Changes In Three-dimensional Structure Research Articles

MICOS Complex Loss Governs Age-Associated Murine Mitochondrial Architecture and Metabolism in the Liver, While Sam50 Dictates Diet Changes.

The liver, the largest internal organ and a metabolic hub, undergoes significant declines due to aging, affecting mitochondrial function and increasing the risk of systemic liver diseases. How the mitochondrial three-dimensional (3D) structure changes in the liver across aging, and the biological mechanisms regulating such changes confers remain unclear. In this study, we employed Serial Block Face-Scanning Electron Microscopy (SBF-SEM) to achieve high-resolution 3D reconstructions of murine liver mitochondria to observe diverse phenotypes and structural alterations that occur with age, marked by a reduction in size and complexity. We also show concomitant metabolomic and lipidomic changes in aged samples. Aged human samples reflected altered disease risk. To find potential regulators of this change, we examined the Mitochondrial Contact Site and Cristae Organizing System (MICOS) complex, which plays a crucial role in maintaining mitochondrial architecture. We observe that the MICOS complex is lost during aging, but not Sam50. Sam50 is a component of the sorting and assembly machinery (SAM) complex that acts in tandem with the MICOS complex to modulate cristae morphology. In murine models subjected to a high-fat diet, there is a marked depletion of the mitochondrial protein SAM50. This reduction in Sam50 expression may heighten the susceptibility to liver disease, as our human biobank studies corroborate that Sam50 plays a genetically regulated role in the predisposition to multiple liver diseases. We further show that changes in mitochondrial calcium dysregulation and oxidative stress accompany the disruption of the MICOS complex. Together, we establish that a decrease in mitochondrial complexity and dysregulated metabolism occur with murine liver aging. While these changes are partially be regulated by age-related loss of the MICOS complex, the confluence of a murine high-fat diet can also cause loss of Sam50, which contributes to liver diseases. In summary, our study reveals potential regulators that affect age-related changes in mitochondrial structure and metabolism, which can be targeted in future therapeutic techniques.

Computed tomography-based structural rigidity analysis can assess tumor- and treatment-induced changes in rat bones with metastatic lesions

BackgroundBreast cancer (BrCa) is a predominant malignancy, with metastasis occurring in one in eight patients, nearly half of which target the bone, leading to serious complications such as pain, fractures, and compromised mobility. Structural rigidity, crucial for bone strength, becomes compromised with osteolytic lesions, highlighting the vulnerability and increased fracture risk in affected areas. Historically, two-dimensional radiographs have been employed to predict these fracture risks; however, their limitations in capturing the three-dimensional structural and material changes in bone have raised concerns. Recent advances in CT-based Structural Rigidity Analysis (CTRA), offer a promising, more accurate non-invasive 3D approach. This study aims to assess the efficacy of CTRA in monitoring osteolytic lesions’ progression and response to therapy, suggesting its potential superiority over existing methodologies in guiding treatment strategies.MethodsTwenty-seven female nude rats underwent femoral intra-medullary inoculation with MDA-MB-231 human breast cancer cells or saline control. They were divided into Control, Cancer Control, Ibandronate, and Paclitaxel groups. Osteolytic progression was monitored weekly using biplanar radiography, quantitative computed tomography (QCT), and dual-energy X-ray absorptiometry (DEXA). CTRA was employed to predict fracture risk, normalized using the contralateral femur. Statistical analyses, including Kruskal-Wallis and ANOVA, assessed differences in outcomes among groups and over time.ResultsBiplanar radiographs showed treatment benefits over time; however, only certain time-specific differences between the Control and other treatment groups were discernible. Notably, observer subjectivity in X-ray scoring became evident, with significant inter-operator variations. DEXA measurements for metaphyseal Bone Mineral Content (BMC) did not exhibit notable differences between groups. Although diaphyseal BMC highlighted some variance, it did not reveal significant differences between treatments at specific time points, suggesting a limited ability for DEXA to differentiate between treatment effects. In contrast, the CTRA consistently demonstrated variations across different treatments, effectively capturing bone rigidity changes over time, and the axial- (EA), bending- (EI), and torsional rigidity (GJ) outcomes from the CTRA method successfully distinguished differences among treatments at specific time points.ConclusionTraditional approaches, such as biplanar radiographs and DEXA, have exhibited inherent limitations, notably observer bias and time-specific inefficacies. Our study accentuates the capability of CTRA in capturing real-time, progressive changes in bone structure, with the potential to predict fractures more accurately and provide a more objective analysis. Ultimately, this innovative approach may bridge the existing gap in clinical guidelines, ushering in enhanced Clinical Decision Support Tool (CDST) for both surgical and non-surgical treatments.

Switch of cell migration modes orchestrated by changes of three-dimensional lamellipodium structure and intracellular diffusion

Cell migration plays important roles in many biological processes, but how migrating cells orchestrate intracellular molecules and subcellular structures to regulate their speed and direction is still not clear. Here, by characterizing the intracellular diffusion and the three-dimensional lamellipodium structures of fish keratocyte cells, we observe a strong positive correlation between the intracellular diffusion and cell migration speed and, more importantly, discover a switching of cell migration modes with reversible intracellular diffusion variation and lamellipodium structure deformation. Distinct from the normal fast mode, cells migrating in the newly-found slow mode have a deformed lamellipodium with swollen-up front and thinned-down rear, reduced intracellular diffusion and compartmentalized macromolecule distribution in the lamellipodium. Furthermore, in turning cells, both lamellipodium structure and intracellular diffusion dynamics are also changed, with left-right symmetry breaking. We propose a mechanism involving the front-localized actin polymerization and increased molecular crowding in the lamellipodium to explain how cells spatiotemporally coordinate the intracellular diffusion dynamics and the lamellipodium structure in regulating their migrations.

Novel PAX9 compound heterozygous variants in a Chinese family with non-syndromic oligodontia and genotype-phenotype analysis of PAX9 variants.

Studies have reported that >91.9% of non-syndromic tooth agenesis cases are caused by seven pathogenic genes. To report novel heterozygous PAX9 variants in a Chinese family with non-syndromic oligodontia and summarize the reported genotype-phenotype relationship of PAX9 variants. We recruited 28 patients with non-syndromic oligodontia who were admitted to the Hospital of Stomatology Hebei Medical University (China) from 2018 to 2021. Peripheral blood was collected from the probands and their core family members for whole-exome sequencing (WES) and variants were verified by Sanger sequencing. Bioinformatics tools were used to predict the pathogenicity of the variants. SWISS-MODEL homology modeling was used to analyze the three-dimensional structural changes of variant proteins. We also analyzed the genotype-phenotype relationships of PAX9 variants. We identified novel compound heterozygous PAX9 variants (reference sequence NM_001372076.1) in a Chinese family with non-syndromic oligodontia: a new missense variant c.1010C>A (p.T337K) in exon 4 and a new frameshift variant c.330_331insGT (p.D113Afs*9) in exon 2, which was identified as the pathogenic variant in this family. This discovery expands the known variant spectrum of PAX9; then, we summarized the phenotypes of non-syndromic oligodontia with PAX9 variants. We found that PAX9 variants commonly lead to loss of the second molars.

Visualization of wood cell structure during cellulose purification via high resolution X-ray CT and spectroscopy

Wood is a heterogeneous material with multiple scales. Revealing the three-dimensional structure of wood tissue in multiple dimensions works as a prerequisite for the reorganization, modification and high-value utilization of wood. By adopting high resolution X-ray micro computed tomography (XμCT), the three-dimensional structural changes during cellulose purification were reconstructed. In the meantime, the changing process in the chemical composition of wood cell wall was demonstrated in situ using laser Raman spectroscopy imaging technology. Moreover, cellular changes on a two-dimensional scale were observed by ordinary optical, fluorescence, and polarizing microscopes respectively. XμCT results indicated that the disruption of the cell structure of chinese fir (Cunninghamia lanceolata (Lamb.) Hook.) by purification treatment started between the diameter walls of the tracheids, while that of the poplar (Populus sp.) cell structure started between the vessels or between the vessels and the wood rays. Such kind of disruption in cell structure was more pronounced after the hemicellulose was removed, with adjacent cells scattered and deformed. In the first step of matrix removal, the cell wall got thinner primarily out of lignin removal, while in the process of hemicellulose removal, the cell wall swelled with the lye. The Raman images illustrated that the distribution of purified cellulose in the cell wall was related to the degree of cell disruption. In undeformed cell walls, the cellulose was evenly distributed, whereas in shrunken and deformed cell walls, it was unevenly scattered.

Long-range interaction within the chromatin domain determines regulatory patterns in porcine skeletal muscle

Spatial chromatin structure is crucial for understanding the early growth and development of porcine skeletal muscle. However, its characteristic of 3D architecture and elaborate regulation of gene transcription remains unclear. In this study, ChIA-PET method is used to study the changes of early chromatin three-dimensional structure in skeletal muscle of lean type Yorkshire pig and fat type Meishan pig. Integrating the in situ Hi-C data revealed the 3D architecture and long-range interaction of the porcine muscle. The results showed the CTCF/RNAPII mediated long-range interaction shapes the different chromatin architecture and dominates the unique regulation of enhancers. In addition, the results revealed that key myogenic genes like ssc-mir-1 had a unique enhancer regulation function in myogenesis. Interestingly, the FGF6 gene is of breed-specific regulation, implying the difference between two breeds in skeletal muscle development. Our research thus may provide a clue for the porcine genetic improvement of skeletal muscle.

Retinoic acid induced meiosis initiation in female germline stem cells by remodelling three-dimensional chromatin structure.

ObjectivesThis study aimed to clarify the regulation and mechanism of meiotic initiation in FGSC development.Materials and MethodsFGSCs were induced to differentiate into meiosis in differentiation medium. RNA sequencing was performed to analysis the difference of transcription level. High‐through chromosome conformation capture sequencing (Hi‐C) was performed to analysis changes of three‐dimensional chromatin structure. Chromosome conformation capture further confirmed a spatial chromatin loop. ChIP‐qPCR and dual luciferase reporter were used to test the interaction between Stimulated by retinoic acid gene 8 (STRA8) protein and Trip13 promoter.ResultsCompared with FGSCs, the average diameter of STRA8‐positive germ cells increased from 13 μm to 16.8 μm. Furthermore, there were 4788 differentially expressed genes between the two cell stages; Meiosis and chromatin structure‐associated terms were significantly enriched. Additionally, Hi‐C results showed that FGSCs underwent A/B compartment switching (switch rate was 29.81%), the number of topologically associating domains (TADs) increasing, the average size of TADs decreasing, and chromatin loop changes at genome region of Trip13 from undifferentiated stage to meiosis‐initiation stage. Furthermore, we validated that Trip13 promoter contacted distal enhancer to form spatial chromatin loop and STRA8 could bind Trip13 promoter to promote gene expression.ConclusionFGSCs underwent chromatin structure remodelling from undifferentiated stage to meiosis‐initiation stage, which facilitated STRA8 binding to Trip13 promoter and promoting its expression.

Early Three-Dimensional Intrableb Structural Changes in Primary-Open Angle Glaucoma and Exfoliation Glaucoma After Ex-PRESS Surgery.

PurposeTo compare early-stage intrableb structural changes after Ex-PRESS surgery using anterior-segment optical coherence tomography between primary open-angle glaucoma (POAG) and exfoliation glaucoma (XFG).MethodsTwenty-five POAG eyes and 15 XFG eyes that underwent Ex-PRESS surgery were evaluated. Intrableb images were classified into four categories based on previously reported scattering intensity: high-, medium-, and low-scattering walls and fluid-filled spaces. Bleb measurements were evaluated in both groups throughout 6 postoperative months. The 3-year surgical success was defined by the criteria intraocular pressure (IOP) < 18 mmHg and IOP < 15 mmHg with or without medications.ResultsThe fluid-filled space volume at 3 and 6 months (P = 0.005 and P = 0.022, respectively) and the volume ratio of the low-scattering wall to the bleb wall (P = 0.028) at 6 months were significantly smaller in XFG than POAG postoperatively. The volume ratio of the high-scattering wall to the bleb wall was correlated positively (P = 0.007) with the IOP, and that of the low-scattering wall to the bleb wall was correlated negatively (P = 0.002) with the IOP in XFG. The 3-year surgical success rates for both criteria were significantly lower in XFG than POAG.ConclusionsFluid-filled spaces were smaller in XFG than in POAG after Ex-PRESS surgery. The proportion of the high-scattering wall tended to increase and the low-scattering wall tended to decrease in XFG eyes with high IOP. Early-stage intrableb structural changes differed between POAG and XFG and may affect the prognosis.Translational RelevanceOur cutting-edge observation of intrableb fibrosis can be an important predictor of the surgical outcome.

Conformational Changes in Three-Dimensional Chromatin Structure in Paulownia fortunei After Phytoplasma Infection.

Higher-order chromatin structures play important roles in regulating multiple biological processes such as growth and development as well as biotic and abiotic stress response. However, little is known about three-dimensional chromatin structures in Paulownia or about whole-genome chromatin conformational changes that occur in response to Paulownia witches' broom (PaWB) disease. We used high-throughput chromosome conformation capture (Hi-C) to obtain genome-wide profiles of chromatin conformation in both healthy and phytoplasma-infected Paulownia fortunei genome. The heat map results indicated that the strongest interactions between chromosomes were in the telomeres. We confirmed that the main structural characteristics of A/B compartments, topologically associated domains, and chromatin loops were prominent in the Paulownia genome and were clearly altered in phytoplasma-infected plants. By combining chromatin immunoprecipitation sequencing, Hi-C signals, and RNA sequencing data, we inferred that the chromatin structure changed and the modification levels of three histones (H3K4me3/K9ac/K36me3) increased in phytoplasma-infected P. fortunei, which was associated with changes of transcriptional activity. We concluded that for epigenetic modifications, transcriptional activity might function in combination to shape chromatin packing in healthy and phytoplasm-infected Paulownia. Finally, 11 genes (e.g., RPN6, Sec61 subunit-α) that were commonly located at specific topologically associated domain boundaries, A/B compartment switching and specific loops, and had been associated with histone marks were identified and considered as closely related to PaWB stress. Our results provide new insights into the nexus between gene regulation and chromatin conformational alterations in nonmodel plants upon phytopathogen infection and plant disease resistance.

Precipitant-Free Crystallization of Lysozyme and Glucose Isomerase by Drying

Protein crystallization is usually conducted by using precipitants, although the “salting-out” phenomenon is still unclear and complex. Moreover, the addition of precipitants sometimes results in irreversible disordered precipitation of protein molecules. Although precipitant-free lysozyme crystals obtained by centrifugal concentration showed significant changes in three-dimensional structure compared to the structure of salted-out crystals, it was rather difficult to mount crystals from a viscous dense liquid phase after centrifugal concentration, and the quality of the crystals often deteriorated during the mounting process. Here we present novel precipitant-free crystallization methods, which were effective for lysozyme and glucose isomerase. Tetragonal lysozyme crystals were successfully crystallized in a glass capillary simply by drying highly concentrated lysozyme solution in the presence of 0.01 M hydrochloric acid without using any precipitants. Glucose isomerase dissolved in ultra-pure water was also successfully crystallized in hanging drops by drying highly concentrated solution under low-humidity conditions. Oscillation images of the obtained crystals were safely collected without handling; they clearly indicated the crystals had a tetragonal form for lysozyme and an orthorhombic form for glucose isomerase, and their lattice parameters are similar to those of previously reported crystals obtained by salting-out methods.

Frequent SLC12A3 mutations in Chinese Gitelman syndrome patients: structure and function disorder

PurposesThis study was conducted to identify the frequent mutations from reported Chinese Gitelman syndrome (GS) patients, to predict the three-dimensional structure change of human Na–Cl co-transporter (hNCC), and to test the activity of these mutations and some novel mutations in vitro and in vivo.MethodsSLC12A3 gene mutations in Chinese GS patients previously reported in the PubMed, China National Knowledge Infrastructure, and Wanfang database were summarized. Predicted configurations of wild type (WT) and mutant proteins were achieved using the I-TASSER workplace. Six missense mutations (T60M, L215F, D486N, N534K, Q617R, and R928C) were generated by site-directed mutagenesis. 22Na+ uptake experiment was carried out in the Xenopus laevisoocyte expression system. In the study, 35 GS patients and 20 healthy volunteers underwent the thiazide test.ResultsT60M, T163M, D486N, R913Q, R928C, and R959frameshift were frequent SLC12A3 gene mutations (mutated frequency >3%) in 310 Chinese GS families. The protein’s three-dimensional structure was predicted to be altered in all mutations. Compared with WT hNCC, the thiazide-sensitive 22Na+ uptake was significantly diminished for all six mutations: T60M 22 ± 9.2%, R928C 29 ± 12%, L215F 38 ± 14%, N534K 41 ± 15.5%, Q617R 63 ± 22.1%, and D486N 77 ± 20.4%. In thiazide test, the net increase in chloride fractional excretion in 20 healthy controls was significantly higher than GS patients with or without T60M or D486N mutations.ConclusionsFrequent mutations (T60M, D486N, and R928C) and novel mutations (L215F, N534K, and Q617R) lead to protein structure alternation and protein dysfunction verified by 22Na+ uptake experiment in vitro and thiazide test on the patients.

Chromatin Interaction Responds to Breast Muscle Development and Intramuscular Fat Deposition Between Chinese Indigenous Chicken and Fast-Growing Broiler.

Skeletal muscle development and intramuscular fat (IMF) content, which positively contribute to meat production and quality, are regulated by precisely orchestrated processes. However, changes in three-dimensional chromatin structure and interaction, a newly emerged mediator of gene expression, during the skeletal muscle development and IMF deposition have remained unclear. In the present study, we analyzed the differences in muscle development and IMF content between one-day-old commercial Arbor Acres broiler (AA) and Chinese indigenous Lushi blue-shelled-egg chicken (LS) and performed Hi-C analysis on their breast muscles. Our results indicated that significantly higher IMF content, however remarkably lower muscle fiber diameter was detected in breast muscle of LS chicken compared to that of AA broiler. The chromatin intra-interaction was prior to inter-interaction in both AA and LS chicken, and chromatin inter-interaction was heavily focused on the small and gene-rich chromosomes. For genomic compartmentalization, no significant difference in the number of B type compartments was found, but AA had more A type compartments versus LS. The A/B compartment switching of AA versus LS showed more A to B switching than B to A switching. There were no significant differences in the average sizes and distributions of topologically associating domains (TAD). Additionally, approximately 50% of TAD boundaries were overlapping. The reforming and disappearing events of TAD boundaries were identified between AA and LS chicken breast muscles. Among these, the HMGCR gene was located in the TAD-boundary regions in AA broilers, but in TAD-interior regions in LS chickens, and the IGF2BP3 gene was located in the AA-unique TAD boundaries. Both HMGCR and IGF2BP3 genes exhibited increased mRNA expression in one-day-old AA broiler breast muscles. It was demonstrated that the IGF2BP3 and HMGCR genes regulated by TAD boundary sliding were potential biomarkers for chicken breast muscle development and IMF deposition. Our data not only provide a valuable understanding of higher-order chromatin dynamics during muscle development and lipid accumulation but also reveal new insights into the regulatory mechanisms of muscle development and IMF deposition in chicken.

Giant single-crystal-to-single-crystal transformations associated with chiral interconversion induced by elimination of chelating ligands

Numerous single crystals that exhibit single-crystal-to-single-crystal (SCSC) transformations have been reported, and some of them show great promise for application to advanced adsorption materials, magnetic switches, and smart actuators. However, the development of single crystals with super-adaptive crystal lattices capable of huge and reversible structural change remains a great challenge. In this study, we report a ZnII complex that undergoes giant SCSC transformation induced by a two-step thermal elimination of ethylene glycol chelating ligands. Although the structural change is exceptionally large (50% volume shrinkage and 36% weight loss), the single-crystal nature of the complex persists because of the multiple strong hydrogen bonds between the constituent molecules. This allows the reversible zero-dimensional to one-dimension and further to three-dimensional structural changes to be fully characterized by single-crystal X-ray diffraction analyses. The elimination of chelating ligands induces a chiral interconversion in the molecules that manifests as a centric-chiral-polar symmetric variation of the single crystal. The study not only presents a unique material, featuring both a periodic crystal lattice and gel-like super-ductility, but also reveals a possible solid-state reaction method for preparing chiral compounds via the elimination of chelating ligands.

Topological heterogeneity and evaporation dynamics of irregular water droplets

Water droplets sitting between wires are ubiquitous in nature and industry, often showing irregular (non-spherical) droplet shapes. To understand their topological singularity and evaporation mechanism, measuring volume changes of irregular water droplets is essential but highly challenging for small-volume water droplets. Here we experimentally explore topological heterogeneity and evaporation dynamics for irregular water droplets between wires with four-dimensional X-ray microtomography that directly provides images in three spatial dimensions as a function of time, enabling us to get three-dimensional structural and geometric information changes with time. We find that the topological heterogeneity of an irregular droplet is due to the local contact lines and the evaporation dynamics of an irregular droplet is governed by the effective contact radius. This study may offer an opportunity to understand how the topological heterogeneity contributes to the evaporation dynamics of irregular water droplets.

Effects of Spatial Resolution on Burned Forest Classification With ICESat-2 Photon Counting Data

Accurately monitoring forest fire activities is critical to understanding carbon dynamics and climate change. Three-dimensional (3D) canopy structure changes caused by fire make it possible to adopt Light Detection and Ranging (LiDAR) in burned forest classification. This study focuses on the effects of spatial resolution when using LiDAR data to differentiate burned and unburned forests. The National Aeronautics and Space Administration’s (NASA) Ice, Cloud, and land Elevation Satellite-2 (ICESat-2) mission provides LiDAR datasets such as the geolocated photon data (ATL03) and the land vegetation height product (ATL08), which were used in this study. The ATL03 data were filtered by two algorithms: the ATL08 algorithm (ILV) and the adaptive ground and canopy height retrieval algorithm (AGCH), producing classified canopy points and ground points. Six typical spatial resolutions: 10, 30, 60, 100, 200, and 250 m were employed to divide the classified photon points into separate segments along the track. Twenty-six canopy related metrics were derived from each segment. Sentinel-2 images were used to provide reference land cover maps. The Random Forest classification method was employed to classify burned and unburned segments in the temperate forest in California and the boreal forest in Alberta, respectively. Both weak beams and strong beams of ICESat-2 data were included in comparisons. Experiment results show that spatial resolution can significantly influence the canopy structures we detected. Classification accuracies increase along with coarser spatial resolutions and saturate at 100 m segment length, with overall accuracies being 79.43 and 92.13% in the temperate forest and the boreal forest, respectively. Classification accuracies based on strong beams are higher than those of using weak beams due to a larger point density in strong beams. The two filtering algorithms present comparable accuracies in burned forest classification. This study demonstrates that spatial resolution is a critical factor to consider when using spaceborne LiDAR for canopy structure characterization and classification, opening an avenue for improved measurement of forest structures and evaluation of terrestrial vegetation responses to climate change.

Concerted morphogenesis of genital ridges and nephric ducts in the mouse captured through whole-embryo imaging.

During development of the mouse urogenital complex, the gonads undergo changes in three-dimensional structure, body position and spatial relationship with the mesonephric ducts, kidneys and adrenals. The complexity of genital ridge development obscures potential connections between morphogenesis and gonadal sex determination. To characterize the morphogenic processes implicated in regulating gonad shape and fate, we used whole-embryo tissue clearing and light sheet microscopy to assemble a time course of gonad development in native form and context. Analysis revealed that gonad morphology is determined through anterior-to-posterior patterns as well as increased rates of growth, rotation and separation in the central domain that may contribute to regionalization of the gonad. We report a close alignment of gonad and mesonephric duct movements as well as delayed duct development in a gonad dysgenesis mutant, which together support a mechanical dependency linking gonad and mesonephric duct morphogenesis.

Bio-inspired Incrustation Interfacial Polymerization of Dopamine and Cross-linking with Gelatin toward Robust, Biodegradable Three-Dimensional Hydrogels.

In nature, laccase enzymatically catalyzes the reaction of phenolic compounds with oxygen to produce hardened surfaces known as cuticles on insects and plants. Inspired by this natural process, the present work investigated a robust, biodegradable hydrogel synthesized from dopamine and gelatin. This gel is obtained by the oxidation of dopamine dissolved in water, after which the resulting quinone compound automatically undergoes self-polymerization. The oxidized dopamine subsequently undergoes Schiff base and Michael addition reactions with gelatin, such that the exposed gelatin surface cross-links to generate a continuous hardened hydrogel film. Because gelatin transitions between sol and gel states with changes in temperature, two- and three-dimensional structures could be obtained from the gel state. This bio-inspired interfacial cross-linking reaction provides a simple means of forming complex morphologies and represents a promising technique for bio-applications.

The role of three-dimensional chromatin structure changes in tumor progression

The human genome is not a linear structure, but a three-dimensional structure through complex folding and assembly. Chromosome structure capture technology can detect the three-dimensional construction of chromatin. Hi-C sequencing data of various tumors indicate that the chromatin topology associated domains changed during tumor progression and is related to copy number variation. In addition, transformation of the genomic compartment is related to gene expression. However, current researches on three-dimensional structures of tumoral chromatin are still in the stage of exploration, and some conclusions are too superficial to be applied to the clinic immediately, which requires further study.

Molecular docking study of potential phytochemicals and their effects on the complex of SARS-CoV2 spike protein and human ACE2

Angiotensin converting enzyme 2 (ACE2) (EC:3.4.17.23) is a transmembrane protein which is considered as a receptor for spike protein binding of novel coronavirus (SARS-CoV2). Since no specific medication is available to treat COVID-19, designing of new drug is important and essential. In this regard, in silico method plays an important role, as it is rapid and cost effective compared to the trial and error methods using experimental studies. Natural products are safe and easily available to treat coronavirus affected patients, in the present alarming situation. In this paper five phytochemicals, which belong to flavonoid and anthraquinone subclass, have been selected as small molecules in molecular docking study of spike protein of SARS-CoV2 with its human receptor ACE2 molecule. Their molecular binding sites on spike protein bound structure with its receptor have been analyzed. From this analysis, hesperidin, emodin and chrysin are selected as competent natural products from both Indian and Chinese medicinal plants, to treat COVID-19. Among them, the phytochemical hesperidin can bind with ACE2 protein and bound structure of ACE2 protein and spike protein of SARS-CoV2 noncompetitively. The binding sites of ACE2 protein for spike protein and hesperidin, are located in different parts of ACE2 protein. Ligand spike protein causes conformational change in three-dimensional structure of protein ACE2, which is confirmed by molecular docking and molecular dynamics studies. This compound modulates the binding energy of bound structure of ACE2 and spike protein. This result indicates that due to presence of hesperidin, the bound structure of ACE2 and spike protein fragment becomes unstable. As a result, this natural product can impart antiviral activity in SARS CoV2 infection. The antiviral activity of these five natural compounds are further experimentally validated with QSAR study.

Impact of biochar addition on three-dimensional structural changes in aggregates associated with humus during swine manure composting

Aerobic composting is widely used to recycle agricultural organic waste. From a micro perspective, the dynamic changes in the internal structure of compost aggregates during composting can reflect aeration conditions, which is worthy of further study to improve composting efficiency. This study set three composting treatments (swine manure: rice straw = 4:1 and 8:1, swine manure: rice straw: biochar = 8:1:1, wet mass ratio), to detect 3-D microstructures of compost aggregate with the involvement of humus and biochar during composting. The results showed that biochar addition to compost enhanced humic acid formation and humification degree, and it greatly decreased bulk density by 45.89% and increased free air space by 31.25% compared with the initial stage of the compost. Compost materials tended to become looser during composting, and biochar aided an increase in total porosity of compost aggregates by approximately 90% compared with other treatments, mainly attributed to decomposition effects. It is assumed that large aggregates break up with the assistance of biochar, and these small parts of the materials gradually stick together with the formation of humus colloids to develop final dense particles. Therefore, it can be concluded that when biochar is used as an additive, it can improve the physical structure with the involvement of humus during composting.