Molecular Twist-Induced Single-Crystal Isomerization and Valence Tautomeric Transitions in a Cobalt-Dioxolene Complex.

A mononuclear valence tautomeric (VT) complex, [Co(pycz)2(Sq)(Cat)] (1-trans), where pycz = 9-(pyridin-4-yl)-9H-carbazole, Sq⋅- = 3,5-di-tert-butyl-semiquinonato, and Cat2- = 3,5-di-tert-butyl-catecholato, is synthesized in the trans configuration, which undergoes one-step valence tautomeric transition above room temperature. Remarkably, 1-trans can transform into its isomeric structure, [Co(pycz)2(Sq)(Sq)] (1-cis), at temperature above 350 K in a single-crystal-to-single-crystal way by in situ molecular twist, and the resulting 1-cis exhibits a pronounced two-step VT transition during magnetic measurements that is rare for mononuclear VT complexes. Such drastic solid-state structural transformation is reported in VT compounds for the first time, which is actuated by a crystal surface's melting-recrystallization induced phase transition process. DFT calculations offer an underlying mechanism suggesting a concerted bond rotation during the structural transformation. The results demonstrate an unconventional approach that realizes structural transformation of VT complexes and the control of VT performance.

KAT8 is upregulated and recruited to the promoter of Atg8 by FOXO to induce H4 acetylation for autophagy under 20-hydroxyecdysone regulation.

Selective gene expression in cells in physiological or pathological conditions is important for the growth and development of organisms. Acetylation of histone H4 at K16 (H4K16ac) catalyzed by histone acetyltransferase 8 (KAT8) is known to promote gene transcription; however, the regulation of KAT8 transcription and the mechanism by which KAT8 acetylates H4K16ac to promote specific gene expression are unclear. Using the lepidopteran insect Helicoverpa armigera as a model, we reveal that the transcription factor FOXO promotes KAT8 expression and recruits KAT8 to the promoter region of autophagy-related gene 8 (Atg8) to increase H4 acetylation at that location, enabling Atg8 transcription under the steroid hormone 20-hydroxyecdysone (20E) regulation. H4K16ac levels are increased in the midgut during metamorphosis, which is consistent with the expression profiles of KAT8 and ATG8. Knockdown of Kat8 using RNA interference results in delayed pupation and repression of midgut autophagy and decreases H4K16ac levels. Overexpression of KAT8-GFP promotes autophagy and increases H4K16ac levels. FOXO, KAT8, and H4K16ac colocalized at the FOXO-binding region to promote Atg8 transcription under 20E regulation. Acetylated FOXO at K180 and K183 catalyzed by KAT8 promotes gene transcription for autophagy. 20E via FOXO promotes Kat8 transcription. Knockdown or overexpression of FOXO appeared to give similar results as knockdown or overexpression of KAT8. Therefore, FOXO upregulates KAT8 expression and recruits KAT8 to the promoter region of Atg8, where the KAT8 induces H4 acetylation to promote Atg8 transcription for autophagy under 20E regulation. This study reveals the mechanism that KAT8 promotes transcription of a specific gene.

Added value of CE-CT radiomics to predict high Ki-67 expression in hepatocellular carcinoma.

BACKGROUND: This study aimed to develop a computed tomography (CT) model to predict Ki-67 expression in hepatocellular carcinoma (HCC) and to examine the added value of radiomics to clinico-radiological features. METHODS: A total of 208 patients (training set, n = 120; internal test set, n = 51; external validation set, n = 37) with pathologically confirmed HCC who underwent contrast-enhanced CT (CE-CT) within 1 month before surgery were retrospectively included from January 2014 to September 2021. Radiomics features were extracted and selected from three phases of CE-CT images, least absolute shrinkage and selection operator regression (LASSO) was used to select features, and the rad-score was calculated. CE-CT imaging and clinical features were selected using univariate and multivariate analyses, respectively. Three prediction models, including clinic-radiologic (CR) model, rad-score (R) model, and clinic-radiologic-radiomic (CRR) model, were developed and validated using logistic regression analysis. The performance of different models for predicting Ki-67 expression was evaluated using the area under the receiver operating characteristic curve (AUROC) and decision curve analysis (DCA). RESULTS: HCCs with high Ki-67 expression were more likely to have high serum α-fetoprotein levels (P = 0.041, odds ratio [OR] 2.54, 95% confidence interval [CI]: 1.04-6.21), non-rim arterial phase hyperenhancement (P = 0.001, OR 15.13, 95% CI 2.87-79.76), portal vein tumor thrombus (P = 0.035, OR 3.19, 95% CI: 1.08-9.37), and two-trait predictor of venous invasion (P = 0.026, OR 14.04, 95% CI: 1.39-144.32). The CR model achieved relatively good and stable performance compared with the R model (AUC, 0.805 [95% CI: 0.683-0.926] vs. 0.678 [95% CI: 0.536-0.839], P = 0.211; and 0.805 [95% CI: 0.657-0.953] vs. 0.667 [95% CI: 0.495-0.839], P = 0.135) in the internal and external validation sets. After combining the CR model with the R model, the AUC of the CRR model increased to 0.903 (95% CI: 0.849-0.956) in the training set, which was significantly higher than that of the CR model (P = 0.0148). However, no significant differences were found between the CRR and CR models in the internal and external validation sets (P = 0.264 and P = 0.084, respectively). CONCLUSIONS: Preoperative models based on clinical and CE-CT imaging features can be used to predict HCC with high Ki-67 expression accurately. However, radiomics cannot provide added value.

Jujuboside A inhibits oxidative stress damage and enhances immunomodulatory capacity of human umbilical cord mesenchymal stem cells through up-regulating IDO expression.

Impaired immunomodulatory capacity and oxidative stress are the key factors limiting the effectiveness of mesenchymal stem cell transplantation therapy. The present study was aimed to investigate the effects of jujuboside A (JuA) on the protective effect and immunomodulatory capacity of human umbilical cord mesenchymal stem cells (hUC-MSCs). Hydrogen peroxide was used to establish an oxidative damage model of hUC-MSCs, while PBMCs isolated from rats were used to evaluate the effect of JuA pre-treatment on the immunomodulatory capacity of hUC-MSCs. Furthermore, Hoechst 33258 staining, lactate dehydrogenase test, measurement of malondialdehyde, Western blot, high-performance liquid chromatography; and flow cytometry were performed. Our results indicated that JuA (25 µmol·L-1) promoted the proliferation of hUC-MSCs, but did not affect the differentiating capability of these cells. JuA pre-treatment inhibited apoptosis, prevented oxidative damage, and up-regulated the protein expression of nuclear factor-erythroid factor 2-related factor 2 and heme oxygenase 1 in hUC-MSCs in which oxidative stress was induced with H2O2. In addition, JuA pre-treatment enhanced the inhibitory effect of hUC-MSCs against abnormally activated PBMCs, which was related to stimulation of the expression and activity of indoleamine 2,3-dioxygenase. In conclusion, our results demonstrate that JuA pre-treatment can enhance the survival and immunomodulatory ability through pathways related to oxidative stress, providing a new option for the improvement of hUC-MSCs in the clinical setting.

Insulin-like Growth Factor 2 Promotes Tissue-Specific Cell Growth, Proliferation and Survival during Development of Helicoverpa armigera.

During development, cells constantly undergo fate choices by differentiating, proliferating, and dying as part of tissue remodeling. However, we only begin to understand the mechanisms of these different fate choices. Here, we took the lepidopteran insect Helicoverpa armigera, the cotton bollworm, as a model to reveal that insulin-like growth factor 2 (IGF-2-like) prevented cell death by promoting cell growth and proliferation. Tissue remodeling occurs during insect metamorphosis from larva to adult under regulation by 20-hydroxyecdysone (20E), a steroid hormone. An unknown insulin-like peptide in the genome of H. armigera was identified as IGF-2-like by sequence analysis using human IGFs. The expression of Igf-2-like was upregulated by 20E. IGF-2-like was localized in the imaginal midgut during tissue remodeling, but not in larval midgut that located nearby. IGF-2-like spread through the fat body during fat body remodeling. Cell proliferation was detected in the imaginal midgut and some fat body cells expressing IGF-2-like. Apoptosis was detected in the larval midgut and some fat body cells that did not express IGF-2-like, suggesting the IGF-2-like was required for cell survival, and IGF-2-like and apoptosis were exclusive, pointing to a survival requirement. Knockdown of Igf-2-like resulted in repression of growth and proliferation of the imaginal midgut and fat body. Our results suggested that IGF-2-like promotes cell growth and proliferation in imaginal tissues, promoting cell death avoidance and survival of imaginal cells during tissue remodeling. It will be interesting to determine whether the mechanism of action of steroid hormones on insulin growth factors is conserved in other species.

Icarisid II rescues cognitive dysfunction via activation of Wnt/ß-catenin signaling pathway promoting hippocampal neurogenesis in APP/PS1 transgenic mice.

Restoring the compromised neurogenesis has been served as a potential strategy to rescue cognitive dysfunction of Alzheimer's disease (AD). In this study, we explored whether icarisid II (ICS II), a natural product possessing powerful neuroprotection, could recover the neurogenesis dysfunction of APP/PS1 mice, and investigated its underlying mechanisms. Our results showed that oral administration of ICS II could alleviate cognitive injuries of APP/PS1 mice, promote hippocampal neurogenesis, as well as stimulate Wnt/ß-catenin signal pathway confirmed by upregulated Wnt-3a, phosphorylated glycogen synthase kinase-3ß (p-GSK-3ß), and ß-catenin. ICS II also depressed mitochondrial fission evidenced by upregulated Mitofusin 1 (Mfn 1) and Mitofusin 2 (Mfn 2), and downregulated mitochondrial fission 1 protein (Fis 1), mitochondrial fission factor (Mff), and phosphorylated dynamin-related protein 1 (p-Drp 1). However, these effects of ICS II were blunted by XAV-939, an inhibitor of Wnt/ß-catenin signaling pathway. In summary, our findings revealed that ICS II could improve neurogenesis and inhibit mitochondrial fission via activation of the Wnt/ß-catenin signaling pathway, which contributed to cognitive function restoration of APP/PS1 mice. This study discovered a novel mechanism involving neurogenesis regulation underlying the therapeutic effects of ICS II against AD.

Jujuboside a promotes proliferation and neuronal differentiation of APPswe-overexpressing neural stem cells by activating Wnt/ß-catenin signaling pathway.

Mobilization of hippocampal neurogenesis has been considered as a potential strategy for the treatment of neurodegenerative diseases, including Alzheimer's disease (AD). In present study, we evaluated both the neuroprotective effects and the effects on the proliferation and differentiation of APP-overexpressing neural stem cells (APP-NSCs) by Jujuboside A (JuA) in vitro. Our results demonstrated that JuA (50 µM) decreased apoptosis and suppressed oxidative stress damage of APP-NSCs. JuA (50 µM) upregulated the secretion of brain-derived neurotrophic factor and promoted the proliferation and neuronal differentiation of APP-NSCs. Moreover, JuA (50 µM) upregulated Wnt-3a and ß-catenin protein expression, and enhanced the expression of downstream genes Ccnd1, Neurod1 and Prox1. However, XAV-939, an inhibitor of the Wnt/ß-catenin signaling pathway, inhibited these positive effects of JuA. Taken together, these findings suggest that JuA promote proliferation and neuronal differentiation of APP-NSCs partly by activating the Wnt/ß-catenin signaling pathway. We hope that this study will provide a viable strategy for the treatment of AD.

Subunit P60 of phosphatidylinositol 3-kinase promotes cell proliferation or apoptosis depending on its phosphorylation status.

The regulatory subunits (P60 in insects, P85 in mammals) determine the activation of the catalytic subunits P110 in phosphatidylinositol 3-kinases (PI3Ks) in the insulin pathway for cell proliferation and body growth. However, the regulatory subunits also promote apoptosis via an unclear regulatory mechanism. Using Helicoverpa armigera, an agricultural pest, we showed that H. armigera P60 (HaP60) was phosphorylated under insulin-like peptides (ILPs) regulation at larval growth stages and played roles in the insulin/ insulin-like growth factor (IGF) signaling (IIS) to determine HaP110 phosphorylation and cell membrane translocation; whereas, HaP60 was dephosphorylated and its expression increased under steroid hormone 20-hydroxyecdysone (20E) regulation during metamorphosis. Protein tyrosine phosphatase non-receptor type 6 (HaPTPN6, also named tyrosine-protein phosphatase corkscrew-like isoform X1 in the genome) was upregulated by 20E to dephosphorylate HaP60 and HaP110. 20E blocked HaP60 and HaP110 translocation to the cell membrane and reduced their interaction. The phosphorylated HaP60 mediated a cascade of protein phosphorylation and forkhead box protein O (HaFOXO) cytosol localization in the IIS to promote cell proliferation. However, 20E, via G protein-coupled-receptor-, ecdysone receptor-, and HaFOXO signaling axis, upregulated HaP60 expression, and the non-phosphorylated HaP60 interacted with phosphatase and tensin homolog (HaPTEN) to induce apoptosis. RNA interference-mediated knockdown of HaP60 and HaP110 in larvae repressed larval growth and apoptosis. Thus, HaP60 plays dual functions to promote cell proliferation and apoptosis by changing its phosphorylation status under ILPs and 20E regulation, respectively.

The steroid hormone 20-hydroxyecdysone counteracts insulin signaling via insulin receptor dephosphorylation.

The insulin receptor (INSR) binds insulin to promote body growth and maintain normal blood glucose levels. While it is known that steroid hormones such as estrogen and 20-hydroxyecdysone counteract insulin function, the molecular mechanisms responsible for this attenuation remain unclear. In the present study, using the agricultural pest lepidopteran Helicoverpa armigera as a model, we proposed that the steroid hormone 20-hydroxyecdysone (20E) induces dephosphorylation of INSR to counteract insulin function. We observed high expression and phosphorylation of INSR during larval feeding stages that decreased during metamorphosis. Insulin upregulated INSR expression and phosphorylation, whereas 20E repressed INSR expression and induced INSR dephosphorylation in vivo. Protein tyrosine phosphatase 1B (PTP1B, encoded by Ptpn1) dephosphorylated INSR in vivo. PTEN (phosphatase and tensin homolog deleted on chromosome 10) was critical for 20E-induced INSR dephosphorylation by maintaining the transcription factor Forkhead box O (FoxO) in the nucleus, where FoxO promoted Ptpn1 expression and repressed Insr expression. Knockdown of Ptpn1 using RNA interference maintained INSR phosphorylation, increased 20E production, and accelerated pupation. RNA interference of Insr in larvae repressed larval growth, decreased 20E production, delayed pupation, and accumulated hemolymph glucose levels. Taken together, these results suggest that a high 20E titer counteracts the insulin pathway by dephosphorylating INSR to stop larval growth and accumulate glucose in the hemolymph.

Regulating the Topologies of Zirconium-Organic Frameworks for a Crystal Sponge Applicable to Inorganic Matter.

Metal-organic frameworks (MOFs) have been explored as crystal sponges (CSs) to organic substrates, but attention had rarely been paid to inorganic substrates. Herein, hierarchical zirconium-based MOFs exhibiting different topological structures had been fabricated by modulating the functional groups of the V-shaped linkers, including a new 4-fold-interpenetrating one, which displays a great performance as a CS applicable to inorganic matter (I2 and ReO4-) even in the extreme conditions.

Facile fabrication of CuxSy/Carbon composites using lignosulfonate for efficient palladium recovery under strong acidic conditions.

The recovery of noble metals from aqueous systems is of great significance for constructing sustainable framework of modern industry yet remains challenging. Herein, CuxSy/Carbon composites with superior thermal stability and adsorption capacity were successfully synthesized via one-pot hydrothermal method using lignosulfonate as dual role of raw materials. The optimal synthesis conditions were investigated via tailoring the temperature and the mass ratio of reagents. The morphologies and physical properties of the composites were characterized by scanning electron microscope (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). The surface chemistry was analyzed by Zeta potential analysis, Brunauer-Emmet-Teller (BET), and X-ray photoelectron spectroscopy (XPS). The Langmuir model and the pseudo-second-order model well described the adsorption of Pd(II) and Pd(IV) delivered by fabricated composites. The adsorption capacity obtained from Langmuir isotherm model towards Pd(IV) was 114 mg/g and Pd(II) was 101 mg/g, respectively. More importantly, the adsorbed palladium species could be desorbed with hydrochloric acid and thiourea, which suggested good durability and recycling performance of the typical composite. This work might provide a new guidance for the utilization of lignin or its derivatives and enriched the research in the field of noble metal recovery.

Crystallographic Visualization of Postsynthetic Nickel Clusters into Metal-Organic Framework.

Postsynthetic metalation (PSM) has been employed as a robust method for the postsynthetic modification of metal-organic frameworks (MOFs). However, the lack of relevant information that can be obtained for the postsynthetically introduced metallic ions has hindered the development of PSM applications. Thanks to the advancement in single-crystal X-ray diffraction (SCXRD) technology, there have been a few recent examples in which successful postsynthetic introduction of single metal ions into MOFs occurred at the defined chelating sites. These works have provided useful explanations about the complicated host-guest chemistry involved in PSMs. On the other hand, there are only limited examples with crystallographic snapshots of the postsynthetic installation of metal clusters into the pores of MOFs using an ordinary SCXRD due to the loss of crystallinity of parent matrix during the PSM process. Herein, by the careful selection of starting materials and controlling the reaction conditions, we report the first crystallographic visualization of metal clusters inserted into Zr-based MOFs via PSM. The structural advantages of the parent Zr-MOF, which are inherited from the stable Zr6 cluster and triazole-containing dicarboxylate ligand, ensure both the preservation of high crystallinity and the presence of flexible coordination sites for PSM. Furthermore, PSM of metal clusters in a MOF pore space enhances stability of the final samples while also imparting the functionality of a successful catalyst toward ethylene dimerization reaction. The related construction ideas and structural information detailed in this work can help lay the foundation for further advancements using the postmodification of MOFs as well as open new doors for the utilization of SCXRD technology in the field of MOFs.

The steroid hormone 20-hydroxyecdysone binds to dopamine receptor to repress lepidopteran insect feeding and promote pupation.

Holometabolous insects stop feeding at the final larval instar stage and then undergo metamorphosis; however, the mechanism is unclear. In the present study, using the serious lepidopteran agricultural pest Helicoverpa armigera as a model, we revealed that 20-hydroxyecdysone (20E) binds to the dopamine receptor (DopEcR), a G protein-coupled receptor, to stop larval feeding and promote pupation. DopEcR was expressed in various tissues and its level increased during metamorphic molting under 20E regulation. The 20E titer was low during larval feeding stages and high during wandering stages. By contrast, the dopamine (DA) titer was high during larval feeding stages and low during the wandering stages. Injection of 20E or blocking dopamine receptors using the inhibitor flupentixol decreased larval food consumption and body weight. Knockdown of DopEcR repressed larval feeding, growth, and pupation. 20E, via DopEcR, promoted apoptosis; and DA, via DopEcR, induced cell proliferation. 20E opposed DA function by repressing DA-induced cell proliferation and AKT phosphorylation. 20E, via DopEcR, induced gene expression and a rapid increase in intracellular calcium ions and cAMP. 20E induced the interaction of DopEcR with G proteins αs and αq. 20E, via DopEcR, induced protein phosphorylation and binding of the EcRB1-USP1 transcription complex to the ecdysone response element. DopEcR could bind 20E inside the cell membrane or after being isolated from the cell membrane. Mutation of DopEcR decreased 20E binding levels and related cellular responses. 20E competed with DA to bind to DopEcR. The results of the present study suggested that 20E, via binding to DopEcR, arrests larval feeding and promotes pupation.

Structural tuning of zinc-porphyrin frameworks via auxiliary nitrogen-containing ligands towards selective adsorption of cationic dyes.

Three metal-organic frameworks have been synthesized by using N-containing ligands and meso-tetra(4-carboxyphenyl)porphyrin, which all exhibit distinct selective adsorption capacities toward various organic dyes, illustrating the most important influence of the structural tuning.

Unconventional Method for Fabricating Valence Tautomeric Materials: Integrating Redox Center within a Metal-Organic Framework.

Due to the structural advantages displayed by Metal-Organic Frameworks (MOFs), integrating Valence Tautomerism (VT) systems within MOFs could be an effective strategy in order to break through the constraints of the traditional ones. Herein, we report the first successful integration of a VT system into a MOF termed VT-MOF-1. The structural characteristics of VT-MOF-1, such as dinuclear cobalt-catechol clusters and solvent-accessible pores, are both innovative and novel, potentially yielding new vitality within VT field. In addition, VT-MOF-1 exhibits specific behaviors responsive to temperature and different solvent molecules as n-butanol, tert-butanol, and isopropyl alcohol. The entropy values and configurations of the solvent molecules might be responsible for the tunable sensing behaviors.

Facile Fabrication of a Multifunctional Metal-Organic Framework-based Sensor Exhibiting Exclusive Solvochromic Behaviors toward Ketone Molecules.

To probe the efficient strategy for preparing a multifunctional sensing material, the facile synthesis strategies and successful examples are urgently required. Through the utilization of a hexadentate ligand derived from cyclotriphosphazene, which displays spiral configurations and multiple connection modes, a novel metal-organic framework (MOF) was constructed via one-step synthesis from low-cost raw materials. The presence of multiple interaction sites decorating the helical channels of the reported MOF gives rise to exclusive solvochromic-sensing behavior for small ketone molecules such as acetone, acetophenone, and 2,5-diketohexane. Additionally, the helical structure of a manganese-carboxylate chain allows for the pore volume not only be available for the adsorption of large organic molecules but also enables the enantiopure selective separation of 1-phenylethanol (ee 35.99 %). Furthermore, the structural analysis of the acetophenone-encapsulated sample allowed the solvochromic mechanism to be elucidated, which should be ascribed to the strong hydrogen-bonding interaction between the guest molecules and specific sites on a host matrix. The experimental results have not only clearly manifested the vital role of starting materials of MOFs, including the connection modes and spatial configuration, but also have provided very valuable insight for the future assembly of novel multifunctional sensing materials.

Deformation Monitoring of Metro Tunnel with a New Ultrasonic-Based System.

With the rapid construction of metro tunnels in many metropolises, a fast and convenient solution to capture tunnel deformation is desired by civil engineers. This contribution reports an automatic and wireless tunnel deformation monitoring system using ultrasonic transducers. A processing algorithm of the redundant ultrasonic information (RUI) approach is proposed to improve measurement accuracy. The feasibility of this tunnel deformation monitoring method is carefully examined with various probe angles, distances, and surrounding temperature variations. The results indicate that high accuracy can be achieved with different coefficients for various probe angles and sensor distances, as well as temperatures. In addition, a physical tunnel model was fabricated to verify the new processing algorithm of the RUI approach for a wireless tunnel deformation sensing system. The test results reveal that average measurement errors decreased from 7% to 3.75% using the RUI approach. Therefore, it can be concluded that the proposed approach is well suited to the automatic detection of critical conditions such as large deformation events in metro tunnels.

Effects of Selenium on Fusarium Growth and Associated Fermentation Products and the Relationship with Chondrocyte Viability.

This study determined the effects of selenium on the growth of Fusarium strains and the effects of products extracted from the fungal cultures on relevant indicators of chondrocytes injury. The results showed that selenium supplementation resulted in differential effects on the mycelial growth of the strains. Levels of the chondrocyte injury indicators, including cell viability, proteoglycan and type II collagen contents and their mRNA expressions, were all reduced to varying degrees when the chondrocytes were incubated with fermentation extracts, the inhibitory effect varied depending on selenium content supplemented to fungal culture media. The results indicated that certain chain relations existed between the content of selenium in the environment, the production of some metabolites by fungi, and the occurrence of chondrocyte damage. The extent of this relationship and the role it plays in Kaschin-Beck disease pathogenesis merit further study.