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Abstract Sorafenib is widely used in treating advanced hepatocellular carcinoma (HCC). However, its effectiveness in prolonging patient survival is limited by the development of drug resistance. To systematically investigate the resistance mechanisms of Sorafenib, an integrative analysis combining posttranslational modification (PTM) omics and CRISPR/Cas9 knockout library screening was conducted. This analysis identified ubiquitination at lysine 21 (K21) on chaperonin-containing TCP1 subunit 3 (CCT3) as being associated with Sorafenib resistance. Transcriptomic data from HCC patients treated with Sorafenib revealed that CCT3 expression was lower in responders compared to non-responders. Experimentally, inhibiting the expression of CCT3 sensitized HCC cells to Sorafenib and enhanced Sorafenib-induced ferroptosis. Additionally, CCT3 was found to interact with ACTN4, hindering the recycling of transferrin receptor protein 1 (TFRC) to the cell membrane, thus obstructing iron endocytosis. Mechanistically, the inhibition of ferroptosis by CCT3 depends on the deubiquitination of K6-linked non-degradative ubiquitination at its K21, which occurs upon Sorafenib treatment. Moreover, CCT3 knockdown enhanced the anti-tumor effects of Sorafenib in nude mice. In summary, we have identified a novel function of the chaperone protein. Targeting the CCT3/ACTN4/TFRC axis offers a promising strategy to enhance ferroptosis and overcome Sorafenib resistance in HCC.

ObjectivesTo explore the utility of gray-scale ultrasound (GSUS) and mammography (MG) for radiomic analysis in distinguishing between breast adenosis and invasive ductal carcinoma (IDC).MethodsData from 147 female patients with pathologically confirmed breast lesions (breast adenosis: 61 patients; IDC: 86 patients) between January 2018 and December 2022 were retrospectively collected. A training cohort of 113 patients (breast adenosis: 50 patients; IDC: 63 patients) diagnosed from January 2018 to December 2021 and a time-independent test cohort of 34 patients (breast adenosis: 11 patients; IDC: 23 patients) diagnosed from January 2022 to December 2022 were included. Radiomic features of lesions were extracted from MG and GSUS images. The least absolute shrinkage and selection operator (LASSO) regression was applied to select the most discriminant features, followed by logistic regression (LR) to construct clinical and radiomic models, as well as a combined model merging radiomic and clinical features. Model performance was assessed using receiver operating characteristic (ROC) analysis.ResultsIn the training cohort, the area under the curve (AUC) for radiomic models based on MG features, GSUS features, and their combination were 0.974, 0.936, and 0.991, respectively. In the test cohort, the AUCs were 0.885, 0.876, and 0.949, respectively. The combined model, incorporating clinical and all radiomic features, and the MG plus GSUS radiomics model were found to exhibit significantly higher AUCs than the clinical model in both the training cohort and test cohort (p0.05).ConclusionThe effectiveness of radiomic features derived from GSUS and MG in distinguishing between breast adenosis and IDC is demonstrated. Superior discriminatory efficacy is shown by the combined model, integrating both modalities.

The epigenetic machinery has received extensive attention due to its involvement in plant growth, development, and adaptation to environmental changes. Recent studies often highlight the epigenetic regulatory network by discussing various epigenetic mutants across various plant species. However, a systemic understanding of essential epigenetic regulatory mechanisms remains limited due to a lack of representative mutants involved in multiple biological processes. Colorless Non-ripening (Cnr), a spontaneous epimutant isolated from a commercial population, was initially characterized for its role in fruit ripening regulation. Cnr fruits exhibit an immature phenotype with yellow skin, attributed to hypermethylation of the SQUAMOSA PROMOTER BINDING PROTEIN-LIKE-CNR (SlSPL-CNR) promoter, resulting in the repression of gene expression. In addition to DNA methylation, this process also involves histone modification and microRNA, integrating multiple epigenetic regulatory factors. Interestingly, knockout mutants of SlSPL-CNR display phenotypical distinctions from Cnr in fruit ripening, indicating complex genetic and epigenetic control over the non-ripening phenotype in Cnr fruits. Accumulating evidence suggests that Cnr epimutation is pleiotropic, participating in various biological processes such as Cd stress, Fe deficiency, vivipary, and cell death. Therefore, the Cnr epimutant serve as an excellent model for unveiling how epigenetic mechanisms are involved in diverse biological processes. This review paper focuses on recent research advances regarding the Cnr epimutant, delving into its complex genetic and epigenetic regulatory mechanisms, with the aim of enhancing our understanding and facilitating the development of high-quality, high-yield crops through epigenetic modification.

Abstract Zero thermal expansion (ZTE) alloys with high mechanical response are crucial for their practical usage. Yet, unifying the ZTE behavior and mechanical response in one material is a grand obstacle, especially in multicomponent ZTE alloys. Herein, we report a near isotropic zero thermal expansion (α l = 1.10 × 10−6 K−1, 260–310 K) in the natural heterogeneous LaFe54Co3.5Si3.35 alloy, which exhibits a super-high toughness of 277.8 ± 14.7 J cm−3. Chemical partition, in the dual-phase structure, assumes the role of not only modulating thermal expansion through magnetic interaction but also enhancing mechanical properties via interface bonding. The comprehensive analysis reveals that the hierarchically synergistic enhancement among lattice, phase interface, and heterogeneous structure is significant for strong toughness. Our findings pave the way to tailor thermal expansion and obtain prominent mechanical properties in multicomponent alloys, which is essential to ultra-stable functional materials.

Tin‐based halide perovskites garner attention as a promising semiconducting layer material for field‐effect transistors (FETs) owing to their lower effective mass than their lead‐based counterparts. However, they suffer from low ambient stability because Sn2+ is readily oxidized to Sn4+ in air. To address this issue, Ruddlesden–Popper (RP) perovskites featuring large organic cations emerge as promising materials for FETs. In this article, a comprehensive overview of the properties and advantages of RP‐phase tin‐based halide perovskites used in FETs are provided. Recent advancements in 2D and 2D/3D RP tin‐based perovskite FETs are examined, and challenges related to the fabrication of uniform large‐area films and strategies for improving ambient stability and operational durability are discussed. In this review article, the potential of RP perovskites for FET applications is emphasized and the need for further research to unlock their full potential is highlighted.

Abstract Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive scarring interstitial lung disease with an unknown cause. Some patients may experience acute exacerbations (AE), which result in severe lung damage visible on imaging or through examination of tissue samples, often leading to high mortality rates. However, the etiology and pathogenesis of AE-IPF remain unclear. AE-IPF patients exhibit diffuse lung damage, apoptosis of type II alveolar epithelial cells, and an excessive inflammatory response. Establishing a reliable animal model of AE is critical for investigating the pathogenesis. Recent studies have reported a variety of animal models for AE-IPF, each with its own advantages and disadvantages. These models are usually established in mice with bleomycin-induced pulmonary fibrosis, using viruses, bacteria, small peptides, or specific drugs. In this review, we present an overview of different AE models, hoping to provide a useful resource for exploring the mechanisms and targeted therapies for AE-IPF.

IntroductionIdiopathic pulmonary fibrosis (IPF) is characterized by progressive lung dysfunction due to excessive collagen production and tissue scarring. Despite recent advancements, the molecular mechanisms remain unclear.MethodsRNA sequencing identified 475 differentially expressed genes (DEGs) in the TGF-β1-induced primary lung fibrosis model. Gene expression chips GSE101286 and GSE110147 from NCBI gene expression omnibus (GEO) database were analyzed using GEO2R, revealing 94 DEGs in IPF lung tissue samples. The gene ontology (GO) and pathway enrichment, Protein-protein interaction (PPI) network construction, and Maximal Clique Centrality (MCC) scoring were performed. Experimental validation included RT-qPCR, Immunohistochemistry (IHC), and Western Blot, with siRNA used for gene knockdown. A co-expression network was constructed by GeneMANIA.ResultsGO enrichment highlighted significant enrichment of DEGs in TGF-β cellular response, connective tissue development, extracellular matrix components, and signaling pathways such as the AGE-RAGE signaling pathway and ECM-receptor interaction. PPI network analysis identified hub genes, including FN1, COL1A1, POSTN, KIF11, and ECT2. CALD1 (Caldesmon 1), CDH2 (Cadherin 2), and POSTN (Periostin) were identified as dysregulated hub genes in both the RNA sequencing and GEO datasets. Validation experiments confirmed the upregulation of CALD1, CDH2, and POSTN in TGF-β1-treated fibroblasts and IPF lung tissue samples. IHC experiments probed tissue-level expression patterns of these three molecules. Knockdown of CALD1, CDH2, and POSTN attenuated the expression of fibrotic markers (collagen I and α-SMA) in response to TGF-β1 stimulation in primary fibroblasts. Co-expression analysis revealed interactions between hub genes and predicted genes involved in actin cytoskeleton regulation and cell-cell junction organization.ConclusionsCALD1, CDH2, and POSTN, identified as potential contributors to pulmonary fibrosis, present promising therapeutic targets for IPF patients.

Ordered oxygen complexes (OOCs) endow a unique interstitial strengthening mechanism for simultaneously enhancing strength and ductility in HEAs. Here, the authors demonstrate whether such mechanism can be extended to other alloy systems and how the formation of OOCs is tailored.

Recently, there has been a new trend to design chemically heterogeneous austenite by adjusting the various thermal treatment processes in medium Mn steel. In this work, we found that the single or synergistic addition of ferrite stabilizers (e.g., Al) accelerated the heterogeneous distribution of Mn and the formation of a core-shell austenitic structure compared with the addition of an austenite stabilizer (e.g., Cu) under the conventional quenched-annealing process. In addition, the Mn-enriched austenite shell played a significant role in suppressing the martensitic transformation of the Mn-depleted austenite core upon cooling. The sharp Mn gradient distribution corresponded to the heterogeneous kinetics of the deformation-induced martensitic transformation, resulting in the gradual transformation-induced plasticity (TRIP) effect.

The growth of stable and high-mobility semiconductors using industry-compatible methods still attracts interest in electronics community. Here, Noh et al. report wafer-scale ultrathin Bi2S3 and Te semiconductors for high-performance complementary electronics using room temperature thermal evaporation.

Integrated photonic chips leverage the recent developments in integrated circuit technology, along with the control and manipulation of light signals, to realize the integration of multiple optical components onto a single chip. By exploiting the power of light, integrated photonic chips offer numerous advantages over traditional optical and electronic systems, including miniaturization, high-speed data processing and improved energy efficiency. In this review, we survey the current status of quantum computation, optical neural networks and the realization of some algorithms on integrated optical chips.

Abstract Quantum logic gates are backbones of quantum information processing (QIP), wherein the typical three-qubit Fredkin and Toffoli gates are essential in quantum computation and communication. So far, the quantum Fredkin gate has only been demonstrated with pre-entangled input states in free-space optics, which limits its usage for independent input photons. Here, we put forward an exquisite scheme and experimentally perform a proof-of-principle demonstration of three-qubit Fredkin and Toffoli gates on a programmable quantum photonic chip. Our scheme can also be used to realize a series of other two-qubit quantum gates. Our work sheds light on the merits of quantum photonic chip in implementing quantum logic gates, and paves the way for advanced quantum chip processors.

Mg-Si clusters or precipitates can make Al-Mg-Si alloys stronger, but the low bake-hardening response severely restricts their wide application in the automotive field. Here, we report a new strategy to significantly enhance the bake-hardening response of Al-Mg-Si-Cu-Zn alloys to the highest value of 167 MPa, compared with values of traditional 6xxx series alloys (such as, AA6016, AA6111 and AA6022). The ultra-fast bake-hardening response is mainly obtained by the synergy of homogeneous/heterogeneous nucleation of Zn-containing precipitates during the heat treatments. The process discovered here is amenable to large-scale automotive industrial production at low cost, and might be applicable to other Al alloy systems.

Progress on high-performance transistor employing perovskite channels has been limited to date. Here, Zhu et al. report hysteresis-free tin-based perovskite thin-film transistors with high hole mobility of 20 cm2V–1S–1, which can be integrated with commercial metal oxide transistors on a single chip.

Posttranslational modifications (PTMs) of proteins, particularly acetylation, phosphorylation, and ubiquitination, play critical roles in the host innate immune response. PTMs’ dynamic changes and the crosstalk among them are complicated. To build a comprehensive dynamic network of inflammation-related proteins, we integrated data from the whole-cell proteome (WCP), acetylome, phosphoproteome, and ubiquitinome of human and mouse macrophages. Our datasets of acetylation, phosphorylation, and ubiquitination sites helped identify PTM crosstalk within and across proteins involved in the inflammatory response. Stimulation of macrophages by lipopolysaccharide (LPS) resulted in both degradative and non-degradative ubiquitination. Moreover, this study contributes to the interpretation of the roles of known inflammatory molecules and the discovery of novel inflammatory proteins.

Abstract Tin (Sn2+)‐based halide perovskites have been developed as the most promising alternatives to their toxic Pb‐based counterparts in optoelectronic devices. However, the facile tin vacancy formation and easy oxidization characteristics make Sn2+‐based perovskites highly p‐doped with excessive hole concentrations, which significantly hinder their applications. Herein, we demonstrate a potent hole inhibitor of antimony fluoride (SbF3), which possesses a higher hole‐suppression capability than conventional tin fluoride (SnF2). A small amount of SbF3 allows a wide range of hole‐density modulation with no or less SnF2 addition, thus mitigating the negative effects of using only SnF2. A SnF2/SbF3 co‐additive approach was further developed to achieve high‐performance Sn2+ perovskite thin‐film transistors operated in the enhancement mode with a five‐fold enhancement of the field‐effect mobility and improved operational stability compared to using only SnF2. We expect that the SbF3 hole suppressor and co‐additive approach can provide opportunities for the development of high‐efficiency Sn2+‐perovskite optoelectronic devices.

Common wisdom to improve ductility of bulk metallic glasses (BMGs) is to introduce local loose packing regions at the expense of strength. Here the authors enhance structural fluctuations of BMGs by introducing dense local packing regions, resulting in simultaneous increase of ductility and strength.

Abstract Background Tumor metastasis is a major factor for poor prognosis of hepatocellular carcinoma (HCC), but the relationship between ubiquitination and metastasis need to be studied more systematically. We analyzed the ubiquitinome of HCC in this study to have a more comprehensive insight into human HCC metastasis. Methods The protein ubiquitination levels in 15 HCC specimens with vascular invasion and 15 without vascular invasion were detected by ubiquitinome. Proteins with significantly different ubiquitination levels between HCCs with and without vascular invasion were used to predict E3 ubiquitin ligases associated with tumor metastasis. The topological network of protein substrates and corresponding E3 ubiquitin ligases was constructed to identify the key E3 ubiquitin ligase. Besides, the growth, migration and invasion ability of LM3 and HUH7 hepatoma cell lines with and without SYVN1 expression interference were measured by cell proliferation assay, subcutaneous tumor assay, umphal vein endothelium tube formation assay, transwell migration and invasion assays. Finally, the interacting proteins of SYVN1 were screened and verified by protein interaction omics, immunofluorescence, and immunoprecipitation. Ubiquitin levels of related protein substrates in LM3 and HUH7 cells were compared in negative control, SYVN1 knockdown, and SYVN1 overexpression groups. Results In this study, our whole‐cell proteomic dataset and ubiquitinomic dataset contained approximately 5600 proteins and 12,000 ubiquitinated sites. We discovered increased ubiquitinated sites with shorter ubiquitin chains during the progression of HCC metastasis. In addition, proteomic and ubiquitinomic analyses revealed that high expression of E3 ubiquitin‐protein ligase SYVN1 is related with tumor metastasis. Furthermore, we found that SYVN1 interacted with heat shock protein 90 (HSP90) and impacted the ubiquitination of eukaryotic elongation factor 2 kinase (EEF2K). Conclusions The ubiquitination profiles of HCC with and without vascular invasion were significantly different. SYVN1 was the most important E3 ubiquitin‐protein ligase responsible for this phenomenon, and it was related with tumor metastasis and growth. Therefore, SYVN1 might be a potential therapeutic target for HCC.

Metal halide perovskite semiconductors could potentially be used to create field-effect transistors (FETs) with high carrier mobilities. This review summarizes progress achieved recently in three-dimensional (3D) lead-based and two-dimensional (2D) tin-based perovskite FETs, and identifies the evolution of electrical characteristics and stability, then discusses outstanding challenges and provides an outlook on the possibilities offered by this electronic material family for use in backplane drivers for active matrix displays.

Let a,d be two elements in rings and a∥d be the inverse of a along d. When a∥d exists, we obtain several characterizations for the invertibility of aa∥d−a∥da, which is related to the invertibility of elements expressed by certain functions of a,d and suitable elements from the center of the ring. On the other hand, some equivalent conditions for the equality aa∥d=a∥da, as the complement of the previous invertibility in some sense, are given by means of the group inverses and the ring units, respectively. Then, the results obtained are applied in a ∗-ring, namely, when d=a∗, the co-EP and EP properties are deduced correspondingly.

Abstract Objective To investigate the detailed roles and mechanisms of tumor-derived exosomes in progression and metastasis of ovarian cancer in vitro. Methods Exosomes were isolated by differential centrifugation method; the morphology, size and biological markers of exosomes were separately defined by transmission electron microscopy, nanoS90 and Western blotting; Trans-well chambers assay was used to assess the ability of migration and invasion of recipient cells uptaking the exosomes from HO8910PM cells. The downstream molecule was screened by mass spectrometry.CD44 was identified by western blotting and the function of CD44 was identified by trans-well chambers assay and CCK8 assay. Results Exosomes derived from HO8910PM cells could be transferred to HO8910 cells and promote cell migration and invasion in the recipient cells of ovarian cancer. And CD44 could be transferred to the HO8910 cells through exosomes from HO8910PM cells and influence the migration and invasion ability of HO8910 cells. Conclusion The more aggressive subpopulation can transfer a metastatic phenotype to the less one via secreting exosomes within a heterogeneous tumor. CD44 may be a potential therapeutic approach for ovarian cancer.

Designing efficient thin-film transistors and circuits based on transparent p-type semiconductors remains a challenge. Here, the authors propose a solution-based doping approach to realize high performance transparent inorganic p-type semiconductors (Zn-doped CuI) by spin coating at 80 C with good operational stability.

Abstract Background It has been reported that nitric oxide (NO) could ameliorate cadmium (Cd) toxicity in tall fescue; however, the underlying mechanisms of NO mediated Cd detoxification are largely unknown. In this study, we investigated the possible molecular mechanisms of Cd detoxification process by comparative transcriptomic and metabolomic approaches. Results The application of Sodium nitroprusside (SNP) as NO donor decreased the Cd content of tall fescue by 11% under Cd stress (T1 treatment), but the Cd content was increased by 24% when treated with Carboxy-PTIO (c-PTIO) together with Nitro-L-arginine methyl ester (L-NAME) (T2 treatment). RNA-seq analysis revealed that 904 (414 up- and 490 down-regulated) and 118 (74 up- and 44 down-regulated) DEGs were identified in the T1 vs Cd (only Cd treatment) and T2 vs Cd comparisons, respectively. Moreover, metabolite profile analysis showed that 99 (65 up- and 34-down- regulated) and 131 (45 up- and 86 down-regulated) metabolites were altered in the T1 vs Cd and T2 vs Cd comparisons, respectively. The integrated analyses of transcriptomic and metabolic data showed that 81 DEGs and 15 differentially expressed metabolites were involved in 20 NO-induced pathways. The dominant pathways were antioxidant activities such as glutathione metabolism, arginine and proline metabolism, secondary metabolites such as flavone and flavonol biosynthesis and phenylpropanoid biosynthesis, ABC transporters, and nitrogen metabolism. Conclusions In general, the results revealed that there are three major mechanisms involved in NO-mediated Cd detoxification in tall fescue, including (a) antioxidant capacity enhancement; (b) accumulation of secondary metabolites related to cadmium chelation and sequestration; and (c) regulation of cadmium ion transportation, such as ABC transporter activation. In conclusion, this study provides new insights into the NO-mediated cadmium stress response.

Background. Hepatocellular carcinoma (HCC) is the sixth most common kind of cancer worldwide and the third leading cause of cancer mortality. Although a few studies have shown that hydroxyacid oxidase 2 (HAO2) may prevent HCC development, the molecular mechanism is unclear. Methods. We examined the levels of HAO2 expression in 23 pairs of HCC/paracancerous tissues by quantitative real-time polymerase chain reaction (qRT-PCR) and evaluated HAO2’s expression in The Cancer Genome Atlas (TCGA) database. Furthermore, we examined the biological activity of HAO2 utilizing cell-based functional assays. Additionally, we evaluated the relationship between miR-615-5p and HAO2 in Hep3B cells using a dual-luciferase reporter system and assessed the downstream regulatory mechanisms of miR-615-5p on HAO2. Finally, the nude mice tumor formation experiment was used to determine the impact of HAO2 on the tumorigenicity of HCC cells. Results. HAO2 expression was considerably underexpression in HCC tissues and cells, and patients with low HAO2 expression had poorer disease-free survival. Inhibition of cell proliferation, migration, and invasion was observed when HAO2 was overexpressed. miR-615-5p had a negative relation with HAO2, and miR-615-5p restored HAO2’s biological activity in HCC cells. Additionally, the tumor volume and weight were considerably reduced in the OV-HAO2 group compared to the OV-NC group. Conclusion. HAO2 was found to be underexpressed in HCC tissues and cells, and HAO2 overexpression inhibited HCC cell motility, which was negatively regulated by miR-615-5p. Exogenous expression of HAO2 reduced the tumorigenicity of HCC cells in vivo in nude mice.

(1) Background: Enterobius vermicularis infection causes a significant health burden in children. The infection occurs throughout the country and remains a serious public concern in China. Therefore, it is necessary to know the situation of E. vermicularis infection, to provide a scientific basis for the disease control and the optimum conditions for children’s growth. (2) Methods: Descriptive epidemiological analysis was implemented to demonstrate the status and changing trend of E. vermicularis infection from 2016 to 2020, while the spatial distribution characteristics and spatial-temporal clustering were illuminated by spatial autocorrelation analysis and spatio-temporal scanning analysis. (3) Results: The infection of E. vermicularis showed a fluctuating downward trend with a decline of 32.00% in 2020 compared to that in 2016 and was concentrated in central and southern China. There was no significant difference in infection rate between boys and girls, while the high infection rate was presented in 4-, 5- and 6- year-old children. The hotspots and spatial clustering areas were mainly concentrated in southern China. (4) Conclusions: From 2016 to 2020, the infection rate of E. vermicularis in children aged 3 to 9 years in China demonstrated a declining trend, and its distribution showed spatial clustering, mainly in southern China. Therefore, it is necessary to strengthen surveillance and implement control measures in combination with health education and environmental improvement.

Abstract Developing transparent p‐type semiconductors and conductors has attracted significant interest in both academia and industry because metal oxides only show efficient n‐type characteristics at room temperature. Among the different candidates, copper iodide (CuI) is one of the most promising p‐type materials because of its widely adjustable conductivity from transparent electrodes to semiconducting layers in transistors. CuI can form thin films with high transparency in the visible light region using various low‐temperature deposition techniques. This progress report aims to provide a basic understanding of CuI‐based materials and recent progress in the development of various devices. The first section provides a brief introduction to CuI with respect to electronic structure, defect states, charge transport physics, and overviews the CuI film deposition methods. The material design concepts through doping/alloying approaches to adjust the optoelectrical properties are also discussed in the first section. The following section presents recent advances in state‐of‐the‐art CuI‐based devices, including transparent electrodes, thermoelectric devices, p–n diodes, p‐channel transistors, light emitting diodes, and solar cells. In conclusion, current challenges and perspective opportunities are highlighted.

Bronchial artery-pulmonary artery fistula secondary to pulmonary tuberculosis is an important cause of hemoptysis in adults, but it's relatively rare in children. Bronchial artery-pulmonary artery fistulas are mostly congenital in children and may have no clinical manifestations in the early stage. Congenital bronchial artery-pulmonary fistula with pulmonary tuberculosis can lead to hemoptysis. From 2016 to 2020, two children with pulmonary tuberculosis complicated with bronchial artery and pulmonary artery fistula were admitted and treated in our hospital. We reminded pediatricians to pay attention to a variety of etiology combined with the possibility of children's hemoptysis.

Cancer chemotherapy can be hindered by drug resistance which leads to lower drug efficiency. Here, we have developed a drug delivery system that tethers doxorubicin to the surface of gold nanorods via a pH-sensitive linkage (AuNRs@DOX), for a combined photothermal and chemical therapy for cancer. First, AuNRs@DOX is ingested by HepG2 liver cancer cells. After endocytosis, the acidic pH triggers the release of doxorubicin, which leads to chemotherapeutic effects. The gold nanorods are not only carriers of DOX, but also photothermal conversion agents. In the presence of an 808 nm near-infrared laser, AuNRs@DOX significantly enhance the cytotoxicity of doxorubicin via the photothermal effect, which induces elevated apoptosis of hepG2 cancer cells, leading to better therapeutic effects in vitro and in vivo. Keywords: Gold nanorods, Doxorubicin, pH responsive, Photothermal therapy, Combinational therapy

Epigenetic modifications (or epigenetic tags) on DNA and histones not only alter the chromatin structure, but also provide a recognition platform for subsequent protein recruitment and enable them to acquire executive instructions to carry out specific intracellular biological processes. In cells, different epigenetic-tags on DNA and histones are often recognized by the specific domains in proteins (readers), such as bromodomain (BRD), chromodomain (CHD), plant homeodomain (PHD), Tudor domain, Pro-Trp-Trp-Pro (PWWP) domain and malignant brain tumor (MBT) domain. Recent accumulating data reveal that abnormal intracellular histone modifications (histone marks) caused by tumors can be modulated by small molecule-mediated changes in the activity of the above domains, suggesting that small molecules targeting histone-mark reader domains may be the trend of new anticancer drug development. Here, we summarize the protein domains involved in histone-mark recognition, and introduce recent research findings about small molecules targeting histone-mark readers in cancer therapy.

L-Ascorbate (Asc) plays important roles in plant development, hormone signaling, the cell cycle and cellular redox system, etc. The higher content of Asc in plant chloroplasts indicates its important role in the photosystem. The objective of this study was to study the roles of Asc in tall fescue leaves against heat stress. After a heat stress treatment, we observed a lower value of the maximum quantum yield for primary photochemistry (φPo), which reflects the inhibited activity of the photochemical phase of photosystem II (PSII). Moreover, we observed a higher value of efficiency of electron transfer from QB to photosystem I acceptors (δR0), which reflects elevated activity of the thermal phase of the photosystem of the tall fescue. The addition of Asc facilitate the behavior of the photochemical phase of the PSII by lowering the ROS content as well as that of the alternative electron donor to provide electron to the tyrosine residue of the D1 protein. Additionally, exogenous Asc reduces the activity of the thermal phase of the photosystem, which could contribute to the limitation of energy input into the photosystem in tall fescue against heat stress. Synthesis of the Asc increased under heat stress treatment. However, under heat stress this regulation does not occur at the transcription level and requires further study.

Inflammation causes many diseases that are serious threats to human health. However, the molecular mechanisms underlying regulation of inflammation and inflammasome activation are not fully understood which has delayed the discovery of new anti-inflammatory drugs of urgent clinic need. Here, we found that the natural compound Teuvincenone F, which was isolated and purified from the stems and leaves of Premna szemaoensis, could significantly inhibit lipopolysaccharide (LPS)–induced pro-inflammatory cytokines production and NLRP3 inflammasome activation. Our results showed that Teuvincenone F attenuated K63-linked ubiquitination of NF-κB-essential modulator (NEMO, also known as IKKγ) to suppress LPS-induced phosphorylation of NF-κB, and inhibited mRNA expression of IL-1β, IL-6, TNF-α, and NLRP3. In addition, we found that decreased NLRP3 expression by Teuvincenone F suppressed NLRP3 inflammasome activation and IL-1β/IL-18 maturation. In vivo, we revealed that Teuvincenone F treatment relieved LPS-induced inflammation. In conclusion, Teuvincenone F is a highly effective natural compound to suppress LPS-induced inflammation by attenuating K63-linked ubiquitination of NEMO, highlighting that Teuvincenone F may be a potential new anti-inflammatory drug for the treatment of inflammatory and NLRP3 inflammasome-driven diseases.