Protective effect of Helianthus annuus seed byproduct extract on ultraviolet radiation-induced injury in skin cells.

Helianthus annuus seed byproduct is a residual product obtained after seed oil extraction. The present study investigated the preventive and repair effects of the H. annuus seed byproduct ethanol extract (HSE) on ultraviolet radiation (UVR)-induced injury in human immortalized keratinocytes (HaCaTs) and human skin fibroblasts (HSFs). Results revealed that the total phenolic acid and oligosaccharide content in HSE was >50%. HSE had a stronger preventive effect on UVR-induced injury than the repair effect. Moreover, phenolic acids were the main active component of HSE mediating the preventative effect. In HaCaTs and HSFs, HSE prevented UVR-induced injury by inhibiting excessive ROS production. It reduced the secretion of tumor necrosis TNF-α, IL-1α, IL-1ß, IL-6, and IL-8 by inhibiting the level of ROS, thus reducing inflammation-mediated injury to skin cells. In addition, HSE inhibited the expression of various mRNA kinases in the MAPK-ERK/p38/JNK pathway. This downregulated the expression of activator protein-1 (AP-1) mRNA and further reduced the secretion of matrix metalloproteinase (MMP)-1, MMP-3, and MMP-9 as well as reduced UVR-induced injury to the cells. In conclusion, HSE is a broad-spectrum, natural UV filter with high efficiency and low toxicity that has the potential to be used in sunscreen products.

Spin regulation for efficient electrocatalytic N2 reduction over diatomic Fe-Mo catalyst.

Electrocatalytic nitrogen reduction reaction (eNRR) is a promising method for the sustainable production of ammonia as an alternative to the traditional energy-intensive Haber-Bosch process. In this work, an efficient strategy by atomic spin regulation to promote NRR through Fe-transition metal (TM) hybrid heteronuclear dual-atom catalysts has been studied. By means of DFT computations, the stability, activity, and selectivity of 30 kinds of Fe-based dual-atoms anchored on N-doped porous graphene are systematically investigated to evaluate their catalytic performance. Fe/MoNC is screened as an excellent NRR catalyst with the limiting potentials of 0.63 V, and also suppresses HER. In the Fe/MoNC, the neighboring Fe atom regulates the spin state of the Mo center in MoN4 from high-spin state (2.63 µB) to medium-spin state (0.74 µB), which can effectively relieve the strong overlapping between Mo 4d orbital with the NxHy intermediates, promote the desorption of reaction product, and eventually achieve a lower limiting potential. Interestingly, the archetype of the active center of nitrogenase is also a FeMo-cofactor, which is consistent with our screening results. The work may provide new insight into the mechanism of nitrogenase, and promote the rational design of efficient NRR catalysts by atomic spin regulation.

Levistilide a Induces Ferroptosis by Activating the Nrf2/HO-1 Signaling Pathway in Breast Cancer Cells.

Introduction: Breast cancer (BC) is the leading female malignancy, with one million new cases diagnosed worldwide per year. However, the current treatment options for BC patients have difficulty achieving satisfactory efficacy. Ferroptosis is a new mode of regulated cell death that plays a key role in the inhibition of tumorigenesis. Levistilide A (LA), as an active compound extracted from Chuanxiong Rhizoma, might prevent the development of tumors by regulating the critical cellular processes of ferroptosis. Methods: In this study, the underlying mechanisms of LA on ferroptosis in BC were explored in vitro. The effect of LA on the viability and mitochondrial function of BC cells was determined. Moreover, the effect of LA on the expression levels of key molecules involved in ferroptosis and the nuclear factor erythroid-2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) signaling pathway was evaluated. Results: LA significantly reduced cell viability and damaged the mitochondrial structure and function of BC cells in a dose-dependent manner. Furthermore, LA treatment markedly enhanced reactive oxygen species (ROS)-induced ferroptosis by activating the Nrf2/HO-1 signaling pathway. Conclusion: These findings suggest that LA may be a potential lead compound for breast cancer therapy by inducing ferroptosis in tumor cells.

Nucleophilic Dearomatization Strategy to Synthesize Disubstituted 3-Isoquinolinones under Transition Metal-Free Conditions.

Herein, a one-pot protocol for constructing the disubstituted isoquinolinone derivatives via the three-component reactions of 3-haloisoquinolines, alkyl halides, and indoles under transition-metal-free conditions is described. The reaction realized the trifunctionalization of isoquinoline via a dearomatization strategy, which displayed high chemical selectivity, excellent functional group tolerance, and a wide range of substrates, and is environmentally friendly. The three-component coupling involves the construction of new C-N, C═O, and C-C bonds in one step.

Circular RNA CircITCH (has-circ-0001141) suppresses hepatocellular carcinoma (HCC) progression by sponging miR-184.

Aberrant expression of circular RNA (circRNA) is involved in the occurrence of various diseases and tumor development, in which plays a vital role, including hepatocellular carcinoma (HCC). Nevertheless, the regulation mechanism and biological function of circITCH in hepatocellular carcinoma (HCC) remain unclear. The expression level of circular RNA itchy E3 ubiquitin protein ligase (circ-ITCH) was identified and validated by real-time polymerase-chain reaction (RT-qPCR) in HCC cell lines. The stability of circITCH was confirmed by Ribonuclease R (RNase R) assay. Subsequently, through silencing and overexpression of circITCH to investigate the functional roles of circITCH in HCC proliferation, invasion, and apoptosis. We also carried out bioinformatics analysis, luciferase reporter assays to define the relationship between microRNA (miR)-184 and circITCH. Moreover, xenograft mouse models and immunohistochemistry were employed to assess the function of circITCH in HCC. CircITCH (hsa_circ_0001141) was a stable circRNA and downregulated in HCC cells. Overexpression of circITCH inhibited cell proliferation, migration, invasion, and promoted apoptosis in vitro and in vivo, whereas knockdown of circITCH had the opposite effects. Mechanistically, miR-184 could be sponged by circITCH, and its overexpression could mitigate the suppressive effects of circITCH overexpression on HCC progression. Through biological website to predict the target genes of miR-184 may be combined. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to investigate mRNAs with significant functional enrichment and pathways, also which its relationship with HCC-related pathway and immune cells. Our findings reveal that circITCH served as a repressor to restrain HCC malignancy via miR-184. Therefore, circITCH may serve as a potential prognostic marker and therapeutic target for HCC.Abbreviations: HCC: hepatocellular carcinoma; CircRNA: Circular RNA; miRNA: MicroRNA; Circ-ITCH: circular RNA itchy E3 ubiquitin protein ligase; RT-qPCR: real-time polymerase-chain reaction; RNase R: Ribonuclease R; CeRNA: competing endogenous RNAs; SiRNA: small interfering RNA.

Myeloid-derived suppressor cells promote tumor growth and sorafenib resistance by inducing FGF1 upregulation and fibrosis.

BACKGROUND: Considerable evidence implicates myeloid-derived suppressor cells (MDSCs) promote tumor progression and drug resistance. Sorafenib is the standard first-line therapy for advanced hepatocellular carcinoma (HCC). Clinical evidence indicates that sorafenib resistance is associated with increased MDSCs, by which MDSCs exerts these effects is obscure. This study aimed to investigate the mechanism of sorafenib resistance mediated by MDSCs. METHODS: A syngeneic mouse-liver cancer cell line BNL was subcutaneously injected to build a tumor-bearing mouse model, and syngeneic MDSCs were adoptive transferred into the tumor-bearing mouse. Tumor tissue was obtained, and transcriptomic analysis of the tumor was carried out on RNAseq data. A coculture system was used to verify the crosstalk between MDSCs and BNL cells. RESULTS: Adoptive MDSCs transfer into tumor-bearing mice induced an increase of tumor-infiltrating MDSCs, which led to tumor growth and impaired antitumor activity of sorafenib in BNL HCC models. MDSCs transfer contributed to tumor fibrosis and tumor-associated fibroblast (CAF) activation, associated with fibroblast growth factor (FGF1) upregulation. In contrast, MDSC depletion by anti-Ly6G+ reduced fibrosis and increased sorafenib antitumor efficacy. Intriguingly, tumor-infiltrating MDSCs barely expressed FGF1. IL-6 derived from MDSCs increased FGF1 expression in BNL liver cancer cells, and anti-IL-6 attenuated this effect in vitro. MAPK pathway, one of the sorafenib targets, is the downstream signaling of FGF1 and is reactivated by MDSCs-mediated FGF1 upregulation. CONCLUSIONS: Our finding demonstrated that MDSCs led to tumor growth and sorafenib resistance via FGF1 upregulation and subsequent indirect CAF activation. We offered a novel mechanism of MDSCs-driven HCC progression and sorafenib resistance.

Water-Stable Eu6-Cluster-Based fcu-MOF with Exposed Vinyl Groups for Ratiometric and Fluorescent Visual Sensing of Hydrogen Sulfide.

Detection of H2S in the biological system has attracted enormous attention in recent years. In this work, a new vinyl-functionalized metal-organic framework (MOF), [(Me2NH2)2] [Eu6(µ3-OH)8(BDC-CH═CH2)6(H2O)6] (Eu-BDC-CH═CH2, BDC-CH═CH2 = 2-vinylterephthalic acid), was synthesized under solvothermal conditions. The vinyl groups in the ligands can not only modulate the "antenna effect" of the ligand on Eu3+ ions but also serve as an exposed reactive site to allow for the quantitative detection of H2S by Eu-BDC-CH═CH2. The ratiometric fluorescent probe has the advantages of water stability, acid-base stability (pH = 2-11), fast response (<2 min), high selectivity, and sensitivity (LOD = 38.4 µM). We also used Eu-BDC-CH═CH2 to detect and analyze H2S in tap and lake waters, demonstrating the potential of the probe for biological and environmental applications. In addition, the MOF-based agarose hydrogel film allows for the visual detection of H2S via a smartphone by identifying the RGB values. The vinyl-functionalized MOF can thus be a powerful sensing platform for H2S.

Understanding the Doping Chemistry of High Oxidation States in Scheelite CaWO4 by Hydrothermal Conditions.

Doping chemistry has become one of the most effective means of tuning materials' properties for diverse applications. In particular for scheelite-type CaWO4, high-oxidation-state doping is extremely important, since one may expand the scheelite family and further create prospective candidates for novel applications and/or useful spectral signatures for nuclear forensics. However, the chemistry associated with high-valence doping in scheelite-type CaWO4 is far from understanding. In this work, a series of scheelite-based materials (Ca1-x-y-zEuxKy□z)WO4 (□ represents the cation vacancy of the Ca2+ site) were synthesized by hydrothermal conditions and solid-state methods and comparatively studied. For the bulk prepared by the solid-state method, occupation of high-oxidation-state Eu3+ at the Ca2+ sites of CaWO4 is followed by doping of the low-oxidation-state K+ at a nearly equivalent molar amount. The Eu3+ local symmetry is thus varied from the original S4 point group symmetry to C2v point group symmetry. Surprisingly different from the cases in bulk, for the nanoscale counterparts prepared by hydrothermal conditions, the high-oxidation-state Eu3+ was incorporated in CaWO4 at two distinct sites, and its amount is higher than that of the low-oxidation-state K+ even though KOH was used as a mineralizer, creating a certain amount of cation vacancies. Consequently, an apparent split emission of 5D0 → 7F0 was first demonstrated for (Ca1-x-y-zEuxKy□z)WO4. The doping chemistry of high oxidation states uncovered in this work not only provides an explanation for the commonly observed spectral changes in rare-earth-ion-modified scheelite structures, but also points out an advanced direction that can guide the design and synthesis of novel functional oxides by solution chemistry routes.

Metabolomics Analysis on Mice With Depression Ameliorated by Acupoint Catgut Embedding.

Depression is a prevalent mental disease characterized by persistent low mood, lack of pleasure, and exhaustion. Acupoint catgut embedding (ACE) is a kind of modern acupuncture treatment, which has been widely used for the treatment of a variety of neuropsychiatric diseases. To investigate the effects and underlying mechanism of ACE on depression, in this study, we applied ACE treatment at the Baihui (GV20) and Dazhui (GV14) acupoints of corticosterone (CORT)-induced depression model mice. The results showed that ACE treatment significantly attenuated the behavioral deficits of depression model mice in the open field test (OFT), elevated-plus-maze test (EPMT), tail suspension test (TST), and forced swimming test (FST). Moreover, ACE treatment reduced the serum level of adreno-cortico-tropic-hormone (ACTH), enhanced the serum levels of 5-hydroxytryptamine (5-HT), and noradrenaline (NE). Furthermore, metabolomics analysis revealed that 23 differential metabolites in the brain of depression model mice were regulated by ACE treatment for its protective effect. These findings suggested that ACE treatment ameliorated depression-related manifestations in mice with depression through the attenuation of metabolic dysfunction in brain.

Isostructural Single- And Dual-Lanthanide Metal-Organic Frameworks Based On Substituent-Group-Modifying Tetracarboxylate Ligands for Ratiometric Temperature Sensing.

In this study, two substituent-group-modifying tetracarboxylate ligands, 2',5'-dimethoxy-[1,1':4',1″-terphenyl]-3,3″,5,5″-tetracarboxylic acid (H4TPTC-2OMe) and 2',5'-dimethyl-[1,1':4',1″-terphenyl]-3,3″,5,5″-tetracarboxylic acid (H4TPTC-2Me), with similar geometries were used as the organic linkers to construct isostructural lanthanide metal-organic frameworks (LnMOFs). The as-prepared LnTPTC-2OMe and LnTPTC-2Me were structurally elucidated by means of single-crystal and powder X-ray diffraction in addition to thermogravimetric analysis and were assessed as luminescence ratiometric thermometers by obtaining the temperature dependence of the luminescence behaviors. We found that both the single lanthanide EuTPTC-2OMe and the dual lanthanide Eu0.05Tb0.95TPTC-2Me exhibited a distinct S-type luminescence response to temperatures in the range from 313 to 473 K, and their ratiometric parameters can be understood on the basis of the classic Mott-Seitz model. Energy transfers from the ligand to Tb3+ (or Eu3+) and from Tb3+ to Eu3+ in these two systems were investigated theoretically as well as with low-temperature (77 K) time-resolved photoluminescence spectroscopy, quantum yield, and lifetime analysis. Therefore, these two materials possess a good relative sensitivity, a small temperature uncertainty, and a favorable spectral repeatability in addition to a remarkable emission color change, enhancing their potential use for temperature measurement and in situ monitoring in microelectronics.

Embedding Red Emitters in the NbO-Type Metal-Organic Frameworks for Highly Sensitive Luminescence Thermometry over Tunable Temperature Range.

The intrinsic advantages of metal-organic frameworks (MOFs), including extraordinarily high porosities, tailorable architectures, and diverse functional sites, make the MOFs platforms for multifunctional materials. In this study, we synthesized two kinds of isostructural NbO-type Zn2+-based MOFs, where two structurally similar tetracarboxylate ligands, 5,5'-(pyrazine-2,5-diyl)diisophthalic acid (H4PZDDI) and 5,5'-(pyridine-2,5-diyl)diisophthalic acid (H4PDDI), with pyridine or pyrazine moieties, were employed as the organic linkers. By embedding the red-emitting cationic units of pyridinium hemicyanine dye 4-[p-(dimethylamino)styryl]-1-methylpyridinium (DSM) and trivalent europium ion (Eu3+), two types of composites, DSM@ZnPZDDI and DSM@ZJU-56 and Eu3+@ZnPZDDI and Eu3+@ZJU-56, were harvested and evaluated for use as potential ratiometric temperature probes. The temperature-responsive luminescence of these dual-emitting composites was investigated, and their representative features of relative sensitivity, temperature resolution, spectral repeatability, and luminescence color change were discussed. Importantly, compared with the DSM-incorporated composites, Eu3+@ZnPZDDI and Eu3+@ZJU-56 show a much wider sensing temperature range and higher relative sensitivities, suggesting the performance of the composites can be engineered by elaborately combining the host and guest units. Given the rich choices of porous MOFs and emitting units, such a strategy can be useful in the design and preparation of multifunctional dual-emitting sensory materials.

CsCu2I3 Nanocrystals: Growth and Structural Evolution for Tunable Light Emission.

CsCu2I3 mixed with Cs3Cu2I5 has shown potential applications as white-light-emitting materials, while their growth, structural evolution behaviors, and their impact on photoluminescence of CsCu2I3 nanocrystals (NCs) are still not known. In this work, we investigated the growth and structural evolution of CsCu2I3 nanocrystals with increasing reaction temperature. At low temperature and in the presence of a high dosage of oleic acid and oleylamine, Cs3Cu2I5 nanoparticles, rather than CsCu2I3 NCs, preferred to form in the hot-injection reaction system. Increasing the reaction temperature promoted the formation of CsCu2I3 nanorods. Phase-pure CsCu2I3 nanorods were steadily obtained at 180 °C. Structural evolution from less copper-containing NCs to copper-rich ones in the low-temperature reaction condition is highly related to the coordination of copper ions with OAm. More importantly, accompanying the growth of nanorods and structural evolution from Cu3Cs2I5 to CsCu2I3, the color of photoluminescence emission of NCs changed from blue to nearly white and to yellow, but their photoluminescence quantum yield decreased from 36.00 to 9.86%. The finding in this work would give a view to the structural evolution of copper-containing perovskite-like halides, being helpful for adjusting their photoluminescence in white LEDs.

Targeting Myeloid-Derived Suppressor Cells to Enhance the Antitumor Efficacy of Immune Checkpoint Blockade Therapy.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that are activated under pathological conditions, such as cancer, or mature myeloid cells that are converted immune-suppressive cells via tumor-derived exosomes, and potently support the tumor processes at different levels. Currently, multiple studies have demonstrated that MDSCs induce immune checkpoint blockade (ICB) therapy resistance through their contribution to the immunosuppressive network in the tumor microenvironment. In addition, non-immunosuppressive mechanisms of MDSCs such as promotion of angiogenesis and induction of cancer stem cells also exert a powerful role in tumor progression. Thus, MDSCs are potential therapeutic targets to enhance the antitumor efficacy of ICB therapy in cases of multiple cancers. This review focuses on the tumor-promoting mechanism of MDSCs and provides an overview of current strategies that target MDSCs with the objective of enhancing the antitumor efficacy of ICB therapy.

Personalized Body Constitution Inquiry Based on Machine Learning.

Background: Body constitution (BC) is the abstract concept indicating the state of a person's health in Traditional Chinese Medicine (TCM). The doctor identifies the body constitution of the patient through inspection and inquiry. Previous research simulates doctors to identify BC types according to a patient's objective physical indicators. However, the lack of subjective feeling information can reduce the accuracy of the machine to imitate the doctor's diagnosis. The Constitution in Chinese Medicine Questionnaire (CCMQ) is used to collect subjective information but suffers from low acquisition efficiency. Methods: This paper presents a personalized body constitution inquiry method based on a machine learning technique. It employs a random generator, a feature extractor, and a classifier to simulate the doctor inquiry and generate a personalized questionnaire. Specifically, the feature extractor evaluates and sorts the question of the constitution in the CCMQ based on the recognition results of the tongue coating image of patients. The sorted questions and relevant BC label are inputted into the classifier; the best questions are screened out for patients. Results: The experimental results show that our method can select personalized questions from the CCMQ for the patients, significantly reducing the time and the number of questions to answer. It also improves the accuracy of recognizing BC. Compared with the CCMQ, patients had 68.3% fewer questions to answer and the time occupied by answering is reduced by 80.3%. Conclusions: The proposed method can simulate the doctor's inquiry and pick out personalized questions for patients. It can act as auxiliary diagnosis tools to collect subjective patient feelings and help make further judgments on the patient's BC types.

808 nm-Light-Excited Near-Infrared Luminescent Lanthanide Metal-Organic Frameworks for Highly Sensitive Physiological Temperature Sensing.

Ongoing demand for accurate self-calibrated noninvasive thermometers for micro-/nano-scale applications, particular biomedical diagnosis, is driving the development of temperature sensors. Here a new type of lanthanide metal-organic framework having near-infrared absorption and near-infrared emission features is presented, and it is based on efficient Nd3+ -to-Yb3+ energy transfer in 808 nm photoexcitation. The results show that the ratiometric parameter of Nd0.5 Yb0.5 TPTC (TPTC= 1,1':4',1''-terphenyl]-3,3'',5,5''-tetracarboxylic acid) can deliver good exponential-type luminescence response to temperature in the physiological regime (293-328 K) with high relative sensitivity and accurate temperature resolution, as well as good biocompatibility and chemical stability. Such lanthanide-based materials are especially useful in biomedical applications.

Organic titanates: a model for activating rapid room-temperature synthesis of shape-controlled CsPbBr3 nanocrystals and their derivatives.

The application of lead halide perovskite nanocrystals is challenged by the lack of strategies in rapid room-temperature synthesis with controlled morphologies. Here, we report on an initial study of adopting organic titanates as a model activator that promotes rapid room-temperature synthesis of shape-controlled, highly luminescent CsPbBr3 nanocrystals and their derivatives.

Highly Luminescent CsPbX3 (X=Cl, Br, I) Nanocrystals Achieved by a Rapid Anion Exchange at Room Temperature.

Cesium lead halide perovskite (CsPbX3 ) nanocrystals (NCs) exhibit an excellent photoelectric performance, which is directly governed by fine-tuning of the composition and preparation of materials with a special phase structure and morphology. However, it is still facing challenges to achieve highly stable and luminescent CsPbX3 NCs at room temperature. Herein, we report on a novel exchange reaction, in which metal halides MX2 (M=Zn, Mg, Cu, or Ca; X=Cl, Br, or I) solids act as anion source to directly prepare CsPbX3 NCs at room temperature without any pretreatment. Introducing small amount of oleic acid or oleylamine speed up the exchange reaction through different promotion mechanisms. Oleic acid coordinates to the surface of the NCs, which increases the reaction activity, and oleylamine greatly enhances the dissolution of ZnCl2 . XRD and TEM tests demonstrate that the cubic phase structure and the morphology of the parent CsPbX3 were well preserved. Moreover, the band-gap energies and photoluminescence (PL) spectra were readily tunable over the entire visible spectral region of λ=406-685 nm. Our findings could open up the possibilities of using metal halide solids as new anion sources to prepare high-quality CsPbX3 NCs at room temperature.