Proportion Of Tissue Research Articles

To evaluate the divine proportion on silhouette photographs of skeletal class I bimaxillary protrusion cases treated with first premolar extraction- An in-vitro study

Objectives: The aim of the study is to assess the divine proportion of soft tissues seen in bimaxillary protrusion cases and compare this proportion on pre-treatment and post-treatment Silhouette photographs of skeletal (Sk) Class I bimaxillary protrusion patients treated by premolars extraction. Material and Methods: This research was conducted on 50 samples of pre-treatment along with post-treatment outline form photographs of Sk Class I bimaxillary protrusion patients aged 18–30 years in an orthodontics and dentofacial orthopedics department. The samples had an equal distribution with 25 males and females. All profile photos with Class I bimaxillary protrusion were converted into silhouette form. To assess the divine proportion in patient profiles, each silhouette photograph was marked by five anatomic landmarks, which were as follows: Soft-tissue nasion (N), trichion (Tr), subnasale (Sn), stomion (St), and a soft-tissue menton (Me) which was followed by the measurement of six linear dimensions; ratios were measured as R1, R2, R3, R4, and R5. These ratios of the patient’s profile, both before and after the treatment, were then compared to find out the soft-tissue alterations that have taken place in patients having Class I bimaxillary protrusion corrected by the first four premolars extraction. Results: The findings indicate that all post-treatment proportions in males indicated highly noticeable changes in contrast to pre-treatment ratios. However, females revealed highly noticeable differences in R1, R2, and R4 ratios, statistically evident differences were shown by R3 and R5 ratios in contrast to ratios before the treatment. Thus, the proportions appeared to be closer to the divine proportion. Conclusion: The results showed that all the ratios were found to be closer to divine proportion, and thus, premolars extraction in cases with convex facial form does help us to achieve esthetically pleasing faces.

CNSC-03. HIGH EXPRESSION OF PICCOLO AND SYNTAXIN-1A IN PAEDIATRIC MEDULLOBLASTOMA DUE TO BOTH: HIGH NEURONAL FRACTION AND ENDOGENOUS EXPRESSION

Abstract Emerging evidence indicates that the “healthy” nervous system contributes to the pathogenesis of cancer. Tumor cells were found to form ultra-long protrusions with distinct synapses, mainly in the infiltrative zone, resulting in a neuron-to-brain tumor synaptic communication. Located at the presynapse, proteins of the cytomatrix of the active zone have been identified to maintain highly specialized functions in neurons. Further, the proteins were shown to be involved in progression in various tumors, but little is known about their role in brain tumors. This study examined the expression of CAZ proteins in glioma and medulloblastoma. Tumor samples of Astrocytoma, glioblastoma, pilocytic astrocytoma and medulloblastoma were obtained during neurosurgical resection. Transcription rate of following CAZ proteins was measured via qPCR: SNAP25, VAMP1, VAMP2, SYT1, PCLO, BSN, STX1A. To examine amount of neuronal tissue TUBB3 and for glial fraction GFAP were quantified. A medulloblastoma cell line (DAOY) was furthermore analyzed to evaluate origin of high expressed proteins. Medulloblastoma showed high expression of PCLO (pilocytic astrocytoma vs. medulloblastoma p=0.0126) and STX1A (pilocytic astrocytoma vs. medulloblastoma p=0.0006) compared to. Likewise a high transcriptional level of TUBB3 could be seen with significance to pilocytic astrocytoma (2.2 ± 1.4 vs. 0.2 ± 0.17; p = 0.0018), which could indicate a high amount of neuronal tissue in given medulloblastoma samples. To rule out a causal link between high proportion of neuronal tissue and high CAZ expression, a paediatric medulloblastoma cell line was analysed. High expression of PCLO and STX1A in absence of TUBB3 was shown (3.8 and 2.01 vs. 0.059), indicating endogenous expression of CAZ proteins in medulloblastoma.

Middle Pleistocene teeth from Arbreda Cave (Serinyà, northeastern Iberian Peninsula).

We report the discovery and description of three human teeth from the Middle Paleolithic archaeological levels of Arbreda Cave (Serinyà, Catalonia, NE Iberian Peninsula). The teeth, two molars (one right dm2 and one right M2) from Level N (older than 120 kyr) and one P3 from Level J (dated between 71 and 44 kyr), were morphologically described based on microCT images and compared with Neanderthal and Homo sapiens specimens. The teeth belong to a minimum of three individuals: one adult and one infant from Level N and one juvenile from Level J. The premolar from Mousterian Level J, the best preserved of the three teeth, exhibits characteristics to those from our comparative sample of Homo neanderthalensis, such as the crown measurements, EDJ traits, enamel thickness and volume of the pulp cavity. In contrast to the clear Neanderthal characteristics observed in the P3 from Level J, the high degree of dental wear and poor state of preservation precludes definitive taxonomic designations of the two teeth from Level N. However, the crown dimensions and some tissue proportions are consistent with a probable assignation to Homo neanderthalensis. The teeth from Level N come from a context of long and recurrent occupations of the cave, whereas the archaeological context of the tooth from Level J is indicative of short and seasonal occupations of the cave, which may indicate a change in the lifestyle strategies of the last Neanderthals of the Iberian Peninsula.

Comparison of Eosinophil Profile and Lund Kennedy Score in Patients with Nasal Polyps.

Nasal polyps are epithelial and stromal non-neoplastic proliferations of nasal cavity and paranasal sinuses. Nasal polyps are a consequence of damage in the epithelium of the nasal mucosa. Since eosinophils are the main inflammatory cells in the substantial proportion of nasal polyp tissues, they are considered potentially responsible for the etiopathogenesis and prognosis of the disease. This cross-sectional observational study was conducted in the department of ENT, H&NS, Government Medical College, Srinagar. A total of 62 patients were included in the study. The recorded data was compiled and entered in a spreadsheet (Microsoft Excel) and then exported to data editor of SPSS Version 20.0 (SPSS Inc., Chicago, Illinois, USA). A total of 62 patients participated in the study. Majority of subjects were in the age group of 60-69 and the least number in 20-29. 47 patients had a mean lund kennedyscore of 13.34 ± 1.178 with peripheral eosinophil count of ≥ 500 and 15 patients had a score of 7.00 ± 0.632 with peripheral eosinophil count of < 500. 50 patients had a mean lund kennedy score of 13.04 ± 1.359 with tissue eosinophil count of ≥ 10/HPF and 12 patients had a score of 7.16 ± 0.669 with atissue eosinophil count of < 10/HPF. The conducted study indicates that the levels of tissue and peripheral osinophils are positively related to severity of nasal polyps as indicated by Lund Kennedy scores. Also, our study concluded that the disease has male preponderance.

Maximizing Breast Cancer Detection Through Screening: A Comparative Analysis of Imaging-Based Approaches

Introduction/BackgroundThis study estimates the percentage of detectable breast cancers in the screening population that could be found with primary and supplemental screening, and provides cost estimates for population wide supplemental screening in the U.S. Materials and MethodsPublished estimates on cancer detection rates of 2D mammography, tomosynthesis (DBT), whole breast ultrasound (US), molecular breast imaging (MBI), contrast-enhanced mammography (CEM), and MRI, the number of mammograms conducted in the United States in 2023, and the proportion of dense breast tissue, were utilized. The maximum number of detectable cancers was projected from incremental cancer detection rates of the most sensitive supplemental screening method. The proportion of cancers detectable for each modality was calculated. In 2023, Medicare reimbursement rates were used to estimate supplemental screening costs. ResultsOut of 469,437 detectable cancers, 2D mammography could detect 190,531 (41%), leaving 278,906 undetected. Adding supplemental screening could detect a combined 220,165 cancers (47%) with DBT, 237,596 (51%) with US, 331,727 (71%) with MBI, 377,049 (80%) with CEM and 469,437 (100%) with MRI. The imaging cost in US dollars to provide supplemental screening to all individuals with dense breasts in 2023 was $933M for tomosynthesis, $1.84B for US, $3.87B for CEM, $4.16B for MBI, and $6.36B for MRI. ConclusionThe study highlights potential benefits from supplemental breast cancer screening, suggesting the combination of mammography and breast MRI offers the most effective detection method though at the highest imaging cost. These findings provide valuable insights to guide future research and inform decision-making in supplemental breast cancer screening strategies.

Low-dose apatinib optimizes the vascular normalization and enhances the antitumor effect of PD-1 inhibitor in gastric cancer.

Apatinib is a tyrosine kinase inhibitor that has shown potential in combination with immune checkpoint inhibitors (ICIs) in gastric cancer (GC); however, its role in GC is unclear. This research aims to investigate the effect of low-dose apatinib in GC, and analyze the mechanisms of its underlying action. A mouse model of GC was established, and the experimental mice were divided into different groups for different treatment: group NS (normal saline), group A (low-dose apatinib 50 mg/kg), group B (high-dose apatinib 200 mg/kg), group C [programmed cell death protein 1 (PD-1) inhibitor monotherapy], and group D (PD-1 inhibitor combined with low-dose apatinib). After 14 days of treatment, the tumor and blood samples were collected from all mice for histological and cytokine detection. Compared with the control group, mice in the low-dose apatinib group showed smaller tumor volumes and slower growth. CD31/α-smooth muscle actin (α-SMA) double staining revealed significantly higher coverage of perivascular cells in the low-dose apatinib group by contrast to the control and high-dose apatinib groups, suggesting that low-dose apatinib may alleviate hypoxia. Compared to the high-dose apatinib group, the expression of hypoxia inducible factor 1 alpha (HIF1α) significantly decreased in the low-dose apatinib group. Hematoxylin and eosin (HE) staining results showed a higher proportion of necrotic tumor tissues in the group of mice treated with low-dose apatinib combined with PD-1 inhibitor than in other groups. In addition, this combined treatment significantly reduced the expression of NG2 and HIF1α in mouse tumor tissues, indicating a more normalized vascular density, and also increased the proportion of CD8+ T cells. Low-dose apatinib enhances the antitumor effect of PD-1 inhibitor by normalizing tumor-related blood vessels, alleviating intratumor hypoxia and altering immunosuppressive microenvironment (IM).

Dihydroquercetin-Loaded Liposomes Change Fibrous Tissue Distribution in the Bleomycin-Induced Fibrosis Model.

The effects of the antioxidant dihydroquercetin (DHQ) were studied in a model of pulmonary fibrosis. DHQ penetration into the lesion was facilitated by encapsulation into liposomes. Pulmonary fibrosis was modeled in rats by intratracheal injection of bleomycin. For the first 7 days, the rats in the treatment group received a liposomal emulsion with DHQ, while in the comparator group rats received saline. In the control group, intact rats did not receive any exposure. Thirty days after the initiation, lung function and the pathological lesion volume were assessed by 7T 1H MRI and the lungs were taken for histologic examination. The proportion of fibrous tissue was counted by Masson's trichrome staining. Both experimental groups were characterized by a significant functional pulmonary deficiency, with low mortality and a small lesion area. In the rats treated with DHQ, the distribution of fibrous tissue was significantly altered. Significantly more fibrous tissue was found in the center of the lesion, while significantly less was in the interstitial space of alveoli. Lung density at the same time was lower in the treated lungs. Dihydroquercetin encapsulated in liposomes affects the mechanisms of bleomycin-induced pulmonary fibrosis progression in rats. While accelerated fibrosis of the lesion can restrict inflammatory processes, delayed fibrosis of the interstitium can further improve the functional state of the lungs.

Metabolomic profiling of pheochromocytomas in dogs: Catecholamine phenotype and tricarboxylic acid cycle metabolites.

In humans with pheochromocytomas (PCCs), targeted metabolomics is used to determine the catecholamine phenotype or to uncover underlying pathogenic variants in tricarboxylic acid (TCA) cycle genes such as succinate dehydrogenase subunits (SDHx). To analyze catecholamine contents and TCA cycle metabolites of PCCs and normal adrenals (NAs). Ten healthy dogs, 21 dogs with PCC. Prospective observational study. Dogs diagnosed with PCC based on histopathological and immunohistochemical confirmation were included. Tissue catecholamine contents and TCA metabolites in PCCs and NAs were measured by liquid chromatography with mass spectrometry or electrochemical detection. Compared to NAs, PCCs had significantly higher tissue proportion of norepinephrine (88% [median: range, 38%-98%] vs 14% [11%-26%]; P < .001), and significantly lower tissue proportion of epinephrine (12% [1%-62%] vs 86% [74%-89%]; P < .001). Pheochromocytomas exhibited significantly lower fumarate (0.4-fold; P < .001), and malate (0.5-fold; P = .008) contents than NAs. Citrate was significantly higher in PCCs than in NAs (1.6-fold; P = .015). One dog in the PCC group had an aberrant succinate : fumarate ratio that was 25-fold higher than in the other PCCs, suggesting an SDHx mutation. This study reveals a distinct catecholamine content and TCA cycle metabolite profile in PCCs. Metabolite profiling might be used to uncover underlying pathogenic variants in TCA cycle genes in dogs.

Response of leaf anatomical structure of Larix gmelinii to climate warming and provenance variation.

Exploring the response of leaf anatomical structure to climate warming is helpful for understanding the adaptive mechanisms of trees to climate change. We conducted a warming experiment by transplanting seedlings of Larix gmelinii from 11 provenances to two common gardens, and examined the response of leaf anatomical structure to climate warming. The results showed that warming significantly increased leaf thickness (TL), upper epidermal mesophyll thickness (TUEM), lower epidermal mesophyll thickness (TLEM), endodermal thickness (TE), vascular bundle diameter (DVB), transfer tissue thickness (TTT), and the percentage of mesophyll thickness to TL(PMT), and significantly decreased the upper epidermal thickness (TUE) and the percentage of epidermal thickness to TL (PE). The mesophyll thickness was positively associated with chlorophyll concentration and maximum net photosynthetic rate. The responses of TL, TUEM, TLEM, TE, DVB, TTT, TUE, PMT and PE to warming differed among all the provenances.As the aridity index of the original site increased, the magnitude of the warming treatment's effect decreased for TL, TUEM, TLEM, TTT and PMT, and increased for TUE and PE. Warming increased the thickness and proportion of profit tissue (e.g., mesophyll) and decreased the thickness and proportion of defensive tissue (e.g., epidermis), and those changes varied among provenances. L. gmelinii could adapt to climate warming by adjusting leaf anatomical structure, and this ability was weak for trees from provenance with high aridity index.

A polymeric nanoplatform enhances the cGAS-STING pathway in macrophages to potentiate phagocytosis for cancer immunotherapy

Immunosuppressive tumor-associated macrophages (TAMs) account for a high proportion of the tumor tissue and significantly impede immunoefficacy. Furthermore, the signal regulatory protein α (SIRPα) expressed in TAMs adversely correlates with macrophage activation and phagocytosis, resulting in immunosurveillance escape. To address these difficulties, a mannose-modified, pH-responsive nanoplatform with resiquimod (R848) and 2′, 3′-cyclic GMP-AMP (cGAMP) co-encapsulation (named M-PNP@R@C) is designed to polarize TAMs and lower SIRPα expression. The co-delivery of R848 and cGAMP synergistically facilitates the polarization of TAMs from the anti-inflammatory M2 phenotype into the pro-inflammatory M1 phenotype, thereby enhancing antitumor immunotherapy. Remarkably, activation of the cGAMP-mediated stimulator of interferon genes (STING) in TAMs significantly downregulates the expression of SIRPα, which synergizes with the cluster of differentiation 47 (CD47) antibody for the dual blockade of the CD47-SIRPα axis. Further analysis of single-cell RNA sequencing indicates that STING activation downregulates SIRPα by regulating intracellular fatty acid oxidation metabolism. In vivo studies indicate that M-PNP@R@C significantly inhibits tumor growth with a potent antitumor immune response in melanoma graft tumor models. After synergy with anti-CD47, the double blockade strategies of the SIRPα/CD47 axis result in a notable inhibition of lung metastasis. A prolonged survival rate is observed after combination treatment with CD47 and programmed death ligand-1 antibodies for the triple immune checkpoint blockade. In summary, our study provides original insights into the potential role of the STING pathway in macrophage-based immunotherapy, thus offering a potential combinatorial strategy for cancer therapy.

Associations between quantitative measures of mammographic density and terminal ductal lobular unit involution in Chinese breast cancer patients

BackgroundHigher mammographic density (MD), a radiological measure of the proportion of fibroglandular tissue in the breast, and lower terminal duct lobular unit (TDLU) involution, a histological measure of the amount of epithelial tissue in the breast, are independent breast cancer risk factors. Previous studies among predominantly white women have associated reduced TDLU involution with higher MD.MethodsIn this cohort of 611 invasive breast cancer patients (ages 23–91 years [58.4% ≥ 50 years]) from China, where breast cancer incidence rates are lower and the prevalence of dense breasts is higher compared with Western countries, we examined the associations between TDLU involution assessed in tumor-adjacent normal breast tissue and quantitative MD assessed in the contralateral breast obtained from the VolparaDensity software. Associations were estimated using generalized linear models with MD measures as the outcome variables (log-transformed), TDLU measures as explanatory variables (categorized into quartiles or tertiles), and adjusted for age, body mass index, parity, age at menarche and breast cancer subtype.ResultsWe found that, among all women, percent dense volume (PDV) was positively associated with TDLU count (highest tertile vs. zero: Expbeta = 1.28, 95% confidence interval [CI] 1.08–1.51, ptrend = < .0001), TDLU span (highest vs. lowest tertile: Expbeta = 1.23, 95% CI 1.11–1.37, ptrend = < .0001) and acini count/TDLU (highest vs. lowest tertile: Expbeta = 1.22, 95% CI 1.09–1.37, ptrend = 0.0005), while non-dense volume (NDV) was inversely associated with these measures. Similar trend was observed for absolute dense volume (ADV) after the adjustment of total breast volume, although the associations for ADV were in general weaker than those for PDV. The MD-TDLU associations were generally more pronounced among breast cancer patients ≥ 50 years and those with luminal A tumors compared with patients < 50 years and with luminal B tumors.ConclusionsOur findings based on quantitative MD and TDLU involution measures among Chinese breast cancer patients are largely consistent with those reported in Western populations and may provide additional insights into the complexity of the relationship, which varies by age, and possibly breast cancer subtype.

Development of implantable electrode based on bioresorbable Mg alloy for tissue welding application

An implantable electrode based on bioresorbable Mg-Nd-Zn-Zr alloy was developed for next-generation radiofrequency (RF) tissue welding application, aiming to reduce thermal damage and enhance anastomotic strength. The Mg alloy electrode was designed with different structural features of cylindrical surface (CS) and continuous long ring (LR) in the welding area, and the electrothermal simulations were studied by finite element analysis (FEA). Meanwhile, the temperature variation during tissue welding was monitored and the anastomotic strength of welded tissue was assessed by measuring the avulsion force and burst pressure. FEA results showed that the mean temperature in the welding area and the proportion of necrotic tissue were significantly reduced when applying an alternating current of 110 V for 10 s to the LR electrode. In the experiment of tissue welding ex vivo, the maximum and mean temperatures of tissues welded by the LR electrode were also significantly reduced and the anastomotic strength of welded tissue could be obviously improved. Overall, an ideal welding temperature and anastomotic strength which meet the clinical requirement can be obtained after applying the LR electrode, suggesting that Mg-Nd-Zn-Zr alloy with optimal structure design shows great potential to develop implantable electrode for next-generation RF tissue welding application.

Elucidating the Relationship between Neutrophil-Lymphocyte Ratio and Plaque Composition in Patients with Drug-Eluting Stent Restenosis by Virtual Histology-Intravascular Ultrasound.

(1) Background: In-stent Restenosis (ISR) is a major factor influencing the prognosis and revascularization of target lesions. The plaque composition is unclear; therefore, it is critical to investigate ISR composition to identify clinical intervention markers. (2) Methods: This study was conducted on 36 patients with drug-eluting stent restenosis. The patients were classified into a Low Neutrophil-Lymphocyte Ratio (L-NLR) and High Neutrophil-Lymphocyte Ratio (H-NLR) according to the median NLR level of 36 patients. Discrepancies in the current information such as baseline data, biochemical examination, cardiac ultrasound data, etc., were examined to identify the underlying risk factors, and a multifactorial linear regression analysis of plaque properties was conducted. (3) Results: NLR = 2.64 was utilized to classify 18 patients into the L-NLR group and 18 patients into the H-NLR group. There were statistically significant differences in age, a pre-percutaneous coronary intervention (PCI) SYNTAX II score, a C-reactive protein (CRP), interleukin (IL)-6, plaque loading, a fibro-lipid tissue area, calcified nubs, and virtual histology-thin fibrous cap atherosclerotic (VH-TCFA). The significant impacts of variations in age, neutrophil-lymphocyte ratio (NLR) levels, and IL-6 levels on the plaque stress and percentage of the fibro-lipid tissue in virtual histology-intravascular ultrasound (VH-IVUS) were identified through multifactorial linear regression. (4) Conclusions: The high NLR group demonstrated increased myocardial injury severity, consistent with higher SYNTAX II scores, a higher plaque burden, and higher proportions of vulnerable components. NLR proved to be a risk factor for both the plaque load and the proportion of the fibro-lipid tissue in ISR.

Two-Part Mixed Effects Mixture Model for Zero-Inflated Longitudinal Compositional Data

Compositional data (CD) is mostly analyzed using ratios of components and log-ratio transformations to apply known multivariable statistical methods. Therefore, CD where some components equal zero represents a problem. Furthermore, when the data is measured longitudinally, and appear to come from different sub-populations, the analysis becomes highly complex. Our objective is to build a statistical model addressing structural zeros in longitudinal CD and apply it to the analysis of radiation-induced lung damage (RILD) over time. We propose a two-part mixed-effects model extended to the case where the non-zero components of the vector might come from a two-component mixture population. Maximum likelihood estimates for fixed effects and variance components were calculated by an approximate Fisher scoring procedure base on sixth-order Laplace approximation. The expectation-maximization (EM) algorithm estimates the mixture model’s probability. This model was used to analyze the radiation therapy effect on tissue change in one patient with non-small cell lung cancer (NSCLC), utilizing five CT scans over 24 months. Instead of using voxel-level data, voxels were grouped into larger subvolumes called patches. Each patch’s data is a CD vector showing proportions of dense, hazy, or normal tissue. Proposed method performed reasonably for estimation of the fixed effects, and their variability. However, the model produced biased estimates of the nuisance parameters in the model.

Highly parallel production of designer organoids by mosaic patterning of progenitors

Organoids derived from human stem cells are a promising approach for disease modeling, regenerative medicine, and fundamental research. However, organoid variability and limited control over morphological outcomes remain as challenges. One open question is the extent to which engineering control over culture conditions can guide organoids to specific compositions. Here, we extend a DNA "velcro" cell patterning approach, precisely controlling the number and ratio of human induced pluripotent stem cell-derived progenitors contributing to nephron progenitor (NP) organoids and mosaic NP/ureteric bud (UB) tip cell organoids within arrays of microwells. We demonstrate long-term control over organoid size and morphology, decoupled from geometric constraints. We then show emergent trends in organoid tissue proportions that depend on initial progenitor cell composition. These include higher nephron and stromal cell representation in mosaic NP/UB organoids vs. NP-only organoids and a "goldilocks" initial cell ratio in mosaic organoids that optimizes the formation of proximal tubule structures.

Histopathologic patterns of female genital tuberculosis with clinical correlation: a 10-year (2013–2022) retrospective cross-sectional study

ObjectiveUnderdiagnosis of female genital tuberculosis (FGTB) often leads to infertility. In this study, we aimed to determine the site and histopathologic patterns of FGTB and its correlation with clinical presentation and acid-fast bacilli (AFB) status.MethodsA retrospective cross-sectional study was conducted on 122 patients with a histopathological diagnosis of FGTB at the Department of Pathology, College of Health Sciences (CHS), Tikur Anbessa Specialized Hospital (TASH), Addis Ababa University (AAU), from January 1, 2013, to August 30, 2022.ResultsFemale genital tuberculosis was found in 0.94% of the gynecology specimens examined. The most common presentations were menstrual disturbance, abdominopelvic pain, and infertility. Among patients with FGTB, 4.6% exhibited misleading clinical and radiologic findings, leading to suspicion of malignancy and subsequent aggressive surgical management. The endometrium was the most frequently affected organ, followed by the fallopian tube, ovary, cervix, and vulva. In the majority of tuberculous endometritis cases (53.3%), histopathology revealed early-stage granulomas. Acid-fast bacilli were found in a significant proportion (42.6%) of FGTB tissues with TB histopathology. The ovary had the highest rate of AFB detection, followed by the fallopian tube, endometrium, and cervix.ConclusionFemale genital tuberculosis should be considered in reproductive-age women presenting with menstrual irregularities, abdominopelvic pain, infertility, or an abdominopelvic mass. The endometrium is commonly affected, displaying early granulomas with low AFB positivity.

Molecular Regulation of Thermogenic Mechanisms in Beige Adipocytes.

Adipose tissue is conventionally recognized as a metabolic organ responsible for storing energy. However, a proportion of adipose tissue also functions as a thermogenic organ, contributing to the inhibition of weight gain and prevention of metabolic diseases. In recent years, there has been significant progress in the study of thermogenic fats, particularly brown adipose tissue (BAT). Despite this progress, the mechanism underlying thermogenesis in beige adipose tissue remains highly controversial. It is widely acknowledged that beige adipose tissue has three additional thermogenic mechanisms in addition to the conventional UCP1-dependent thermogenesis: Ca2+ cycling thermogenesis, creatine substrate cycling thermogenesis, and triacylglycerol/fatty acid cycling thermogenesis. This paper delves into these three mechanisms and reviews the latest advancements in the molecular regulation of thermogenesis from the molecular genetic perspective. The objective of this review is to provide readers with a foundation of knowledge regarding the beige fats and a foundation for future research into the mechanisms of this process, which may lead to the development of new strategies for maintaining human health.

A Mesoporous Gold Sensor Unveils Phospho PD-L1 in Extracellular Vesicles as a Proxy for PD-L1 Expression in Lung Cancer Tissue.

Immune checkpoint inhibitors (ICIs) targeting programmed cell death ligand 1 (PD-L1), or its receptor, PD-1 have improved survival in patients with non-small-cell lung cancer (NSCLC). Assessment of PD-L1 expression requires tissue biopsy or fine needle aspiration that are currently used to identify patients most likely to respond to single agent anti-PD-1/PD-L1 therapy. However, obtaining sufficient tissue to generate a PD-L1 tissue proportion score (TPS) ≥ 50% using immunohistochemistry remains a challenge that potentially may be overcome by liquid biopsies. This study utilized a mesoporous gold sensor (MGS) assay to examine the phosphorylation status of PD-L1 in plasma extracellular vesicles (EV pPD-L1) and PD-L1 levels in plasma from NSCLC patient samples and their association with tumor PD-L1 TPS. The 3-dimensional mesoporous network of the electrodes provides a large surface area, high signal-to-noise ratio, and a superior electro-conductive framework, thereby significantly improving the detection sensitivity of PD-L1 nanosensing. Test (n = 20) (Pearson's r = 0.99) and validation (n = 45) (Pearson's r = 0.99) cohorts show that EV pPD-L1 status correlates linearly with the tumor PD-L1 TPS assessed by immunohistochemistry irrespective of the tumor stage, with 64% of patients overall showing detectable EV pPD-L1 levels in plasma. In contrast to the EV pPD-L1 results, plasma PD-L1 levels did not correlate with the tumor PD-L1 TPS score or EV pPD-L1 levels. These data demonstrate that EV pPD-L1 levels may be used to select patients for appropriate PD-1 and PD-L1 ICI therapy regimens in early, locally advanced, and advanced NSCLC and should be tested further in randomized controlled trials. Most importantly, the assay used has a less than 24h turnaround time, facilitating adoption of the test into the routine diagnostic evaluation of patients prior to therapy.

Imprinted Grb10, encoding growth factor receptor bound protein 10, regulates fetal growth independently of the insulin-like growth factor type 1 receptor (Igf1r) and insulin receptor (Insr) genes

BackgroundOptimal size at birth dictates perinatal survival and long-term risk of developing common disorders such as obesity, type 2 diabetes and cardiovascular disease. The imprinted Grb10 gene encodes a signalling adaptor protein capable of inhibiting receptor tyrosine kinases, including the insulin receptor (Insr) and insulin-like growth factor type 1 receptor (Igf1r). Grb10 restricts fetal growth such that Grb10 knockout (KO) mice are at birth some 25-35% larger than wild type. Using a mouse genetic approach, we test the widely held assumption that Grb10 influences growth through interaction with Igf1r, which has a highly conserved growth promoting role.ResultsShould Grb10 interact with Igf1r to regulate growth Grb10:Igf1r double mutant mice should be indistinguishable from Igf1r KO single mutants, which are around half normal size at birth. Instead, Grb10:Igf1r double mutants were intermediate in size between Grb10 KO and Igf1r KO single mutants, indicating additive effects of the two signalling proteins having opposite actions in separate pathways. Some organs examined followed a similar pattern, though Grb10 KO neonates exhibited sparing of the brain and kidneys, whereas the influence of Igf1r extended to all organs. An interaction between Grb10 and Insr was similarly investigated. While there was no general evidence for a major interaction for fetal growth regulation, the liver was an exception. The liver in Grb10 KO mutants was disproportionately overgrown with evidence of excess lipid storage in hepatocytes, whereas Grb10:Insr double mutants were indistinguishable from Insr single mutants or wild types.ConclusionsGrb10 acts largely independently of Igf1r or Insr to control fetal growth and has a more variable influence on individual organs. Only the disproportionate overgrowth and excess lipid storage seen in the Grb10 KO neonatal liver can be explained through an interaction between Grb10 and the Insr. Our findings are important for understanding how positive and negative influences on fetal growth dictate size and tissue proportions at birth.

The Vascular Cambia of Dodder and its Allies

The vascular cambia of 20 species of the dodder and its allies belonging to the CassythaceaE, Convolvulaceae and Cuscutaceae were surveyed to assess their phenetic and phylogenetic significance. In natural condition all of them contain anomalous cambia. The Cassythaceae bore transitory cambium in the normal position but atypical by asmmetric activity. (The Cambium alternatelt retards accemtuates xylem formation on several segments and there are profuse sehizongenous spaces in wood. Haustoria contains both traheids and vessels).In stems and roots of the Convolvulaceae a series of widely different anomalous cambia were found which sometimes differed in stems and roots of the same species. Stems of arborescent group had bands of interxylary phloem in concentric rings, while in the primitive twiners these are arranged in radial plates. In general, a tendency was to increase the proportion of soft tissue. In Cuscutaceae the specified anomaly was the interfascicular cambium. Ray initials were absent but fusiform initials differentiated into profuse parenchyma cells and a few vessel elements.Haustorium develops only imperforate tracheary elements. The evolutionary history vascular cambium in the Convolvulaceae was mainly one of reduction in activity and area. Thus the vesselless haustorium of Cuscutaceae. may be regarded as a reduced farm in with the vessel bearing haustorium of Cassythaceae. It 1s also concluded that the primitive condition of Cuscutaceae is possibly derived from the general condition of Convolvulaceae.