Gut symbionts alleviate MASH through a secondary bile acid biosynthetic pathway.

The gut microbiota has been found to play an important role in the progression of metabolic dysfunction-associated steatohepatitis (MASH), but the mechanisms have not been established. Here, by developing a click-chemistry-based enrichment strategy, we identified several microbial-derived bile acids, including the previously uncharacterized 3-succinylated cholic acid (3-sucCA), which is negatively correlated with liver damage in patients with liver-tissue-biopsy-proven metabolic dysfunction-associated fatty liver disease (MAFLD). By screening human bacterial isolates, we identified Bacteroides uniformis strains as effective producers of 3-sucCA both in vitro and in vivo. By activity-based protein purification and identification, we identified an enzyme annotated as ß-lactamase in B. uniformis responsible for 3-sucCA biosynthesis. Furthermore, we found that 3-sucCA is a lumen-restricted metabolite and alleviates MASH by promoting the growth of Akkermansia muciniphila. Together, our data offer new insights into the gut microbiota-liver axis that may be leveraged to augment the management of MASH.

Dopant-additive synergism enhances perovskite solar modules.

Perovskite solar cells (PSCs) are among the most promising photovoltaic technologies owing to their exceptional optoelectronic properties1,2. However, the lower efficiency, poor stability and reproducibility issues of large-area PSCs compared with laboratory-scale PSCs are notable drawbacks that hinder their commercialization3. Here we report a synergistic dopant-additive combination strategy using methylammonium chloride (MACl) as the dopant and a Lewis-basic ionic-liquid additive, 1,3-bis(cyanomethyl)imidazolium chloride ([Bcmim]Cl). This strategy effectively inhibits the degradation of the perovskite precursor solution (PPS), suppresses the aggregation of MACl and results in phase-homogeneous and stable perovskite films with high crystallinity and fewer defects. This approach enabled the fabrication of perovskite solar modules (PSMs) that achieved a certified efficiency of 23.30% and ultimately stabilized at 22.97% over a 27.22-cm2 aperture area, marking the highest certified PSM performance. Furthermore, the PSMs showed long-term operational stability, maintaining 94.66% of the initial efficiency after 1,000 h under continuous one-sun illumination at room temperature. The interaction between [Bcmim]Cl and MACl was extensively studied to unravel the mechanism leading to an enhancement of device properties. Our approach holds substantial promise for bridging the benchtop-to-rooftop gap and advancing the production and commercialization of large-area perovskite photovoltaics.

Oriented nucleation in formamidinium perovskite for photovoltaics.

The black phase of formamidinium lead iodide (FAPbI3) perovskite shows huge promise as an efficient photovoltaic, but it is not favoured energetically at room temperature, meaning that the undesirable yellow phases are always present alongside it during crystallization1-4. This problem has made it difficult to formulate the fast crystallization process of perovskite and develop guidelines governing the formation of black-phase FAPbI3 (refs. 5,6). Here we use in situ monitoring of the perovskite crystallization process to report an oriented nucleation mechanism that can help to avoid the presence of undesirable phases and improve the performance of photovoltaic devices in different film-processing scenarios. The resulting device has a demonstrated power-conversion efficiency of 25.4% (certified 25.0%) and the module, which has an area of 27.83 cm2, has achieved an impressive certified aperture efficiency of 21.4%.

Gut bacteria alleviate smoking-related NASH by degrading gut nicotine.

Tobacco smoking is positively correlated with non-alcoholic fatty liver disease (NAFLD)1-5, but the underlying mechanism for this association is unclear. Here we report that nicotine accumulates in the intestine during tobacco smoking and activates intestinal AMPKα. We identify the gut bacterium Bacteroides xylanisolvens as an effective nicotine degrader. Colonization of B. xylanisolvens reduces intestinal nicotine concentrations in nicotine-exposed mice, and it improves nicotine-exacerbated NAFLD progression. Mechanistically, AMPKα promotes the phosphorylation of sphingomyelin phosphodiesterase 3 (SMPD3), stabilizing the latter and therefore increasing intestinal ceramide formation, which contributes to NAFLD progression to non-alcoholic steatohepatitis (NASH). Our results establish a role for intestinal nicotine accumulation in NAFLD progression and reveal an endogenous bacterium in the human intestine with the ability to metabolize nicotine. These findings suggest a possible route to reduce tobacco smoking-exacerbated NAFLD progression.

ATX1 and HUB1/2 promote recruitment of the transcription elongation factor VIP2 to modulate the floral transition in Arabidopsis.

Histone 2B ubiquitination (H2Bub) and trimethylation of H3 at lysine 4 (H3K4me3) are associated with transcription activation. However, the function of these modifications in transcription in plants remains largely unknown. Here, we report that coordination of H2Bub and H3K4me3 deposition with the binding of the RNA polymerase-associated factor VERNALIZATION INDEPENDENCE2 (VIP2) to FLOWERING LOCUS C (FLC) modulates flowering time in Arabidopsis. We found that RING domain protein HISTONE MONOUBIQUITINATION1 (HUB1) and HUB2 (we refer as HUB1/2), which are responsible for H2Bub, interact with ARABIDOPSIS TRITHORAX1 (ATX1), which is required for H3K4me3 deposition, to promote the transcription of FLC and repress the flowering time. The atx1-2 hub1-10 hub2-2 triple mutant in FRIGIDIA (FRI) background displayed early flowering like FRI hub1-10 hub2-2 and overexpression of ATX1 failed to rescue the early flowering phenotype of hub1-10 hub2-2. Mutations in HUB1 and HUB2 reduced the ATX1 enrichment at FLC, indicating that HUB1 and HUB2 are required for ATX1 recruitment and H3K4me3 deposition at FLC. We also found that the VIP2 directly binds to HUB1, HUB2, and ATX1 and that loss of VIP2 in FRI hub1-10 hub2-2 and FRI atx1-2 plants resulted in early flowering like that observed in FRI vip2-10. Loss of function of HUB2 and ATX1 impaired VIP2 enrichment at FLC, and reduced the transcription initiation and elongation of FLC. In addition, mutations in VIP2 reduced HUB1 and ATX1 enrichment and H2Bub and H3K4me3 levels at FLC. Together, our findings revealed that HUB1/2, ATX1, and VIP2 coordinately modulate H2Bub and H3K4me3 deposition, FLC transcription, and flowering time.

CD155 is essential for skeletal muscle regeneration by regulating satellite cell proliferation and differentiation.

CD155, a member of the immunoglobulin superfamily, is closely related to cell proliferation, adhesion, and migration. CD155 is overexpressed on the surface of cancer cells to promote cell proliferation and is upregulated in damaged tissues as a stress-induced molecule. The process of skeletal muscle regeneration after injury is complex and involves injurious stimulation and subsequent satellite cell proliferation. However, the role of CD155 in this process remains unelucidated. This study aimed to explore the role of CD155 in injured skeletal muscle regeneration and to clarify its effect on satellite cell proliferation and differentiation. Here, quantitative real-time polymerase chain reaction (RT-qPCR) and immunofluorescence results indicated that CD155 expression in satellite cells increased after skeletal muscle injury. CD155 knockout in mice impaired the regeneration of skeletal muscle. A bone marrow transplantation mouse model was constructed and revealed that CD155 on skeletal muscle tissues, not immune cells, affected muscle regeneration. In vitro, CD155 knockdown in myoblasts inhibited their proliferation and differentiation. The transcriptomic analysis also indicated that CD155 absence can impair the biological proliferation and differentiation process of myoblasts. Our research demonstrates that CD155 directly promotes injured muscle regeneration by regulating satellite cell proliferation and differentiation, which may be a potential therapeutic molecule for skeletal muscle injury.

Strain-Controlled Galvanic Synthesis of Platinum Icosahedral Nanoframes and Their Enhanced Catalytic Activity toward Oxygen Reduction.

The unique strain distribution on the surface of a Pd icosahedral nanocrystal is leveraged to control the sites for oxidation and reduction involved in the galvanic replacement reaction. Specifically, Pd is oxidized and dissolved from the center of each {111} facet due to its tensile strain, while the Pt(II) precursor adsorbs onto the vertices and edges featuring a compressive strain, followed by surface reduction and conformal deposition of the Pt atoms. Once the galvanic reaction is initiated, the {111} facets become more vulnerable to oxidation and dissolution, as the vertices and edges are protected by the deposited Pt atoms. The site-selected galvanic reaction naturally results in the formation of Pt icosahedral nanoframes covered by compressively strained {111} facets, which show enhanced catalytic activity and durability toward oxygen reduction relative to commercial Pt/C.

Thermal Stability of Au Rhombic Dodecahedral Nanocrystals Can Be Greatly Enhanced by Coating Their Surface with an Ultrathin Shell of Pt.

Rhombic dodecahedral nanocrystals have been considered particularly difficult to synthesize because they are enclosed by {110}, a low-index facet with the greatest surface energy. Recently, we demonstrated the use of seed-mediated growth for the facile and robust synthesis of Au rhombic dodecahedral nanocrystals (AuRD). While the unique shape and surface structure of AuRD are desirable for potential applications in plasmonics and catalysis, respectively, their high surface energy makes them highly susceptible to thermal degradation. Here we demonstrate that it is feasible to greatly improve the thermal stability with some sacrifice to the plasmonic properties of the original AuRD by coating their surface with an ultrathin shell made of Pt. Our in situ electron microscopy analysis indicates that the ultrathin Pt coating can increase the thermal stability from 60 up to 450 °C, a trend that is also supported by the results from a computational study.

Elucidating the Role of Reduction Kinetics in the Phase-Controlled Growth on Preformed Nanocrystal Seeds: A Case Study of Ru.

This study demonstrates the crucial role of reduction kinetics in phase-controlled synthesis of noble-metal nanocrystals using Ru nanocrystals as a case study. We found that the reduction kinetics played a more important role than the templating effect from the preformed seed in dictating the crystal structure of the deposited overlayers despite their intertwined effects on successful epitaxial growth. By employing two different polyols, a series of Ru nanocrystals with tunable sizes of 3-7 nm and distinct patterns of crystal phase were synthesized by incorporating different types of Ru seeds. Notably, the use of ethylene glycol and triethylene glycol consistently resulted in the formation of Ru shell in natural hexagonal close-packed (hcp) and metastable face-centered cubic (fcc) phases, respectively, regardless of the size and phase of the seed. Quantitative measurements and theoretical calculations suggested that this trend was a manifestation of the different reduction kinetics associated with the precursor and the chosen polyol, which, in turn, affected the reduction pathway (solution versus surface) and packing sequence of the deposited Ru atoms. This work not only underscores the essential role of reduction kinetics in controlling the packing of atoms and thus the phase taken by Ru nanocrystals but also suggests a potential extension to other noble-metal systems.

Mechanochemically Enabled Metastable Niobium Tungsten Oxides.

Metastable compounds have greatly expanded the synthesizable compositions of solid-state materials and have attracted enormous amounts of attention in recent years. Especially, mechanochemically enabled metastable materials synthesis has been very successful in realizing cation-disordered materials with highly simple crystal structures, such as rock salts. Application of the same strategy for other structural types, especially for non-close-packed structures, is peculiarly underexplored. Niobium tungsten oxides (NbWOs), a class of materials that have been under the spotlight because of their diverse structural varieties and promising electrochemical and thermoelectric properties, are ideally suited to fill such a knowledge gap. In this work, we develop a new series of metastable NbWOs and realize one with a fully cation-disordered structure. Furthermore, we find that metastable NbWOs transform to a cation-disordered cubic structure when applied as a Li-ion battery anode, highlighting an intriguing non-close-packed-close-packed conversion process, as evidenced in various physicochemical characterizations, in terms of diffraction, electronic, and vibrational structures. Finally, by comparing the cation-disordered NbWO with other trending cation-disordered oxides, we raise a few key structural features for cation disorder and suggest a few possible research opportunities for this field.

Cord blood-derived biologics lead to robust axonal regeneration in benzalkonium chloride-injured mouse corneas by modulating the Il-17 pathway and neuropeptide Y.

BACKGROUND: Umbilical cord blood-derived therapeutics, such as serum (UCS) and platelet-rich plasma (UCPRP), are popular treatment options in clinical trials and can potentially be utilized to address a clinically unmet need caused by preservatives, specifically benzalkonium chloride (BAK), present in ophthalmic formulations. As current clinical interventions for secondary injuries caused by BAK are suboptimal, this study will explore the feasibility of utilizing UCS and UCPRP for cornea treatment and investigate the underlying mechanisms associated with this approach. METHODS: Mice's corneas were administered BAK to induce damage. UCS and UCPRP were then utilized to attempt to treat the injuries. Ocular tests were performed on the animals to evaluate recovery, while immunostaining, RNA-seq, and subsequent bioinformatics analysis were conducted to investigate the treatment mechanism. RESULTS: BAK administration led to widespread inflammatory responses in the cornea. Subsequent treatment with UCS and UCPRP led to the downregulation of immune-related 'interactions between cytokine receptors' and 'IL-17 signaling' pathways. Although axonal enhancers such as Ngf, Rac2, Robo2, Srgap1, and Rock2 were found to be present in the injured group, robust axonal regeneration was observed only in the UCS and UCPRP treatment groups. Further analysis revealed that, as compared to normal corneas, inflammation was not restored to pre-injury levels post-treatment. Importantly, Neuropeptide Y (Npy) was also involved in regulating immune responses, indicating neuroimmune axis interactions. CONCLUSIONS: Cord blood-derived therapeutics are feasible options for overcoming the sustained injuries induced by BAK in the cornea. They also have potential applications in areas where axonal regeneration is required.

Lightweight, Strong, and Transparent Wood Films Produced by Capillary Driven Self-Densification.

Wood delignification and densification enable the production of high strength and/or transparent wood materials with exceptional properties. However, processing needs to be more sustainable and besides the chemical delignification treatments, energy intense hot-pressing calls for alternative approaches. Here, this study shows that additional softening of delignified wood via a mild swelling process using an ionic liquid-water mixture enables the densification of tube-line wood cells into layer-by-layer sheet structures without hot-pressing. The natural capillary force induces self-densification in a simple drying process resulting in a transparent wood film. The as-prepared films with ≈150 µm thickness possess an optical transmittance ≈70%, while maintaining optical haze >95%. Due to the densely packed sheet structure with a large interfacial area, the reassembled wood film is fivefold stronger and stiffer than the delignified wood in fiber direction. Owing to a low density, the specific tensile strength and elastic modulus are as high as 282 MPa cm3 g-1 and 31 GPa cm3 g-1. A facile and highly energy efficient wood nanotechnology approach are demonstrated toward more sustainable materials and processes by directly converting delignified wood into transparent wood omitting polymeric matrix infiltration or mechanical pressing.

Deficiency of thrombospondin-2 alleviates intimal hyperplasia in mice by modulating vascular smooth muscle cell proliferation and migration.

Thrombospondin-2 (Tsp2), a glycoprotein in the extracellular matrix, plays a critical role in the maintenance of vascular homeostasis. However, its role in the pathogenesis of cardiovascular disorders such as intimal hyperplasia is not fully elucidated. This study, therefore, aims to explore the effect of Tsp2 on intimal hyperplasia and its associated underlying mechanisms. Intimal hyperplasia (IH) was established using a modified wire-mediated femoral artery injury model. Immunofluorescence and qPCR identified upregulated Tsp2 expression in the injured femoral artery compared with the uninjured femoral artery. Similarly, TSP2 expression was also increased in human samples from the atherosclerotic femoral artery and colocalized with vascular smooth muscle cells (VSMCs). Compared with the wild-type littermates, Tsp2 knockout mice displayed a mitigated IH in the injured femoral artery, as demonstrated by a decreased neointimal area and intimal/median ratio. Primary mouse VSMCs were cultured to explore the mechanism by which Tsp2 influenced IH in vitro. PDGF-stimulated VSMCs presented an elevated Tsp2 expression and enhanced migration and proliferation. However, Tsp2 knockdown by siRNA blocked the increased migration and proliferation of VSMCs. Further analysis identified an association between Notch3 and IH when the intracellular domain of Notch3 (Nicd3) was upregulated in PDGF-stimulated VSMCs and femoral arteries with IH in human tissues. Along with the overexpression and downregulation of Tsp2, the Nicd3 expression was also up and downregulated accordingly. Tsp2 was associated with IH and may serve as a therapeutic target for IH. Downregulation of Tsp2 could mitigate the progression of IH by modulating the proliferation and migration of VSMCs.

KF-catalyzed direct thiomethylation of carboxylic acids with DMSO to access methyl thioesters.

With dimethyl sulfoxide (DMSO) as the methylthio source, a KF-catalyzed strategy was employed for the direct thiomethylation of carboxylic acids with DMSO for the preparation of methyl thioesters. In this process, a wide range of methyl thioesters were obtained in moderate to excellent yields. This novel strategy features the first use of DMSO as a methylthiolating agent for the construction of methyl thioesters, transition metal-free conditions, inexpensive reagents, easy workup, broad substrate scope and sustainability. Additionally, this procedure can be readily scaled up to a gram scale.

Manipulating Reactivity of Ir(CH2)0-2+ Cations toward Dinitrogen at Room Temperature: A Unique Dependence on the Organic Ligand Structures.

Nitrogen (N2) activation at room temperature has long been a great challenge. Therefore, the rational design of reactive species to adsorb N2, which is a prerequisite for cleavage of the strong N≡N triple bond in industrial and biological processes, is highly desirable and meaningful. Herein, the N2 adsorption process is controlled by regulating the types and numbers of organic ligands, and the organic ligands are produced through the reactions of Ir+ with methane and ethane. CH4 molecules dissociate on the Ir+ cations to form Ir(CH2)1,2+. The reaction of Ir+ with C2H6 can generate HIrC2H3+, which is different from the structure of Ir(CH2)2+ obtained from Ir+/CH4. The reactivity order of N2 adsorption is Ir(CH2)2+ > HIrC2H3+ ≫ HIrCH+ ≈ Ir+ (almost inert under similar reaction conditions), indicating that different organic ligand structures affect reactivity dramatically. The main reason for this interesting reactivity difference is that the lowest unoccupied molecular orbital (LUMO) level of Ir(CH2)2+ is much closer to the highest occupied molecular orbital (HOMO) level of N2 than those of the other three systems. This study provides new insights into the adsorption of N2 on metal-organic ligand species, in which the organic ligand dominates the reactivity, and it discovers new clues in designing effective transition metal carbine species for N2 activation.

Unsupervised machine learning cluster analysis to identification EVAR patients clinical phenotypes based on radiomics.

OBJECTIVE: This study used unsupervised machine learning (UML) cluster analysis to explore clinical phenotypes of endovascular aortic repair (EVAR) for abdominal aortic aneurysm (AAA) patients based on radiomics. METHOD: We retrospectively reviewed 1785 patients with infra-renal AAA who underwent elective EVAR procedures between January 2010 and December 2020. Pyradiomics was used to extract the radiomics features. Statistical analysis was applied to determine the radiomics features that related to severe adverse events (SAEs) after EVAR. The selected features were used for UML cluster analysis in training set and validation in test set. Comparison of basic characteristics and radiomics features of different clusters. The Kaplan-Meier analysis was conducted to generate the cumulative incidence of freedom from SAEs rate. RESULT: A total of 1180 patients were enrolled. During the follow-up, 353 patients experienced EVAR-related SAEs. In total, 1223 radiomics features were extracted from each patient, of which 23 radiomics features were finally preserved to identify different clinical phenotypes. 944 patients were allocated to the training set. Three clusters were identified in training set, in which patients had identical clinical characteristics and morphological features, while varied considerably of selected radiomics features. This encouraging performance was further approved in the test set. In addition, each cluster was well differentiated from other clusters and Kaplan-Meier analysis showed significant differences of freedom from SAEs rate between different clusters both in the training (p = .0216) and test sets (p = .0253). CONCLUSION: Based on radiomics, UML cluster analysis can identify clinical phenotypes in EVAR patients with distinct long-term outcomes.

Time-Varying Channel Estimation Based on Distributed Compressed Sensing for OFDM Systems.

For orthogonal frequency division multiplexing (OFDM) systems in high-mobility scenarios, the estimation of time-varying multipath channels not only has a large error, which affects system performance, but also requires plenty of pilots, resulting in low spectral efficiency. To address these issues, we propose a time-varying multipath channel estimation method based on distributed compressed sensing and a multi-symbol complex exponential basis expansion model (MS-CE-BEM) by exploiting the temporal correlation and the joint delay sparsity of wideband wireless channels within the duration of multiple OFDM symbols. Furthermore, in the proposed method, a sparse pilot pattern with the self-cancellation of pilot intercarrier interference (ICI) is adopted to reduce the input parameter error of the MS-CE-BEM, and a symmetrical extension technique is introduced to reduce the modeling error. Simulation results show that, compared with existing methods, this proposed method has superior performances in channel estimation and spectrum utilization for sparse time-varying channels.

Integrated Metabolomics and Transcriptomics Analyses of the Biosynthesis of Arbutin and 6'-O-Caffeoylarbutin in Vaccinium dunalianum Cell Suspension Cultures Fed with Hydroquinone.

Arbutin and 6'-O-caffeoylarbutin (CA) from Vaccinium dunalianum Wight are known for their ability to inhibit melanin synthesis. To boost the production of arbutin and CA, precursor feeding with hydroquinone (HQ) was studied in V. dunalianum suspension cells. The effect of HQ on the biosynthesis of arbutin and CA in the suspension cells was investigated using high-performance liquid chromatography (HPLC), and possible molecular mechanisms were analyzed using metabolomics and transcriptomics analyses. HPLC analysis only showed that the addition of HQ significantly enhanced arbutin synthesis in cells, peaking at 15.52 ± 0.28 mg·g-1 after 0.5 mmol·L-1 HQ treatment for 12 h. Subsequently, metabolomics identified 78 differential expression metabolites (DEMs), of which arbutin and CA were significantly up-regulated metabolites. Moreover, transcriptomics found a total of 10,628 differential expression genes (DEGs). The integrated transcriptomics and metabolomics revealed that HQ significantly enhanced the expression of two arbutin synthase (AS) genes (Unigene0063512 and Unigene0063513), boosting arbutin synthesis. Additionally, it is speculated that CA was generated from arbutin and 3,4,5-tricaffeoylquinic acid catalyzed by caffeoyl transferase, with Unigene0044545, Unigene0043539, and Unigene0017356 as potentially associated genes with CA synthesis. These findings indicate that the precursor feeding strategy offers a promising approach for the mass production of arbutin and CA in V. dunalianum suspension cells and provides new insights for CA biosynthesis in V. dunalianum.

Surface-enhanced Raman scattering spectroscopy monitoring and degradation of organic pollutants using a novel nanowire.

A multifunctional Ag/AlOOH nanowires (ANW) composite substrate was constructed, which not only accomplishes highly sensitive detection of organic dye molecules, but also has excellent performance in the degradation of pollutants. The ANW in the Ag/ANW substrate possesses a high aspect ratio, which extends the distribution area of Ag and enables a large number of hot spots on the active substrate. Additionally, due to the abundant OH groups on the ANW, there is an increased number of anchor sites for adsorbed metal ions in the Ag/ANW compound, thus contributing to the enhancement and degradation of molecules. Moreover, the constructed multifunctional Ag/ANW nanocomplexes also show great promise for practical applications, providing a reference for the detection and degradation of contaminants.

Microbial inoculants using spent mushroom substrates as carriers improve soil multifunctionality and plant growth by changing soil microbial community structure.

Peat is typically used as a carrier for microbial inoculants; however, due to its non-renewable nature alternatives need to be identified as reliable and renewable carriers for mineral-solubilizing inoculants. In pot experiments, solid microbial inoculants were comprised of peat (P), biochar (BC), and spent mushroom substrates (SMS) using Medicago sativa L. as experimental materials, and the purpose of this study is to assess the effect of solid microbial inoculants on soil multifunctionality and plant growth. The results revealed that the SMS microbial inoculant had the greatest positive impact on plant biomass and significantly stimulated soil multifunctionality which is typically managed or assessed based on various soil functions or processes that are crucial for sustaining productivity, in contrast to the peat microbial inoculant, particularly at a supply level of 100 g/pot. There was no significant correlation between soil multifunctionality and bacterial/fungal microbial diversity. However, according to the co-occurrence network of bacteria and fungi, soil multifunctionality was intimately correlated with the biodiversity of the main ecological clusters (modules) of bacteria and fungi, rather than to the entire soil microbial community structure. The keystone species of module hubs and connectors play critical roles in maintaining the stability of ecological clusters of microbial co-occurrence networks and linkages between ecological clusters. Soil pH is a major predictor of changes in plant biomass, and leads to changes therein by affecting the major ecological clusters of bacterial and fungal co-occurrence networks. These results suggested that SMS may serve as a good alternative to peat as a carrier of mineral-solubilizing microorganisms to maintain soil multifunctionality and promote plant growth.