Fragmentation Analysis Research Articles

Frequency analysis of food bolus fragmentation through a vertical pipe

Frequency analysis of food bolus fragmentation through a vertical pipe

Photoresponsive 'chemo-free' phytotherapy: formulation development for the treatment of triple-negative breast cancer.

Aim: The present investigation aimed to develop a chemo-free, nanophytosomal system to treat triple-negative breast cancer (TNBC) via a phyto-photo dual treatment strategy. Method: Size, shape, surface analysis, photoprovoked release profile, photothermal stability, (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide assay, apoptotic assay, DNA fragmentation, in vitro cellular uptake evaluation, mitochondrial membrane potential and caspase-3 assay, andphotodynamic evaluation. Results: Biological experiments using MDA-MB-231 cells displayed dose-dependent synergistic anti-TNBC activity of PhytoS/Houttuynia cordata extract (HCE)/IR780 as compared with Phyto/HCE, PhytoS/IR780 and even more promising under laser treatment. Apoptotic assay and DNA fragmentation analysis also showed enhanced anti-TNBC effects. Investigation found that HCE acts via suppression ofmitochondrial membrane potential and inducing caspase-3 activity in cells. Conclusion: Our findings suggested that photo-empowered phytotherapy can be employed effectively and safely against TNBC.

Application of Air Deck Method to Reduce the Impact of Ground Vibration and Optimization of Limestone Fragment Size in Blasting Activities at PT Semen Baturaja (Persero), Tbk.

The field experiment of applying the air deck method to the limestone blasting activities of PT Semen Baturaja (Persero), aims to reduce the impact of ground vibration considering that mining activities are approaching residential areas. In addition, the size of the fragmentation of the blasting results is very important for the effectiveness of the crushing plant. To determine the effectiveness of the application of the air deck method in limestone mining (quarry), blasting planning activities are carried out by dividing the two blasting locations, namely blasting with the air deck method and without using an air deck. By using a zig-zag blasting pattern and the number of holes of 50 Lb, the depth of the drill holes is 9 meters (without air deck) and 13 meters and the type of explosive used is Nonel. From the results of the analysis of limestone blasting with data processing using the split desktop 2.0 demo application, the ground vibration value (micromater system) was obtained. The average value of ground vibration (pVS) shows a smaller value using the air deck method of 0.68 mm/sec while without air deck of 0.74 mm/sec. The results of limestone fragmentation analysis with the air deck method obtained size <75cm reached 91.93%, while for without air deck it was 80.27%. These results show that the air deck method can be applied as a method to assist the Company in reducing ground vibration and limestone fragmentation effectively and efficiently by considering natural factors including geographical factors.

RELATIONSHIP BETWEEN SPERM DNA FRAGMENTATION AND EMBRYO DEVELOPMENT IN IVF PATIENTS

Infertility is a condition in married couples who have regular and adequate sexual intercourse for more than one year without using contraception, but have not had a pregnancy or offspring. Factors that cause infertility can be caused by men, women, or even both. Approximately 10% - 15% of couples of reproductive age experience infertility, with the contribution of the male factor, which is equal to 40% -50%. The analysis of embryo development and spermatozoa DNA fragmentation aims to analyze the function of spermatozoa in infertile men and to determine the relationship between sperm DNA fragmentation and embryo development in IVF patients. This study was an experimental study with a total of 30 samples of husband's patients who carried out the IVF program who met the researcher's inclusion criteria. The statistical test results obtained showed that there was a significant relationship between the DNA fragmentation index (DFI) (P<0.05), therefore it can be concluded that further research is needed so that many more things can be explored. of other causes of infertility.

Vanadium oxide 3- methoxy salen, a synthetic biologically active complex against HeLa and McCoy cell lines

Background: Vanadium is an essential dietary microelement that plays a key role in metabolic pathways and has anti-neoplastic effects. In this regard, vanadium oxide 3-methoxy salen complex was produced and its anticancer effects were evaluated against HeLa and McCoy cell lines.
 Methods: Schiff bases produced from equivalents of Vanadyl acetylacetonate [VO(acac)2] in methanol were used to make a vanadium oxide 3-methoxy salen complex. Then, The antioxidant property of compound, cell viability and cytotoxicity assay, DNA fragmentation analysis and determination of the apoptosis pathway genes were evaluated.
 Results: The result showed that the compound with an RC50 value of 126.3 µM demonstrated considerable free radical scavenging activity. The combination strongly suppressed the viability and proliferation of HeLa and McCoy cell lines in a dose-dependent manner, with IC50 values of 213 µM and 175 µM, respectively. When the viability and cytotoxicity values of the treated cells were compared, it was discovered that the cells had died of apoptosis, which was validated by DNA fragmentation analysis. Capspase 3, Bcl2 antagonist/killer, and Bcl2 associated X protein (Bax) gene expression levels all increased significantly in a quantitative investigation of apoptotic pathway genes, with 2-CT values of 2.36, 2.63, and 3.18, respectively.
 Conclusion: In HeLa and McCoy malignant cell lines, lower quantities of the complex caused programmed cell death. This potential of complex can be used in cancer chemoprevention and cancer therapy.

Discriminating Between Apoptosis, Necrosis, Necroptosis, and Ferroptosis by Microscopy and Flow Cytometry.

Apoptosis is a mode of programmed cell death that plays important roles in tissue sculpting during development, in the maintenance of tissue homeostasis in the adult, and in the eradication of injured or infected cells during pathological processes. Numerous physiological as well as pathological stimuli trigger apoptosis, such as engagement of plasma-membrane-associated Fas, TRAIL, or TNF receptors, growth factor deprivation, hypoxia, radiation, and exposure to diverse cytotoxic drugs. Apoptosis is coordinated by members of the caspase family of cysteine proteases, which, upon activation, trigger a series of dramatic morphological and biochemical changes including retraction from the substratum, cell shrinkage, extensive and protracted plasma membrane blebbing, chromatin condensation, DNA hydrolysis, nuclear fragmentation, and proteolytic cleavage of numerous caspase substrates. These dramatic structural and biochemical alterations result not only in the controlled dismantling of the cell, but also in the rapid recognition and removal of apoptotic cells by phagocytes through the cell surface display of phagocytotic triggers such as phosphatidylserine. Necrosis, which is typically nonprogrammed or imposed upon the cell by overwhelming membrane or organelle damage, is characterized by high-amplitude cell swelling, followed by rapid plasma membrane rupture and release of cellular contents into the extracellular space. Necrosis is often provoked by infectious agents or severe departure from physiological conditions due to toxins, temperature extremes, or physical injury. However, forms of programmed necrosis (necroptosis, pyroptosis, ferroptosis) can also occur in specific circumstances. Nonprogrammed and programmed necrosis can be distinguished from apoptosis by morphological features, based on the rapid uptake of vital dyes, and through the application of specific inhibitors of key molecules associated with the latter modes of cell death. This unit describes protocols for the measurement of apoptosis and necrosis and for distinguishing apoptosis from programmed as well as conventional necrosis. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Analysis of cell morphology by phase-contrast microscopy Alternative Protocol 1: Assessment of morphological changes using eosin-methylene blue staining Alternative Protocol 2: Analysis of nuclear morphology by fluorescence microscopy Support Protocol: Preparation of cytospins Basic Protocol 2: Measurement of plasma membrane composition with annexin V and propidium iodide Basic Protocol 3: Measurement of DNA fragmentation by flow cytometry Alternative Protocol 3: Analysis of DNA fragmentation by the TUNEL assay Basic Protocol 4: Measurement of caspase activation by flow cytometry Basic Protocol 5: Discriminating between apoptosis, necrosis, necroptosis, and ferroptosis.

Sperm DNA Fragmentation: Causes, Effects and Relevance in IVF Outcomes

Sperm DNA fragmentation, characterized by damaged or broken DNA strands within sperm cells, has been recognized as an important factor in male infertility and poor ART outcome. This lecture aims to provide an overview of the causes, effects, and relevance of sperm DNA fragmentation in in vitro fertilization (IVF) outcomes and look into the latest evidences from the literatures. Causes: Sperm DNA fragmentation can result from various factors, including oxidative stress, advanced paternal age, lifestyle factors such as smoking and excessive alcohol consumption, environmental exposures, genotoxic agents, and underlying genetic abnormalities. These factors can induce DNA damage during sperm development, during the transit of sperm through the male reproductive tract or during the storage of the sperm in epididymis. Relevance in IVF Outcomes: The assessment of sperm DNA fragmentation has emerged as a valuable tool in evaluating male infertility and predicting IVF success. Several methods, including the sperm chromatin structure assay (SCSA), terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL), comet assay, and other commercial detection kits, are available to measure sperm DNA fragmentation. Previous small cohort studies have demonstrated that higher levels of sperm DNA fragmentation are associated with lower pregnancy rates, decreased embryo quality, and an increased risk of pregnancy loss in IVF cycles. Therefore, incorporating sperm DNA fragmentation analysis into the routine assessment of male infertility can aid in optimizing treatment strategies and improving IVF outcomes. Recent evidences: Latest large clinical studies showed a limited association to IVF outcome. The DFI remains controversial as a predictive tool. Nonetheless, sperm DNA fragmentation is still believed to be a significant factor affecting male fertility and IVF outcomes. Further research is warranted to explore the mechanisms underlying DNA fragmentation, develop standardized assessment methods, and explore potential interventions to mitigate the adverse effects of sperm DNA damage on IVF success.

Development of a Multiplication Factor for the Kuz-Ram Model to Match the Fragment Size Obtained from Wipfrag Image Analysis

The degree to which the rock is fragmented by blasting operations significantly impacts the productivity of the opencast mining operation. Over image analysis-based tools, the Kuz-Ram empirical model is preferred for determining the mean fragment size of a blasted muck pile. The fragmentation analysis results by the Kuz-Ram model are said to report the overestimation of the size of the fragments. On the other hand, while accurate, measuring the mean fragment size by image-based analysis is also time-consuming and expensive. Therefore, in the present research, the fragmentation difference index (Fdi) is introduced as a new multiplication factor to reduce the discrepancy in the results obtained using the Kuz-Ram model and the image-based analysis. The error minimization method of least squares is used to formulate the objective function of Fdi. The proposed equation is tested using data sets that weren't used in the model's development. Statistical indicators viz. the coefficient of determination (R2 ) and Root Mean Square Error (RMSE) have been used to evaluate the model's performance. These are found to be 0.80 and 0.007, respectively. The values obtained by multiplying Fdi by the Kuz-Ram results match those of the Wipfrag study, with an average error of 2.09%. Therefore, the suggested methodology will assist the field engineers in cost-effectively calculating the mean fragment size before blasting utilizing only the findings from the Fdi and Kuz-Ram models.

A Review of the Blast Fragmentation Analysis Techniques used in Surface Mines

Fragmentation refers to the process of breaking solid in-situ rock masses into smaller pieces during excavation or material handling operations. The fragment size distribution and degree of fragmentation within the blasted rock mass stand as a critical aspect for optimizing the efficiency of loading, transportation, crushing, and milling operations. The analysis of blast fragmentation analysis is done by several existing modern techniques which include the visual analysis method, photogrammetric method, and image analysis method, etc. In this study, all the blast fragmentation techniques are reviewed, and the advantages and disadvantages of all the methods are discussed. Along with that, a blast fragmentation analysis is conducted for the rock pile images of a blasting site collected from Dongri Buzurg Mine (MOIL), India using the image processing technique in WipFrag software. The feasibility of the blasting patterns is judged based on the uniformity coefficient (Cu) and the coefficient of gradation (Cg) which are found to be 4.47 and 0.94 respectively. The fragmentation for the muck pile is found to be uniform and well-graded for the blast site and the methodology used is found to be simple yet effective for the analysis.

Green synthesis of iron oxide nanoparticles from Spermacoce ocymoides Burm.f. plant extracts for targeted lung cancer A549 cell therapy

The present study evaluated the synthesis of iron oxide nanoparticles using Spermacoce ocymoides Burm.f. plant extracts, and the effects of plant based iron oxide nanoparticles on A549 lung cancer cells were investigated to elucidate their impact on cellular morphology, mitochondrial function, and apoptotic pathways. Spermacoce ocymoides plant based iron oxide nanoparticles were characterised by X-ray diffraction, Atomic force microscopy, FTIR, and UV-Vis absorption spectroscopy. Iron oxide nanoparticle treatment caused considerable morphological alterations in A549 cells, including cell shrinkage, detachment, membrane blabbing, and distorted shape, consistent with cellular stress and potential apoptotic events. MMP analysis revealed a dose-dependent decrease in mitochondrial membrane potential, implying that nanoparticles have an effect on mitochondrial function. The presence of reactive oxygen species suggested that oxidative stress was involved in the cellular response to iron oxide nanoparticles. Additionally, DNA fragmentation analysis confirmed the activation of apoptotic pathways, with the nanoparticles themselves serving as a positive control for inducing apoptosis. The observed morphological changes, altered mitochondrial function, ROS production, and DNA fragmentation collectively point towards apoptotic cell death pathways being triggered by the nanoparticles.
 KEY WORDS: Spermacoce ocymoides, Iron oxide nanoparticles, A549 cells, Apoptotic
 Bull. Chem. Soc. Ethiop. 2024, 38(1), 123-134. DOI: https://dx.doi.org/10.4314/bcse.v38i1.10

SRNAfrag: a pipeline and suite of tools to analyze fragmentation in small RNA sequencing data.

Fragments derived from small RNAs such as small nucleolar RNAs are biologically relevant but remain poorly understood. To address this gap, we developed sRNAfrag, a modular and interoperable tool designed to standardize the quantification and analysis of small RNA fragmentation across various biotypes. The tool outputs a set of tables forming a relational database, allowing for an in-depth exploration of biologically complex events such as multi-mapping and RNA fragment stability across different cell types. In a benchmark test, sRNAfrag was able to identify established loci of mature microRNAs solely based on sequencing data. Furthermore, the 5' seed sequence could be rediscovered by utilizing a visualization approach primarily applied in multi-sequence-alignments. Utilizing the relational database outputs, we detected 1411 snoRNA fragment conservation events between two out of four eukaryotic species, providing an opportunity to explore motifs through evolutionary time and conserved fragmentation patterns. Additionally, the tool's interoperability with other bioinformatics tools like ViennaRNA amplifies its utility for customized analyses. We also introduce a novel loci-level variance-score which provides insights into the noise around peaks and demonstrates biological relevance by distinctly separating breast cancer and neuroblastoma cell lines after dimension reduction when applied to small nucleolar RNAs. Overall, sRNAfrag serves as a versatile foundation for advancing our understanding of small RNA fragments and offers a functional foundation to further small RNA research. Availability: https://github.com/kenminsoo/sRNAfrag.

Surface-induced dissociation of protein complex ions in a modified electrostatic linear ion trap

The electrostatic linear ion trap (ELIT) is a device that can provide mass analysis via frequency measurement, followed by Fourier transformation from the frequency domain to the time domain, or via time measurement in a multi-reflection time-of-flight measurement. ELIT devices have been demonstrated to be capable of relatively high mass measurement resolution as well as high-resolution ion isolation capabilities. We have been exploring the possibility of developing the ELIT geometry as a stand-alone high-performance tandem mass spectrometer for native mass spectrometry (MS) studies. In this context, it is desirable to use an activation method capable of dissociating the high-mass complexes encountered in native MS. To this end, we describe the implementation of surface-induced dissociation (SID) in an ELIT and describe initial results for protein complexes generated under native conditions in which ion isolation, fragmentation, and product ion mass analysis all occur within the ELIT.

Study on the Spatiotemporal Evolution of the Ecological Landscape and Construction of an Ecological Network: A Case Study of Hebei Province

Research on the establishment of a regional ecological network can provide a scientific basis and valuable guidance for the protection of regional animals and plants, water conservation, sustainable resource utilization, and optimization of land use patterns. This study investigated the impacts of land use changes on the ecological security pattern using morphological spatial pattern analysis (MSPA), the minimum cumulative resistance (MCR) model, and the analysis of spatiotemporal changes and fragmentation of land use types. The results indicate that from 2000 to 2020, the dominant trend in land use types was the expansion of cultivated land, grass land, and wood land. Although the proportion of cultivated land was the largest and was concentrated in the southern part of Hebei Province, the total area of cultivated land showed a decline. Landscape index calculations revealed an increase in fragmentation of the overall landscape ecological patches, while the spatial and quantitative distribution of landscape types gradually became more uniform. Furthermore, 52 patches with the highest landscape index were identified as ecological sources, mainly located in northern Hebei Province in 2020. MSPA calculations showed that elevation, slope, and land use type contributed significantly to the comprehensive resistance surface. Using the MCR model, an ecological network for Hebei Province was constructed, consisting of 114 ecological corridors and 28 ecological nodes. The ecological corridors exhibited a distribution pattern of high density in the north and low density in the south, while the ecological nodes enhanced overall ecological connectivity in the region. Based on the current ecological environment, it is recommended to increase the number of ecological corridors and ecological nodes to enhance ecosystem stability.

Impact of Liquid Biopsy Preanalytics on cfDNA Fragmentation Analyses

Impact of Liquid Biopsy Preanalytics on cfDNA Fragmentation Analyses

Land Cover Change and Fragmentation Analysis in Sintang Regency, West Kalimantan, Indonesia

The increasing number of human populations and their needs have driven changes in forest cover to become infrastructure, agricultural land, and plantations. Sintang Regency has a natural forest structure upstream of the Kapuas River and the Kayan River, which the local community uses for transportation and sources of livelihood. In this study, we wanted to analyze the level of fragmentation in Sintang Regency. We used landcover data in the mapping periods of 2010, 2015, and 2020, with MoEF classification—fragmentation analysis using ArcGIS 10.6 and FRAGSTATS v4.2.1 software at class and patch levels analysis. The result showed decreased natural forest while estate crop and mining increased. As an impact of decreasing forest area, it also reduced the total core area and connectivity; the intact forest > 50,000 ha was isolated in 2020. The fragmentation of forests will impact reduced habitat for wildlife and loss of ecological function of the landscape.

Alternative Tissue Fixation Protocols Dramatically Reduce the Impact of DNA Artifacts, Unraveling the Interpretation of Clinical Comprehensive Genomic Profiling

Formalin-fixed paraffin-embedded (FFPE) samples represent the cornerstone of tissue-based analysis in precision medicine. Targeted next-generation sequencing panels are routinely used to analyze a limited number of genes to guide treatment decision-making for advanced-stage patients. The number and complexity of genetic alterations to be investigated are rapidly growing; in several instances, a comprehensive genomic profiling analysis is needed. The poor quality of genetic material extracted from FFPE samples may impact the feasibility/reliability of sequencing data. We sampled 9 colorectal cancers to allow 4 parallel fixations: (1) neutral buffered formalin (NBF), (2) acid-deprived formalin fixation (ADF), (3) precooled ADF (coldADF), and (4) glyoxal acid free (GAF). DNA extraction, fragmentation analysis, and sequencing by 2 large next-generation sequencing panels (OCAv3 and TSO500) followed. We comprehensively analyzed library and sequencing quality controls and the quality of sequencing results. Libraries from coldADF samples showed significantly longer reads than the others with both panels. ADF-derived and coldADF-derived libraries showed the lowest level of noise and the highest levels of uniformity with the OCAv3 panel, followed by GAF and NBF samples. The data uniformity was confirmed by the TSO500 results, which also highlighted the best performance in terms of the total region sequenced for the ADF and coldADF samples. NBF samples had a significantly smaller region sequenced and displayed a significantly lower number of evaluable microsatellite loci and a significant increase in single-nucleotide variations compared with other protocols. Mutational signature 1 (aging and FFPE artifact related) showed the highest (37%) and lowest (17%) values in the NBF and coldADF samples, respectively. Most of the identified genetic alterations were shared by all samples in each lesion. Five genes showed a different mutational status across samples and/or panels: 4 discordant results involved NBF samples. In conclusion, acid-deprived fixatives (GAF and ADF) guarantee the highest DNA preservation/sequencing performance, thus allowing more complex molecular profiling of tissue samples.

New Cytotoxic Monoalkyl Glycerol Ether from the Red Sea Soft Coral Nephthea mollis.

A new monoalkyl glycerol ether, 3-(n-henicosyloxy)propane-1,2-diol (1), was isolated from the CH2 Cl2 /MeOH crude extract of the Red Sea soft coral Nephthea mollis. Additionally, three known related analogs were identified: chimyl alcohol (2), batyl alcohol (3), and 3-(icosyloxy)propane-1,2-diol (4). The chemical structure of 3-(n-henicosyloxy)propane-1,2-diol was determined using advanced spectroscopic analyses, including 1D, 2D Nuclear Magnetic Resonance (NMR), Electron Ionization mass spectra (EI-MS), and High-Resolution Electron Spray Ionization mass spectra (HR-ESI-MS) analyses. Furthermore, the identification of chimyl alcohol, batyl alcohol and 3-(icosyloxy)propane-1,2-diol was achieved by studying their EI mass fragmentation analyses and comparing their mass data with those previously reported in the literature. The cytotoxic activity of the Nephthea mollis crude extract and 3-(n-henicosyloxy)propane-1,2-diol was evaluated against five human cancer cell lines: HepG2 (hepatocellular carcinoma), MCF-7 (breast carcinoma), NCI-1299 (lung carcinoma), HeLa (cervical cancer cell), and HT-29 (colon adenocarcinoma). Moreover, 3-(n-henicosyloxy)propane-1,2-diol revealed moderate cytotoxicity against the HeLa cell lines with an IC50 value of 24.1 μM, while showing inactivity against the remaining cell lines (IC50 >100 μM).

Identification of Daphnane Diterpenoids from Wikstroemia indica Using Liquid Chromatography with Tandem Mass Spectrometry.

Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) has emerged as a powerful tool for the rapid identification of compounds within natural resources. Daphnane diterpenoids, a class of natural compounds predominantly found in plants belonging to the Thymelaeaceae and Euphorbiaceae families, have attracted much attention due to their remarkable anticancer and anti-HIV activities. In the present study, the presence of daphnane diterpenoids in Wikstroemia indica, a plant belonging to the Thymelaeaceae family, was investigated by LC-MS/MS analysis. As a result, 21 daphnane diterpenoids (1-21) in the stems of W. indica were detected. Among these, six major compounds (12, 15, 17, 18, 20, and 21) were isolated and their structures were unequivocally identified through a comprehensive analysis of the MS and NMR data. For the minor compounds (1-11, 13, 14, 16, and 19), their structures were elucidated by in-depth MS/MS fragmentation analysis. This study represents the first disclosure of structurally diverse daphnane diterpenoids in W. indica, significantly contributing to our understanding of bioactive diterpenoids in plants within the Thymelaeaceae family.

Experimental and Theoretical Analysis of the Thiol-Promoted Fragmentation of 2-Halo-3-tosyl-oxanorbornadienes.

2-Halo-3-tosyl-oxanorbornadienes are able to accept two thiol molecules through an initial nucleophilic substitution, giving isolable oxabicyclic thiovinyl sulfones that, subsequently, can react with a second thiol molecule via thio-Michael addition. The resulting oxanorbornenic thioketals undergo retro-Diels-Alder (rDA) fragmentation to release a furan derivative and a ketene S,S-acetal. The substitution pattern of the oxanorbornadienic skeleton influences the rate of the rDA through electronic and steric factors examined by quantum mechanical calculations.

FRI008 Impact Of Sleep Fragmentation And Estradiol Suppression On Leptin, Ghrelin, Satiety And Hunger In Women: An Experimental Menopause Model To Understand Menopause-related Body Fat Gain

Abstract Disclosure: S.A. Rahman: Consulting Fee; Self; Sultan & Knight Limited, Bambu Vault LLC, Lucidity Lighting Inc. Grant Recipient; Self; Seoul Semiconductor Co. Ltd, Biological Innovation and Optimization Systems, LLC, Merck & Co, Inc, Pfizer Inc, Vanda Pharmaceuticals Inc, Lighting Science Group. Speaker; Self; Starry Skies Lake Superior, University of Minnesota Medical School, PennWell Corp, and Seoul Semiconductor Co. Ltd. Stock Owner; Self; Melcort Inc. L.K. Grant: None. A. Cohn: None. M.D. Nathan: None. J. Harder: Consulting Fee; Self; Atman Health; O’Rourke & Hawk, LLP. Grant Recipient; Self; Brigham and Women’s Hospital; President and Fellows of Harvard College. Owner/Co-Owner; Self; Jessica Harder, MD. Stock Owner; Self; Atman Health. Other; Self; Centerfield Media Holding Company. I. Gonsalvez: None. F.A. Scheer: Consulting Fee; Self; University of Alabama at Birmingham. Other; Self; Board of Directors for the Sleep Research Society. E.B. Klerman: Consulting Fee; Self; Circadian Therapeutics, The National Sleep Foundation, Sanofi-Genzynel. Other; Self; Travel support from the Sleep Research Society. S. Crawford: None. T. Luo: None. E. Menezes: None. A. Roy: None. A. Joseph: None. A. Wiley: None. U.B. Kaiser: None. H. Joffe: Consulting Fee; Self; Bayer, Hello Therapeutics. Grant Recipient; Self; National Institutes of Health, Merck, Pfizer. Body fat increases during the menopause transition. In addition to menopause-related estradiol (E2) decline, sleep fragmentation (wake episodes interrupting sleep) due to hot flashes, without a reduction in total sleep time, is common. We examined whether E2 decline and sleep fragmentation decrease the satiety hormone, leptin, increase the orexigenic hormone, ghrelin, and their behavioral correlates satiety and hunger, which would promote positive energy balance and body fat gain. We studied 38 healthy premenopausal female volunteers (mean age [±SD] 29.7±6.7 years) in a 5-night inpatient study under eucaloric conditions, once in the mid-to-late follicular phase (high-E2) and again after gonadotropin-releasing hormone agonist-induced E2-suppression (hypo-E2) in a subset (n=27). Each inpatient study involved 2 nights of unfragmented sleep followed by 3 nights of experimentally induced sleep fragmentation to achieve ∼1hr of wake after sleep-onset without reducing total sleep time. Serum for leptin and acetylated ghrelin assays and self-reported satiety and hunger via visual analog scales were collected fasting ∼1hr after waking each morning. Values were normalized relative to each individual’s baseline (high-E2, unfragmented sleep) and then compared between conditions using generalized linear mixed models. Mean (±SD) levels of leptin and ghrelin at baseline were 38.5±21.2 ng/mL and 640.9±362.0 pg/mL, respectively. Compared to the high-E2 state, omnibus analysis of E2 suppression during both unfragmented and fragmented sleep showed significant reduction from the high-E2 to hypo-E2 state in satiety-promoting leptin levels (least squares mean % of baseline [±SE]: 101.0±1.1% vs. 90.0±3.0%, p=0.001), but unchanged self-rated satiety (109.3±7.8% vs. 102.6±15.6%, p=0.58). E2 suppression also did not change hunger-promoting ghrelin levels (101.0±3.1% vs. 97.0±1.4%, p=0.13) or self-rated hunger (103.3±6.6% vs. 133.2±30.5%, p=0.28). Omnibus analysis of sleep fragmentation during both high-E2 and hypo-E2 states showed that, relative to unfragmented sleep, leptin levels were unchanged (94.0±1.5% vs. 96.7±2.5%, p=0.22), but self-rated satiety was significantly lower (113.1±11.0% vs. 99.2±11.9%, p=0.048) after sleep fragmentation. There was a trend towards the lowest satiety in the hypo-E2 sleep fragmented state (interaction p=0.052). Sleep fragmentation did not change ghrelin levels (100.7±1.8% vs. 97.3±2.7%, p=0.13) or self-rated hunger (103.0±6.2% vs. 133.6±30.0%, p=0.25). These results demonstrate significant adverse changes in leptin and satiety in women induced, respectively, by E2 suppression and sleep fragmentation, independent of aging. Findings support likely independent contributions of E2 decline and sleep fragmentation during the menopause transition toward positive energy balance and body fat gain. Funding: NIH R01AG053838 (PI: H Joffe). Presentation: Friday, June 16, 2023