Search

Trehalose has an important function for alleviating various abiotic stress in plants. Nevertheless, the functional and evolutionary characteristics of trehalose biosynthesis genes in mangrove plants is not documented. Here, using typical mangrove Avicennia marina, we found the trehalose content decreased in the roots and leaves and T6P increased significantly in the leaves under tidal submergence. Then, the basic physicochemical properties and gene structure of trehalose biosynthesis genes (AmTPS and AmTPP), and the conserved domain and motifs of AmTPS and AmTPP proteins were analyzed. The collinearity analysis and Ka/Ks values indicated that AmTPS and AmTPP are evolutionarily conserved. Tissue-specific expression profiling showed that most AmTPS and AmTPP genes have tissue specificity. RNA-Seq analysis showed that five AmTPS genes were markedly up-regulated in A. marina treated with tidal submergence. Subcellular localization analysis revealed three genes including AmTPS10B, AmTPS11A and AmTPS11C out of these five up-regulated AmTPS genes work in plasma membrane, cytoplasm and nucleus. Finally, integrative analysis of bioinformatics and RNA-Seq analysis were performed to excavate transcription factors that may regulate AmTPS and AmTPP genes in A. marina response to submergence. Taken together, these findings provide new insights into the response to tidal submergence in A. marina at the aspect of trehalose., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Hai-Lei Zheng reports financial support was provided by National Natural Science Foundation of China. Hai-Lei Zheng reports financial support was provided by National Key Research and Development Program of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Mangroves are dominant flora of intertidal zones along tropical and subtropical coastline around the world that offer important ecological and economic value. Recently, the genomes of mangroves have been decoded, and massive omics data were generated and deposited in the public databases. Reanalysis of multi-omics data can provide new biological insights excluded in the original studies. However, the requirements for computational resource and lack of bioinformatics skill for experimental researchers limit the effective use of the original data. To fill this gap, we uniformly processed 942 transcriptome data, 386 whole-genome sequencing data, and provided 13 reference genomes and 40 reference transcriptomes for 53 mangroves. Finally, we built an interactive web-based database platform MangroveDB (https://github.com/Jasonxu0109/MangroveDB), which was designed to provide comprehensive gene expression datasets to facilitate their exploration and equipped with several online analysis tools, including principal components analysis, differential gene expression analysis, tissue-specific gene expression analysis, GO and KEGG enrichment analysis. MangroveDB not only provides query functions about genes annotation, but also supports some useful visualization functions for analysis results, such as volcano plot, heatmap, dotplot, PCA plot, bubble plot, population structure, and so on. In conclusion, MangroveDB is a valuable resource for the mangroves research community to efficiently use the massive public omics datasets., (© 2024 John Wiley & Sons Ltd.)

Cadmium (Cd) pollution poses a significant ecological risk to mangrove ecosystems. Trehalose has excellent potential to mitigate the adverse effects of heavy metals. Unfortunately, the mechanisms related to trehalose-mediated heavy metal tolerance in plants remain elusive. In the present study, we firstly found that Cd induced the accumulation of trehalose and the differential expression of trehalose biosynthesis genes in the roots of mangrove plant Avicennia marina. Then, we found that the application of exogenous trehalose could alleviate the negative effects of Cd on A. marina by phenotypic observation. In addition, photosynthetic parameters and cellular ultrastructure analyses demonstrated that exogenous trehalose could improve the photosynthesis and stabilize the chloroplast and nuclear structure of the leaves of A. marina. Besides, exogenous trehalose could inhibit the Cd 2+ influx from the root to reduce the Cd 2+ content in A. marina. Subsequently, substrate sensitivity assay combined with ion uptake analysis using yeast cells showed that several trehalose biosynthesis genes may have a regulatory function for Cd 2+ transport. Finally, we further identified a positive regulatory factor, AmTPS6, which enhances the Cd tolerance in transgenic Arabidopsis thaliana. Taken together, these findings provide new understanding to the mechanism of Cd tolerance in mangrove A. marina at trehalose aspect and a theoretical basis for the conservation of mangroves in coastal wetlands., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Nitriles (R-C≡N) have been investigated since the late eighteenth century and are ubiquitous encounters in organic and inorganic syntheses. In contrast, heavier nitriles, which contain the heavier analogues of carbon and nitrogen, are sparsely investigated species. Here we report the synthesis and isolation of a phosphino-silylene featuring an N-heterocyclic carbene-phosphinidene and a highly sterically demanding silyl group as substituents. Due to its unique structural motif, it can be regarded as a Lewis base-stabilized heavier nitrile. The Si-P bond displays multiple bond character and a bent R-Si-P geometry, the latter indicating fundamental differences between heavier and classical nitriles. In solution, a quantitative unusual rearrangement to a phosphasilenylidene occurs. This rearrangement is consistent with theoretical predictions of rearrangements from heavier nitriles to heavier isonitriles. Our preliminary reactivity studies revealed that both isomers exhibit highly nucleophilic silicon centres capable of oxidative addition and coordination to iron tetracarbonyl., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Herein, we report the reactivity of N-heterocyclic carbene stabilized silylene-phosphinidene IDippPSi(TMS) 2 SiTol 3 (IDipp = 1,3-bis(2,6-diisopropylphenyl)-imidazolin-2-ylidene) with ammonia, which results in an intermolecular 1,5-hydroamination and dearomatization of the NHC wingtip. DFT calculations reveal an unprecedented mechanism involving ammonia coordination to the silicon center, Meisenheimer-type complex formation, and a proton abstraction by the dearomatized aryl moiety.

AMP-activated protein kinase (AMPK), a crucial regulatory kinase, monitors energy levels, conserving ATP and boosting synthesis in low-nutrition, low-energy states. Its sensitivity links microenvironmental changes to cellular responses. As the primary support structure and endocrine organ, the maintenance, and repair of bones are closely associated with the microenvironment. While a series of studies have explored the effects of specific microenvironments on bone, there is lack of angles to comprehensively evaluate the interactions between microenvironment and bone cells, especially for bone marrow mesenchymal stem cells (BMMSCs) which mediate the differentiation of osteogenic lineage. It is noteworthy that accumulating evidence has indicated that AMPK may serve as a hub between BMMSCs and microenvironment factors, thus providing a new perspective for us to understand the biology and pathophysiology of stem cells and bone. In this review, we emphasize AMPK's pivotal role in bone microenvironment modulation via ATP, inflammation, reactive oxygen species (ROS), calcium, and glucose, particularly in BMMSCs. We further explore the use of AMPK-activating drugs in the context of osteoarthritis and osteoporosis. Moreover, building upon the foundation of AMPK, we elucidate a viewpoint that facilitates a comprehensive understanding of the dynamic relationship between the microenvironment and bone homeostasis, offering valuable insights for prospective investigations into stem cell biology and the treatment of bone diseases., (© 2024 Wiley Periodicals LLC.)

Alcoholic liver disease (ALD) caused by chronic alcohol abuse involves complex processes from steatosis to fibrosis, cirrhosis, and hepatocellular carcinoma, posing a global health issue. Bromodomain protein 4 (BRD4) typically serves as a "reader" modulating the functions of transcription factors involved in various biological processes and disease progression. However, the specific mechanisms underlying alcoholic liver injury remain unclear. In this study, we detected aberrant BRD4 expression in the alcohol-induced ALD mouse model of chronic and binge ethanol feeding developed by the National Institute on Alcohol Abuse and Alcoholism, consistent with the in vitro results in Aml-12 mouse hepatocytes. Blocking and inhibiting BRD4 restored the impaired autophagic flux and lysosomal functions in alcohol-treated Aml-12 cells, whereas BRD4 overexpression reduced the expression levels of autophagy marker and lysosomal genes. Furthermore, mouse BRD4 knockdown, mediated by a short hairpin RNA carried by the adeno-associated virus serotype 8, significantly attenuated the alcohol-induced hepatocyte damage, including lipid deposition and inflammatory cell infiltration. Mechanistically, BRD4 overexpression in alcoholic liver injury inhibited the expression of sirtuin (SIRT)1 in Aml-12 cells. Chromatin immunoprecipitation and dual-luciferase reporter assays revealed that BRD4 functions as a transcription factor and suppressor, actively binding to the SIRT1 promoter region and inhibiting its transcription. SIRT1 activated autophagy, which was suppressed in alcoholic liver injury via Beclin1 deacetylation. In conclusion, our study revealed that BRD4 negatively regulated the SIRT1/Beclin1 axis and that its deficiency alleviated alcohol-induced liver injury in mice, thus providing a new strategy for ALD treatment., (Copyright © 2024. Published by Elsevier Inc.)

Kuey teow is one of the delicacies of Guangdong, China and is a gluten-free noodle dish made from rice. It has a short storage period and extending the shelf life by quick freezing induces quality deterioration due to temperature fluctuations. To improve its freeze-thaw frozen storage quality, this paper examined the effects of hydroxypropyl corn starch (HCS), guar gum (GG), and compound phosphates (CP) on the quality of quick-frozen kuey teow during freeze-thaw cycles. The mechanism was investigated by identifying changes in the moisture status, aging degree of the starch, and textural and cooking characteristics. The results showed that all three additions improved the toughness, chewiness and steaming characteristics of the kuey teow, with CP significantly enhancing chewiness. XRD and FTIR results revealed that GG more significantly inhibited the decrease of starch crystallinity, while HCS inhibited starch aging. GG, HCS and CP all improved the hydration characteristics and water holding capacity of rice starch. GG enhances the ability of starch to bind more tightly with water, resulting in a more uniform water distribution and a more continuous and tight structure of the kuey teow. This study will provide a theoretical basis for compounding and optimizing the quick-freezing of kuey teow., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Mitotic catastrophe (MC), which occurs under dysregulated mitosis, represents a fascinating tactic to specifically eradicate tumor cells. Whether pyroptosis can be a death form of MC remains unknown. Proteasome-mediated protein degradation is crucial for M-phase. Bortezomib (BTZ), which inhibits the 20S catalytic particle of proteasome, is approved to treat multiple myeloma and mantle cell lymphoma, but not solid tumors due to primary resistance. To date, whether and how proteasome inhibitor affected the fates of cells in M-phase remains unexplored. Here, we show that BTZ treatment, or silencing of PSMC5, a subunit of 19S regulatory particle of proteasome, causes G2- and M-phase arrest, multi-polar spindle formation, and consequent caspase-3/GSDME-mediated pyroptosis in M-phase (designated as mitotic pyroptosis). Further investigations reveal that inhibitor of WEE1/PKMYT1 (PD0166285), but not inhibitor of ATR, CHK1 or CHK2, abrogates the BTZ-induced G2-phase arrest, thus exacerbates the BTZ-induced mitotic arrest and pyroptosis. Combined BTZ and PD0166285 treatment (named BP-Combo) selectively kills various types of solid tumor cells, and significantly lessens the IC50 of both BTZ and PD0166285 compared to BTZ or PD0166285 monotreatment. Studies using various mouse models show that BP-Combo has much stronger inhibition on tumor growth and metastasis than BTZ or PD0166285 monotreatment, and no obvious toxicity is observed in BP-Combo-treated mice. These findings disclose the effect of proteasome inhibitors in inducing pyroptosis in M-phase, characterize pyroptosis as a new death form of mitotic catastrophe, and identify dual inhibition of proteasome and WEE family kinases as a promising anti-cancer strategy to selectively kill solid tumor cells., (© 2024. The Author(s).)

Breast cancer, the most prevalent malignancy in women, often progresses to bone metastases, especially in older individuals. Dormancy, a critical aspect of bone-metastasized breast cancer cells (BCCs), enables them to evade treatment and recur. This dormant state is regulated by bone marrow mesenchymal stem cells (BMMSCs) through the secretion of various factors, including those associated with senescence. However, the specific mechanisms by which BMMSCs induce dormancy in BCCs remain unclear. To address this gap, a bone-specific senescence-accelerated murine model, SAMP6, was utilized to minimize confounding systemic age-related factors. Confirming senescence-accelerated osteoporosis, distinct BMMSC phenotypes were observed in SAMP6 mice compared to SAMR1 counterparts. Notably, SAMP6-BMMSCs exhibited premature senescence primarily due to telomerase activity loss and activation of the p21 signaling pathway. Furthermore, the effects of conditioned medium (CM) derived from SAMP6-BMMSCs versus SAMR1-BMMSCs on BCC proliferation were examined. Intriguingly, only CM from SAMP6-BMMSCs inhibited BCC proliferation by upregulating p21 expression in both MCF-7 and MDA-MB-231 cells. These findings suggest that the senescence-associated secretory phenotype (SASP) of BMMSCs suppresses BCC viability by inducing p21, a pivotal cell cycle inhibitor and tumor suppressor. This highlights a heightened susceptibility of BCCs to dormancy in a senescent microenvironment, potentially contributing to the increased incidence of breast cancer bone metastasis and recurrence observed with aging., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: In clear cell renal cell carcinoma (ccRCC), the role of Regulatory T cells (Treg cells) as prognostic and immunotherapy response predictors is not fully explored., Methods: Analyzing renal clear cell carcinoma datasets from TISCH, TCGA, and GEO, we focused on 8 prognostic Treg genes to study patient subtypes in ccRCC. We assessed Treg subtypes in relation to patient prognosis, tumor microenvironment, metabolism. Using Cox regression and principal component analysis, we devised Treg scores for individual patient characterization and explored the molecular role of C1QL1, a critical gene in the Treg model, through in vivo and in vitro studies., Results: Eight Treg-associated prognostic genes were identified, classifying ccRCC patients into cluster A and B. Cluster A patients showed poorer prognosis with distinct clinical and molecular profiles, potentially benefiting more from immunotherapy. Low Treg scores correlated with worse outcomes and clinical progression. Low scores also suggested that patients might respond better to immunotherapy and targeted therapies. In ccRCC, C1QL1 knockdown reduced tumor proliferation and invasion via NF-kb-EMT pathways and decreased Treg cell infiltration, enhancing immune efficacy., Conclusions: The molecular subtype and Treg score in ccRCC, based on Treg cell marker genes, are crucial in personalizing ccRCC treatment and underscore C1QL1's potential as a tumor biomarker and target for immunotherapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

We report a galactosyl diiodo-BODIPY-based nanoparticles as type-I photosensitizer (PS) with high water solubility for HepG2 cell targeted photodynamic therapy. Functionalized galactoside and glucoside were introduced into diiodo-BODIPY to obtain BP1 and BP2, respectively. The glycolyl PSs could self-assemble to form the nanoparticles BP1-NP and BP2-NP with red-shifted near-infrared (NIR) absorption and fluorescence at 682 nm and 780 nm, as well as excellent chemo- and photo-stability. In comparison to the monomer in DMSO, the aggregated photosensitizers in the nanoparticles enabled the sensitization of oxygen to superoxide (O 2 ˙ - ) through a type-I process, while repressing the generation of singlet oxygen ( 1 O 2 ) through a type-II process. The galactosyl-modified BP1-NPs could target and concentrate on HepG2 cells, subsequently generating O 2 ˙ - and 1 O 2 to trigger cell death under 660 nm light irradiation. This work provides an efficient strategy for the construction of glycoside-recognized type-I photosensitizers for tumor cell imaging and photodynamic therapy., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Acute liver injury (ALI) is a complex, life-threatening inflammatory liver disease, and persistent liver damage leads to rapid decline and even failure of liver function. However, the pathogenesis of ALI is still not fully understood, and no effective treatment has been discovered. Recent evidence shows that many circular RNAs (circRNAs) are associated with the occurrence of liver diseases. In this study we investigated the mechanisms of occurrence and development of ALI in lipopolysaccharide (LPS)-induced ALI mice. We found that expression of the circular RNA circDcbld2 was significantly elevated in the liver tissues of ALI mice and LPS-treated RAW264.7 cells. Knockdown of circDcbld2 markedly alleviates LPS-induced inflammatory responses in ALI mice and RAW264.7 cells. We designed and synthesized a series of hesperidin derivatives for circDcbld2, and found that hesperetin derivative 2a (HD-2a) at the concentrations of 2, 4, 8 μM effectively inhibited circDcbld2 expression in RAW264.7 cells. Administration of HD-2a (50, 100, 200 mg/kg. i.g., once 24 h in advance) effectively relieved LPS-induced liver dysfunction and inflammatory responses. RNA sequencing analysis revealed that the anti-inflammatory and hepatoprotective effects of HD-2a were mediated through downregulating circDcbld2 and suppressing the JAK2/STAT3 pathway. We conclude that HD-2a downregulates circDcbld2 to inhibit the JAK2/STAT3 pathway, thereby inhibiting the inflammatory responses in ALI. The results suggest that circDcbld2 may be a potential target for the prevention and treatment of ALI, and HD-2a may have potential as a drug for the treatment of ALI., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Understanding strongly correlated quantum materials, such as high-T_{c} superconductors, iron-based superconductors, and twisted bilayer graphene systems, remains as one of the outstanding challenges in condensed matter physics. Quantum simulation with ultracold atoms in particular optical lattices, which provide orbital degrees of freedom, is a powerful tool to contribute new insights to this endeavor. Here, we report the experimental realization of an unconventional Bose-Einstein condensate of ^{87}Rb atoms populating degenerate p orbitals in a triangular optical lattice, exhibiting remarkably long coherence times. Using time-of-flight spectroscopy, we observe that this state spontaneously breaks the rotational symmetry and its momentum spectrum agrees with the theoretically predicted coexistence of exotic stripe and loop-current orders. Like certain strongly correlated electronic systems with intertwined orders, such as high-T_{c} cuprate superconductors, twisted bilayer graphene, and the recently discovered chiral density-wave state in kagome superconductors AV_{3}Sb_{5} (A=K, Rb, Cs), the newly demonstrated quantum state, in spite of its markedly different energy scale and the bosonic quantum statistics, exhibits multiple symmetry breakings at ultralow temperatures. These findings hold the potential to enhance our comprehension of the fundamental physics governing these intricate quantum materials.

Mangrove Avicennia marina has the importantly potential for cadmium (Cd) pollution remediation in coastal wetlands. Unfortunately, the molecular mechanisms and transporter members for Cd uptake by the roots of A. marina are not well documented. In this study, photosynthetic and phenotypic analysis indicated that A. marina is particularly tolerant to Cd. The content and flux analysis indicated that Cd is mainly retained in the roots, with greater Cd influx in fine roots than that in coarse roots, and higher Cd influx in the root meristem zone as well. Using transcriptomic analysis, a total of 5238 differentially expressed genes were identified between the Cd treatment and control group. Moreover, we found that 54 genes were responsible for inorganic ion transport. Among these genes, AmHMA2, AmIRT1, and AmPCR2 were localized in the plasma membrane and AmZIP1 was localized in both plasma membrane and cytoplasm. All above gene encoding transporters showed significant Cd transport activities using function assay in yeast cells. In addition, the overexpression of AmZIP1 or AmPCR2 in Arabidopsis improved the Cd tolerance of transgenic plants. This is particularly significant as it provides insight into the molecular mechanism for Cd uptake by the roots of mangrove plants and a theoretical basis for coastal wetland phytoremediation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aims: This study aimed to elucidate the role of Interleukin-11 (IL-11) in hepatic fibrosis (HF) and its potential as a therapeutic target for HF treatment., Materials and Methods: We investigated IL-11 expression in patients with varying degrees of liver injury through ELISA and immunohistochemistry. A CCl 4 -induced HF mouse model was constructed to study IL-11 expression and cell apoptosis using Western blotting (WB) and other techniques. The expression of IL-11 was silenced using rAAV8 in the mouse model. In vitro stimulation of hepatic stellate cells (LX-2) with TGF-β1, and of LO-2 cells with exogenous IL-11, were performed. Cell supernatants of TGF-β1-stimulated LX-2 were used to culture LO-2 cells, with apoptosis monitored via flow cytometry and WB., Key Findings: Increased IL-11 levels were observed in patients and the HF mouse model, with silencing reducing IL-11 expression. In vitro experiments revealed increased endogenous IL-11 in TGF-β1-stimulated LX-2 cells and an increase in apoptotic index, IL11RA, and gp130 in IL-11-stimulated LO-2 cells. Cell apoptosis was reduced in the siRNA/IL11, siRNA/IL11RA, and anti-IL11 groups. WB and immunohistochemistry results showed upregulated p-JNK, p-ERK, and p-P53 expressions in the CCl 4 -induced HF mouse model and IL-11-treated LO-2 cells., Significance: Our findings suggest IL-11 enhances LX-2 cell activation and proliferation, and promotes LO-2 cell apoptosis through JNK/ERK signaling pathways. This suggests that targeting IL-11 secretion may serve as a potential therapeutic strategy for HF, providing a foundation for its clinical application in HF treatment., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

Soliton mode locking in high-Q microcavities provides a way to integrate frequency comb systems. Among material platforms, AlGaAs has one of the largest optical nonlinearity coefficients, and is advantageous for low-pump-threshold comb generation. However, AlGaAs also has a very large thermo-optic effect that destabilizes soliton formation, and femtosecond soliton pulse generation has only been possible at cryogenic temperatures. Here, soliton generation in AlGaAs microresonators at room temperature is reported for the first time, to the best of our knowledge. The destabilizing thermo-optic effect is shown to instead provide stability in the high-repetition-rate soliton regime (corresponding to a large, normalized second-order dispersion parameter D 2 /κ). Single soliton and soliton crystal generation with sub-milliwatt optical pump power are demonstrated. The generality of this approach is verified in a high-Q silica microtoroid where manual tuning into the soliton regime is demonstrated. Besides the advantages of large optical nonlinearity, these AlGaAs devices are natural candidates for integration with semiconductor pump lasers. Furthermore, the approach should generalize to any high-Q resonator material platform.

Thermal silica is a common dielectric used in all-silicon photonic circuits. Additionally, bound hydroxyl ions (Si-OH) can provide a significant component of optical loss in this material on account of the wet nature of the thermal oxidation process. A convenient way to quantify this loss relative to other mechanisms is through OH absorption at 1380 nm. Here, using ultra-high-quality factor (Q-factor) thermal-silica wedge microresonators, the OH absorption loss peak is measured and distinguished from the scattering loss baseline over a wavelength range from 680 nm to 1550 nm. Record-high on-chip resonator Q-factors are observed for near-visible and visible wavelengths, and the absorption limited Q-factor is as high as 8 billion in the telecom band. Hydroxyl ion content level around 2.4 ppm (weight) is inferred from both Q measurements and by secondary ion mass spectroscopy (SIMS) depth profiling.

Hepatic fibrosis (HF) is a reversible wound-healing response characterized by excessive extracellular matrix (ECM) deposition and secondary to persistent chronic injury. Bromodomain protein 4 (BRD4) commonly functions as a "reader" to regulate epigenetic modifications involved in various biological and pathological events, but the mechanism of HF remains unclear. In this study, we established a CCl 4 -induced HF model and spontaneous recovery model in mice and found aberrant BRD4 expression, which was consistent with the results in human hepatic stellate cells (HSCs)- LX2 cells in vitro. Subsequently, we found that distriction and inhibition of BRD4 restrained TGFβ-induced trans-differentiation of LX2 cells into activated, proliferative myofibroblasts and accelerated apoptosis, and BRD4 overexpression blocked MDI-induced LX2 cells inactivation and promoted the proliferation and inhibited apoptosis of inactivated cells. Additionally, adeno-associated virus serotype 8-loaded short hairpin RNA-mediated BRD4 knockdown in mice significantly attenuated CCl 4 -induced fibrotic responses including HSCs activation and collagen deposition. Mechanistically, BRD4 deficiency inhibited PLK1 expression in activated LX2 cells, and ChIP and Co-IP assays revealed that BRD4 regulation of PLK1 was dependent on P300-mediated acetylation modification for H3K27 on the PLK1 promoter. In conclusion, BRD4 deficiency in the liver alleviates CCl 4 -induced HF in mice, and BRD4 participates in the activation and reversal of HSCs through positively regulating the P300/H3K27ac/PLK1 axis, providing a potential insight for HF therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Hexagonal optical lattices offer a tunable platform to study exotic orbital physics in solid state materials. Here, we present a versatile high-precision scheme to implement a hexagonal optical lattice potential, which is engineered by overlapping two independent triangular optical sublattices generated by laser beams with slightly different wavelengths around 1064 nm. This enables us to precisely control the detailed structure of the hexagonal lattice by adjusting the relative position and the relative lattice depth of the two triangular optical sublattices. Taking advantage of the sensitive dependence of the second Bloch band on small lattice deformations, we propose a strategy to optimize the optical lattice geometry with an extremely high precision. This method can also be extended to other lattice configurations involving more than two sublattices. Our work provides the experimental requirements in the search for novel orbital physics of ultracold atoms, for example, in the flat p-band of the hexagonal optical lattice.

The roles of micropeptides in cell cycle regulation and cancer development remain largely unknown. Here we found that a micropeptide STMP1 (small transmembrane protein 1) was up-regulated in multiple malignancies including hepatocellular carcinoma (HCC), and its high level was associated with short recurrence-free survival of HCC patients. Gain- and loss-of-function analyses revealed that STMP1 accelerated cell proliferation and clonogenicity in vitro and tumor growth in vivo, and silencing STMP1 blocked G1/S transition. Mechanistically, STMP1 promoted the mRNA and protein levels of CCNE2, CDK2, and E2F1. STMP1 was localized in the inner membrane of mitochondria and interacted with mitochondrial complex IV and then enhanced its activity. Moreover, treatment with the mitochondrial complex IV inhibitor tetrathiomolybdate dramatically abrogated the promoting effect of STMP1 on cell proliferation and the expression of cyclin E2, CDK2, and E2F1. These results suggest that STMP1 may promote G1/S transition and cell proliferation by enhancing mitochondrial complex IV activity, which highlights STMP1 as a new regulator of the cell cycle and a potential target for anti-cancer therapy., Competing Interests: Declaration of interests The authors declare no conflict of interest., (Copyright © 2022 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Cu-based metal-organic frameworks have attracted much attention for electrocatalytic CO 2 reduction, but they are generally instable and difficult to control the product selectivity. We report flexible Cu(I) triazolate frameworks as efficient, stable, and tunable electrocatalysts for CO 2 reduction to C 2 H 4 /CH 4 . By changing the size of ligand side groups, the C 2 H 4 /CH 4 selectivity ratio can be gradually tuned and inversed from 11.8 : 1 to 1 : 2.6, giving C 2 H 4 , CH 4 , and hydrocarbon selectivities up to 51 %, 56 %, and 77 %, respectively. After long-term electrocatalysis, they can retain the structures/morphologies without formation of Cu-based inorganic species. Computational simulations showed that the coordination geometry of Cu(I) changed from triangular to tetrahedral to bind the reaction intermediates, and two adjacent Cu(I) cooperated for C-C coupling to form C 2 H 4 . Importantly, the ligand side groups controlled the catalyst flexibility by the steric hindrance mechanism, and the C 2 H 4 pathway is more sensitive than the CH 4 one., (© 2022 Wiley-VCH GmbH.)

Background: Peripheral nerve inflammation or lesion can affect contralateral healthy structures, and thus result in mirror-image pain. Supraspinal structures play important roles in the occurrence of mirror pain. The anterior cingulate cortex (ACC) is a first-order cortical region that responds to painful stimuli. In the present study, we systematically investigate and compare the neuroimmune changes in the bilateral ACC region using unilateral- (spared nerve injury, SNI) and mirror-(L5 ventral root transection, L5-VRT) pain models, aiming to explore the potential supraspinal neuroimmune mechanism underlying the mirror-image pain., Methods: The up-and-down method with von Frey hairs was used to measure the mechanical allodynia. Viral injections for the designer receptors exclusively activated by designer drugs (DREADD) were used to modulate ACC glutamatergic neurons. Immunohistochemistry, immunofluorescence, western blotting, protein microarray were used to detect the regulation of inflammatory signaling., Results: Increased expressions of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and chemokine CX3CL1 in ACC induced by unilateral nerve injury were observed on the contralateral side in the SNI group but on the bilateral side in the L5-VRT group, representing a stronger immune response to L5-VRT surgery. In remote ACC, both SNI and L5-VRT induced robust bilateral increase in the protein level of Nav1.6 (SCN8A), a major voltage-gated sodium channel (VGSC) that regulates neuronal activity in the mammalian nervous system. However, the L5-VRT-induced Nav1.6 response occurred at PO 3d, earlier than the SNI-induced one, 7 days after surgery. Modulating ACC glutamatergic neurons via DREADD-Gq or DREADD-Gi greatly changed the ACC CX3CL1 levels and the mechanical paw withdrawal threshold. Neutralization of endogenous ACC CX3CL1 by contralateral anti-CX3CL1 antibody attenuated the induction and the maintenance of mechanical allodynia and eliminated the upregulation of CX3CL1, TNF-α and Nav1.6 protein levels in ACC induced by SNI. Furthermore, contralateral ACC anti-CX3CL1 also inhibited the expression of ipsilateral spinal c-Fos, Iba1, CD11b, TNF-α and IL-6., Conclusions: The descending facilitation function mediated by CX3CL1 and its downstream cascade may play a pivotal role, leading to enhanced pain sensitization and even mirror-image pain. Strategies that target chemokine-mediated ACC hyperexcitability may lead to novel therapies for the treatment of neuropathic pain., (© 2022. The Author(s).)

Oncogenic c-Myc is a master regulator of G1/S transition. Long non-coding RNAs (lncRNAs) emerge as new regulators of various cell activities. Here, we found that lncRNA SnoRNA Host Gene 17 (SNHG17) was elevated at the early G1-phase of cell cycle. Both gain- and loss-of function studies disclosed that SNHG17 increased c-Myc protein level, accelerated G1/S transition and cell proliferation, and consequently promoted tumor cell growth in vitro and in vivo. Mechanistically, the 1-150-nt of SNHG17 physically interacted with the 1035-1369-aa of leucine rich pentatricopeptide repeat containing (LRPPRC) protein, and disrupting this interaction abrogated the promoting role of SNHG17 in c-Myc expression, G1/S transition, and cell proliferation. The effect of SNHG17 in stimulating cell proliferation was attenuated by silencing c-Myc or LRPPRC. Furthermore, silencing SNHG17 or LRPPRC increased the level of ubiquitylated c-Myc and reduced the stability of c-Myc protein. Analysis of human hepatocellular carcinoma (HCC) tissues revealed that SNHG17, LRPPRC, and c-Myc were significantly upregulated in HCC, and they showed a positive correlation with each other. High level of SNHG17 or LRPPRC was associated with worse survival of HCC patients. These data suggest that SNHG17 may inhibit c-Myc ubiquitination and thus enhance c-Myc level and facilitate proliferation by interacting with LRPPRC. Our findings identify a novel SNHG17-LRPPRC-c-Myc regulatory axis and elucidate its roles in G1/S transition and tumor growth, which may provide potential targets for cancer therapy., (© 2021. The Author(s).)

Although a plethora of gene carriers have been developed for potential gene therapy, imageable stimuli-responsive gene vectors with fast access to the nucleus, high biocompatibility, and transfection efficiency are still scarce. Herein, we report the design and synthesis of four dendrite-shaped cationic liposomes, MPA-HBI-R /DOPE (R: n -butyl, 1 ; n -octyl, 2 ; n -dodecyl, 3 ; palmyl, 4 ), prepared via esterification of 4-alkoxybenzylideneimidazolinone containing aliphatic chains of different lengths (HBI-R), the green fluorescent protein (GFP) chromophore, with a di[12]aneN 3 unit. Liposomes were fabricated via the self-assembly of MPA-HBI-R , assisted with 1,2-dioleoyl- sn -glycerol-3-phosphorylethanolamine (DOPE). These liposomes ( MPA-HBI-R/ DOPE) exhibited efficient DNA condensation, pH-responsive degradation, excellent cellular biocompatibility (up to 150 μM), and high transfection efficiency. Molecular docking experiments were also used to verify the optimal interaction between MPA-HBI-R and DNA, as well as the fluorescence enhancements. In particular, MPA-HBI-2 /DOPE delivered DNA into the nucleus in less than an hour, and its luciferase transfection activity was more than 10 times that by Lipo2000, across multiple cell lines. The GFP chromophore conjugation allowed trackable intracellular delivery and release of DNA in real time via fluorescence imaging. Furthermore, efficient red fluorescent protein (RFP) transfection in zebrafish, with an efficiency of more than 6 times that by Lipo2000, was also achieved. The results not only realized, for the first time, the combination of gene delivery and GFP-simulated light emission, allowing fluorescent tracking and highly efficient gene transfection, but also offered valuable insights into the use of biomimetic chromophore for the development of the next-generation nonviral vectors.

Topological superfluidity is an important concept in electronic materials as well as ultracold atomic gases 1 . However, although progress has been made by hybridizing superconductors with topological substrates, the search for a material-natural or artificial-that intrinsically exhibits topological superfluidity has been ongoing since the discovery of the superfluid 3 He-A phase 2 . Here we report evidence for a globally chiral atomic superfluid, induced by interaction-driven time-reversal symmetry breaking in the second Bloch band of an optical lattice with hexagonal boron nitride geometry. This realizes a long-lived Bose-Einstein condensate of 87 Rb atoms beyond present limits to orbitally featureless scenarios in the lowest Bloch band. Time-of-flight and band mapping measurements reveal that the local phases and orbital rotations of atoms are spontaneously ordered into a vortex array, showing evidence of the emergence of global angular momentum across the entire lattice. A phenomenological effective model is used to capture the dynamics of Bogoliubov quasi-particle excitations above the ground state, which are shown to exhibit a topological band structure. The observed bosonic phase is expected to exhibit phenomena that are conceptually distinct from, but related to, the quantum anomalous Hall effect 3-7 in electronic condensed matter., (© 2021. The Author(s).)

Two-photon fluorescent Acenaphtho[1,2-b]quinoxaline (ANQ) and the hydrophilic di-(triazole-[12]aneN 3 ) moieties were combined through an alkyl chain (ANQ-A-M) or a β-hairpin motif with two aromatic γ-amino acid residues (ANQ-H-M) to explore their capabilities for in vitro and in vivo gene delivery and tracing. ANQ-A-M and ANQ-H-M showed the same maximum absorption at 420 nm, and their fluorescent intensities around 650 nm were varied in different solvents and became poor in the protic solvents. Gel electrophoresis assays indicated that both compounds completely retarded the migration of pDNA at 20 μM in the presence of DOPE. However, the DNA condensation with ANQ-H-M was not reversible, and the particle size of the corresponding complexes were larger indicated from the SEM and DLS measurements. In vitro transfections indicated ANQ-A-M/DOPE achieved Luciferase and GFP expressions were to be 7.9- and 5.7-fold of those by Lipo2000 in A549 cells respectively. However, ANQ-H-M showed very poor transfection efficiency in Luciferase expression. With the help of single/two-photon fluorescence imaging it clearly demonstrated that the successful transfection of ANQ-A-M was attributed to its cellular uptake, apparent lysosomal escape, and reversible release of DNA; and the poor transfection of ANQ-H-M was resulted from the aggregation of the DNA complexes which prevented them from the cellular uptake, and also the strong binding ability which is not easy to release DNA. ANQ-A-M/DOPE also exhibited robust gene silencing (83% knockdown of Luciferase) and GFP expression (2.47-fold higher) efficiency compared with Lipo2000 in A549 and zebrafish, respectively. The work demonstrated that the linkage structure between fluorescent and di(triazole-[12]aneN 3 ) played the important role for their gene delivery performance, and that ANQ-A-M represents a vector with the strong transfection efficiency in vitro and in vivo as well as the efficient real time bioimaging properties, which is potential for the development in biomedical research., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Construction of multifunctional nonviral gene vectors to execute defined tasks holds great potential for the precise and effective treatment of gene-associated diseases. Herein, we have developed four large π-conjugation triphenylamine derivatives bearing two polar [12]aneN 3 heads and a lipophilic tail for applications in gene delivery, one/two-photon-triggered near-infrared (NIR) fluorescence bioimaging, and combined photodynamic therapy (PDT) and gene therapy of cancer. These compounds possess typical NIR aggregation-induced emission characteristics, mega Stokes shifts, strong two-photon excitation fluorescence, and excellent DNA condensation abilities. Among them, vector 4 with a tail of n -hexadecane realized a transfection efficiency as high as 6.7 times that of the commercial transfection agent Lipofectamine 2000 in HEK293T cell lines. Using vector 4 as an example, transfection process tracking and ex vivo / in vivo tumoral imaging and retention with high resolution, high brightness, deep tissue penetration, and good biosafety were demonstrated. In addition, efficient singlet oxygen ( 1 O 2 ) generation by the DNA complex formed by vector 4 ( 4 /DNA) resulted in effective PDT. Combined with anticancer gene therapy, collaborative cancer treatment with a dramatically enhanced cancer cell-killing effect was achieved. The development of this "three birds, one stone" approach suggests a new and promising strategy for better cancer treatment and real-time tracking of gene delivery.

A series of unnatural tripeptides, each consisting of two aromatic γ-amino acid residues and an ϖ-amino acid residue, are designed to probe their folding into hairpin conformations. The ϖ-amino acid residues, with aliphatic or aromatic spacers of different sizes, serve as the loop of the hairpins. Studies based on one-dimensional (1D) 1H NMR performed at different concentrations, solvent polarity, and temperature, along with 2D-NMR studies, demonstrated that the doubly H-bonded aromatic γ-amino acid residues play important roles in driving these tripeptides into the hairpin conformation. The loop based on 5-aminovaleric acid, which offers a four-carbon (CH2)4 spacer, enhanced the stability of the corresponding hairpin, while loops having a shorter, a longer and a more rigid spacer disfavored the formation of the hairpins. Results from computational studies are in good agreement with the experimental observations. Furthermore, the crystal structure of peptide 1b revealed the expected hairpin conformation in the solid state. This turn motif, which contains H-bonded aromatic γ-amino acid residues as the core unit and an ϖ-amino acid residue serving as the loop, provides a new platform that can be used to obtain a variety of turn conformations by incorporating diverse amino acids into the loops.

A novel one-pot triple-reaction strategy for the asymmetric construction of polycyclic skeletons with multiple consecutive chiral centers through aza-Michael/Michael/Wittig/ketyl radical addition/esterification processes is reported. A wide range of polycyclic tetrahydroquinoline derivatives were smoothly obtained from easily available starting materials with good results (up to 80% yield, >20:1 dr, >99% ee) under mild conditions. In this transformation, five chemical bonds and five consecutive chiral centers were successively formed.

Although a plethora of nonviral gene vectors have been developed for potential gene therapy, imageable gemini surfactants with stimuli-responsiveness and high transfection efficiency are still scarce for gene delivery. Herein, three gemini amphiphiles ( DEDPP-4/8/12 ) consisting of an aggregation-induced emission (AIE) central fluorophore: 5,6-diphenylpyrazine-2,3-diester ( DEDPP ), decorated with triazole-[12]aneN 3 as the hydrophilic moiety and alkyl chains of various lengths as the hydrophobic moiety, were designed and synthesized for trackable gene delivery via optical imaging. All three amphiphiles exhibited ultralow critical micelle concentrations (CMCs) (up to 3.40 × 10 -6 M), prominent two-photon absorption properties, and solvatochromic fluorescence. Gel electrophoresis assays demonstrated that the migration of plasmid DNA was completely retarded after condensation with these gemini amphiphiles at low concentrations (up to 10 μM). In addition, the ester bond in these amphiphiles may facilitate vector degradation and DNA release, in response to esterase and the acidic environment inside cells. Upon self-assembly with DOPE to form liposomes, DEDPP-8/ DOPE achieved the best transfection efficiency in four cell lines, and the transfection efficiency of DEDPP-8/ DOPE in HeLa cell lines was 23.5-fold higher than that of Lipo2000, which is unusually high for small organic molecule-based nonviral vectors. Furthermore, excellent transfection efficiency of DEDPP-8/ DOPE was obtained in the presence of serum, and the red fluorescence protein (RFP) gene was successfully transfected in zebrafish embryos. Both one- and two-photon fluorescence imaging clearly demonstrated the delivery process of plasmid DNA. This study demonstrated that gemini-type amphiphiles composed of a two-photon fluorophore core conjugated with triazole-[12]aneN 3 via an ester bond afforded an unprecedentedly high transfection efficiency with excellent biocompatibility, which may provide new insights for the design and development of multifunctional nonviral gene vectors for imageable gene delivery.

Hair follicles are easily accessible skin appendages that protect against cold and potential injuries. Hair follicles contain various pools of stem cells, such as epithelial, melanocyte, and mesenchymal stem cells (MSCs) that continuously self-renew, differentiate, regulate hair growth, and maintain skin homeostasis. Recently, MSCs derived from the dermal papilla or dermal sheath of the human hair follicle have received attention because of their accessibility and broad differentiation potential. In this review, we describe the applications of human hair follicle-derived MSCs (hHF-MSCs) in tissue engineering and regenerative medicine. We have described protocols for isolating hHF-MSCs from human hair follicles and their culture condition in detail. We also summarize strategies for maintaining hHF-MSCs in a highly proliferative but undifferentiated state after repeated in vitro passages, including supplementation of growth factors, 3D suspension culture technology, and 3D aggregates of MSCs. In addition, we report the potential of hHF-MSCs in obtaining induced smooth muscle cells and tissue-engineered blood vessels, regenerated hair follicles, induced red blood cells, and induced pluripotent stem cells. In summary, the abundance, convenient accessibility, and broad differentiation potential make hHF-MSCs an ideal seed cell source of regenerative medical and cell therapy., Competing Interests: Conflict-of-interest statement: Liu JY reports grants from the China National Natural Science Foundation, grants from the Joint Construction Project between Jilin Province and Provincial Colleges, grants from the Jilin Province Science and Technology Development Plan, grants from the Innovative Special Industry Fund Project in Jilin Province, grants from the Open Research Project of the State Key Laboratory of Industrial Control Technology, Zhejiang University, China, during the conduct of the study., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Skin wounding is very common and may be slow to heal. Increasing evidence shows that exosomes derived from mesenchymal stem cells (MSCs) dramatically enhance skin wound healing in a paracrine manner. However, the mechanism underlying this phenomenon has not yet been elucidated. Thus, the objective of the present study was to identify the signaling pathways and paracrine factors by which MSC-derived exosomes promote de novo skin tissue regeneration in response to wound healing., Methods: In vitro and in vivo skin wound healing models were created by treating immortalized human keratinocytes (HaCaT) with hydrogen peroxide (H 2 O 2 ) and excising full-thickness mouse skin, respectively. Exosomes were extracted from human umbilical cord Wharton's jelly MSCs (hucMSC-Ex) by ultracentrifugation of cell culture supernatant., Results: The hucMSC-Ex treatment significantly increased HaCaT cell proliferation and migration in a time- and dose-dependent manner, suppressed HaCaT apoptosis induced with H 2 O 2 by inhibiting nuclear translocation of apoptosis-inducing factor (AIF) and upregulating poly ADP ribose polymerase 1 (PARP-1) and poly (ADP-ribose) (PAR). The animal experiments showed that relative to hucMSCs, hucMSC-Ex attenuated full-thickness skin wounding by enhancing epidermal re-epithelialization and dermal angiogenesis., Conclusions: These findings indicated that direct administration of hucMSC-Ex may effectively treat cutaneous wounding and could be of great value in clinical settings.

To evaluate the safety and efficiency of sunitinib and sorafenib in the treatment of renal cell carcinoma (RCC).Databases were searched up till February 28, 2018. Two reviewers independently assessed trials for eligibility, quality, and extracted relevant data. Results are expressed as risk ratio (RR) or hazard ratio (HR) with 95% confidence intervals (CI). Six studies including 3112 patients were accessed. Sorafenib group exhibited higher median progression-free survival (mPFS) compared to sunitinib group (MD, -1.30; 95% CI, -2.56 to -0.03), especially in the first-line treatment (MD, -1.33; 95% CI, -2.61 to -0.04). However, sunitinib significantly reduced the risk of progression-free survival (PFS) compared to sorafenib (HR, 0.71; 95% CI, 0.6-0.82). Sunitinib also significantly reduced risk of overall survival (OS) compared to sorafenib (HR, 0.79; 95% CI, 0.65-0.92), while median OS was similar in both groups (MD, -0.48; 95% CI, -3.40-2.43). With regards to safety, the risk of rash (RR, 0.31, 95% CI, 0.12-0.79) was greater in sunitinib than sorafenib group, while the risk of decreased appetite (RR 2.10, 95% CI: 1.33-3.30) and dehydration (RR 2.73, 95% CI: 1.14-6.56) was smaller in contrast.Based on risk of PFS and OS, sunitinib was a better treatment option for RCC treatment while patients faced with severe skin reaction. And for those Asian patients classified under MSKCC moderate risk, whether in first or second-line treatment, had difficulty in feeding, sorafenib is a better choice for prolong mPFS.

A tandem catalytic strategy for the asymmetric synthesis of spirocyclopentanone pyrazolones bearing three contiguous stereocenters and two quaternary carbons with good stereoselectivities has been developed. This strategy, using pyrazolones as efficient C1 synthons and involving a polarity reversal process, not only overcame the energy barrier of the dearomatization process but also avoided nucleophilic addition of the hydroxy group in the enol form tautomer. Futhermore, spirocyclopentanones could be transformed into spirocyclohexamide pyrazolone with the Lawesson reagent.

Three nonviral gene vectors, TPA-BI-A / B / C , have been designed and synthesized by the combination of one or two hydrophilic [12]aneN 3 moieties and two-photon fluorescent triphenylamine-benzylideneimidazolone (TPA-BI) units through different ester linkage. Spectroscopic characterization demonstrated that TPA-BI-A / B / C had strong aggregation-induced emissions (AIE), large Stokes shifts (230, 284, and 263 nm), and large two-photon absorption cross sections (δ 2PA ) (67, 592, and 80 GM). Gel electrophoresis indicated that the three compounds completely condensed DNA at 15 μM in the presence of DOPE, and showed the lipase- and pH-triggered reversible release of DNA and the fluorescent recognition of the different lengths of ssDNA and dsDNA. The optimal TPA-BI-C /DOPE-mediated luciferase and GFP activity was 146% and 290% higher than those of Lipo2000. The transfection process of DNA could be traced clearly through one- and two-photon fluorescence spectra, and displayed in a 3D-video. TPA-BI-C /DOPE successfully transfected the GFP gene into zebrafish, which was superior to Lipo2000 (192%). In conclusion, TPA-BI-C /DOPE is the first nonviral gene vector with the abilities of pH/lipase enzyme responsiveness, one/two-photon fluorescent tracking of intracellular delivery of DNA, and successful transfection in vivo and in vitro, even better than Lipo2000.

Herein, we describe a variety of chiral hybrid pyrroidine-indole polycyclic derivatives with quaternary and continuous chiral centers were synthesized in good yields with excellent stereoselectivities through an asymmetric, intermolecular, and formal [3 + 2] cyclization reaction catalyzed by a bifunctional catalyst. In addition, the selection of substituents of substrates is the key to success, and both the hydroxyl group and the trifluoromethyl group play essential roles in the reaction.

A sequential and general strategy has been successfully developed for the synthesis of spiropyrazolone scaffolds. This intriguing transformation of the asymmetric multicomponent catalysis process was realized with the combination of Michael addition/chlorination/nucleophilic substitution in a one-pot sequence, giving rise to a series of spiropyrazolones with fully substituted cyclopropanes and spiro-dihydrobenzofurans containing continuous stereogenic centers in good yields with excellent stereoselectivities.

A variety of axially chiral biaryldiols were synthesized in good yields with excellent atropo-enantioselectivities through construction of axially chiral indoles catalyzed by asymmetric hydrogen-bond donors. In addition, the new axially chiral compounds were proved to be efficient and practical catalysts for asymmetric catalysis. The strategy not only provides a novel method to synthesize axially chiral compounds but also extends the scope of chiral catalysts.

Although thousands of long noncoding RNAs (lncRNAs) have been annotated, only a limited number of them have been functionally characterized. Here, we identified an oncogenic lncRNA, named lnc-UCID (lncRNA up-regulating CDK6 by interacting with DHX9). Lnc-UCID was up-regulated in hepatocellular carcinoma (HCC), and a higher lnc-UCID level was correlated with shorter recurrence-free survival of HCC patients. Both gain-of-function and loss-of function studies revealed that lnc-UCID enhanced cyclin-dependent kinase 6 (CDK6) expression and thereby promoted G1/S transition and cell proliferation. Studies from mouse xenograft models revealed that tumors derived from lnc-UCID-silenced HCC cells had a much smaller size than those from control cells, and intratumoral injection of lnc-UCID small interfering RNA suppressed xenograft growth. Mechanistically, the 850-1030-nt domain of lnc-UCID interacted physically with DEAH (Asp-Glu-Ala-His) box helicase 9 (DHX9), an RNA helicase. On the other hand, DHX9 post-transcriptionally suppressed CDK6 expression by binding to the 3'-untranslated region (3'UTR) of CDK6 mRNA. Further investigation disclosed that lnc-UCID enhanced CDK6 expression by competitively binding to DHX9 and sequestering DHX9 from CDK6-3'UTR. In an attempt to explore the mechanisms responsible for lnc-UCID up-regulation in HCC, we found that the lnc-UCID gene was frequently amplified in HCC. Furthermore, miR-148a, whose down-regulation was associated with an increase of lnc-UCID in HCC, could bind lnc-UCID and inhibit its expression. Conclusion: Up-regulation of lnc-UCID, which may result from amplification of its gene locus and down-regulation of miR-148a, can promote HCC growth by preventing the interaction of DHX9 with CDK6 and subsequently enhancing CDK6 expression. These findings provide insights into the biological functions of lncRNAs, the regulatory network of cell cycle control, and the mechanisms of HCC development, which may be exploited for anticancer therapy., (© 2019 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of American Association for the Study of Liver Diseases.)

Objective: To explore the protective effect of NANOG against hydrogen peroxide (H2O2) -induced cell damage in the human hair follicle mesenchymal stem cells (hHF-MSCs)., Methods: NANOG was expressed from a lentiviral vector, pLVX-IRES-ZsGreen. NANOG hHF-MSCs and vector hHF-MSCs were treated with 400 μmol/L hydrogen peroxide (H2O2) for 2 h, the cell survival rate, cell morphology, ROS production, apoptosis and expression of AKT, ERK, and p21 were determined and compared., Results: Our results showed that NANOG could activate AKT and upregulate the expression of p-AKT, but not p-ERK. When treated with 400 μmol/L H2O2, NANOG hHF-MSCs showed higher cell survival rate, lower ROS production and apoptosis, higher expression of p-AKT, higher ratio of p-AKT/AKT., Conclusion: Our results suggest that NANOG could protect hHF-MSCs against cell damage caused by H2O2 through activating AKT signaling pathway., (Copyright © 2019 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. An Expression of Concern for this article was previously published while an investigation was conducted (see related editorial: https://doi.org/10.1016/j.biopha.2022.113812). This retraction notice supersedes the Expression of Concern published earlier. Concern was raised about the reliability of the heart images shown in Figure 1A, which appear to contain similar features to those found in other publications, as detailed here: https://pubpeer.com/publications/108A0BE9F52724D6879E23FAE7F361; and here: https://docs.google.com/spreadsheets/d/1r0MyIYpagBc58BRF9c3luWNlCX8VUvUuPyYYXzxWvgY/edit#gid=262337249. Concerns over the provenance of the flow cytometry data in Figure 7A were also raised. The journal requested the corresponding author comment on these concerns and provide the associated raw data. The authors did not respond to this request and therefore the Editor-in-Chief decided to retract the article., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

An N-heterocyclic carbene-catalyzed asymmetric [3 + 3] spiroannulation of β-ketothioamide was successfully developed. β-Ketothioamides exhibit an unusual reactivity to undergo a previously challenging lactamization reaction, and the desired spiro-piperidinone derivatives containing two vicinal stereogenic centers were synthesized in good to high yields with high stereoselectivities, whose structure can be converted to the corresponding imide and δ-lactam derivatives smoothly.

Here a highly efficient cascade approach is reported that combines a cycloaddition reaction with a regioselective strain-release process to afford diverse heterocyclic frameworks through bifunctional catalysis. The cooperation of hydrogen-bonding network activation and a regiodivergent strain-assisted effect is the key to promoting this complex chemical transformation, leading to the generation of two different ring systems in high yields with excellent stereoselectivities. The reaction proceeded by a mechanism involving a "spring-loaded" intermediate with switchable C-C bond cleavages achieved by controllable ring-strain release. This reaction was also amenable to gram scale synthesis with only 0.1 mol % catalyst loading., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To explore the clinical effect of exercise rehabilitation during perioperative period on residual pain, gait and activities of daily living (ADL) in patients with lumbar spinal stenosis (LSS) after lumbar percutaneous transforaminal endoscopic discectomy(PTED)., Methods: The clinical data of 48 patients with LSS underwent PTED from December 2015 to December 2016 were retrospectively analyzed. Patients were divided into observation group and control group according to different rehabilitation patterns, being 24 cases in each group. The patients of observation group received exercise rehabilitation and the patients of control group received conventional rehabilitation. Visual analogue scale(VAS), Oswestry Disability Index (ODI) and the ratio of supporting phase were recorded before operation and 12 days, 6 months after operation. The correlation between the ratio of supporting phase and VAS, ODI was analyzed., Results: The ratio of supporting phase of observation group was significantly higher than that of control group at 12 days after operation( P <0.05). The VAS and ODI in observation group were significantly lower than that of control group at 6 months after operation( P <0.01). There was no correlation between the ratio of supporting phase and ODI or VAS in two groups ( P >0.05)., Conclusions: Lumbar percutaneous transforaminal endoscopic discectomy combined with exercise rehabilitation during the perioperative period can release or eliminate postoperative residual pain, improve gait balance, enable activities of daily living, and has a positive effect in patients with lumbar spinal stenosis., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© 2018 by the China Journal of Orthopaedics and Traumatology Press.)

An efficient method has been successfully developed to achieve the asymmetric C-H functionalization of indoles in the carbocyclic ring via organocatalysis, and a variety of tetrahydropyranoindoles were synthesized in good yields with excellent stereoselectivities. Further study on thermodynamic calculations indicated that the process was promoted by generating more thermodynamically stable products. This strategy, together with traditional C-3 functionalization of hydroxyindoles, could realize the switchable, regiodivergent asymmetric modification of indoles.

Objective: To investigate the morphologic characteristics of the retromaxillary posterior ethmoid. Method: A total of 103 outpatients encountered in our hospital during March 2012 and December 2012,who completed paranasal sinus CT examination,were included in this study.Patients had no sinus trauma,surgery or tumor history.Their paranasal sinus CT scans were analyzed from scheduled axial and coronal plane.The incidence and imaging features of the retromaxillary posterior ethmoid were observed. Result: The retromaxillary posterior ethmoid(RMPE)was the posterior ethmoid cell that expanded along the lamina papyracea toward the infraorbital region.RMPE was located behind the posterior wall of the maxillary sinus and under the orbital floor.The occurrence rate of the RMPE was 74.3%.The ethmomaxillary septum is the bony septum the between the maxillary sinus and posterior ethmoid.Anatomical confirmation of RMPE is based mainly on the presence of the ethmomaxillary septum.RMPE is located at the back of ethmomaxillary septum.The sagittal angulation of the ethmomaxillary septum ranged from 22 to 87 degrees,with an average of(50.34±12.10)degrees. Conclusion: The ethmomaxillary septum is important for anatomic recognition of the RMPE.Accurate identification of the RMPE before ESS can help improve the removal of the posterior ethmoid sinus.

Vascular mimicry (VM) is a critical complement for microcirculation and is implicated in tumor progression. We showed that IL-6 derived from tumor cells and stroma cells promoted tumor cells to form a VM structure, whereas blocking the IL-6 signaling by RNA interference, IL-6-neutralizing antibody, or STAT3 inhibitor suppressed the VM formation of tumor cells. Mechanism investigations revealed that IL-6 stimulated VM formation by activating STAT3, in turn upregulating VE-cadherin expression and MMP2 activity. Further analyses identified a positive association between the activation of IL-6-STAT3 signaling and the formation of the VM structure in human HCC tissues. However, miR-29b repressed the expression of STAT3 and MMP2 by directly binding to the 3' UTRs of their mRNAs. Consistently, both gain- and loss-of-function analyses showed that miR-29b suppressed tumor cells to form tube structures in vitro. The in vivo studies further disclosed that intratumoral injection of the miR-29b-expressing viruses significantly inhibited the IL-6-promoted VM formation in mouse xenografts, and downregulation of miR-29b was correlated with the presence of VM in human HCC tissues. This study elucidates a miR-29b-IL-6 signaling cascade and its role in VM formation, which provide potential targets for cancer therapy., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

A variety of spirocyclohexene pyrazolones were synthesized in good yields with excellent stereoselectivities through an asymmetric, intermolecular, quaternary carbon center forming [3 + 3] cycloaddition reaction catalyzed by a bifunctional catalyst. The vinylogous pyrazolones used as binucleophilic synthons in this reaction exhibited superior ability for constructing pyrazolone related spirocyclic scaffolds.