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Poly (ADP-ribose) polymerase 1 (PARP1) is a DNA-binding protein that is involved in various biological functions, including DNA damage repair and transcription regulation. It plays a crucial role in cisplatin resistance. Nevertheless, the exact regulatory pathways governing PARP1 have not yet been fully elucidated. In this study, we present evidence suggesting that the hepatitis B X-interacting protein (HBXIP) may exert regulatory control over PARP1. HBXIP functions as a transcriptional coactivator and is positively associated with PARP1 expression in tissues obtained from hepatoma patients in clinical settings, and its high expression promotes cisplatin resistance in hepatoma. We discovered that the oncogene HBXIP increases the level of PARP1 m6A modification by upregulating the RNA methyltransferase WTAP, leading to the accumulation of the PARP1 protein. In this process, on the one hand, HBXIP jointly activates the transcription factor ETV5, promoting the activation of the WTAPpromoter and further facilitating the promotion of the m6A modification of PARP1 by WTAP methyltransferase, enhancing the RNA stability of PARP1. On the other hand, HBXIP can also jointly activate the transcription factor CEBPA, enhance the activity of the PARP1promoter, and promote the upregulation of PARP1 expression, ultimately leading to enhanced DNA damage repair capability and promoting cisplatin resistance in hepatoma. Notably, aspirin inhibits HBXIP, thereby reducing the expression of PARP1. Overall, our research revealed a novel mechanism for increasing PARP1 abundance, and aspirin therapy could overcome cisplatin resistance in hepatoma.

C/EBP homologous protein (CHOP) triggers the death of multiple cancers viaendoplasmic reticulum (ER) stress. However, the function and regulatory mechanism of CHOP in liver cancer remain elusive. We have reported that late endosomal/lysosomal adapter, mitogen-activated protein kinase and mTOR activator 5 (LAMTOR5) suppresses apoptosis in various cancers. Here, we show that the transcriptional and posttranscriptional inactivation of CHOP mediated by LAMTOR5 accelerates liver cancer growth. Clinical bioinformatic analysis revealed that the expression of CHOP was low in liver cancer tissues and that its increased expression predicted a good prognosis. Elevated CHOP contributed to destruction of LAMTOR5-induced apoptotic suppression and proliferation. Mechanistically, LAMTOR5-recruited DNA methyltransferase 1 (DNMT1) to the CpG3 region (−559/−429) of the CHOP promoter and potentiated its hypermethylation to block its interaction with general transcription factor IIi (TFII-I), resulting in its inactivation. Moreover, LAMTOR5-enhanced miR-182/miR-769 reduced CHOP expression by targeting its 3’UTR. Notably, lenvatinib, a first-line targeted therapy for liver cancer, could target the LAMTOR5/CHOP axis to prevent liver cancer progression. Accordingly, LAMTOR5-mediated silencing of CHOP viathe regulation of ER stress-related apoptosis promotes liver cancer growth, providing a theoretical basis for the use of lenvatinib for the treatment of liver cancer.

Programmed death ligand-1 (PD-L1)/PD-1 checkpoint extensively serves as a central mediator of immunosuppression. A tumor-promoting role for abundant PD-L1 in several cancers is revealed. However, the importance of PD-L1 and how the PD-L1 expression is controlled in breast cancer remains obscure. Here, the mechanisms of controlling PD-L1 at the transcription and protein acetylation levels in promoting breast cancer growth are presented. Overexpressed PD-L1 accelerates breast cancer growth in vitro and in vivo. RNA-seq uncovers that PD-L1 can induce some target genes affecting many cellular processes, especially cancer development. In clinical breast cancer tissues and cells, PD-L1 and HBXIP are both increased, and their expressions are positively correlated. Mechanistic exploration identifies that HBXIP stimulates the transcription of PD-L1 through co-activating ETS2. Specifically, HBXIP induces PD-L1 acetylation at K270 site through interacting with acetyltransferase p300, leading to the stability of PD-L1 protein. Functionally, depletion of HBXIP attenuates PD-L1-accelerated breast tumor growth. Aspirin alleviates breast cancer via targeting PD-L1 and HBXIP. Collectively, the findings display new light into the mechanisms of controlling tumor PD-L1 and broaden the utility for PD-L1 as a target in breast cancer therapy.

Sorafenib, which inhibits multiple kinases, is an effective frontline therapy for hepatocellular carcinoma (HCC). Ferroptosis is a form of iron-dependent programmed cell death regulated by lipid peroxidation, which can be induced by sorafenib treatment. Oncoprotein hepatitis B X-interacting protein (HBXIP) participates in multiple biological pro-tumor processes, including growth, metastasis, drug resistance, and metabolic reprogramming. However, the role of HBXIP in sorafenib-induced ferroptotic cell death remains unclear. In this study, we demonstrated that HBXIP prevents sorafenib-induced ferroptosis in HCC cells. Sorafenib decreased HBXIP expression, and overexpression of HBXIP blocked sorafenib-induced HCC cell death. Interestingly, suppression of HBXIP increased malondialdehyde (MDA) production and glutathione (GSH) depletion to promote sorafenib-mediated ferroptosis and cell death. Ferrostatin-1, a ferroptosis inhibitor, reversed the enhanced anticancer effect of sorafenib caused by HBXIP silencing in HCC cells. Regarding the molecular mechanism, HBXIP transcriptionally induced the expression of stearoyl-CoA desaturase (SCD) via coactivating the transcriptional factor ZNF263, resulting in the accumulation of free fatty acids and suppression of ferroptosis. Functionally, activation of the HBXIP/SCD axis reduced the anticancer activity of sorafenib and suppressed ferroptotic cell death in vivo and in vitro. HBXIP/SCD axis-mediated ferroptosis can serve as a novel downstream effector of sorafenib. Our results provide new evidence for clinical decisions in HCC therapy.

In this study, we investigated the changes in peripheral blood inflammatory factors and intestinal flora in acquired immune deficiency syndrome (AIDS) and human immunodeficiency virus (HIV)-positive individuals (AIDS/HIV patients), and explored the relationships among intestinal flora, peripheral blood inflammatory factors, and CD4+T lymphocytes. Thirty blood and stool samples from an AIDS group and a control group were collected. The levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined by enzyme-linked immunosorbent assay (ELISA), and the number of CD4+T lymphocytes by a FACSCount automated instrument. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the messenger RNA (mRNA) levels of Bifidobacterium, Lactobacillus, Escherichia coli, Enterococcus faecalis, and Enterococcus faecium. Correlations among intestinal flora, inflammatory factor levels, and CD4+T lymphocyte values were evaluated using the Spearman correlation coefficient. The levels of TNF-α and IL-6 in the AIDS group were higher than those in the control group, while the number of CD4+T lymphocytes was lower. The amounts of Bifidobacteriumand Lactobacillusin the AIDS group were significantly lower than those in control group, while the amounts of E. coli, E. faecalis, and E. faeciumwere much higher. The amounts of Bifidobacteriumand Lactobacilluswere negatively correlated with the content of TNF-α and IL-6 and the CD4+T lymphocyte count, while those correlations were reversed for E. coli, E. faecalis, and E. faecium. The intestinal microbiota of AIDS/HIV patients were disordered, and there was a correlation between the amount of intestinal flora and the number of CD4+T lymphocytes and the levels of TNF-α and IL-6. 本研究探究获得性免疫缺陷综合征 (AIDS) 和人类免疫缺陷病毒 (HIV) 阳性个体患者外周血炎症因子和肠道菌群的变化, 同时探讨了肠道菌群、 外周血炎症因子和CD4+T 淋巴细胞之间的关系。 首次探讨了 AIDS 和 HIV 阳性个体患者中肠道菌群、 外周血炎症因子和 CD4+T 淋巴细胞之间的关系。 从艾滋病组和对照组分别收集 30 份血液和粪便样本。 使用酶联免疫吸附测定 (ELISA) 法测定肿瘤坏死因子 (TNF-α) 和白细胞介素-6 (IL-6) 的水平; 用流式细胞仪测定 CD4+T 淋巴细胞数目; 采用实时定量聚合酶链式反应 (qRT-PCR) 法检测双歧杆菌、 乳酸菌、 大肠杆菌、 粪肠球菌和屎肠球菌的 mRNA 水平; 采用 Spearman 分析肠道菌群、 炎症因子与 CD4+T 淋巴细胞之间的相关性。 不但 AIDS/HIV 患者体内肠道菌群紊乱, 而且肠道菌群数量与 CD4+T 淋巴细胞数量以及T NF-α、 IL-6 水平存在相关性。

We have reported that hepatitis B X-interacting protein (HBXIP, also termed LAMTOR5) can act as an oncogenic transcriptional co-activator to modulate gene expression, promoting breast cancer development. Pyruvate kinase muscle isozyme M2 (PKM2), encoded by PKMgene, has emerged as a key oncoprotein in breast cancer. Yet, the regulatory mechanism of PKM2 is still unexplored. Here, we report that HBXIP can upregulate PKM2 to accelerate proliferation of estrogen receptor positive (ER+) breast cancer. Immunohistochemistry analysis using breast cancer tissue microarray uncovered a positive association between the expression of HBXIP and PKM2. We also discovered that PKM2 expression was positively related with HBXIP expression in clinical breast cancer patients by real-time PCR assay. Interestingly, in ER+ breast cancer cells, HBXIP was capable of upregulating PKM2 expression at mRNA and protein levels in a dose-dependent manner, as well as increasing the activity of PKMpromoter. Mechanistically, HBXIP could stimulate PKMpromoter through binding to the −779/−579 promoter region involving co-activation of E2F transcription factor 1 (E2F1). In function, cell viability, EdU, colony formation, and xenograft tumor growth assays showed that HBXIP contributed to accelerating cell proliferation through PKM2 in ER+ breast cancer. Collectively, we conclude that HBXIP induces PKM2 through transcription factor E2F1 to facilitate ER+ breast cancer cell proliferation. We provide new evidence for the mechanism of transcription regulation of PKM2 in promotion of breast cancer progression.

The practical utilization of the hydrogen evolution reaction (HER) necessitates the creation of electrocatalysts that are both efficient and abundant in earth elements, capable of operating effectively within a wide pH range. However, this objective continues to present itself as an arduous obstacle. In this research, we propose the incorporation of sulfur vacancies in a novel heterojunction formed by MoS2@CoS2, designed to exhibit remarkable catalytic performances. This efficacy is attributed to the advantageous combination of the low work function and space charge zone at the interface between MoS2and CoS2in the heterojunction. The MoS2@CoS2heterojunction manifests outstanding hydrogen evolution activity over an extensive pH range. Remarkably, achieving a current density of 10 mA cm–2in aqueous solutions 1.0 M KOH, 0.5 M H2SO4, and 1.0 M phosphate-buffered saline (PBS), respectively, requires only an overpotential of 48, 62, and 164 mV. The Tafel slopes for each case are 43, 32, and 62 mV dec–1, respectively. In this study, the synergistic effect of MoS2and CoS2is conducive to electron transfer, making the MoS2@CoS2heterojunction show excellent electrocatalytic performance. The synergistic effects arising from the heterojunction and sulfur vacancy not only contribute to the observed catalytic prowess but also provide a valuable model and reference for the exploration of other efficient electrocatalysts. This research marks a significant stride toward overcoming the challenges associated with developing electrocatalysts for practical hydrogen evolution applications.

Aspirin can efficiently inhibit liver cancer growth, but the mechanism is poorly understood. In this study, we report that aspirin modulates glucose uptake through downregulating glucose transporter 1 (GLUT1), leading to the inhibition of hepatoma cell proliferation. Our data showed that aspirin significantly decreased the levels of reactive oxygen species (ROS) and glucose consumption in hepatoma cells. Interestingly, we identified that GLUT1 and HIF1α could be decreased by aspirin. Mechanically, we demonstrated that the -1008/-780 region was the regulatory element of transcriptional factor NF-κB in GLUT1 promoter by luciferase report gene assays. PDTC, an inhibitor of NF-κB, could suppress the expression of GLUT1 in HepG2 and H7402 cells, followed by affecting the levels of ROS and glucose consumption. CoCl2-activated HIF1α expression could slightly rescue the GLUT1 expression inhibited by aspirin or PDTC, suggesting that aspirin depressed GLUT1 through targeting NF-κB or NF-κB/HIF1α signaling. Moreover, we found that GLUT1 was highly expressed in clinical HCC tissues relating to their paired adjacent normal tissues. Importantly, we observed that high level of GLUT1 was significantly correlated with the poor relapse-free survival of HCC patients by analysis of public data. Functionally, overexpression of GLUT1 blocked the PDTC-induced or aspirin-induced inhibition of glucose metabolism in HepG2 cells. Conversely, aspirin failed to work when GLUT1 was stably knocked down in the cells. Administration of aspirin could depress the growth of hepatoma cells through controlling GLUT1 in vitro and in vivo. Thus, our finding provides new insights into the mechanism by which aspirin depresses liver cancer.

Mammalian hepatitis B X-interacting protein (HBXIP) is an 18-kDa protein that regulates a large number of transcription factors such as TF-IID, E2F1, SP1, STAT3, c-Myc, and LXR by serving as an oncogenic transcription coactivator and plays an important role in the development of breast cancer. We previously showed that HBXIP as an oncoprotein could enhance the promoter activity of MDM2 through coactivating p53, promoting the MDM2 transcription in breast cancer. In this study we investigated the molecular mechanisms underlying the modulation of MDM2/p53 interaction by HBXIP in human breast cancer MCF-7 cells in vitro and in vivo. We showed that HBXIP could up-regulate MDM2 through inducing DNA methylation of miR-18b, thus suppressing the miR-18b expression, leading to the attenuation of p53 in breast cancer cells. In addition, HBXIP could promote the phosphorylation of MDM2 by increasing the level of pAKT and bind to pMDM2, subsequently enhancing the interaction between MDM2 and p53 for the down-regulation of p53 in breast cancer cells. In MCF-7 breast cancer xenograft nude mice, we also observed that overexpression of HBXIP promoted breast cancer growth through the miR-18b/MDM2 and pAKT/MDM2 pathways. In conclusion, oncoprotein HBXIP suppresses miR-18b to elevate MDM2 and activates pAKT to phosphorylate MDM2 for enhancing the interaction between MDM2 and p53, leading to p53 degradation in promotion of breast cancer growth. Our findings shed light on a novel mechanism of p53 down-regulation during the development of breast cancer.

The aim of this study was to identify specific laboratory indices to distinguish Epstein-Barr virus–associated hemophagocytic lymphohistiocytosis (EBV-HLH) in children.

We prepared alginate-chitosan (ALG-CTS) complexes through ionic interaction, and then obtained Cu (II)-imprinted alginate-chitosan complex microspheres (Cu-ALG-CTS) by coupling with ionic imprinting technology. To investigate the effects of experimental conditions on adsorption behavior, we performed a series of experiments including changing the initial concentration of Cu (II) ions and adsorption time. We found that the adsorption capacity increases with the initial concentration of Cu (II) ions. The Cu (II) ions adsorption reaches the maximum of 70.54mg/g after adsorbing for 13h when the initial concentration of Cu (II) ions is 60μg/ml. Cu-ALG-CTS shows much higher adsorption for Cu (II) ions than Zn (II) ions. And the adsorption kinetics and equilibrium adsorption isotherm were further studied.

A novel sensing element for direct detection of L-Tryptophan (L-Trp) in human serum was proposed by combination of electrochemical transduction and molecular imprinting technique. The sensing element was prepared by electropolymerization of o-phenylenediamine (o-PD) on the gold electrode in the presence of template L-Trp. The electrochemical property of the sensor was characterized by differential pulse voltammetry (DPV). The linear response range of the sensor for L-Trp concentration was 1×10-8 mol/L~21×10-8 mol/L with a detection limit of 0.3×10-8 mol/L. The results show that this approach has the potential to generate a universal inexpensive assay methodology of high sensitivity, specificity and simplicity to detect L-Trp.

Abstract. In this study, the simultaneous adsorption characteristics of ammonium and phosphate from aqueous solution by calcium chloride-modified zeolite were investigated. Results showed that the adsorption kinetic data of ammonium and phosphate onto the calcium chloride-modified zeolite could be well described by a pseudo-second-order model. The adsorption equilibrium data of ammonium onto the calcium chloride-modified zeolite fitted to the Langmuir isotherm model better than the Freundlich and Dubinin-Radushkevich isotherm models. The phosphate removal efficiency of calcium chloride-modified zeolite increased with the initial concentration of ammonium in aqueous solution. The ammonium removal efficiency of calcium chloride-modified zeolite increased with increasing solution pH from 7.0 to 9.0, but decreased with increasing solution pH from 9.0 to 10.0. The phosphate removal efficiency of calcium chloride-modified zeolite increased dramatically with increasing solution pH from 7.0 to 9.0, but decreased with increasing solution pH from 9.0 to 10.0. The mechanism for the adsorption of ammonium onto the calcium chloride-modified zeolite was ions exchange, and the mechanism for the removal of phosphate by the calcium chloride-modified zeolite was chemical precipitation.

In situ grafting on surface was developed to modify porous microspheres. Functional monomers were grafted onto the porous microspheres. The grafting yield was up to 54.6%. The self-assembly of functional monomer and L-tryptophan molecules was verified by UV spectrometry. The surface imprinted polymer microspheres (SMIPs) were synthesized based on the in situ grafting on surface. The competitive binding experiments were carried out to assess the recognition. The results showed good selectivity of the SMIPs towards target molecule. Langmuir and Freundlich adsorption models were applied to description of the experimental adsorption isotherm. The analysis suggested that the adsorbing behavior of SMIPs was in agreement with Langmuir isotherm equation.

Summary:Molecularly imprinted polymers with specific recognition to salicylic acid (SA‐MIPs) were prepared by oil‐in‐water emulsion polymerization using salicylic acid as template, acrylamide as functional monomer, and ethylene glycol dimethacrylate as crosslinker. The morphology and size distribution of the SA‐MIPs were detected by SEM and photon cross correlation spectrometry. Equilibrium binding experiments and Scatchard analyses were carried out to investigate the selectivity of the SA‐MIPs. The results show that the SA‐MIPs exhibit a higher affinity and selectivity to salicylic acid than to m‐hydroxybenzoic acid and sulfosalicylic acid. Two classes of binding sites were produced in the SA‐MIPs and the equilibrium dissociation constants were estimated to be 2.03 and 9.97 mmol/L, respectively.