae), inhabiting the deserts of North Africa to the Middle East, is interesting not only for its unusual biology, but also for its peculiar morphological structure. The monotypic genus Gymnarrhena, with uncertain position in the Asteraceae for a long time, is currently included in the tribe Gymnarrheneae and a separate subfamily Gymnarrhenoideae. The objective of the study was to examine fruit and seed structure in G. micrantha to consider possible phylogenetic relationships of the genus based on carpological characters. It was found that fruit structural organization in G. micrantha, with simply arranged pericarp and seed coat, parenchymatous and poorly differentiated on the tissue, corresponds to that of the early diverging evolutionary lines of Asteraceae, in which the states of these characters are considered to be plesiomorphic in the family. It has been suggested that taxonomically important structural features of Gymnarrhena cypsela include the structure of the apical region, pericarp and seed coat, the place of pappus attachment and its structure, the type of pappus hygroscopic tissue, and morphophysiological features of receptacular bracts surrounding the cypsela. The study did not confirm the relationship of Gymnarrhena with the tribes Corymbieae and Cichorieae, the seed coat of which differs markedly from the seed coat of Gymnarrhena in the presence of fine porosity of the exotesta cell walls. A set of the anatomical and carpological characters indicates a possible relationship of Gymnarrhena with the basal subtribes Cardopatiinae and Carlininae of the tribe Cardueae. The morphophysiological adaptation of G. micrantha and Cousiniopsis atractyloides cypselae to dissemination in desert conditions, similar in structural details, apparently suggests a close relationship between the subfamilies Gymnarrhenoideae and Carduoideae.

CiBAR1 loss in mice causes laterality defects, pancreatic degeneration, and altered glucose tolerance.

Bin/Amphiphysin/Rvs (BAR) domains are highly conserved domains found in all eukaryotes. BAR domain proteins form crescent-shaped dimers that sense and sculpt curved lipid membranes and play key roles in various cellular processes. However, their functions in mammalian development are poorly understood. We previously demonstrated that Chibby1-interacting BAR domain-containing 1 (ciBAR1, formerly known as FAM92A) localizes to the ciliary base and plays a critical role in ciliogenesis. Here, we report ciliopathy phenotypes of ciBAR1-KO mice. We found that ∼28% of ciBAR1-KO mice show embryonic lethality because of randomized left-right asymmetry; the rest survive into adulthood with no gross morphological abnormalities. Histological assessments of ciliated tissues revealed exocrine pancreatic lesions. Although overall endocrine islet morphology appeared to be normal, ciBAR1-KO mice showed impaired glucose tolerance. Examination of ductal and islet cilia revealed that cilia number and length were significantly reduced in ciBAR1-KO pancreata. ciBAR1-KO MEFs also exhibited ciliary defects. Our findings indicate that ciBAR1 plays a critical role in ciliogenesis depending on the tissue and cell type in mice.

FRESH 3D Bioprinting of Collagen Types I, II, and III.

Collagens play a vital role in the mechanical integrity of tissues as well as in physical and chemical signaling throughout the body. As such, collagens are widely used biomaterials in tissue engineering; however, most 3D fabrication methods use only collagen type I and are restricted to simple cast or molded geometries that are not representative of native tissue. Freeform reversible embedding of suspended hydrogel (FRESH) 3D bioprinting has emerged as a method to fabricate complex 3D scaffolds from collagen I but has yet to be leveraged for other collagen isoforms. Here, we developed collagen type II, collagen type III, and combination bioinks for FRESH 3D bioprinting of millimeter-sized scaffolds with micrometer scale features with fidelity comparable to scaffolds fabricated with the established collagen I bioink. At the microscale, single filament extrusions were similar across all collagen bioinks with a nominal diameter of ∼100 μm using a 34-gauge needle. Scaffolds as large as 10 × 10 × 2 mm were also fabricated and showed similar overall resolution and fidelity across collagen bioinks. Finally, cell adhesion and growth on the different collagen bioinks as either cast or FRESH 3D bioprinted scaffolds were compared and found to support similar growth behaviors. In total, our results expand the range of collagen isoform bioinks that can be 3D bioprinted and demonstrate that collagen types I, II, III, and combinations thereof can all be FRESH printed with high fidelity and comparable biological response. This serves to expand the toolkit for the fabrication of tailored collagen scaffolds that can better recapitulate the extracellular matrix properties of specific tissue types.

Intra-rater Reliability of B-mode Ultrasound in the Measurement of Soft Tissue Thickness and Composition over the Lateral Proximal Femur

ObjectivesComprehensive characterization of soft tissue composition and distribution over the lateral proximal femur is necessary to improve our understanding of fall-related hip fractures; however, a protocol that produces reliable data is needed. Accordingly, the aim of this study was to assess the intra-rater reliability of B-mode ultrasound measured muscle, adipose, and total soft tissue thicknesses over the lateral proximal femur in a simulated sideways fall configuration. MethodsTwenty-five young adults (12 males, 13 females, age (SD) = 20.8 (1.9) years) underwent B-mode ultrasound imaging of 12 locations over their lateral proximal femur while in a side-lying position. Side-lying was chosen to allow imaging of the tissues impacted during a lateral fall event. Muscle, adipose, and total soft tissue thicknesses were measured at each location (further grouped into posterolateral, lateral, and anterolateral locations for statistical analysis) and two-way mixed model absolute agreement intraclass correlation coefficients (ICCs) and standard error of measurement were used to assess reliability of tissue type, location, and sex. ResultsICCs were excellent (ICC > 0.9) for each tissue type, measurement location, and sex. There were interactions between tissue type, measurement location, and sex on reliability. While measures of adipose thickness were excellent across all conditions, reliability of muscle and total soft tissue thickness measurements were dependent on measurement location and sex. ConclusionsThis ultrasound imaging protocol demonstrated good-to-excellent reliability of soft tissue-specific thickness measurements over the lateral proximal femur. This protocol has implications for subject-specific hip fracture risk screening tools and biomechanical models of impact dynamics that incorporate biofidelic soft tissue morphology.

Therapeutic potential of agents targeting cannabinoid type 2 receptors in organ fibrosis.

The endocannabinoid system has garnered attention as a potential therapeutic target in a range of pathological disorders. Cannabinoid receptors type 2 (CB2) are a class of G protein-coupled receptors responsible for transmitting intracellular signals triggered by both endogenous and exogenous cannabinoids, including those derived from plants (phytocannabinoids) or manufactured synthetically (synthetic cannabinoids). Recent recognition of the role of CB2 receptors in fibrosis has fueled interest in therapeutic targeting of CB2 receptors in fibrosis. Fibrosis is characterized by the alteration of the typical cellular composition within the tissue parenchyma, resulting from exposure to diverse etiological factors. The pivotal function of CB2 agonists has been widely recognized in the regulation of inflammation, fibrogenesis, and various other biological pathologies. The modulation of CB2 receptors, whether by enhancing their expression or activating their function, has the potential to provide benefits in numerous conditions, particularly by avoiding any associated adverse effects on the central nervous system. The sufficient activation of CB2 receptors resulted in the complete suppression of gene expression related to transforming growth factor β1 and its subsequent fibrogenic response. Multiple reports have also indicated the diverse functions that CB2 agonists possess in mitigating chronic inflammation and subsequent fibrosis development in various types of tissues. While currently in the preclinical stage, the advancement of CB2 compounds has garnered significant attention within the realm of drug discovery. This review presents a comprehensive synthesis of various independent experimental studies elucidating the pivotal role of identified natural and synthetic CB2 agonists in the pathophysiology of organ fibrosis, specifically in the cardiac, hepatic, and renal systems.

An update on epigenetic mechanisms in endometriosis.

The etiopathogenesis of endometriosis, a chronic debilitating disease affecting nearly 10% of women, has evaded elucidation until the recent epigenetic discoveries. Although still deemed multifactorial, endometriosis is likely predisposed in women with genetic and epigenetic alterations, which are activated by environmental factors. There are many epigenetic changes that have recently been associated with endometriosis: DNA methylation and phosphorylation, modifications to histones and non-coding RNA, and chromatin remodeling and organization. Gene markers, such as HOXA10, SF-1, and GATA transcription factors, are also debatably correlated to endometriosis. An improved understanding of the etiopathogenesis of endometriosis may propel our field toward our objectives: sooner and more efficient detection as well as targeted therapy. In this comprehensive review, we will identify and discuss the current literature on epigenetic changes seen in endometriosis. A primary computerized search was performed on PubMed and Google scholar of publications from 1990 to 2022. We searched for keyword terms such as "endometriosis" and "endometriosis epigenetics." We also looked through the references of prior articles to find other relevant articles to this topic. Articles were categorized by type of epigenetic change found such as DNA hypo- or hyper- methylation, histone hyper- or hypo-acetylation, chromatin remodeling, and non-coding RNA-mediated down-regulation and the research was elaborated in sections based on the type of epigenetic change. There are many articles on TET, DNMTs, EZH2, HDACs, HATs, let-7 family, miRNAs, Hox proteins, GATA family, sirtuins (e.g. SIRT1, SIRT3), ARID1A, SF-1, USF1, USF2, STRA6, ESR1, ESR2, PGR, ALDHIA2, and CTCF; however, the studies analyzed in this review were heterogeneous in comparison populations, analysis methods, tissues types (e.g. endometriomas, ectopic endometriotic tissue, eutopic endometrial tissue). Due to this, it is difficult to synthesize over-arching conclusions based on the current literature; however, there are many epigenetic changes and genes linked to endometriosis as noted in the literature.

Manipulation of Spindle Position Using Magnetic Tweezers in Sea Urchin Embryos.

The regulation of mitotic spindle position and orientation, and consequent division plane specification, is critical for early embryo development, tissue architecture and stem cells. Accordingly, defects in spindle positioning have been associated with the emergence of tissue disorders and mis-specification of cell fates, causing the formation of tumors, for instance, in stem cell populations. In such context, methods to physically manipulate mitotic spindle position or orientation in living cells bear the promise of dissecting the causal impact of spindle mis-positioning on cell or tissue behavior. Here, we describe a method to directly modulate mitotic spindle position and orientation with in vivo magnetic tweezers in developing sea urchin embryos. This method allows formonitoring the impact of spindle orientation on embryo development and quantifying forces and torques needed to move or rotate spindles. It may be transposable to many other cell, embryo or tissue types.

Tissue-specific, temporal, and core gene-dependent expression patterns of Hsp70s reveal functional allocation in Chlamys farreri under heat stress

Heat shock proteins 70 KDa (Hsp70s) engage in a broad spectrum of cellular functions in response to various stressors. Marine bivalves face substantial threats from the rising seawater temperature attributed to global warming. In the present study, expression patterns of Hsp70s in Zhikong scallop Chlamys farreri (CfHsp70s) were determined in embryos and larvae at all developmental stages, in healthy adult tissues, and across four various tissues exposed to high temperature for acute and chronic periods through in silico analysis. Spatiotemporal expressions suggested CfHsp70s performed specific functional differentiations in scallop's development and growth. Regulatory expression patterns of CfHsp70s, characterized by predominant down-regulation in the mantle, gill and hemocytes, as well as contrasting up-regulation in the heart, suggest differential functional allocation of CfHsp70s among tissues in response to heat stress. Particularly, a core set of 14 CfHsp70s, especially the nine members of the Hsp70B2s, characterized by gene expansion, intron-less structure, shorter gene length, preference for hydrophilic amino acids, and coordinated expression profiles, was predominantly responsible for the inducible up-regulations observed across all four tissue types. Collectively, the tissue-specific, temporal and core gene-dependent expression patterns of CfHsp70s illustrate the functional allocation and molecular evolution of Hsp70 family members in Zhikong scallops.

Computed tomography versus near-infrared spectroscopy for the assessment of coronary atherosclerosis.

Coronary computed tomography angiography (CCTA) has been proposed as an alternative to intravascular imaging for assessing plaque pathology. We aimed to assess the efficacy of CCTA against near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) in evaluating atheroma burden and composition and for guiding coronary interventions. Seventy patients with a chronic coronary syndrome were recruited and underwent CCTA and NIRS-IVUS. The imaging data were matched, and the estimations of lumen, vessel wall and plaque dimensions and composition of the two modalities were compared. The primary endpoint of the study was the efficacy of CCTA in detecting lipid-rich plaques identified by NIRS-IVUS. Secondary endpoints included the performance of CCTA in evaluating coronary artery pathology in the studied segments and its value in stent sizing, using NIRS-IVUS as the reference standard. In total, 186 vessels were analysed. The attenuated plaque volume on CCTA had weak accuracy in detecting lipid-rich plaques (58%; p=0.029). Compared to NIRS-IVUS, CCTA underestimated the lumen volume (309.2 mm3 vs 420.4 mm3; p=0.001) and plaque dimensions (total atheroma volume 116.1 mm3 vs 292.8 mm3; p<0.001 and percentage atheroma volume 27.67% vs 41.06%; p<0.001) and overestimated the lipid component (lipid core burden index 48.6 vs 33.8; p=0.007). In the 86 lesions considered for revascularisation, CCTA underestimated the reference vessel area (8.16 mm2 vs 12.30 mm2; p<0.001) and overestimated the lesion length (23.5 mm vs 19.0 mm; p=0.029) compared to NIRS-IVUS. CCTA has limited efficacy in assessing plaque composition and quantifying lumen and plaque dimensions and tissue types, which may potentially impact revascularisation planning.

A Comparison Between Three Types of Scaffolds for Pulp Regeneration: A Histological Study on Dogs.

This study aims to compare the application of three types of normal scaffolds-native chitosan, enzymatically modified chitosan, and blood clot (BC)-on pulp regeneration in the teeth of experimental dogs through histological examination, to determine the quantity and type of new tissues formed within the root canal. The research sample consisted of 32 root canals from 20 premolars of two male local experimental dogs. The sample was randomly divided into a control group, in which no intervention was performed on the teeth, and three experimental groups based on the type of scaffold used: the BC group, the native chitosan combined with BC (NCS + BC) group, and the enzymatically modified chitosan combined with BC (EMCS + BC) group. Mechanical and chemical cleaning of the canals was performed, followed by the application of the studied scaffolds within the root canals. After 3 months, the teeth were extracted and prepared for histological study, where two variables were studied: the percentage of total vital tissue (soft and hard; VT%) and the percentage of soft vital tissue only (ST%). A one-way ANOVA and Bonferroni tests were used to determine significant differences between the groups at a 95% confidence level. The VT% values were significantly higher in the EMCS + BC group compared to both the NCS + BC and BC groups. The ST% values were also significantly higher in the EMCS + BC group compared to the BC group. However, no significant differences in ST% values were observed between the NCS + BC group and either the BC or EMCS + BC groups. Within the limitations of this study, we conclude that the application of enzymatically modified chitosan scaffolds combined with BC yields superior results in pulp regeneration, which contributes to the formation of pulp-like tissue and cells resembling odontoblasts, as well as apex closure with tissue resembling bone tissue.

The fuzzy MAD stroke conjecture, using fuzzy C means to classify multimodal apparent diffusion for ischemic stroke lesion stratification

BackgroundIn conjunction with an epidemiologically determined treatment window, current radiological acute ischemic stroke practice discerns two lesion (stage) types: core (dead tissue, identified by diffusion-weighted imaging (DWI)) and penumbra (tissue region receiving just enough blood flow to be potentially salvageable, identified by the perfusion diffusion mismatch). However, advancements in preclinical and clinical studies have indicated that this approach may be too rigid, warranting a more fine-grained patient-tailored approach. This study aimed to demonstrate the ability to noninvasively provide insights into the current in vivo stroke lesion cascade. MethodsTo elucidate a finer-grained depiction of the acute focal ischemic stroke cascade in vivo, we retrospectively applied our multimodal apparent diffusion (MAD) method to multi-b-value DWI, up to a b-value of 10,000 s/mm2 in 34 patients with acute focal ischemic stroke. Fuzzy C Means was used to cluster the MAD parameters. ResultsWe discerned 18 clusters consistent with normal appearing tissue (NAT) types and 14 potential ischemic lesion (stage) types, providing insights into the variability and aggressiveness of lesion progression and current anomalous stroke-related imaging features. Of the 529 ischemic stroke lesion instances previously identified by two radiologists, 493 (92 %) were autonomously identified; 460 (87 %) were identified as efficaciously or better than the radiologists. ConclusionsThe data analyzed included a small number of clinical patients without follow-up or contemporaneous histology; therefor, the findings and theorizing should be treated as conjecture. Nevertheless, each identified NAT and lesion type is consistent with the known underpinnings of physiological tissues and pathological ischemic stroke lesion (stage) types. Several findings should be considered in current clinical imaging: WM fluid accumulation, BBB compromise conundrum, b1000 identified core may not be dead tissue, and a practical reason for DWI (pseudo) normalization.

First person – Ayyappa Raja Desingu Rajan

ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Disease Models &amp; Mechanisms, helping researchers promote themselves alongside their papers. Ayyappa Raja Desingu Rajan is first author on ‘ Generation of a zebrafish neurofibromatosis model via inducible knockout of nf2a/b’, published in DMM. Ayyappa Raja is a postdoctoral researcher in the lab of Marianne Bronner at California Institute of Technology, Pasadena, CA, USA. Using the neural crest as a model, Ayyappa Raja investigates lineage decisions that contribute to specific tissue types, such as the meninges, and how developmental gene programs can go array in cancers such as meningiomas and neurofibromatosis.

Energy-based bond graph models of glucose transport with SLC transporters.

The SLC (solute carrier) superfamily mediates the passive transport of small molecules across apical and basolateral cell membranes in nearly all tissues. In this paper we employ bond graph approaches to develop models of SLC transporters that conserve mass, charge and energy, respectively, and which can be parameterised for a specific cell and tissue type for which the experimental kinetic data is available. We show how analytic expressions that preserve thermodynamic consistency can be derived for a representative four- or six-state model, given reasonable assumptions associated with steady-state flux conditions. We present details on fitting parameters for SLC2A2 (a GLUT transporter) and SLC5A1 (an SGLT transporter) to experimental data and show how well the steady-state flux expressions match the full kinetic analysis. Since the bond graph approach will not be familiar to many readers, we provide a detailed description of the approach and illustrate its application to a number of familiar biophysical processes.

Thermogenic adipose tissues: promising therapeutic targets for metabolic diseases: Thermogenic fats and obesity.

The ongoing increase in the prevalence of obesity and its comorbidities such as cardiovascular disease, type 2 diabetes (T2D) and dyslipidemia warrants discovery of novel therapeutic options for these metabolic diseases. Obesity is characterized by white adipose tissue expansion due to chronic positive energy balance as a result of excessive energy intake and/or reduced energy expenditure. Despite various efforts to prevent/reduce obesity including lifestyle and behavioral interventions, surgical weight reduction approaches and pharmacological methods, there has been limited success in significantly reducing obesity prevalence. Recent research has shown that thermogenic adipocyte (brown and beige) activation or formation, respectively, could potentially act as a therapeutic strategy to ameliorate obesity and its related disorders. This can be achieved through the ability of these thermogenic cells to enhance energy expenditure and regulate circulating levels of glucose and lipids. Thus, unraveling the molecular mechanisms behind the formation and activation of brown and beige adipocytes holds the potential for probable therapeutic paths to combat obesity. In this review, we provide a comprehensive update on the development and regulation of different adipose tissue types. We also emphasize recent interventions in harnessing therapeutic potential of thermogenic adipocytes by bioactive compounds and new pharmacological anti-obesity agents.

Co-pyrolysis of corn stalk and high-density polyethylene with emphasis on the fibrous tissue difference on thermal behavior and kinetics

The thermal properties of various corn stalk tissues (including stem, husk, ear, cob, and leaf), high-density polyethylene (HDPE), and their blends were investigated using thermogravimetric analysis under a nitrogen atmosphere. The results indicate that the thermal decomposition process of corn stalk tissue/HDPE mixtures is delayed with an increasing heating rate, regardless of the tissue type. Besides, the structural differences among various corn stalk tissues significantly influence their thermal behavior, product distribution, and co-pyrolysis kinetics with HDPE. Pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) was conducted to analyze the pyrolytic products of the blends with different corn stalk tissues, revealing that corn cob/HDPE blends produce a higher yield of valuable chemicals, such as the furan derivates and aromatic hydrocarbons. Kinetic analysis was further performed using Kissinger-Akahira-Sunose (KAS) and Flynn-Wall-Ozawa (FWO) methods to determine the activation energy for the reactions occurring during co-pyrolysis. The co-pyrolysis of corn cob/HDPE blend requires the least activation energy (149.3 kJ/mol) among five blends, which was ascribed to the high hemicellulose content in corn cob. Moreover, machine learning algorithms, including random forest (RF) and gradient boost regression tree (GBRT), were applied to predict mass loss in the corn fiber/HDPE blends, which showed RF possessed superior accuracy over GBRT. These findings suggest that isolating plant tissues during the feedstock pre-management could enhance the valorization performance of lignocellulose-waste plastic co-pyrolysis.