Obesity disrupts the pituitary-hepatic UPR communication leading to NAFLD progression.

Obesity alters levels of pituitary hormones that govern hepatic immune-metabolic homeostasis, dysregulation of which leads to nonalcoholic fatty liver disease (NAFLD). However, the impact of obesity on intra-pituitary homeostasis is largely unknown. Here, we uncovered a blunted unfolded protein response (UPR) but elevated inflammatory signatures in pituitary glands of obese mice and humans. Furthermore, we found that obesity inflames the pituitary gland, leading to impaired pituitary inositol-requiring enzyme 1α (IRE1α)-X-box-binding protein 1 (XBP1) UPR branch, which is essential for protecting against pituitary endocrine defects and NAFLD progression. Intriguingly, pituitary IRE1-deletion resulted in hypothyroidism and suppressed the thyroid hormone receptor B (THRB)-mediated activation of Xbp1 in the liver. Conversely, activation of the hepatic THRB-XBP1 axis improved NAFLD in mice with pituitary UPR defect. Our study provides the first evidence and mechanism of obesity-induced intra-pituitary cellular defects and the pathophysiological role of pituitary-liver UPR communication in NAFLD progression.

Highly Efficient Self-Assembly of Heterometallic [2]Catenanes and Cyclic Bis[2]catenanes via Orthogonal Metal-Coordination Interactions.

Although catenated cages have been widely constructed due to their unique and elegant topological structures, cyclic catenanes formed by the connection of multiple catenane units have been rarely reported. Herein, based on the orthogonal metal-coordination-driven self-assembly, we prepare a series of heterometallic [2]catenanes and cyclic bis[2]catenanes, whose structures are clearly evidenced by single-crystal X-ray analysis. Owing to the multiple positively charged nature, as well as the potential synergistic effect of the Cu(I) and Pt(II) metal ions, the cyclic bis[2]catenanes display broad-spectrum antibacterial activity. This work not only provides an efficient strategy for the construction of heterometallic [2]catenanes and cyclic bis[2]catenanes but also explores their applications as superior antibacterial agents, which will promote the construction of advanced supramolecular structures for biomedical applications.

Multicomponent, Multicavity Metallacages That Contain Different Binding Sites for Allosteric Recognition.

The encapsulation of different guest molecules by their different recognition domains of proteins leads to selective binding, catalysis, and transportation. Synthetic hosts capable of selectively binding different guests in their different cavities to mimic the function of proteins are highly desirable but challenging. Here, we report three ladder-shaped, triple-cavity metallacages prepared by multicomponent coordination-driven self-assembly. Interestingly, the porphyrin-based metallacage is capable of heteroleptic encapsulation of fullerenes (C60 or C70) and coronene using its different cavities, allowing distinct allosteric recognition of coronene upon the addition of C60 or C70. Owing to the different binding affinities of the cavities, the metallacage hosts one C60 molecule in the central cavity and two coronene units in the side cavities, while encapsulating two C70 molecules in the side cavities and one coronene molecule in the central cavity. The rational design of multicavity assemblies that enable heteroleptic encapsulation and allosteric recognition will guide the further design of advanced supramolecular constructs with tunable recognition properties.

Guest-Regulated Generation of Reactive Oxygen Species from Porphyrin-Based Multicomponent Metallacages for Selective Photocatalysis.

The development of novel materials for highly efficient and selective photocatalysis is crucial for their practical applications. Herein, we employ the host-guest chemistry of porphyrin-based metallacages to regulate the generation of reactive oxygen species and further use them for the selective photocatalytic oxidation of benzyl alcohols. Upon irradiation, the sole metallacage (6) can generate singlet oxygen (1O2) effectively via excited energy transfer, while its complex with C70 (6⊃C70) opens a pathway for electron transfer to promote the formation of superoxide anion (O2⋅-), producing both 1O2 and O2⋅-. The addition of 4,4'-bipyridine (BPY) to complex 6⊃C70 forms a more stable complex (6⊃BPY) via the coordination of the Zn-porphyrin faces of 6 and BPY, which drives fullerenes out of the cavities and restores the ability of 1O2 generation. Therefore, benzyl alcohols are oxidized into benzyl aldehydes upon irradiation in the presence of 6 or 6⊃BPY, while they are oxidized into benzoic acids when 6⊃C70 is employed as the photosensitizing agent. This study demonstrates a highly efficient strategy that utilizes the host-guest chemistry of metallacages to regulate the generation of reactive oxygen species for selective photooxidation reactions, which could promote the utilization of metallacages and their related host-guest complexes for photocatalytic applications.

Oligomeric HIV-1 Integrase Structures Reveal Functional Plasticity for Intasome Assembly and RNA Binding.

Integrase (IN) performs dual essential roles during HIV-1 replication. During ingress, IN functions within an oligomeric "intasome" assembly to catalyze viral DNA integration into host chromatin. During late stages of infection, tetrameric IN binds viral RNA and orchestrates the condensation of ribonucleoprotein complexes into the capsid core. The molecular architectures of HIV-1 IN assemblies that mediate these distinct events remain unknown. Furthermore, the tetramer is an important antiviral target for allosteric IN inhibitors. Here, we determined cryo-EM structures of wildtype HIV-1 IN tetramers and intasome hexadecamers. Our structures unveil a remarkable plasticity that leverages IN C-terminal domains and abutting linkers to assemble functionally distinct oligomeric forms. Alteration of a newly recognized conserved interface revealed that both IN functions track with tetramerization in vitro and during HIV-1 infection. Collectively, our findings reveal how IN plasticity orchestrates its diverse molecular functions, suggest a working model for IN-viral RNA binding, and provide atomic blueprints for allosteric IN inhibitor development.

Enhancing soil texture classification with multivariate scattering correction and residual neural networks using visible near-infrared spectra.

Soil texture is one of the most important indicators of soil physical properties, which has traditionally been measured through laborious procedures. Approaches utilizing visible near-infrared spectroscopy, with their advantages in efficiency, eco-friendliness and non-destruction, are emerging as potent alternatives. Nevertheless, these approaches often suffer from limitations in classification accuracy, and the substantial impact of spectral preprocessing, model integration, and sample matrix effect is commonly disregarded. Here a novel 11-class soil texture classification strategy that address this challenge by combining Multiplicative Scatter Correction (MSC) with Residual Network (ResNet) models was presented, resulting in exceptional classification accuracy. Utilizing the LUCAS dataset, collected by the Land Use and Cover Area frame Statistical Survey project, we thoroughly evaluated eight spectral preprocessing methods. Our findings underscored the superior performance of MSC in reducing spatial complexity within spectral data, showcasing its crucial role in enhancing model precision. Through comparisons of three 1D CNN models and two ResNet models integrated with MSC, we established the superior performance of the MSC-incorporated ResNet model, achieving an overall accuracy of 98.97 % and five soil textures even reached 100.00 %. The ResNet model demonstrated a marked superiority in classifying datasets with similar features, as observed by the confusion matrix analysis. Moreover, we investigated the potential benefit of pre-categorization based on land cover type of the soil samples in enhancing the accuracy of soil texture classification models, achieving overall classification accuracies exceeding 99.39 % for woodland, grassland, and farmland with the 2-layer ResNet model. The proposed work provides a pioneering and efficient strategy for rapid and precise soil texture identification via visible near-infrared spectroscopy, demonstrating unparalleled accuracy compared to existing methods, thus significantly enhancing the practical application prospects in soil, agricultural and environmental science.

Study on articular surface morphology of atlantoaxial lateral mass based on differential manifold.

OBJECTIVES: To propose a surface reconstruction algorithm based on a differential manifold (a space with local Euclidean space properties), which can be used for processing of clinical images and for modeling of the atlantoaxial joint. To describe the ideal anatomy of the lateral atlantoaxial articular surface by measuring the anatomical data. METHODS: Computed tomography data of 80 healthy subjects who underwent cervical spine examinations at our institution were collected between October 2019 and June 2022, including 46 males and 34 females, aged 37.8 ± 5.1 years (28-59 years). A differential manifold surface reconstruction algorithm was used to generate the model based on DICOM data derived by Vision PACS system. The lateral mass articular surface was measured and compared in terms of its sagittal diameter, transverse diameter, articular surface area, articular curvature and joint space height. RESULTS: There was no statistically significant difference between left and right sides of the measured data in normal adults (P > 0.05). The atlantoaxial articular surface sagittal diameter length was (15.83 ± 1.85) and (16.22 ± 1.57) mm on average, respectively. The transverse diameter length of the articular surface was (16.29 ± 2.16) and (16.49 ± 1.84) mm. The lateral articular surface area was (166.53 ± 7.69) and (174.48 ± 6.73) mm2 and the curvature was (164.03 ± 5.27) and (153.23 ± 9.03)°, respectively. The joint space height was 3.05 ± 0.11mm, respectively. There is an irregular articular space in the lateral mass of atlantoaxial, and both upper and lower surfaces of the articular space are concave. A sagittal plane view shows that the inferior articular surface of the atlas is mainly concave above; however, the superior articular surface of the axis is mainly convex above. In the coronal plane, the inferior articular surface of the atlas is mostly concave above, with most concave vertices located in the medial region, and the superior articular surface of the axis is mainly concave below, with most convex vertices located centrally and laterally. CONCLUSION: A differential manifold algorithm can effectively process atlantoaxial imaging data, fit and control mesh topology, and reconstruct curved surfaces to meet clinical measurement applications with high accuracy and efficiency; the articular surface of the lateral mass of atlantoaxial mass in normal adults has relatively constant sagittal diameter, transverse diameter and area. The distance difference between joint spaces is small, but the shape difference of articular surfaces differs greatly.

Isoreticular Preparation of Tetraphenylethylene-based Multicomponent Metallacages towards Light-Driven Hydrogen Production.

Multicomponent metallacages can integrate the functions of their different building blocks to achieve synergetic effects for advanced applications. Herein, based on metal-coordination-driven self-assembly, we report the preparation of a series of isoreticular tetraphenylethylene-based metallacages, which are well characterized by multinuclear NMR, ESI-TOF-MS and single-crystal X-ray diffraction techniques. The suitable integration of photosensitizing tetraphenylethylene units as faces and Re catalytic complexes as the pillars into a single metallacage offers a high photocatalytic hydrogen production rate of 1707 µmol g-1 h-1 , which is one of the highest values among reported metallacages. Femtosecond transient absorption and DFT calculations reveal that the metallacage can serve as a platform for the precise and organized arrangement of the two building blocks, enabling efficient and directional electron transfer for highly efficient photocatalytic performance. This study provides a general strategy to integrate multifunctional ligands into a certain metallacage to improve the efficiency of photocatalytic hydrogen production, which will guide the future design of metallacages towards photocatalysis.

Photosynthesis of Hydrogen Peroxide Based on g-C3 N4 : The Road of a Cost-Effective Clean Fuel Production.

Emerging artificial photosynthesis promises to offer a competitive means for solar energy conversion and further solves the energy crisis facing the world. Hydrogen peroxide (H2 O2 ), which is considered as a benign oxidant and a prospective liquid fuel, has received worldwide attention in the field of artificial photosynthesis on account of the source materials are just oxygen, water, and sunlight. Graphitic carbon nitride (g-C3 N4 )-based photocatalysts for H2 O2 generation have attracted extensive research interest due to the intrinsic properties of g-C3 N4 . In this review, research processes for H2 O2 generation on the basis of g-C3 N4 , including development, fabrication, merits, and disadvantages, and the state-of-the-art methods to enhance the performance are summarized after a brief introduction and the mechanism analysis of an efficient catalytic system. Also, recent applications of g-C3 N4 -based photocatalysts for H2 O2 production are reviewed, and the significance of active sites and synthetic pathways are highlighted from the view of reducing barriers. Finally, this paper ends with some concluding remarks to reveal the issues and opportunities of g-C3 N4 -based photocatalysts for producing H2 O2 in a high yield.

Hexaphenyltriphenylene-Based Multicomponent Metallacages: Host-Guest Complexation for White-Light Emission.

A hexaphenyltriphenylene-based hexatopic pyridyl ligand is designed and used to prepare three hexagonal prismatic metallacages via metal-coordination-driven self-assembly. Owing to the planar conjugated structures of the hexaphenyltriphenylene skeleton, such metallacages show good host-guest complexation with a series of emissive dyes, which have been further used to tune their emission in solution. Interestingly, based on their complementary emission colors, white light emission is achieved in a mixture of the host metallacages and the guests.

Impact of craniocervical junction abnormality on vertebral artery hemodynamics: based on computational fluid dynamics analysis.

Background and purpose: A three-dimensional reconstruction and data analysis of the vertebral artery (VA) with craniocervical junction abnormality (CJA) was performed by computational fluid dynamics (CFD) based on images to assess the impact of CJA on vertebral artery hemodynamics. Methods: Retrospective analysis of combined head and neck computed tomography angiography (CTA) images of 60 patients with CJA and 60 normal patients admitted to our department from January 2018 to June 2022. The VA was reconstructed in three dimensions using CFD-related software, and the results were visualized to derive vertebral artery lumen diameter (D), peak systolic velocity (PSV), mean blood flow velocity (MV), wall pressure (P), wall shear stress (WSS), normalized WSS (NWSS), etc. Statistical analysis was used to analyze whether the data related to hemodynamics in the CJA group and the control group were statistically significant. Results: The lumen diameter of the vertebral artery in the CJA group were less than the control group, and the difference was statistically significant (3.354 ± 0.562 vs. 3.744 ± 0.520, p < 0.05); the PSV, MV, P, WSS, and NWSS of the CJA group were increased compared with the control group, and the difference was statistically significant (1.235 ± 0.182 vs. 1.104 ± 0.145, 0.339 ± 0.063 vs. 0.307 ± 0.042, 24576.980 ± 7095.836 vs. 20824.281 ± 6718.438, 34.863 ± 6.816 vs. 31.080 ± 5.438, 0.272 ± 0.075 vs. 0.237 ± 0.067, p < 0.05). Conclusion: In the complex CJA, the possibility of hemodynamic variation in the VAs is higher than in the normal population. The hemodynamic aspects of the vertebral artery in patients with CJA, such as diameter, flow velocity, flow, wall pressure and shear force, differ from those in the normal population and may lead to the occurrence of clinical symptoms, such as dizziness, so preoperative examinations such as combined head and neck CTA should be performed to clarify the vascular abnormalities.

Towards 100 Gbps over 100 km: System Design and Demonstration of E-Band Millimeter Wave Communication.

Long-range E-band communication with fiber-equivalent speed is emerging extensively as a critical technology in the next-generation communication. This paper firstly reviews the relevant progress in recent research. A brief survey is presented on high-speed, long-range E-band communication systems and their relevant techniques that are essential to the link design, including antenna, power amplifier (PA), channel, and digital baseband processing. In the second part, we review our recent field trial of a long-range air-to-ground E-band link, which maintains steady transmission from a slow-moving helium balloon to the ground station with a vertical dimension of 20 km. The improvement directions and future research topics are then discussed.

cis-Dipyridyl porphyrin-based multicomponent organoplatinum(II) bismetallacycles for photocatalytic oxidation.

Three porphyrin-based bismetallacycles are prepared via multi-component metal-coordination-driven self-assembly. Owing to different tetracarboxylic ligands in their structures, they show distinct coordination geometries and stacking modes, which inhibit the self-aggregation of porphyrin and offer improved singlet oxygen generation efficiency. These bismetallacycles are successfully used for the photooxidation of methyl(phenyl)sulfane, showing their potential applications toward photocatalysis.

Precise Synthesis of Concentric Ring, Helicoid, and Ladder Metallo-Polymers with Chevron-Shaped Monomers.

Molecular geometry represents one of the most important structural features and governs physical properties and functions of materials. Nature creates a wide array of substances with distinct geometries but similar chemical composition with superior efficiency and precision. However, it remains a formidable challenge to construct abiological macromolecules with various geometries based on identical repeating units, owing to the lack of corresponding synthetic approaches for precisely manipulating the connectivity between monomers and feasible techniques for characterizing macromolecules at the single-molecule level. Herein, we design and synthesize a series of tetratopic monomers with chevron stripe shape which serve as the key precursors to produce four distinct types of metallo-macromolecules with well-defined geometries, viz., the concentric hexagon, helicoid polymer, ladder polymer, and cross-linked polymer, via platinum-acetylide couplings. Concentric hexagon, helicoid, and ladder metallo-polymers are directly visualized by transmission electron microscopy, atomic force microscopy, and ultra-high-vacuum low-temperature scanning tunneling microscopy at the single-molecule level. Finally, single-walled carbon nanotubes (SWCNTs) are selected as the guest to investigate the structure-property relationship based on such macromolecules, among which the helicoid metallo-polymer shows high efficiency in wrapping SWCNTs with geometry-dependent selectivity.

Emissive Metallacage-Cored Polyurethanes with Self-Healing and Shape Memory Properties.

The structures of the crosslinks in supramolecular polymer networks play an important role on their properties and functions. Herein, emissive metallacages are used as crosslinks to prepare metallacage-cored polyurethanes. The mechanical properties including storage modulus, toughness, Young's modulus and breaking strength of polymers are greatly enhanced with the increase of crosslinking densities. Moreover, such polymers not only exhibit good fluorescence in the solid state, but also show self-healing and shape memory properties owing to the dynamic reversible non-covalent bonds in their structures. This study not only offers a convenient strategy to prepare metallacage-crosslinked networks, but also explores their applications as self-healing and shape memory materials, which will promote the study of metallacage-cored supramolecular networks as smart materials.

Porphyrin-Based Multicomponent Metallacage: Host-Guest Complexation toward Photooxidation-Triggered Reversible Encapsulation and Release.

The development of supramolecular hosts with effective host-guest properties is crucial for their applications. Herein, we report the preparation of a porphyrin-based metallacage, which serves as a host for a series of polycyclic aromatic hydrocarbons (PAHs). The association constant between the metallacage and coronene reaches 2.37 × 107 M-1 in acetonitrile/chloroform (ν/ν = 9/1), which is among the highest values in metallacage-based host-guest complexes. Moreover, the metallacage exhibits good singlet oxygen generation capacity, which can be further used to oxidize encapsulated anthracene derivatives into anthracene endoperoxides, leading to the release of guests. By employing 10-phenyl-9-(2-phenylethynyl)anthracene whose endoperoxide can be converted back by heating as the guest, a reversible controlled release system is constructed. This study not only gives a type of porphyrin-based metallacage that shows desired host-guest interactions with PAHs but also offers a photooxidation-responsive host-guest recognition motif, which will guide future design and applications of metallacages for stimuli-responsive materials.

Epistatic interaction effect between chromosome 1BL (Yr29) and a novel locus on 2AL facilitating resistance to stripe rust in Chinese wheat Changwu 357-9.

KEY MESSAGE: Four stable QTL for adult plant resistance were identified in wheat line Changwu 357-9, including a new QTL on 2AL showing significant interaction with Yr29 to reduce stripe rust severity. Stripe rust (yellow rust) is a serious disease of bread wheat (Triticum aestivum L.) worldwide. Genetic resistance is considered the most economical, effective and environmentally friendly method to control the disease and to minimize the use of fungicides. The current study focused on characterizing the components of stripe rust resistance and understanding the interactions in Changwu 357-9 (CW357-9)/Avocet S RIL population. A genetic linkage map constructed using a new GenoBaits Wheat 16K Panel and the 660K SNP array had 5104 polymorphic SNP markers spanning 3533.11 cM. Four stable QTL, consistently identified across five environments, were detected on chromosome arms 1BL, 2AL, 3DS, and 6BS in Changwu357-9. The most effective QTL QYrCW357-1BL was Yr29. The 6BS QTL was identified as Yr78, which has been combined with the 1BL QTL in many wheat cultivars and breeding lines. The novel QTL on 2AL with moderate effect showed a stable and significant epistatic interaction with Yr29. The QTL on 3DL should be same as QYrsn.nwafu-3DL and enriches the overall stripe rust resistance gene pool for breeding. Polymorphisms of flanking AQP markers AX-110020417 (for QYrCW357-1BL), AX-110974948 (for QYrCW357-2AL), AX-109466386 (for QYrCW357-3DL), and AX-109995005 (for QYrCW357-6BS) were evaluated in a diversity panel including 225 wheat cultivars and breeding lines. These results suggested that these high-throughput markers could be used to introduce QYrCW357-1BL, QYrCW357-2AL, QYrCW357-3DL, and QYrCW357-6BS into commercial wheat cultivars. Combinations of these genes with other APR QTL should lead to higher levels of stripe rust resistance along with the beneficial effects of multi-disease resistance gene Yr29 on improving resistance to other diseases.

Hexaphenylbenzene-Based Deep Blue-Emissive Metallacages as Donors for Light-Harvesting Systems.

We herein report the preparation of a series of hexaphenylbenzene (HPB)-based deep blue-emissive metallacages via multicomponent coordination-driven self-assembly. These metallacages feature prismatic structures with HPB derivatives as the faces and tetracarboxylic ligands as the pillars, as evidenced by NMR, mass spectrometry and X-ray diffraction analysis. Light-harvesting systems were further constructed by employing the metallacages as the donor and a naphthalimide derivative (NAP) as the acceptor, owing to their good spectral overlap. The judiciously chosen metallacage serves as the antenna, providing the suitable energy to excite the non-emissive NAP, and thus resulting in bright emission for NAP in the solid state. This study provides a type of HPB-based multicomponent emissive metallacage and explores their applications as energy donors to light up non-emissive fluorophores in the solid state, which will advance the development of emissive metallacages as useful luminescent materials.

ADH5-mediated NO bioactivity maintains metabolic homeostasis in brown adipose tissue.

Brown adipose tissue (BAT) thermogenic activity is tightly regulated by cellular redox status, but the underlying molecular mechanisms are incompletely understood. Protein S-nitrosylation, the nitric-oxide-mediated cysteine thiol protein modification, plays important roles in cellular redox regulation. Here we show that diet-induced obesity (DIO) and acute cold exposure elevate BAT protein S-nitrosylation, including UCP1. This thermogenic-induced nitric oxide bioactivity is regulated by S-nitrosoglutathione reductase (GSNOR; alcohol dehydrogenase 5 [ADH5]), a denitrosylase that balances the intracellular nitroso-redox status. Loss of ADH5 in BAT impairs cold-induced UCP1-dependent thermogenesis and worsens obesity-associated metabolic dysfunction. Mechanistically, we demonstrate that Adh5 expression is induced by the transcription factor heat shock factor 1 (HSF1), and administration of an HSF1 activator to BAT of DIO mice increases Adh5 expression and significantly improves UCP1-mediated respiration. Together, these data indicate that ADH5 controls BAT nitroso-redox homeostasis to regulate adipose thermogenesis, which may be therapeutically targeted to improve metabolic health.

A putative long noncoding RNA-encoded micropeptide maintains cellular homeostasis in pancreatic ß cells.

Micropeptides (microproteins) encoded by transcripts previously annotated as long noncoding RNAs (lncRNAs) are emerging as important mediators of fundamental biological processes in health and disease. Here, we applied two computational tools to identify putative micropeptides encoded by lncRNAs that are expressed in the human pancreas. We experimentally verified one such micropeptide encoded by a ß cell- and neural cell-enriched lncRNA TCL1 Upstream Neural Differentiation-Associated RNA (TUNAR, also known as TUNA, HI-LNC78, or LINC00617). We named this highly conserved 48-amino-acid micropeptide beta cell- and neural cell-regulin (BNLN). BNLN contains a single-pass transmembrane domain and localizes at the endoplasmic reticulum (ER) in pancreatic ß cells. Overexpression of BNLN lowered ER calcium levels, maintained ER homeostasis, and elevated glucose-stimulated insulin secretion in pancreatic ß cells. We further assessed the BNLN expression in islets from mice fed a high-fat diet and a regular diet and found that BNLN is suppressed by diet-induced obesity (DIO). Conversely, overexpression of BNLN enhanced insulin secretion in islets from lean and obese mice as well as from humans. Taken together, our study provides the first evidence that lncRNA-encoded micropeptides play a critical role in pancreatic ß cell functions and provides a foundation for future comprehensive analyses of micropeptide function and pathophysiological impact on diabetes.