Chromomycins from soil-derived Streptomyces sp. inhibit the growth of human non-small cell lung cancer cells by targeting c-FLIP.

Three chromomycin derivatives, chromomycins A3 (1, CA3), A5 (2, CA5), and monodeacetylchromomycin A3 (3, MDA-CA3), were identified from the soil-derived Streptomyces sp. CGMCC 26516. A reinvestigation of the structure of CA5 is reported, of which the absolute configuration was unambiguously determined for the first time to be identical with that of CA3 based on nuclear magnetic resonance (NMR) data analysis as well as NMR and electronic circular dichroism calculations. Compounds 1-3 showed potent cytotoxicity against the non-small-cell lung cancer (NSCLC) cells (A549, H460, H157-c-FLIP, and H157-LacZ) and down-regulated the protein expression of c-FLIP in A549 cells. The IC50 values of chromomycins in H157-c-FLIP were higher than that in H157-LacZ. Furthermore, si-c-FLIP promoted anti-proliferation effect of chromomycins in NSCLC cells. In nude mice xenograft model, 1 and 2 both showed more potent inhibition on the growth of H157-lacZ xenografts than that of H157-c-FLIP xenografts. These results verify that c-FLIP mediates the anticancer effects of chromomycins in NSCLC.

Encephalitozoon hellem infection after haploidentical allogeneic hematopoietic stem cell transplantation in children: a case report.

Background: Encephalitozoon hellem (E. hellem) infection is a zoonotic disease, rarely observed in individuals, causing various clinical manifestations including diarrhea, keratoconjunctivitis, cystitis, etc. E. hellem infection after hematopoietic stem-cell transplantation (HSCT) is a rare, serious complication. Case presentation: Herein, we present a case of E. hellem infection developing during HLA-haploidentical HSCT in a 9-year-old boy who suffered from aplastic anemia. On 15 days after HSCT, the patient developed recurrent and prolonged fever, diarrhea and hematuria. It is challenging to differentiate whether the symptoms mentioned in this case are caused by graft-versus-host disease (GVHD) or a specific infection. Based on the result of metagenomic next-generation sequencing (mNGS) and clinical observation, the patient was diagnosed as E. hellem infection, and received albendazole and decreased the immunosuppressive treatment. Finally, he had recovered. Conclusion: We should pay attention to the uncommon disease caused by the E. hellem infection after HSCT, especially in cases with immune reconstitution unrecovered. Among those rare infection, mNGS can be performed for better understanding the source of infection and targeted therapy, which can benefit the patients.

Ionizing radiation induces neurotoxicity in Xenopus laevis embryos through neuroactive ligand-receptor interaction pathway.

Ionizing radiation (IR) poses a significant threat to both the natural environment and biological health. Exposure to specific doses of ionizing radiation early in an organism's development can lead to developmental toxicity, particularly neurotoxicity. Through experimentation with Xenopus laevis (X. laevis), we examined the effects of radiation on early developmental stage. Our findings revealed that radiation led to developmental abnormalities and mortality in X. laevis embryos in a dose-dependent manner, disrupting redox homeostasis and inducing cell apoptosis. Additionally, radiation caused neurotoxic effects, resulting in abnormal behavior and neuron damage in the embryos. Further investigation into the underlying mechanisms of radiation-induced neurotoxicity indicated the potential involvement of the neuroactive ligand-receptor interaction pathway, which was supported by RNA-Seq analysis. Validation of gene expression associated with this pathway and analysis of neurotransmitter levels confirmed our hypothesis. In addition, we further validated the important role of this signaling pathway in radiation-induced neurotoxicity through edaravone rescue experiments. This research establishes a valuable model for radiation damage studying and provides some insight into radiation-induced neurotoxicity mechanisms.

First-principles study of two-dimensional transition metal carbide Mn+1CnO2(M = Nb,Ta).

In the present work, the three stable MXenes Mn+1CnO2(M = Nb,Ta) are explored based on first-principles calculations. These materials are important derivatives of 2D materials and exhibit distinctive properties, holding vast potential in nanodevices. All these Mn+1CnO2(M = Nb,Ta) materials exhibit outstanding superconducting performance, with corresponding superconducting transition temperatures of 23.00 K, 25.00 K, and 29.00 K. Analysis reveals that the high superconducting transition temperatures of MXenes Mn+1CnO2(M = Nb,Ta) are closely associated with the high value of the logarithmic average of phonon frequencies,ωlog, and the strong electron-phonon coupling, attributed to the crucial contribution of low-frequency phonons. Additionally, we applied strain treatments of 2% and 4% to Mn+1CnO2(M = Nb,Ta), resulting in varying changes in superconducting transition temperatures under different strains.

Exosome-transported circ_0061407 and circ_0008103 play a tumour-repressive role and show diagnostic value in non-small-cell lung cancer.

BACKGROUND: Circular RNAs (circRNAs), one of the major contents of exosomes, have been shown to participate in the occurrence and progression of cancers. The role and the diagnostic potential of exosome-transported circRNAs in non-small-cell lung cancer (NSCLC) remain largely unknown. METHODS: The NSCLC-associated exosomal circ_0061407 and circ_0008103 were screened by circRNA microarray. The role of circ_0061407 and circ_0008103 in NSCLC was examined in vitro and in vivo. The encapsulation of the two circRNAs into exosomes and the transport to recipient cells were observed by confocal microscopy. The effects of exosome-transported circ_0061407 and circ_0008103 on recipient cells were investigated using a co-culture device. Bioinformatics analyses were performed to predict the mechanisms by which circ_0061407 and circ_0008103 affected NSCLC. The quantitative polymerase chain reaction was used to quantify the exosome-containing circ_0061407 and circ_0008103 in the serum samples of healthy, pneumonia, benign lung tumours, and NSCLC. The diagnostic efficacy was evaluated using receiver operating characteristic curves. RESULTS: The levels of circ_0061407 and circ_0008103 within exosomes were down-regulated in the serum of patients with NSCLC. The up-regulation of circ_0061407 and circ_0008103 inhibited the proliferation, migration/invasion, cloning formation of NSCLC cells in vitro and inhibited lung tumour growth in vivo. Circ_0061407 and circ_0008103 were observed to be packaged in exosomes and transported to recipient cells, where they inhibited the proliferation, migration/invasion, and cloning formation abilities of the recipient cells. Moreover, circ_0061407 and circ_0008103 might be involved in the progression of NSCLC by interacting with microRNAs and proteins. Additionally, lower serum exosomal circ_0061407 and circ_0008103 levels were associated with advanced pathological staging and distant metastasis. CONCLUSIONS: This study identified two novel exosome-transported circRNAs (circ_0061407 and circ_0008103) associated with NSCLC. These findings may provide additional insights into the development of NSCLC and potential diagnostic biomarkers for NSCLC.

Quinomycins with an unusual N-methyl-3-methylsulfinyl-alanine residue from a Streptomyces sp.

Four new echinomycin congeners, quinomycins M-P (1-4) were isolated from the cultures of the soil-derived Streptomyces sp. CPCC205575. The planar structures were determined by comprehensive analyses of NMR and HRESIMS/MS data. The absolute configurations were elucidated by the advanced Marfey's method combined with biosynthetic gene analysis. Compounds 1-4 represent the first examples of quinomycin-type natural products with the sulfur atom at the N,S-dimethylcysteine residue oxidized as a sulfoxide group forming the unusual N-methyl-3-methylsulfinyl-alanine residue. Bioassay results revealed that the oxidation of the sulfur atom at the Cys or Cys' residues led to dramatic decrease of cytotoxicity and antimicrobial activity.

Thiostrepton suppresses triple-negative breast cancer through downregulating c-FLIP/SMAD2/3 signaling pathway.

Triple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis of breast cancer. Thiostrepton exerts anti-tumor activities against several cancers including TNBC. Herein we discussed the new molecular mechanisms of thiostrepton in TNBC. Thiostrepton inhibited MDA-MB-231 cell viability, accompanied by a decrease of c-FLIP and p-SMAD2/3. c-FLIP overexpression reduced the sensitivity of MDA-MB-231 cells to thiostrepton, while SMAD2/3 knockdown increased the sensitivity of MDA-MB-231 cells to thiostrepton. Moreover, c-FLIP overexpression significantly increased the expression and phosphorylation of SMAD2/3 proteins and vice versa. In conclusion, our study reveals c-FLIP/SMAD2/3 signaling pathway as a novel mechanism of antitumor activity of thiostrepton.

Abnormal Bone Turnover Observed in Obese Children Based on Puberty Stage -Specific Bone Turnover Marker Reference.

CONTEXT: Childhood and adolescence are critical periods for lifelong bone health. The impact of obesity on these phases is controversial, which may be due to the lack of standards for age-, sex-, and puberty-specific Bone turnover markers (BTMs) which could sensitively reflect bone metabolism. OBJECTIVE: To generate age-, sex, and puberty stage-specific BTMs reference curves in children and adolescents and to explore the effect of obesity on bone metabolism in the Chinese population. METHODS: Our study was part of the Evaluation and Monitoring on School-based Nutrition and Growth in Shenzhen study. 800 participants aged 6∼18 years with normal body mass index (BMI) were selected to establish BTM reference curves for boys and girls at different ages under different pubertal development stages. Additionally, 200 participants with obesity (BMI >P95th) were matched with healthy children from the original cohort at a 1:1 ratio. All participants underwent bone mineral density assessment, and serum levels of P1NP and ß-CTX were measured. RESULTS: The BTMs values presented significant age, sex, and puberty stage differences. Analysis of serum BTMs based on the established reference revealed a higher percentage of low-level P1NP in boys with obesity (P=0.005); no significant difference was observed in girls. However, the obese group showed a significantly higher proportion of high ß-CTX levels for girls, not boys (P=0.022). CONCLUSIONS: We provide age-, sex-, and puberty stage-specific P1NP and ß-CTX reference curve. According to these, obesity appeared to be a negative factor for bone formation in boys and for bone resorption in girls.

Isolation and antioxidant activity of peptides from Chinese hairy tofu.

Hairy tofu is a famous Chinese snack that is made from soybeans and rich in various nutrients. In order to further explore the antioxidant peptides of hairy tofu hydrolysates, seven proteases were used to hydrolyze hairy tofu. The results of in vitro radical scavenging activity showed that hairy tofu hydrolysates obtained by pancreatin exhibited the highest antioxidant activity. After Sephadex G-25 gel filtration and reversed-phase high-performance liquid chromatography (RP-HPLC), 97 peptides were identified in the most antioxidant fraction using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). Among them, nine peptides were synthesized and their antioxidant activities were assessed using a H2O2-induced oxidative 293T cell model. Finally, four peptides (QCESHK, LAWNEGR, NLQGENEWDQK, and FTEMWR) at concentrations of < 50 µg/ml significantly decreased the malondialdehyde content compared with the model group, displaying in vivo antioxidant activity and low cytotoxicity. Overall, this research provided the choice of using hairy tofu peptides as antioxidant products in the pharmaceutical and food industries.

LncRNA AL139294.1 can be transported by extracellular vesicles to promote the oncogenic behaviour of recipient cells through activation of the Wnt and NF-κB2 pathways in non-small-cell lung cancer.

BACKGROUND: Extracellular vesicles (EVs) participate in cancer development via cell-to-cell communication. Long non-coding RNAs (lncRNAs), one component of EVs, can play an essential role in non-small-cell lung cancer (NSCLC) through EV-mediated delivery. METHODS: The NSCLC-associated lncRNA AL139294.1 in EVs was identified via lncRNA microarray analysis. The role of AL139294.1 in NSCLC was examined in vitro and in vivo. Confocal microscopy was used to observe the encapsulation of AL139294.1 into EVs and its transport to recipient cells. A co-culture device was used to examine the effects of transported AL139294.1 on the oncogenic behaviour of recipient cells. Dual-luciferase reporter assay was performed to verify the direct interaction of miR-204-5p with AL139294.1 and bromodomain-containing protein 4 (BRD4). AL139294.1 and miR-204-5p in EVs were quantified using quantitative polymerase chain reaction. Receiver operating characteristic analyses were conducted to evaluate the diagnostic efficiency. RESULTS: The lncRNA AL139294.1 in EVs promoted NSCLC progression in vitro and in vivo. After AL139294.1 was encapsulated into EVs and transported to recipient cells, it promoted the cells' proliferation, migration, and invasion abilities by competitively binding with miR-204-5p to regulate BRD4, leading to the activation of the Wnt and NF-κB2 pathways. Additionally, the expression of serum lncRNA AL139294.1 in EVs was increased, whereas miR-204-5p in EVs was decreased in NSCLC. High levels of lncRNA AL139294.1 and low levels of miR-204-5p in EVs were associated with advanced pathological staging, lymph node metastasis, and distant metastasis, underscoring their promising utility for distinguishing between more and less severe manifestations of the disease. CONCLUSIONS: This study reveals a novel lncRNA in EVs associated with NSCLC, namely, AL139294.1, providing valuable insights into the development of NSCLC and introducing potential diagnostic biomarkers for NSCLC.

Bulk RNA-sequencing, single-cell RNA-sequencing analysis, and experimental validation reveal iron metabolism-related genes CISD2 and CYP17A1 are potential diagnostic markers for recurrent pregnancy loss.

BACKGROUND: Recurrent pregnancy loss (RPL) is associated with variable causes. Its etiology remains unexplained in about half of the cases, with no effective treatment available. Individuals with RPL have an irregular iron metabolism. In the present study, we identified key genes impacting iron metabolism that could be used for diagnosing and treating RPL. METHODS: We obtained gene expression profiles from the Gene Expression Omnibus (GEO) database. The Molecular Signatures Database was used to identify 14 gene sets related to iron metabolism, comprising 520 iron metabolism genes. Differential analysis and a weighted gene co-expression network analysis (WGCNA) of gene expression revealed two iron metabolism-related hub genes. Reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry were used on clinical samples to confirm our results. The receiver operating characteristic (ROC) analysis and immune infiltration analysis were conducted. In addition, we analyzed the distribution of genes and performed CellChat analysis by single-cell RNA sequencing. RESULTS: The expression of two hub genes, namely, CDGSH iron sulfur domain 2 (CISD2)and Cytochrome P450 family 17 subfamily A member 1 (CYP17A1), were reduced in RPL, as verified by both qPCR and immunohistochemistry. The Gene Ontology (GO) analysis revealed the genes predominantly engaged in autophagy and iron metabolism. The area under the curve (AUC) demonstrated better diagnostic performance for RPL using CISD2 and CYP17A1. The single-cell transcriptomic analysis of RPL demonstrated that CISD2 is expressed in the majority of cell subpopulations, whereas CYP17A1 is not. The cell cycle analysis revealed highly active natural killer (NK) cells that displayed the highest communications with other cells, including the strongest interaction with macrophages through the migratory inhibitory factor (MIF) pathway. CONCLUSIONS: Our study suggested that CISD2 and CYP17A1 genes are involved in abnormal iron metabolism, thereby contributing to RPL. These genes could be used as potential diagnostic and therapeutic markers for RPL.

[Inhibitory effect and molecular mechanism of sinomenine on human hepatocellular carcinoma HepG2 and SK-HEP-1 cells].

This study aimed to investigate the effect and molecular mechanism of sinomenine on proliferation, apoptosis, metastasis, and combination with inhibitors in human hepatocellular carcinoma HepG2 cells and SK-HEP-1 cells. The effect of sinomenine on the growth ability of HepG2 and SK-HEP-1 cells were investigated by CCK-8 assay, colony formation assay, and BeyoClick~(TM) EdU-488 staining. The effect of sinomenine on DNA damage was detected by immunofluorescence assay, and the effect of sinomenine on apoptosis of human hepatocellular carcinoma cells was clarified by Hoechst 33258 staining and CellEvent~(TM) Cystein-3/7Green ReadyProbes~(TM) reagent assay. Cell invasion assay and 3D tumor cell spheroid invasion assay were performed to investigate the effect of sinomenine on the invasion ability of human hepatocellular carcinoma cells in vitro. The effect of sinomenine on the regulation of protein expression related to the protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/signal transducer and activator of transcription 3(STAT3) signaling pathway in HepG2 and SK-HEP-1 cells was examined by Western blot. Molecular docking was used to evaluate the strength of affinity of sinomenine to the target cysteinyl aspartate specific proteinase-3(caspase-3) and STAT3, and combined with CCK-8 assay to detect the changes in cell viability after combination with STAT3 inhibitor JSI-124 in combination with CCK-8 assay. The results showed that sinomenine could significantly reduce the cell viability of human hepatocellular carcinoma cells in a concentration-and time-dependent manner, significantly inhibit the clonogenic ability of human hepatocellular carcinoma cells, and weaken the invasive ability of human hepatocellular carcinoma cells in vitro. In addition, sinomenine could up-regulate the cleaved level of poly ADP-ribose polymerase(PARP), a marker of apoptosis, and down-regulate the protein levels of p-Akt, p-mTOR, and p-STAT3 in human hepatocellular carcinoma cells. Molecular docking results showed that sinomenine had good affinity with the targets caspase-3 and STAT3, and the sensitivity of sinomenine to hepatocellular carcinoma cells was diminished after STAT3 was inhibited. Therefore, sinomenine can inhibit the proliferation and invasion of human hepatocellular carcinoma cells and induce apoptosis, and the mechanism may be attributed to the activation of caspase-3 signaling and inhibition of the Akt/mTOR/STAT3 pathway. This study can provide a new reference for the in-depth research and clinical application of sinomenine and is of great significance to further promote the scientific development and utilization of sinomenine.

[Morin induces autophagy and apoptosis in hepatocellular carcinoma cells through Akt/mTOR/STAT3 pathway].

This study investigated the effect and mechanism of morin in inducing autophagy and apoptosis in hepatocellular carcinoma cells through the protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/signal transducer and activator of transcription protein 3(STAT3) pathway. Human hepatocellular carcinoma SK-HEP-1 cells were stimulated with different concentrations of morin(0, 50, 100, 125, 200, and 250 µmol·L~(-1)). The effect of morin on the viability of SK-HEP-1 cells was detected by Cell Counting Kit-8(CCK-8). The effect of morin on the proliferation and apoptosis of SK-HEP-1 cells was investigated using colony formation assay, flow cytometry, and BeyoClick~(TM) EdU-488 with different concentrations of morin(0, 125, and 250 µmol·L~(-1)). The changes in the autophagy level of cells treated with morin were examined by transmission electron microscopy and autophagy inhibitors. The impact of morin on the expression levels of proteins related to the Akt/mTOR/STAT3 pathway was verified by Western blot. Compared with the control group, the morin groups showed decreased viability of SK-HEP-1 cells in a time-and concentration-dependent manner, increased number of apoptotic cells, up-regulated expression level of apoptosis marker PARP, up-regulated phosphorylation level of apoptosis-regulating protein H2AX, decreased number of positive cells and the colony formation rate, an upward trend of expression levels of autophagy-related proteins LC3-Ⅱ, Atg5, and Atg7, and decreased phosphorylation levels of Akt, mTOR, and STAT3. These results suggest that morin can promote apoptosis, inhibit proliferation, and induce autophagy in hepatocellular carcinoma cells, and its mechanism of action may be related to the Akt/mTOR/STAT3 pathway.

Short-axis PET image quality improvement based on a uEXPLORER total-body PET system through deep learning.

PURPOSE: The axial field of view (AFOV) of a positron emission tomography (PET) scanner greatly affects the quality of PET images. Although a total-body PET scanner (uEXPLORER) with a large AFOV is more sensitive, it is more expensive and difficult to widely use. Therefore, we attempt to utilize high-quality images generated by uEXPLORER to optimize the quality of images from short-axis PET scanners through deep learning technology while controlling costs. METHODS: The experiments were conducted using PET images of three anatomical locations (brain, lung, and abdomen) from 335 patients. To simulate PET images from different axes, two protocols were used to obtain PET image pairs (each patient was scanned once). For low-quality PET (LQ-PET) images with a 320-mm AFOV, we applied a 300-mm FOV for brain reconstruction and a 500-mm FOV for lung and abdomen reconstruction. For high-quality PET (HQ-PET) images, we applied a 1940-mm AFOV during the reconstruction process. A 3D Unet was utilized to learn the mapping relationship between LQ-PET and HQ-PET images. In addition, the peak signal-to-noise ratio (PSNR) and structural similarity index measure (SSIM) were employed to evaluate the model performance. Furthermore, two nuclear medicine doctors evaluated the image quality based on clinical readings. RESULTS: The generated PET images of the brain, lung, and abdomen were quantitatively and qualitatively compatible with the HQ-PET images. In particular, our method achieved PSNR values of 35.41 ± 5.45 dB (p < 0.05), 33.77 ± 6.18 dB (p < 0.05), and 38.58 ± 7.28 dB (p < 0.05) for the three beds. The overall mean SSIM was greater than 0.94 for all patients who underwent testing. Moreover, the total subjective quality levels of the generated PET images for three beds were 3.74 ± 0.74, 3.69 ± 0.81, and 3.42 ± 0.99 (the highest possible score was 5, and the minimum score was 1) from two experienced nuclear medicine experts. Additionally, we evaluated the distribution of quantitative standard uptake values (SUV) in the region of interest (ROI). Both the SUV distribution and the peaks of the profile show that our results are consistent with the HQ-PET images, proving the superiority of our approach. CONCLUSION: The findings demonstrate the potential of the proposed technique for improving the image quality of a PET scanner with a 320 mm or even shorter AFOV. Furthermore, this study explored the potential of utilizing uEXPLORER to achieve improved short-axis PET image quality at a limited economic cost, and computer-aided diagnosis systems that are related can help patients and radiologists.

The impact of executive compensation incentive on corporate innovation capability: Evidence from agro-based companies in China.

This paper aims to examine the impact of executive compensation incentive on corporate innovation capability by dividing executive compensation incentive into short-term monetary incentive and long-term equity incentive. We also investigate the interaction between the two types of executive compensation incentive. Data are collected from China's agro-based companies during 2012-2019, and multiple regression analysis is utilized. The empirical results show that short-term monetary incentive has no impact on innovation capability, while long-term equity incentive stimulates innovation capability. Regarding company ownership, the impact of long-term equity incentive in state-owned enterprises is greater than that in private-owned enterprises. In addition, the complementary effect between short-term and long-term compensation incentive has a positive impact on innovation capability regardless of company ownership. The findings of this paper could help agribusiness managers to design the reasonable incentive system to incentivize corporate executives and enhance the capability of independent innovation.

Boningmycin induces AMPK-mediated endoplasmic reticulum-associated degradation of PD-L1 protein in human cancer cells.

Anti-PD-1/PD-L1 monoclonal antibodies have displayed remarkable clinical benefits and revolutionized the treatment of multiple tumor types, but the low response rates and immune-related adverse events limit their application, which promoting the development of small molecule agents to improve the efficacy of PD-1/PD-L1 blockade therapy. Boningmycin (BON), a new small molecule belonging to bleomycin (BLM) family, exhibits potent anticancer activity in vitro and in vivo, as well as negligible lung toxicity, thereby can be an alternative of BLM. However, understandings about the anticancer mechanism of BLM-related compounds are extremely rare, it remains unclear if they affect PD-L1 level in a manner similar to that of other antitumor drugs. In this study, we discover that BON significantly reduces PD-L1 protein level in NCI-H460 and HT-1080 cells. Meanwhile, BON decreases the protein level of PD-L1 in a tumor xenograft model of NCI-H460 cells. Nevertheless, the mRNA level is not influenced after BON exposure. Furthermore, BON-induced PD-L1 reduction is proteasome- dependent. By using specific inhibitors and RNA interference technology, we confirm that the decline of PD-L1 protein by BON is mediated by AMPK-activated endoplasmic reticulum-associated degradation pathway, which is like to the action of metformin. Last but not the least, BON has synergism on gefitinib in vitro and in vivo. In conclusion, it is the first report demonstrating that BON decreases PD-L1 protein level through AMPK-mediated endoplasmic reticulum-associated degradation pathway. These findings will benefit the clinical transformation of BON and aid in the elucidation of molecular mechanism of BLM-related compounds.

Alkylamine-Grafted Molybdenum Disulfide Nanosheets for Enhanced Dispersion Stability and Lubricity Properties.

The unique structure and ultralow interlayer shear strength give molybdenum disulfide (MoS2) materials a broad prospect for energy savings, economic benefits, and extended operating life of lubrication systems. Herein, we prepared an effective integration strategy to prepare novel small-sized and chemically grafted MoS2 to solve the problems of poor dispersibility and easy agglomeration of MoS2. The MoS2 powder was stripped and oxidized to generate active centers using acid oxidation and high-speed ultrasonic crushing to obtain two different types of alkylamine chemically, covalently grafted, oxidized MoS2 nanosheets as lubricant additives to achieve friction reduction and antiwear. The chemical changes and structural characteristics of different types of alkylamine molecules upon covalent interaction with oxidized MoS2 were investigated in detail by FTIR, XPS, TGA, XRD, and TEM analyses. The results showed that the alkylamine-grafted MoS2 oxide nanosheets had good dispersion in 15# industrial white oil, and friction experiments confirmed that the alkylamine-grafted MoS2 oxide (MoS2-O-OLA) nanosheets exhibited better friction and wear resistance such that, compared with pure 15# industrial white oil, the 0.02 wt % MoS2-O-OLA nanosheets could significantly reduce friction (36.2%) and wear (22.4%). The field-emission scanning electron microscopy (FESEM) and EDS analyses of the wear surface showed that MoS2-O-OLA nanosheets play an important role in improving tribological properties by generating interlayer slippage at the steel ball contact interface, thereby forming surface protection and a uniform oil film.

Cancer Stem-Like Cells-Oriented Surface Self-Assembly to Conquer Radioresistance.

Cancer stem-like cells (CSCs), capable of indefinite self-renewal and differentiation, are considered to be the root cause of tumor radiotherapy (RT) resistance. However, the CSCs-targeted therapy still remains to be a great challenge because they are commonly located in the deep tumor making drugs hard to approach, and their hypoxic and acidic niche can further aggravate radioresistance. Herein, based on the finding that hypoxic CSCs highly express carbonic anhydrase IX (CAIX) on the cell membrane, a CAIX-targeted induced in situ self-assembly system on the surface of CSC is reported to overcome hypoxic CSC-mediated radioresistance. Via the sequential processes of "monomer release-target accumulation-surface self-assembly", the constructed peptide-based drug delivery system (CA-Pt) exhibits the advantages of deep penetration, amplified CAIX inhibition, and enhanced cellular uptake, which greatly relieves the hypoxic and acidic microenvironment to promote the hypoxic CSC differentiation and combines with platinum to boost the RT-inducing DNA damage. In both lung cancer tumor mouse and zebrafish embryo models, CA-Pt treatment can effectively assist RT in suppressing tumor growth and preventing tumor invasion and metastasis. This study uses a surface-induced self-assembly strategy to differentiate hypoxic CSCs, which may provide a universal treatment strategy for overcoming tumor radioresistance.

Regional Dynamic Neuroimaging Changes of Adults with Autism Spectrum Disorder.

Most neuroimaging studies investigating autism spectrum disorder (ASD) have focused on static brain function, but ignored the dynamic features of spontaneous brain activities in the temporal dimension. Research of dynamic brain regional activities might help to fully investigate the mechanisms of ASD patients. This study aimed to examine potential changes in the dynamic characteristics of regional neural activities in adult ASD patients and to detect whether the changes were associated with Autism Diagnostic Observation Schedule (ADOS) scores. Resting-state functional MRI was obtained on 77 adult ASD patients and 76 healthy controls. The dynamic regional homogeneity (dReHo) and dynamic amplitude of low-frequency fluctuations (dALFF) were compared between the two groups. Correlation analyses were also performed between dReHo and dALFF in areas showing group differences and ADOS scores. In ASD group, significant differences in dReHo were observed in the left middle temporal gyrus (MTG.L). Besides, we found increased dALFF in the left middle occipital gyrus (MOG.L), left superior parietal gyrus (SPG.L), left precuneus (PCUN.L), left inferior temporal gyrus (ITG.L), and right inferior frontal gyrus, orbital part (ORBinf.R). Furthermore, a significant positive correlation was found between dALFF in the PCUN.L and the ADOS_TOTAL scores, ADOS_SOCIAL scores; the dALFF in the ITG.L, SPG.L was positively associated with ADOS_SOCIAL scores. In conclusion, adults with ASD have a wide area of dynamic regional brain function abnormalities. These suggested that dynamic regional indexes might be used as a powerful measure to help us obtain a more comprehensive understanding of neural activity in adult ASD patients.

TeKo: Text-Rich Graph Neural Networks With External Knowledge.

Graph neural networks (GNNs) have gained great prevalence in tackling various analytical tasks on graph-structured data (i.e., networks). Typical GNNs and their variants adopt a message-passing principle that obtains network representations by the attribute propagates along network topology, which however ignores the rich textual semantics (e.g., local word-sequence) that exist in numerous real-world networks. Existing methods for text-rich networks integrate textual semantics by mainly using internal information such as topics or phrases/words, which often suffer from an inability to comprehensively mine the textual semantics, limiting the reciprocal guidance between network structure and textual semantics. To address these problems, we present a novel text-rich GNN with external knowledge (TeKo), in order to make full use of both structural and textual information within text-rich networks. Specifically, we first present a flexible heterogeneous semantic network that integrates high-quality entities as well as interactions among documents and entities. We then introduce two types of external knowledge, that is, structured triplets and unstructured entity descriptions, to gain a deeper insight into textual semantics. Furthermore, we devise a reciprocal convolutional mechanism for the constructed heterogeneous semantic network, enabling network structure and textual semantics to collaboratively enhance each other and learn high-level network representations. Extensive experiments illustrate that TeKo achieves state-of-the-art performance on a variety of text-rich networks as well as a large-scale e-commerce searching dataset.