Comparative three-dimensional genome architectures of adipose tissues provide insight into human-specific regulation of metabolic homeostasis.

Elucidating the regulatory mechanisms of human adipose tissues (ATs) evolution is essential for understanding human-specific metabolic regulation, but the functional importance and evolutionary dynamics of three-dimensional (3D) genome organizations of ATs are not well defined. Here, we compared the 3D genome architectures of anatomically distinct ATs from humans and six representative mammalian models. We recognized evolutionarily conserved and human-specific chromatin conformation in ATs at multiple scales, including compartmentalization, topologically associating domain (TAD), and promoter-enhancer interactions (PEI), which have not been described previously. We found PEI are much more evolutionarily dynamic with respect to compartmentalization and topologically associating domain. Compared to conserved PEIs, human-specific PEIs are enriched for human-specific sequence, and the binding motifs of their potential mediators (transcription factors) are less conserved. Our data also demonstrated that genes involved in the evolutionary dynamics of chromatin organization have weaker transcriptional conservation than those associated with conserved chromatin organization. Furthermore, the genes involved in energy metabolism and the maintenance of metabolic homeostasis are enriched in human-specific chromatin organization, while housekeeping genes, health-related genes, and genetic variations are enriched in evolutionarily conserved compared to human-specific chromatin organization. Finally, we showed extensively divergent human-specific 3D genome organizations among one subcutaneous and three visceral ATs. Together, these findings provide a global overview of 3D genome architecture dynamics between ATs from human and mammalian models and new insights into understanding the regulatory evolution of human ATs.

A Geometrically Flexible Three-Dimensional Nanocarbon.

The development of architecturally unique molecular nanocarbons by bottom-up organic synthesis is essential for accessing functional organic materials awaiting technological developments in fields such as energy, electronics, and biomedicine. Herein, we describe the design and synthesis of a triptycene-based three-dimensional (3D) nanocarbon, GFN-1, with geometrical flexibility on account of its three peripheral π-panels being capable of interconverting between two curved conformations. An effective through-space electronic communication among the three π-panels of GFN-1 has been observed in its monocationic radical form, which exhibits an extensively delocalized spin density over the entire 3D π-system as revealed by electron paramagnetic resonance and UV-vis-NIR spectroscopies. The flexible 3D molecular architecture of GFN-1, along with its densely packed superstructures in the presence of fullerenes, is revealed by microcrystal electron diffraction and single-crystal X-ray diffraction, which establish the coexistence of both propeller and tweezer conformations in the solid state. GFN-1 exhibits strong binding affinities for fullerenes, leading to host-guest complexes that display rapid photoinduced electron transfer within a picosecond. The outcomes of this research could pave the way for the utilization of shape and electronically complementary nanocarbons in the construction of functional coassemblies.

A nomogram to predict the risk of proliferative lupus nephritis in patients with systemic lupus erythematosus involving the kidneys.

Proliferative lupus nephritis (PLN) is a serious organ-threatening manifestation of systemic lupus erythematosus (SLE) that is associated with high mortality and renal failure. Here, we analyzed data from 1287 SLE patients with renal manifestations, including 780 of which were confirmed as proliferative or non-proliferative LN patients by renal biopsy, divided into a training cohort (547 patients) and a validation cohort (233 patients). By applying a least absolute shrinkage and selection operator (LASSO) regression approach combined with multivariate logistic regression analysis to build a nomogram for prediction of PLN that was then assessed by receiver operating characteristic (ROC) curves, calibration curves, and clinical decision curves (DCA) in both the training and validation cohorts. The area under the ROC curve (AUC) of the model in the training cohort was 0.921 (95% confidence interval (CI): 0.895-0.946), the AUC of internal validation in the training cohort was 0.909 and the AUC of external validation was 0.848 (95% CI: 0.796-0.900). The nomogram showed good performance as evaluated using calibration and DCA curves. Taken together, our results indicate that our nomogram that comprises 12 significantly relevant variables could be clinically valuable to prognosticate on the risk of PLN in SLE, so as to improve patient prognoses.

Adaptive Helical Chirality in Supramolecular Microcrystals for Circularly Polarized Lasing.

Chiral organic molecules offer a promising platform for exploring circularly polarized lasing, which, however, faces a great challenge that the spatial separation of molecular chiral and luminescent centers limits chiroptical activity. Here we develop a helically chiral supramolecular system with completely overlapped chiral and luminescent units for realizing high-performance circularly polarized lasing. Adaptive helical chirality is obtained by incorporating chiral agents into organic microcrystals. Benefiting from the efficient coupling of stimulated emission with the adaptive helical chirality, the supramolecular microcrystals enable high-performance circularly polarized lasing emission with dissymmetry factors up to ~ 0.7. This work opens up the way to rational design of chiral organic materials for circularly polarized lasing.

Exploring high-resolution chromatin interaction changes and functional enhancers of myogenic marker genes during myogenic differentiation.

Skeletal muscle differentiation (myogenesis) is a complex and highly coordinated biological process regulated by a series of myogenic marker genes. Chromatin interactions between gene's promoters and their enhancers have an important role in transcriptional control. However, the high-resolution chromatin interactions of myogenic genes and their functional enhancers during myogenesis remain largely unclear. Here, we used circularized chromosome conformation capture coupled with next generation sequencing (4C-seq) to investigate eight myogenic marker genes in C2C12 myoblasts (C2C12-MBs) and C2C12 myotubes (C2C12-MTs). We revealed dynamic chromatin interactions of these marker genes during differentiation and identified 163 and 314 significant interaction sites (SISs) in C2C12-MBs and C2C12-MTs, respectively. The interacting genes of SISs in C2C12-MTs were mainly involved in muscle development, and histone modifications of the SISs changed during differentiation. Through functional genomic screening, we also identified 25 and 41 putative active enhancers in C2C12-MBs and C2C12-MTs, respectively. Using luciferase reporter assays for putative enhancers of Myog and Myh3, we identified eight activating enhancers. Furthermore, dCas9-KRAB epigenome editing and RNA-Seq revealed a role for Myog enhancers in the regulation of Myog expression and myogenic differentiation in the native genomic context. Taken together, this study lays the groundwork for understanding 3D chromatin interaction changes of myogenic genes during myogenesis and provides insights that contribute to our understanding of the role of enhancers in regulating myogenesis.

Three Dimensional Shape Reconstruction via Polarization Imaging and Deep Learning.

Deep-learning-based polarization 3D imaging techniques, which train networks in a data-driven manner, are capable of estimating a target's surface normal distribution under passive lighting conditions. However, existing methods have limitations in restoring target texture details and accurately estimating surface normals. Information loss can occur in the fine-textured areas of the target during the reconstruction process, which can result in inaccurate normal estimation and reduce the overall reconstruction accuracy. The proposed method enables extraction of more comprehensive information, mitigates the loss of texture information during object reconstruction, enhances the accuracy of surface normal estimation, and facilitates more comprehensive and precise reconstruction of objects. The proposed networks optimize the polarization representation input by utilizing the Stokes-vector-based parameter, in addition to separated specular and diffuse reflection components. This approach reduces the impact of background noise, extracts more relevant polarization features of the target, and provides more accurate cues for restoration of surface normals. Experiments are performed using both the DeepSfP dataset and newly collected data. The results show that the proposed model can provide more accurate surface normal estimates. Compared to the UNet architecture-based method, the mean angular error is reduced by 19%, calculation time is reduced by 62%, and the model size is reduced by 11%.

Physicochemical properties and risk assessment of perishable waste primary products.

Fertilization has become one of the most important ways to recycle perishable waste. In order to reveal the effect of the nutrient of the perishable waste primary products on the market and the possible impact of their application, 136 perishable waste primary products were sampled in nine cities in Zhejiang province, China. The result shows that these products have high nutrient content (average nutrient content was 5.00%). However, the conductivity (7.19 mS/cm) total soluble salt content (12.07%), and grease content (5.99%) were too high. The excessive salt and grease may cause harm to soil and crops, and become the main limiting factors for the fertilizer utilization of perishable waste. Heavy metal content of most of the samples met current commercial organic fertilizer standards, except that lead and chromium content of some samples exceeded the limit standard. Toluene, ethylbenzene, m & p-xylene were generally detected in the samples. These toxic and harmful substances have brought risks to the safe use of perishable waste into fertilizers.

A Method to Replace NaCl as a Flotation Solution for Extracting MPs in Soil: A Case Study of the Jiaxing Agricultural Soil from China.

Microplastics (MPs) have become an important global issue in recent years. However, MPs in the soil have received far less attention than water. Effective and nondestructive extraction of MPs is important for studying MPs in agricultural soils. This study uses different floatation solutions as experiments and uses MgCl2 as the floatation solution of the density extraction method. Five types of standard MPs (PE, PP, PS, PVC, and PET) are used as the objects of this experiment. The recovery of the two particle sizes was between 90.82% and 109.69%. The extracted standard MPs were then subjected to IR and Raman spectroscopic analysis, and the results showed that Raman spectroscopy was more suitable for the identification of the extracted MPs. Finally, this method collected and verified a vast number of soil samples and further analyzed the abundance and characteristics of the collected MPs.

TetrazineBox: A Structurally Transformative Toolbox.

Synthetic macrocycles capable of undergoing allosteric regulation by responding to versatile external stimuli are the subject of increasing attention in supramolecular science. Herein, we report a structurally transformative tetracationic cyclophane containing two 3,6-bis(4-pyridyl)-l,2,4,5-tetrazine (4-bptz) units, which are linked together by two p-xylylene bridges. The cyclophane, which possesses modular redox states and structural post-modifications, can undergo two reversibly consecutive two-electron reductions, affording first its bisradical dicationic counterpart, and then subsequently the fully reduced species. Furthermore, one single-parent cyclophane can afford effectively three other new analogs through box-to-box cascade transformations, taking advantage of either reductions or an inverse electron-demand Diels-Alder (IEDDA) reaction. While all four new tetracationic cyclophanes adopt rigid and symmetric box-like conformations, their geometries in relation to size, shape, electronic properties, and binding affinities toward polycyclic aromatic hydrocarbons can be readily regulated. This structurally transformative tetracationic cyclophane performs a variety of new tasks as a result of structural post-modifications, thus serving as a toolbox for probing the radical properties and generating rapidly a range of structurally diverse cyclophanes by efficient divergent syntheses. This research lays a solid foundation for the introduction of the structurally transformative tetracationic cyclophane into the realm of mechanically interlocked molecules and will provide a toolbox to construct and operate intelligent molecular machines.

Integration of Enzymes and Photosensitizers in a Hierarchical Mesoporous Metal-Organic Framework for Light-Driven CO2 Reduction.

Protection of enzymes with synthetic materials is a viable strategy to stabilize, and hence to retain, the reactivity of these highly active biomolecules in non-native environments. Active synthetic supports, coupled to encapsulated enzymes, can enable efficient cascade reactions which are necessary for processes like light-driven CO2 reduction, providing a promising pathway for alternative energy generation. Herein, a semi-artificial system-containing an immobilized enzyme, formate dehydrogenase, in a light harvesting scaffold-is reported for the conversion of CO2 to formic acid using white light. The electron-mediator Cp*Rh(2,2'-bipyridyl-5,5'-dicarboxylic acid)Cl was anchored to the nodes of the metal-organic framework NU-1006 to facilitate ultrafast photo-induced electron transfer when irradiated, leading to the reduction of the coenzyme nicotinamide adenine dinucleotide at a rate of about 28 mM·h-1. Most importantly, the immobilized enzyme utilizes the reduced coenzyme to generate formic acid selectively from CO2 at a high turnover frequency of about 865 h-1 in 24 h. The outcome of this research is the demonstration of a feasible pathway for solar-driven carbon fixation.

Single-Crystal Polycationic Polymers Obtained by Single-Crystal-to-Single-Crystal Photopolymerization.

The efficient preparation of single-crystalline ionic polymers and fundamental understanding of their structure-property relationships at the molecular level remains a challenge in chemistry and materials science. Here, we describe the single-crystal structure of a highly ordered polycationic polymer (polyelectrolyte) and its proton conductivity. The polyelectrolyte single crystals can be prepared on a gram-scale in quantitative yield, by taking advantage of an ultraviolet/sunlight-induced topochemical polymerization, from a tricationic monomer-a self-complementary building block possessing a preorganized conformation. A single-crystal-to-single-crystal photopolymerization was revealed unambiguously by in situ single-crystal X-ray diffraction analysis, which was also employed to follow the progression of molecular structure from the monomer, to a partially polymerized intermediate, and, finally, to the polymer itself. Collinear polymer chains are held together tightly by multiple Coulombic interactions involving counterions to form two-dimensional lamellar sheets (1 nm in height) with sub-nanometer pores (5 Å). The polymer is extremely stable under 254 nm light irradiation and high temperature (above 500 K). The extraordinary mechanical strength and environmental stability-in combination with its impressive proton conductivity (∼3 × 10-4 S cm-1)-endow the polymer with potential applications as a robust proton-conducting material. By marrying supramolecular chemistry with macromolecular science, the outcome represents a major step toward the controlled synthesis of single-crystalline polyelectrolyte materials with perfect tacticity.

Deficient of LRRC8A attenuates hypoxia-induced necrosis in 3T3-L1 cells.

Under acute hypoxia, multiple ion channels on the cell membrane are activated, causing cell swelling and eventually necrosis. LRRC8A is an indispensable protein of the volume-regulated anion channel (VRAC), which participates in swelling and the acceleration of cell necrosis. In this study, we revealed a dynamic change in the expression level of the LRRC8 family during hypoxia in 3T3-L1 cells. The disruption of LRRC8A in 3T3-L1 cells was also associated with a significant anti-necrotic phenotype upon hypoxia accompanied by the reduced expression of necrosis-related genes. In vivo, differential expression of LRRC8 family members was also identified between high-altitude pigs and their low-altitude relatives. Taken these findings together, this study demonstrates the involvement of LRRC8A in hypoxia-induced cell necrosis.

Assembly of a Porous Supramolecular Polyknot from Rigid Trigonal Prismatic Building Blocks.

Herein we report a hydrogen-bonded three-dimensional porous supramolecular polyknot assembled from a rigid trigonal prismatic triptycene building block with six extended peripheral aryl-carboxyl groups. Within this superstructure, three arrays of undulated 2D rhombic subnets, which display an inclined polycatenation, are interconnected to give an unprecedented uninodal six-connected net with a point symbol of (3.44.610). Such an entanglement results in a trefoil knot motif, which, as the basic repeating unit, is fused and interlocked with itself three-dimensionally to afford a supramolecular polyknot. This example highlights the ability of supramolecular systems to form topologically complex architectures using geometrically simple building blocks.

Reticular Access to Highly Porous acs-MOFs with Rigid Trigonal Prismatic Linkers for Water Sorption.

Metal-organic frameworks (MOFs) based on edge-transitive 6-c acs nets are well-developed and can be synthesized from trinuclear metal clusters and ditopic ligands, i.e., MOF-235 and MIL-88. The rational design of noncatenated acs-MOFs by symmetry-matching between trigonal prismatic organic ligands and trinuclear clusters, however, remains a great challenge. Herein, we report a series of acs-MOFs (NU-1500) based on trivalent trinuclear metal (Fe3+, Cr3+, and Sc3+) clusters and a rigid trigonal prismatic ligand courtesy of reticular chemistry. The highly porous and hydrolytically stable NU-1500-Cr can be activated directly from water and displays an impressive water vapor uptake with small hysteresis.

Ligand-Directed Reticular Synthesis of Catalytically Active Missing Zirconium-Based Metal-Organic Frameworks.

Zirconium-based metal-organic frameworks (Zr-MOFs) based on edge-transitive nets such as fcu, spn, she, csq, and ftw with diverse potential applications have been widely reported. Zr-MOFs based on the highly connected 6,12-connected alb net, however, remain absent on account of synthetic challenges. Herein we report the ligand-directed reticular syntheses and isoreticular expansion of a series of Zr-MOFs with the edge-transitive alb net from 12-connected hexagonal-prismatic Zr6 nodes and 6-connected trigonal-prismatic linkers, i.e., microporous NU-1600, mesoporous NU-1601, and mesoporous NU-1602. These Zr-MOFs exhibit remarkable activities toward the destruction of a nerve agent (soman) and a nerve agent simulant (DMNP).

Interpenetration Isomerism in Triptycene-Based Hydrogen-Bonded Organic Frameworks.

We describe an example of "interpenetration isomerism" in three-dimensional hydrogen-bonded organic frameworks. By exploiting the crystallization conditions for a peripherally extended triptycene H6 PET, we can modulate the interpenetration of the assembled frameworks, yielding a two-fold interpenetrated structure PETHOF-1 and a five-fold interpenetrated structure PETHOF-2 as interpenetration isomers. In PETHOF-1, two individual nets are related by inversion symmetry and form an interwoven topology with a large guest-accessible volume of about 80 %. In PETHOF-2, five individual nets are related by translational symmetry and are stacked in an alternating fashion. The activated materials show permanent porosity with Brunauer-Emmett-Teller surface areas exceeding 1100 m2 g-1 . Synthetic control over the framework interpenetration could serve as a new strategy to construct complex supramolecular architectures from simple organic building blocks.

Co-culture systems-based strategies for articular cartilage tissue engineering.

Cartilage engineering facilitates repair and regeneration of damaged cartilage using engineered tissue that restores the functional properties of the impaired joint. The seed cells used most frequently in tissue engineering, are chondrocytes and mesenchymal stem cells. Seed cells activity plays a key role in the regeneration of functional cartilage tissue. However, seed cells undergo undesirable changes after in vitro processing procedures, such as degeneration of cartilage cells and induced hypertrophy of mesenchymal stem cells, which hinder cartilage tissue engineering. Compared to monoculture, which does not mimic the in vivo cellular environment, co-culture technology provides a more realistic microenvironment in terms of various physical, chemical, and biological factors. Co-culture technology is used in cartilage tissue engineering to overcome obstacles related to the degeneration of seed cells, and shows promise for cartilage regeneration and repair. In this review, we focus first on existing co-culture systems for cartilage tissue engineering and related fields, and discuss the conditions and mechanisms thereof. This is followed by methods for optimizing seed cell co-culture conditions to generate functional neo-cartilage tissue, which will lead to a new era in cartilage tissue engineering.

A Molecular Propeller with Three Nanohoop Blades: Synthesis, Characterization, and Solid-State Packing.

Nanoscale carbon-rich molecular architectures are not only aesthetically appealing but also of practical importance for energy and biomedical technologies. Herein, we report the synthesis of cyclic-oligophenylene-based nanopropeller 1 by using an efficient synthon strategy involving sequential intramolecular bisboronate homocoupling and reductive aromatization by H2 SnCl4 . The nanopropeller molecules pack into a layered hexagonal lattice featuring long-ranged nano-sized channels and a total guest-accessible volume of 48 %, as revealed by X-ray diffraction studies. We suggest that such a solid-state arrangement is determined by the interplay between the propeller architecture and the intermolecular van der Waals interactions.

Unveiling an oxidative stress-linked diagnostic signature and molecular subtypes in preeclampsia: novel insights into pathogenesis.

Preeclampsia (PE) is a complex pregnancy disorder characterized by hypertension and organ dysfunction, affecting both maternal and fetal health. Oxidative stress has been implicated in the pathogenesis of PE, but the underlying molecular mechanisms remain poorly understood. In this study, we aimed to identify a diagnostic signature and molecular subtypes associated with oxidative stress in PE to gain novel insights into its pathogenesis. The ssGSEA algorithm evaluated oxidative stress-related pathway scores using transcriptional data from the GSE75010 dataset. Oxidative stress-related genes (ORGs) were co lected from these pathways, and hub ORGs associated with PE were identified using the LASSO and logistic regression models. A nomogram prediction model was constructed using the identified ORGs. Consensus clustering identified two molecular subgroups related to oxidative stress, labeled as C1 and C2, with unique immune characteristics and inflammatory pathway profiles. Seventy ORGs associated with oxidative stress, ce l death, and inflammation-related pathways were identified in PE. EGFR, RIPK3, and ALAD were confirmed as core ORGs for PE biomarkers. The C1 and C2 subgroups exhibited distinct immune characteristics and inflammatory pathway profiles. This study provides novel insights into the role of oxidative stress in PE pathogenesis. A diagnostic signature and molecular subtypes associated with oxidative stress were identified, which may improve understanding, diagnosis, and management of PE.

The impacts of biodegradable and non-biodegradable microplastic on the performance and microbial community characterization of aerobic granular sludge.

Introduction: Microplastics (MPs), identified as emerging contaminants, have been detected across diverse environmental media. Their enduring presence and small size facilitate the adsorption of organic pollutants and heavy metals, leading to combined pollution effects. MPs also accumulate in the food chain thus pose risks to animals, plants, and human health, garnering significant scholarly attention in recent years. Aerobic granular sludge (AGS) technology emerges as an innovative approach to wastewater treatment. However, the impacts of MPs on the operational efficiency and microbial characteristics of AGS systems has been insufficiently explored. Methods: This study investigated the effects of varying concentration (10, 50, and 100 mg/L) of biodegradable MPs (Polylactic Acid, PLA) and non-biodegradable MPs (Polyethylene Terephthalate, PET) on the properties of AGS and explored the underlying mechanisms. Results and discussions: It was discovered that low and medium concentration of MPs (10 and 50 mg/L) showed no significant effects on COD removal by AGS, but high concentration (100 mg/L) of MPs markedly diminished the ability to remove COD of AGS, by blocking most of the nutrient transport channels of AGS. However, both PLA and PE promoted the nitrogen and phosphorus removal ability of AGS, and significantly increased the removal efficiency of total inorganic nitrogen (TIN) and total phosphorus (TP) at stages II and III (P < 0.05). High concentration of MPs inhibited the growth of sludge. PET noticeably deteriorate the sedimentation performance of AGS, while 50 mg/L PLA proved to be beneficial to sludge sedimentation at stage II. The addition of MPs promoted the abundance of Candidatus_Competibacter and Acinetobacter in AGS, thereby promoting the phosphorus removal capacity of AGS. Both 50 mg/L PET and 100 mg/L PLA caused large amount of white Thiothrix filamentous bacteria forming on the surface of AGS, leading to deterioration of the sludge settling performance and affecting the normal operation of the reactor. Comparing with PET, AGS proved to be more resistant to PLA, so more attention should be paid to the effect of non-biodegradable MPs on AGS in the future.